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Interleukin-18 Binding Protein (IL-18BP): A Long Journey From Discovery to Clinical Application

  • Soohyun Kim;Hyeon Yu;Tania Azam;Charles A. Dinarello
    • IMMUNE NETWORK
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    • v.24 no.1
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    • pp.1.1-1.6
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    • 2024
  • IL-18 binding protein (IL-18BP) was originally discovered in 1999 while attempting to identify an IL-18 receptor ligand binding chain (also known as IL-18Rα) by subjecting concentrated human urine to an IL-18 ligand affinity column. The IL-18 ligand chromatography purified molecule was analyzed by protein microsequencing. The result revealed a novel 40 amino acid polypeptide. To isolate the complete open reading frame (ORF), various human and mouse cDNA libraries were screened using cDNA probe derived from the novel IL-18 affinity column bound molecule. The identified entire ORF gene was thought to be an IL-18Rα gene. However, IL-18BP has been proven to be a unique soluble antagonist that shares homology with a variety of viral proteins that are distinct from the IL-18Rα and IL-18Rβ chains. The IL-18BP cDNA was used to generate recombinant IL-18BP (rIL-18BP), which was indispensable for characterizing the role of IL-18BP in vitro and in vivo. Mammalian cell lines were used to produce rIL-18BP due to its glycosylation-dependent activity of IL-18BP (approximately 20 kDa). Various forms of rIL-18BP, intact, C-terminal his-tag, and Fc fusion proteins were produced for in vitro and in vivo experiments. Data showed potent neutralization of IL-18 activity, which seems promising for clinical application in immune diseases involving IL-18. However, it was a long journey from discovery to clinical use although there have been various clinical trials since IL-18BP was discovered in 1999. This review primarily covers the discovery of IL-18BP along with how basic research influences the clinical development of IL-18BP.

Analysis of Molecular Species of Vegetable Oil Triglycerides by Capillary Column GC-MS (Capillary Column GC-MS에 의한 식물유 트리글리세리드 분자종의 분석)

  • Yoon, Hyeung-Sik;Kim, Seon-Bong;Park, Yeung-Ho
    • Korean Journal of Food Science and Technology
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    • v.21 no.3
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    • pp.391-398
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    • 1989
  • Triglyceride molecular species In some vegetable oils were analyzed by capillary column gas chromatography and electron impact ionization mass spectrometry utilizing selected ion monitoring. Triglycerides were separated according to their molecular weights and their degrees of unsaturation on $25m{\times}0.25mm$ fused silica open tubular capillary column coated with a phenylmethylsilicone gum stationary phase and in an analysis time less than 13 min. Triglyceride molecular species were identified by analyzing the fragment ions having the same time on the selected ion monitoring profile . The major triglyceride molecular species in each oils were $C_{18:1}.\;C_{18:2}.\;C_{18:2}(OLL:18.3%),\;C_{18:2}.\;C_{18:2}.\;C_{18:2}(LLL;\;14.3%),\;C_{18:0}.\;C_{18:2}.\;C_{18:2}(SLL;\;14.1%),\;C_{16:0}.\;C_{18:2}.\;C_{18:2}(PLL;\;13.2%),\;C_{16:0}.\;C_{18:2}.\;C_{18:1}(PLO;\;11.6%)$ in corn oil, $C_{18:2}.\;C_{18:2}.\;C_{18:2}(LLL;\;18.0%),\;C_{18:1}.\;C_{18:2}.\;C_{18:2}(OLL;\;18.0%),\;C_{16:0}.\;C_{18:2}.\;C_{18:2}(PLL;\;17.1%)$ in safflower oil, $C_{16:0}.\;C_{18:2}.\;C_{18:2}(PLL;\;23.5%),\;C_{16:0}.\;C_{18:2}.\;C_{18:1}(PLO;\;13.8%),\;C_{18:0}.\;C_{18:1}.\;C_{18:1}(SOO;\;13.5%),\;C_{18:1}.\;C_{18:2}.\;C_{18:2}(OLL;\;10.6%)$ in cottonseed oil.

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Triglyceride Composition of Some Vegetable Oils 1. Triglyceride Composition of Sesame Oil (식물유의 Triglyceride 조성 1. 참기름의 Triglyceride 조성)

  • Park Yeung-Ho;WADA Shun;KOIZUMI Chiaki
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.14 no.1
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    • pp.1-6
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    • 1981
  • In this study, sesame oil was chosen as the experimental sample and analysed for its triglyceride composition by high-performance liquid chromatography(HPLC) in combination with gas liquid chromatography(GLC). The triglycerides were separated from sesame oil by liquid chromatographies on Bio-Beads SX-2 and on Sephadex LH-20, and fractionated into five groups on the basis of their partition numbers by reverse phase HPLC on a column packed with $\mu-Bondapak$ C18 using methanol-chloroform mix-ture as a solvent. Each of these collected fractions gave one to three peaks in the GLC chromatograms according to the acyl carbon number of the triglyceride, and fatty acid composition of the triglyceride was also analysed by GLC. From the results, it was found that the sesame oil consists with twenty one kinds of triglyceri-des, and the major triglycerides of sesame oil are those of $(2\;{\times}\;C18:1,\;C18:2\;;\;17.1\%),\;(C18:1,\;2{\times}C18:2\;;\;17.0\%),$ $(3\;{\times}\;C18:2\;;\;17.0\%),\;(3\;{\times}\;C18:1\;;\;10.9\%),$ $(3\;{\times}\;C18:2\;;\;9.6\%),\;(C16:0,\;C18:1,C18:2\;;\;7.9\%),$ $(C16:0,\;2\;{\times}\;C18:1\;;\;7.4\%),\;(C16:0,\;2\;{\times}\;C18:2\;;\;6.8\%),$ $(C18:0,\;C18:1,\;C18:2\;;\;3.1\%),\;(2\;{\times}\;C18:0,\;C18:2\;;\;1.5\%)$ $(C18:0,\;2\;{\times}\;C18:1\;;\;1.4\%),\;(C16:0,\;C18:0,\;C18:1\;;\;1.3\%),$ $(2\;{\times}\;C16:0,\;C18:1\;;\;1.2\%),\;and\;(C16:0,C18:0,\;C18:2\;;\;1.0\%)$.

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Studies on the Triglyceride Composition of some Vegetable Oils -III. Triglyceride Composition of Olive Oil- (식물유(植物油)의 Triglyceride조성(組成)에 관한 연구(硏究) -제3보(第3報) : 올리브기름의 Triglyceride조성(組成)-)

  • Choi, Su-An;Park, Yeung-Ho
    • Korean Journal of Food Science and Technology
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    • v.15 no.1
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    • pp.66-69
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    • 1983
  • Triglyceride fraction was separated from olive oil by thin layer chromatography (TLC) and fractionated into four groups by high performance liquid chromatography (HPLC). Compositions of the triglycerides and fatty acids of four fractions were determined by gas liquid chromatography (GLC). The olive oil contained higher concentrations of C-52 and C-54 triglycerides having partition numbers of 48. The fatty acid compositions of these triglycerides were mainly composed of C18:1 and C18:2 fatty acids. From these results, the possible fatty acid combinations of major triglycerides of olive oil were estimated to be(3C18:1;50.6%), (1C16:0, 2C18:1;23.51%), (2C18:1, 1C18:2;5.48%), (1C18:0, 2 18:1;4.55%), (1C16:0, 1C18:1, 1C18:2;2.94%), (2C16:0, 1C18:1;2.35%), (1 C16:1, 2 C18:1;2.21%), (1C18:1, 2C18:2;1.06%), (1 C14:0, 2 C18:1;1.03%).

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May 18th Gwangju Democratization Archives Collection Development Strategy for Advancement of Human Rights Awareness and Democracy (인권 의식과 민주주의의 진전을 위한 5·18광주민주화운동 기록의 수집전략)

  • Lee, Sangmin
    • The Korean Journal of Archival Studies
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    • no.48
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    • pp.5-44
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    • 2016
  • This paper examines the characteristics of the May 18th (5 18) Gwangju Democratization Movement archives to suggest a collection development strategy for the May 18th archives collection network. Individual public and civilian archives collecting the May 18th archives separately should form a cooperative collection network based on documentation strategy. Most of all, May 18th archives are human rights records and should be understood and collected as human rights records. International principles support the collection of the May 18th archives as human rights archives by prohibiting destruction of relevant temporary records and encouraging the victims' right to access to their records. As the May 18th archives were mostly produced by many multiple agencies, this multi-provenance and diversity of the records necessitate the building of an archives portal for the records registries and online search. To document the undocumented past and the victims, the collection network should focus on oral history project as a major part of its collection development strategy. Finally, the May 18th archives collection network should build a cooperative relations with the unwilling public agencies which have the archives holdings. Therefore, the collection development strategy should include advocacy and awareness activities for promoting cooperation from these public agencies and public archives, and the people in general.

Depletion of Cytoplasmic Tail of UL18 Enhances and Stabilizes the Surface Expression of UL18

  • Kim, Jung-Sik;Kim, Bon-Gi;Yoon, Il-Hee;Kim, Sang-Joon;Park, Chung-Gyu
    • IMMUNE NETWORK
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    • v.8 no.4
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    • pp.130-136
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    • 2008
  • Background: Human cytomegalovirus UL18, a MHC class I homologue, has been considered a natural killer (NK) cell decoy. It ligates LIR-1/ILT2 (CD85j), an NK inhibitory receptor, to prevent lysis of infected target cells. However, precise role of UL18 to NK cell cytotoxicity is yet elusive. Difficulty in clarifying the function of UL18 lies in complication in detecting UL18 mainly due to low level expression of UL18 on the surface and gradual loss of its expression. Methods: To overcome this hurdle, cDNA of cytoplasmic tail-less UL18 was constructed and expressed in swine endothelial cell (SEC). The expression level and its stability in the cell surface were monitored with FACS analysis. Results: Surface expression of UL18 is up-regulated by removing cytoplasmic tail portion from UL18F (a full sequence of UL18). SECs transfected with a cDNA of UL18CY (a cytoplasmic tail-less UL18) stably expressed UL18 molecule on the surface without gradual loss of its expression during 6 week continuous cultures. In the NK cytotoxicity assay, UL18 functions either inhibiting or activating NK cell cytotoxicity according to the source of NK cells. We found that there is individual susceptibility in determining whether the engagement of NK cell and UL18 results in overall inhibiting or activating NK cell cytotoxicity. Conclusion: In this study, we found that cytoplasmic tail is closely related to the regulatory function for controlling surface expression of UL18. Furthermore, by constructing stable cell line in which UL18 expression is up-regulated and stable, we provided a useful tool to clarify exact functions of UL18 on various immune cells having ILT2 receptor.

Production of $[^{18}F]F_2$ Gas for Electrophilic Substitution Reaction (친전자성 치환반응을 위한 $[^{18}F]F_2$ Gas의 생산 연구)

  • Moon, Byung-Seok;Kim, Jae-Hong;Lee, Kyo-Chul;An, Gwang-Il;Cheon, Gi-Jeong;Chun, Kwon-Soo
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.4
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    • pp.228-232
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    • 2006
  • Purpose: electrophilic $^{18}F(T_{1/2}=110\;min)$ radionuclide in the form of $[^{18}F]F_2$ gas is of great significance for labeling radiopharmaceuticals for positron omission tomography (PET). However, its production In high yield and with high specific radioactivity is still a challenge to overcome several problems on targetry. The aim of the present study was to develop a method suitable for the routine production of $[^{18}F]F_2$ for the electrophilic substitution reaction. Materials and Methods: The target was designed water-cooled aluminum target chamber system with a conical bore shape. Production of the elemental fluorine was carried out via the $^{18}O(p,n)^{18}F$ reaction using a two-step irradiation protocol. In the first irradiation, the target filled with highly enriched $^{18}O_2$ was irradiated with protons for $^{18}F$ production, which were adsorbed on the inner surface of target body. In the second irradiation, the mixed gas ($1%[^{19}F]F_2/Ar$) was leaded into the target chamber, fellowing a short irradiation of proton for isotopic exchange between the carrier-fluorine and the radiofluorine absorbed in the target chamber. Optimization of production was performed as the function of irradiation time, the beam current and $^{18}O_2$ loading pressure. Results: Production runs was performed under the following optimum conditions: The 1st irradiation for the nuclear reaction (15.0 bar of 97% enriched $^{18}O_2$, 13.2 MeV protons, 30 ${\mu}A$, 60-90 min irradiation), the recovery of enriched oxygen via cryogenic pumping; The 2nd irradiation for the recovery of absorbed radiofluorine (12.0 bar of 1% $[^{19}F]fluorine/argon$ gas, 13.2 MeV protons, 30 ${\mu}A$, 20-30 min irradiation) the recovery of $[^{18}F]fluorine$ for synthesis. The yield of $[^{18}F]fluorine$ at EOB (end of bombardment) was achieved around $34{\pm}6.0$ GBq (n>10). Conclusion: The production of $^{18}F$ electrophilic agent via $^{18}O(p,n)^{18}F$ reaction was much under investigation. Especially, an aluminum gas target was very advantageous for routine production of $[^{18}F]fluorine$. These results suggest the possibility to use $[^{18}F]F_2$ gas as a electrophilic substitution agent.

Triglyceride Composition of Kidney Bean (Phaseolus vulgaris L.) (강남콩(Phaseolus vulgaris L.)의 Triglyceride 조성)

  • Kwon, Yong-Ju;Uhm, Tai-Boong;Kim, Choong-Ki;Kim, Sang-Phil;Ko, Seuk-Beum;Lee, Tae-Kyoo;Yang, Hee-Cheon
    • Korean Journal of Food Science and Technology
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    • v.19 no.6
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    • pp.533-536
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    • 1987
  • Lipids of Kidney bean were extracted by the mixture of chloroform-methanol-water (1:2:0.8, v/v) and from these lipids, triglycerides were separated by thin-layer chromatography(TLC) and then reseparated into different fractions by high performance liquid chromatography (HPLC) depending on the polarity of the triglycerides. The triglyceride and fatty acid composition of these fractions were determined by gas liquid chromatography (GLC). From these results, the major triglycerides of Kidney bean lipids were estimated to be $C_{18:2}C_{18:3}C_{18:3}$ (26.6%), $C_{18:2}C_{18:2}C_{18:3}$ (18.5%), $C_{18:3}C_{18:3}C_{18:3}$ (14.9%).

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The Implicit Representation of the May 18 Gwangju Democratic Movement (광주·전남 출신 대학생이 5·18민주화운동에 대해 지니는 암묵적 표상)

  • Jaechang Bae
    • Korean Journal of Culture and Social Issue
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    • v.23 no.4
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    • pp.497-525
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    • 2017
  • This study verified whether university students of Gwangju and Jeollanam-do recall negative information like violence and death faster than positive information like democratic community about the May 18 Gwangju democratic movement in implicit dimension. University students of Gwangju responded faster when the May 18 combined with the pictures of negative content. However, university students of Jeollanam-do responded marginally faster when the May 18 combined with the pictures of positive content. In addition, the students performed implicit evaluation test towards the May 18. The students of Gwangju showed a slightly negative attitude towards the May 18, while the students of Jeollanam-do showed a positive attitude towards the May 18. This study acquires significance because it confirmed that university students of Gwangju have an implicit representation similar to trauma and a terrible feeling about the May 18.

Method to Reduce the Activity Loss and Pain when Injecting 18F-Florbetaben (18F-Florbetaben 주사 시 Activity 손실과 통증 감소를 위한 방법)

  • Kwon, Hyeong Jin;Choi, Jin Wook;Lee, Hyeong Jin;Woo, Jae Ryong;Kim, Yoo Kyeong
    • The Korean Journal of Nuclear Medicine Technology
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    • v.20 no.2
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    • pp.42-45
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    • 2016
  • Purpose Neuracep is used to other diagnostic evaluations of the brain to estimate beta-amyloid neuritic plaque density in adult patients with cognitive impairment and inspected cognitive impairment. $^{18}F-Florbetaben$ specially has moderate lipophilicity and property of the added ethanol. It is the subject of interest of the patient pain and residual activity after injecting. Our study is effective injection method of the radiopharmaceutical and patient care. So it is for the highest quality image. Materials and Methods Patients were targeted 70 subjects, it was injected mean $259{\pm}74MBq$ to the patients ($^{18}F-FDG$: 20 subjects, $^{18}F-FP-CIT$: 20 subjects, $^{18}F-Florbetaben$: 30 subjects). After injection (reflusing 2 times, reflusing 3 times) using a 3-way set, it measured the residual activity. When injecting $^{18}F-Florbetaben$, we evaluated the effective injection methods(3-way set method and heparin cap method). The average residual activity after the injection was compared using a statistical analysis of SPSS 12.0(ANOVA, t-test analysis). Also, elemental analysis was performed on $^{18}F-Florbetaben$ by GC (Gas Chromatography). Results When reflusing 2 times measured residual activity as follows ($^{18}F-FDG$: 1.48 MBq, $^{18}F-FP-CIT$: 7.4 MBq, $^{18}F-Florbetaben$: 32.6 MBq). And when reflusing 3 times measured residual activity as follows ($^{18}F-FDG$: 1.85 MBq, $^{18}F-FP-CIT$: 3.7 MBq, $^{18}F-Florbetaben$: 36.3 MBq). There was a significant difference when reflusing 2 times(P < 0.05) and reflusing 3 times (P < 0.05). But when reflusing 3 times, there was no significant difference relation FDG and FP-CIT (P > 0.05). $^{18}F-Florbetaben$ Residual activity according to the injection method was a significant difference (P < 0.05). GC analysis results were measured ethanol: 207665 ppm and acceton: 377.4 ppm. Conclusion $^{18}F-Florbetaben$ was high residual activity compared to FDG and FP-CIT. Heparin cap method was effective when $^{18}F-Florbetaben$ was injected. $^{18}F-Florbetaben's$ ethanol component analysis was highly measured. So it is recommended that inject to 6 sec/ml or more in order to reduce the pain.

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