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Production of $^{11}C$ labeled Radiopharmaceuticals using $[^{11}C]CO_2$ Produced in the KOTRON-13 (한국형 사이클로트론(KOTRON-13)을 이용한 $[^{11}C]CO_2$ 생산과 다양한 $^{11}C$-표지 방사성의약품 생산 적용)

  • Lee, Hong Jin;Park, Jun Hyung;Moon, Byung Seok;Lee, In Won;Lee, Byung Chul;Kim, Sang Eun
    • The Korean Journal of Nuclear Medicine Technology
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    • v.16 no.2
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    • pp.106-109
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    • 2012
  • Purpose : The KOTRON-13 cyclotron was developed and installed in regional cyclotron centers to produce short-lifetime medical radioisotopes. However, this cyclotron has limited capacity to produce $^{11}C$ so far. In present study, we developed an effective $^{11}C$ target system combining with fluorine-18 target and applied to the production of various $^{11}C$ radiopharmaceuticals. Materials and Methods : To develop the optimal $^{11}C$ target system and effective its cooling system, we designed the $^{11}C$ target system by Stopping and Range of Ions in Matter (SRIM) simulation program and considered the cavity pressure during irradiation at target grid. In this investigation, we modified target materials, cavity shapes and the position of cooling system in $^{11}C$ target and then evaluated $[^{11}C]CO_2$ production at different beam currents, thickness of the target foil, oxygen content of nitrogen gas and target gas loading pressure. Also, we evaluate the production of several $^{11}C$ radiopharmaceuticals such as [$^{11}C$]PIB, [$^{11}C$]DASB, and [$^{11}C$]Clozapine. Results : $[^{11}C]CO_2$ was produced about 74 GBq for 30min irradiation at 60 ${\mu}A$ of beam current as following conditions: thickness of the target foil: 19 nm HAVAR, oxygen content of nitrogen: under 50 ppb, target gas loading pressure: 24 bar. Additionally, the cooling system was stable to produce $[^{11}C]CO_2$ at high beam current. The radiochemical yields of [$^{11}C$]PIB, [$^{11}C$]DASB, and [$^{11}C$]Clozapine showed about 26-38% with over 127 GBq/umol of specific activity. Conclusion : The carbon-11 target system in the KOTRON-13 cyclotron was successfully developed and showed stable production of $[^{11}C]CO_2$. These results showed that our $^{11}C$ target system will be compatible with other commercial system for the routine $^{11}C$ radiopharmaceuticals production in the KOTRON-13 cyclotron.

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A Study on ICD-11 through Mapping to KCD-8 - Focusing on the Circulatory and Respiratory System -

  • Hyun-Kyung LEE;Yoo-Kyung BOO
    • Journal of Wellbeing Management and Applied Psychology
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    • v.6 no.3
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    • pp.1-11
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    • 2023
  • Purpose: This research aims to facilitate a smooth transition from KCD-8 to ICD-11 through the study of ICD-11. Research design, data and methodology: Skilled Health Information Managers (HIMs) in Korea performed manual mapping and conducted a study of the code structure of ICD-11 chapters 11 and 12. Results: When comparing the granularity between ICD-11 and KCD-8, 58.1% of ICD-11 codes showed higher granularity, and 38.6% had similar granularity. The granularity of the circulatory system was higher than that of the respiratory system. When comparing the KCD-8 codes mapped by ICD-11 with the total 924 KCD-8 codes, it was found that about 50% of KCD-8 codes were not mapped to ICD-11. This means that 50% of diseases in the KCD-8 do not have individual codes as they did in ICD-11. Conclusions: ICD-11 demonstrated high granularity, indicating its effectiveness in describing cutting-edge medical technology in modern society. However, we also observed that some diseases were removed from KCD-8, while others were added to ICD-11. To ensure smooth statistics transition from KCD8 to ICD-11, especially for leading domestic diseases, integrated management, including the preparation of KCD-9 reflecting ICD-11 and ICD-11 training, will be necessary through the analysis of new codes and the removal of codes.

Consecutive automated production of carbon-11 labeled radiopharmaceuticals by sharing 11C-methylation reagent from one 11C-synthetic module

  • Park, Hyun Sik;Lee, Hong Jin;An, Hyun Ho;Moon, Byung Seok;Lee, Byung Chul;Kim, Sang Eun
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.2 no.2
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    • pp.123-131
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    • 2016
  • Increasing clinical demand for carbon-11 labeled radiopharmaceuticals has triggered technological advances in fields of radiochemistry and automated modules. Even though carbon-11 has a short half-life ($t_{1/2}=20.4min$), the consecutive second production of carbon-11 labeled radiopharmaceutical in one $^{11}C$-synthetic module should be delayed at least over 4 h to avoid the high radiation exposure. We herein aimed to produce two different carbon-11 labeled radiopharmaceuticals ([$^{11}C$]PIB and [$^{11}C$]methionine) by sharing of [$^{11}C$]methylation source in one $^{11}C$-synthetic module. The synthesis of $^{11}C$-labeling reagents ($[^{11}C]CH_3I$ or $[^{11}C]CH_3OTf$) is fully automated using the commercial TRACERlab $FX_{C-pro}$ module and is readily adaptable to $^{11}C$-labeling reactor for [$^{11}C$]PIB as well as another $^{11}C$-labeling apparatus for [$^{11}C$]methionine via the three-way valve. After completing the [$^{11}C$]PIB production, the re-synthesized $[^{11}C]CH_3I$ was passed through the three-way valve connected the polyetheretherketone (PEEK) line and loaded into the C18 Sep-Pak cartridge including the methionine precursor. The labeled product [^${11}C$]methionine was purified by a simple cartridge separation and reformulated into saline. The radiochemical yield of [$^{11}C$]PIB and [$^{11}C$]methionine were $5.3{\pm}0.6%$ and $18.7{\pm}0.8%$ (n.d.c.), respectively, with over 97% of radiochemical purity. The specific activity of [$^{11}C$]PIB was over $110GBq/{\mu}mol$. Total production time of two radiopharmaceuticals needs about 2 h from $1^{st}$ beam irradiation including quality control tests. Final [$^{11}C$]PIB and [$^{11}C$]methionine were satisfied all quality control test standards.

Synthesis and Biological Activity Test of the Sex Pheromone of the Diamond Back Moth (배추좀나방의 성 페로몬의 합성과 생물활성시험)

  • Suk-Ku Kang;Chul-Hee Lee;Jung Han Kim;Jeong-Oon Lee
    • Journal of the Korean Chemical Society
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    • v.32 no.1
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    • pp.60-64
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    • 1988
  • Synthesis and biological activity test are described for the (Z)-11-hexadecen-1-ol, (Z)-11-hexadecen-1-yl acetate, and (Z)-11-hexadecen-l-al, the sex pheromone of the diamond back moth, Plutella xylostella L.. Lithium acetylide was alkylated with 10-bromodecan-1-ol THP ether to give 11-hexadecyn-l-ol THP ether. 11-Hexadecyn-l-ol THP ether was stereoselectively reduced over Pd/BaSO4to yield (Z)-11-hexadecen-l-ol THP ether, which was in turn deprotected to provide (Z)-11-hexadecen-l-ol. (Z)-11-Hexadecen-l-ol was acetylated and oxidized to afford (Z)-11-hexadecen-1-yl acetate and (Z)-11-hexadecen-l-al, respectively. Biological activity test of the synthetic compounds, (Z)-11-hexadecen-l-ol, (Z)-11-hexadecen-1-yl acetate, and (Z)-11-hexadecen-l-al in the ratio of 0.1 : 5 : 5 was tested in the field using polyethylene capsules as containers. The numbers of moth trapped with pheromone vials were counted.

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Interaction of phage K11 lysozyme with phage RNA polymerase (Yeast two-hybrid 시스템을 통한 K11 phage lysozyme과 K11 phage RNA 중합효소와의 결합에 대한 연구)

  • Junn, Hyun-Jung;Lee, Sang-Soo
    • The Journal of Natural Sciences
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    • v.14 no.2
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    • pp.83-91
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    • 2004
  • Recently phage K11 lysozyme was cloned and characterized in our lab. The K11 lysozyme was identified to have dual functions. It not only cuts a peptidoglycan bond in bacterial cell wall but also acts as an inhibitor of K11 RNA polymerase. It has been known that the T7 lysozyme binds specifically to T7 RNA polymerase and inhibits transcription. The dual activities of K11 lysozyme are atreeable to the case of T7 phage lysozyme and RNA polymerare. In order to identify the binding magnitude of K11 lysozyme with K11 RNA polymerase, yeast two-hybrid system was used. K11 phage lysozyme gene was introduced into pLexA plasmid and used as a prey. Also, K11 phage RNA polymerase gene was introduced into pJG4-5 and used as a bait. The binding between K11 lysozyme and K11 RNA polymerase was demonstrated by expression of reporter genes such as lacZ and leu2.

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Phosphorylation Properties of Recombinant OsCPK11, a Calcium-dependent Protein Kinase from Rice (벼의 칼슘-의존적 단백질 카이네즈인 재조합 OsCPK11의 인산화 특성)

  • Cho, Il-Sang;Lee, Su-Hee;Park, Chung-Mo;Kim, Sung-Ha
    • Journal of Life Science
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    • v.27 no.12
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    • pp.1393-1402
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    • 2017
  • In plants, calcium ($Ca^{2+}$)-dependent protein kinases (CDPKs) are important sensors of $Ca^{2+}$ signals. Previous research demonstrated the expression of the OsCPK11 gene in various tissues at the transcription level, but its developmental and biochemical functions at the protein level were not determined. This study was aimed to identify biochemical characteristics of OsCPK11. GST- OsCPK11 was expressed in E. coli and used for an in vitro kinase assay. Biochemical analyses identified OsCPK11 as a CDPK. OsCPK11 autophosphorylated itself and transphosphorylated histone III-s and MBP as substrates in the presence of $Ca^{2+}$. The activity of the recombinant OsCPK11 was influenced by $Mg^{2+}$, with optimum activity detected at pH 7.0-7.5. OsCPK11 activity was not affected by $Mg^{2+}$, $Mn^{2+}$, or $Na^+$ in the presence of a high level of $Ca^{2+}$. Autophosphorylation of OsCPK11 decreased $Ca^{2+}$ sensitivity of OsCPK11. An anti-OsCPK11 rabbit antibody recognized 95.5 kD of GST-OsCPK11, as shown by an immunoblot analysis. These results shed light on the function of OsCPK11 in $Ca^{2+}$-mediated signaling in rice.

Studies on Triterpenoid Corticomimetics (I) Inhibition of Corticoid-$5{\beta}$-reductase by 11-Oxo-oleanolic Acid and 11-Oxo-hederagenin (Corticoid 활성물질의 개발을 위한 기초연구(I) 11-Oxo-oleanolic Acid 및 11-Oxo-hederagenin의 Corticoid-$5{\beta}$-reductase에 대한 조해효과)

  • 한병훈;이혜정;한대석
    • YAKHAK HOEJI
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    • v.26 no.1
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    • pp.1-8
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    • 1982
  • Derivation of triterpenoids and then the screening for corticomimetics among them is our primary interest. $C_{11}$-oxo-triterprenoids except glycyrrhetinic acid are rarely found in the plant kingdom. Based on the facts that $C_{3}$ and $C_{11}$-Oxo-group are essential for the corticoid-like-activity through its competitive inhibition on the corticoid-5.betha.-reductase, it was attempted to produce artificial inhibitor on the enzyme by introducing $C_{11}$-oxo group to the triterpenoids of oleanene series such as oleanolic acid and hederagenin. We could obtain the $C_{11}$-oxo-oleanolic acid m.p. $264-6^{\circ}$, uv ${\lambda}max$ 249 and $C_{11}$-oxo-hederagenin amorp. uv ${\lambda}max$ 251 by acetylation, $CrO_{3}$-oxid., and deacetylation. Glycyrrhetinic acid, a natural 11-oxo-compound and the other 11-oxo-derivatives of oleanolic acid and hederagenin were compared in their inhibitory activity on the corticoid-5.betha.-reductase. The inhibitory activity of those compound were decreased in the order of $C_{11}$-oxo-oleanolic acid, $C_{11}$-oxo- hederagenin, glycyrrhetinic acid. This suggests more strong corticomimetic activity of those artificially derived $C_{11}$-oxo-oleanolic acid and $C_{11}$-oxa-hederagenin. Their Ki value were $4.6{\times}10^{-4}M$ and $5.8{\times}10^{-4}M$ respectively.

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A Possible Physiological Role of Caspase-11 During Germinal Center Reaction

  • Kang, Shin-Jung
    • Animal cells and systems
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    • v.12 no.3
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    • pp.127-136
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    • 2008
  • Caspase-11 has been known as a dual regulator of cytokine maturation and apoptosis. Although the role of caspase-11 under pathological conditions has been well documented, its physiological role has not been studied much. In the present study, we investigated a possible physiological function of caspase-11 during immune response. In the absence of caspase-11, immunized spleen displayed increased cellularity and abnormal germinal center structure with disrupted microarchitecture. The rate of cell proliferation and apoptosis in the immunized spleen was not changed in the caspase-11-deficient mice. Furthermore, the caspase-11-deficient peritoneal macrophages showed normal phagocytotic activity. However, caspase-11-/-splenocytes and macrophages showed defective migrating capacity. The dysregulation of cell migration did not seem to be mediated by caspase-3, interleukin-$1{\alpha}$ or interleukin-$1{\beta}$ which acts downstream of caspase-11. These results suggest that a direct regulation of immune cell migration by caspase-11 is critical for the formation of germinal center microarchitecture during immune response. However, humoral immunity in the caspase-11-deficient mice was normal, suggesting the formation of germinal center structure is not essential for the affinity maturation of the antibodies.

Role of Rab11 on Membrane Trafficking of Rat Vanilloid Receptor, TRPV1 (바닐로이드 수용체 TRPV1의 막수송과정에서의 Rab11의 역할)

  • Um, Ki-Bum;Lee, Soon-Youl
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.12 no.7
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    • pp.3096-3102
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    • 2011
  • Vanilloid receptor, TRPV1 (transient receptor potential vanilloid 1) is a non-selective cation channel that responds to a variety of pain-eliciting material including capsaicin, pH, heat. Although, membrane trafficking of TRPV1 was not much known so far, TRPV1 was reported to interact with FIP3 (family of Rab11 interacting protein 3). FIP3 was identified as one of Rab11 interacting proteins that is recently reported important in membrane trafficking of several channel proteins directly or indirectly. Therefore, in this study, we examined the role of Rab11 in the membrane trafficking of TRPV1 using cell biological and biochemical techniques. Rab11 was found really colocalized with TRPV1 based on the result of confocal microscopy. However, GST-pulldown assay, one of biochemical technique, found that Rab11 did not interact with TRPV1. Although Rab11 does not interact with TRPV1 directly, we hypothesized that Rab11 is indeed involved in the membrane trafficking of TRPV1. In order to examine further the role of Rab11 in the membrane trafficking of TRPV1, the expression of TRPV1 on the membrane was examined when the expression of Rab11 was decreased down to about 50% by siRNA technique and found decreased significantly. From this result, we can conclude that Rab11 is involved in the membrane trafficking of TRPV1 in a way of including FIP3.

Expression Analysis of OsCPK11 by ND0001 oscpk11 Mutants of Oryza sativa L. under Salt, Cold and Drought Stress Conditions (염분, 저온 및 가뭄 스트레스 조건에서 벼 ND0001 oscpk11 돌연변이체의 OsCPK11 발현 분석)

  • Kim, Hyeon-Mi;Kim, Sung-Ha
    • Journal of Life Science
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    • v.31 no.2
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    • pp.115-125
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    • 2021
  • Calcium-dependent protein kinases (CDPKs) are known to be involved in regulating plant responses to abiotic stresses such as salinity, cold temperature and dehydration,. Although CDPKs constitute a large multigene family consisting of 31 genes in rice, only a few rice CDPKs' functions have been identified. Therefore, in order to elucidate the functions of OsCPK11 in rice, this study was intended to focus on the expression pattern analysis of OsCPK11 in wild type and ND0001 oscpk11 mutant plants under these abiotic stresses. For the salt, cold and drought stress treatment, seedlings were exposed to 200 mM NaCl, 4℃ and 20% PEG 6,000, respectively. RT-PCR and quantitative real-time PCR were performed to determine the expression patterns of OsCPK11 in wild type and ND0001 mutant plants. RT-PCR results showed that OsCPK11 transcripts in the wild type and heterozygous mutant were detected, but not in the homozygous mutant. Real-time PCR results showed that relative expression of OsCPK11 of wild type plants was increased and reached to the highest level at 24 hr, at 6 hr and at 24 hr under salt, cold and drought stress conditions, respectively. Relative expression of OsCPK11 of ND0001 homozygous plant was significantly reduced compared to that of wild type. These results suggested that oscpk11 homozygous mutant knocks out OsCPK11 and OsCPK11 might be involved in salt, cold and drought stress signaling by regulating its gene expression.