• Title/Summary/Keyword: CCR4

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Development of a Management Tool of CCD/CCR-centric Standard Clinical Document (CCD/CCR 중심의 표준진료문서 관리 도구의 개발)

  • Lee, In-Keun;Cho, Hune;Kim, Hwa-Sun
    • Journal of the Korean Institute of Intelligent Systems
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    • v.22 no.4
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    • pp.507-514
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    • 2012
  • XML-based standards such as CCD(Continuity of Care Document) and CCR(Continuity of Care Record) have been developed for representation, integration, and exchange of personal health record(PHR), and various of researches on PHR based on the standards have been conducted. These researches have developed and used CCD/CCR parsers each with their own different ways, but it can be hard to develop and update the parsers because of the structural complexity of the standards. Moreover, inter-exchange between CCD and CCR documents in the PHR-related medical information systems should be possible for the interoperability of the systems. Therefore, we proposed a designing method to develop the tools treating XML-based CCD/CCR documents. And we implemented CCD/CCR parser based on the proposed method and developed a converter from CCD to CCR using the parsers. To confirm the usefulness of the developed tool, we performed an experiment of creating CCD documents using the personal health data gathered from chronically ill patients in Kyungpook National University Hospital and of converting from the CCD documents to CCR documents.

Homology Modeling of CCR 4: Novel Therapeutic Target and Preferential Maker for Th2 Cells

  • Shalini, M.;Madhavan, Thirumurthy
    • Journal of Integrative Natural Science
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    • v.7 no.4
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    • pp.234-240
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    • 2014
  • C-C chemokine receptor type 4 (CCR4) is a chemokine receptor with seven transmembrane helices and it belongs to the GPCR family. It plays an important role in asthma, lung disease, atopic dermatitis, allergic bronchopulmonary aspergillosis, cancer, inflammatory bowel disease, the mosquito-borne tropical diseases, such as dengue fever and allergic rhinitis. Because of its role in wide spectrum of disease processes, CCR4 is considered to be an important drug target. Three dimensional structure of the protein is essential to determine the functions. In the present study homology modeling of human CCR4 was performed based on crystal structure of CCR5 chemokine receptor. The generated models were validated using various parameters. Among the generated homology models the best one is selected based on validation result. The model can be used for performing further docking studies to identifying the critical interacting residues.

Molecular Cloning and Characterization of Soybean Cinnamoyl CoA Reductase Induced by Abiotic Stresses

  • So, Hyun-Ah;Chung, Eun-Sook;Cho, Chang-Woo;Kim, Kee-Young;Lee, Jai-Heon
    • The Plant Pathology Journal
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    • v.26 no.4
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    • pp.380-385
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    • 2010
  • Suppression subtractive hybridization was used to isolate wound-induced genes from soybean. One of the wound-induced genes, gmwi143 designated as GmCCR, showed high homology with genes encoding cinnamoyl-CoA reductase (CCR; EC 1.2.1.44). Deduced amino acid sequences encoded by GmCCR showed the highest identity (77%) with those of Acacia CCR. There are 2 CCR genes highly homologous to GmCCR in soybean genome based on Phytozome DB analysis. RNA expression of GmCCR was specifically induced by local and systemic wounding, drought, high salinity or by ultraviolet stress. Our study suggests that GmCCR may be involved in resistance mechanism during abiotic stresses in plants.

CCR7 Ligands Induced Expansion of Memory CD4+ T Cells and Protection from Viral Infection (CCR7 Ligand의 Memory CD4+ T 세포 증가유도 및 바이러스 감염에 대한 방어효과)

  • Eo, Seong-Kug;Cho, Jeong-Gon
    • IMMUNE NETWORK
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    • v.3 no.1
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    • pp.29-37
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    • 2003
  • Background: CC chemokine receptor (CCR) 7 and cognate CCR7 ligands, CCL21 (formerly secondary lymphoid tissue chemokine [SLC]) and CCL19 (formerly Epstein-Barr virus-induced molecule 1 ligand chemokine [ELC]), were known to establish microenvironment for the initiation of immune responses in secondary lymphoid tissue. As described previously, coadministration of DNA vaccine with CCR7 ligand-encoding plasmid DNA elicited enhanced humoral and cellular immunity via increasing the number of dendritic cells (DC) in secondary lymphoid tissue. The author hypothesized here that CCR7 ligand DNA could effectively expand memory CD4+ T cells to protect from viral infection likely via increasing DC number. Methods: To evaluate the effect of CCR7 ligand DNA on the expansion of memory CD4+ T cells, DO11.10.BALB/c transgenic (Tg)-mice, which have highly frequent ovalbumin $(OVA)_{323-339}$ peptide-specific CD4+ T cells, were used. Tg-mice were previously injected with CCR7 ligand DNA, then immunized with $OVA_{323-339}$ peptide plus complete Freund's adjuvant. Subsequently, memory CD4+ T cells in peripheral blood lymphocytes (PBL) were analyzed by FACS analysis for memory phenotype ($CD44^{high}$ and CD62 $L^{low}$) at memory stage. Memory CD4+ T cells recruited into inflammatory site induced with OVA-expressing virus were also analyzed. Finally, the protective efficacy against viral infection was evaluated. Results: CCR7 ligand DNA-treated Tg-mice showed more expanded $CD44^{high}$ memory CD4+ T cells in PBL than control vector-treated animals. The increased number of memory CD4+ T cells recruited into inflammatory site was also observed in CCR7 ligand DNA-treated Tg-mice. Such effectively expanded memory CD4+ T cell population increased the protective immunity against virulent viral infection. Conclusion: These results document that CCR7 and its cognate ligands play an important role in intracellular infection through establishing optimal memory T cell. Moreover, CCR7 ligand could be useful as modulator in DNA vaccination against viral infection as well as cancer.

Investigation of the Binding Site of CCR2 using 4-Azetidinyl-1-aryl-cyclohexane Derivatives: A Membrane Modeling and Molecular Dynamics Study

  • Kothandan, Gugan;Gadhe, Changdev G.;Cho, Seung Joo
    • Bulletin of the Korean Chemical Society
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    • v.34 no.11
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    • pp.3429-3443
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    • 2013
  • Chemokine receptor (CCR2) is a G protein-coupled receptor that contains seven transmembrane helices. Recent pharmaceutical research has focused on the antagonism of CCR2 and candidate drugs are currently undergoing clinical studies for the treatment of diseases like arthritis, multiple sclerosis, and type 2 diabetes. In this study, we analyzed the time dependent behavior of CCR2 docked with a potent 4-azetidinyl-1-aryl-cyclohexane (4AAC) derivative using molecular dynamics simulations (MDS) for 20 nanoseconds (ns). Homology modeling of CCR2 was performed and the 4AAC derivative was docked into this binding site. The docked model of selected conformations was then utilized to study the dynamic behavior of the 4AAC enzyme complexes inside lipid membrane. MDS of CCR2-16b of 4AAC complexes allowed us to refine the system since binding of an inhibitor to a receptor is a dynamic process and identify stable structures and better binding modes. Structure activity relationships (SAR) for 4AAC derivatives were investigated and reasons for the activities were determined. Probable binding pose for some CCR2 antagonists were determined from the perspectives of binding site. Initial modeling showed that Tyr49, Trp98, Ser101, Glu291, and additional residues are crucial for 4AAC binding, but MDS analysis showed that Ser101 may not be vital. 4AAC moved away from Ser101 and the hydrogen bonding between 4AAC and Ser101 vanished. The results of this study provide useful information regarding the structure-based drug design of CCR2 antagonists and additionally suggest key residues for further study by mutagenesis.

The House Dust Mite Allergen, Dermatophagoides pteronyssinus Suppresses the Chemotactic Activity of Human Monocytes

  • Lee, Ji-Sook;Yang, Eun Ju;Kim, In Sik
    • Biomedical Science Letters
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    • v.18 no.4
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    • pp.435-437
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    • 2012
  • House dust mite (HDM) is important in the pathogenesis of allergic diseases including asthma and atopic dermatitis. Dermatophagoides pteronissinus (Dp) is one of major HDM allergens. In this study, we investigated that Dp extract (DpE) affects on the chemotactic activity of monocytes isolated from the peripheral blood. DpE inhibited the migration of human monocytes in response to CC chemokines such as MIP-$1{\alpha}$, RANTES, HCC-4, MCP-1, and TARC. DpE did not alter the expression of CC chemokine receptors (CCRs) such as CCR1, CCR2, CCR3, CCR4, and CCR5. These results indicate that DpE blocks the chemotaxis of human monocytes and its mechanism is not involved in alteration of CCR expression. Better understanding of the effect of DpE on monocytes will enable elucidation of the role of Dp in the development of allergic diseases.

A Comparative Analysis of Classical Data in KCR 4 and CCR 2 (한국목록규칙과 중국문헌편목규칙의 고전자료 목록기술규칙 비교 분석)

  • Han, Mi-Kyung
    • Journal of the Korean Society for Library and Information Science
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    • v.47 no.3
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    • pp.275-293
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    • 2013
  • This study conducted comparative analysis of cataloging descriptions and rules in KCR 4 and CCR 2, as follows, for the purpose of seeking understanding of classical materials cataloging rules and networking of oriental historical data cataloging (bibliographical descriptions). First, to compare the general rules, the objects of descriptions and composition of descriptions, recording order, and punctuation and information source of descriptions were analyzed. As a result, KCR 4 is more detailed in terms of author role identifications and information source regulations and CCR2 is more detailed in terms of regulations related to printing and publications and serial publications. Second, to compare the details, the main titles and liability indications, edition details, publication details and format details, and note details. As a result, regarding the description of edition type and publication details, KCR4 has detailed regulations and CCR2 has characteristic summary in terms of note details.

Overexpression of AtCAF1, CCR4-associated factor 1 homologue in Arabidopsis thaliana, negatively regulates wounding-mediated disease resistance

  • Kwon, Tack-Min;Yi, Young-Byung;Nam, Jae-Sung
    • Journal of Plant Biotechnology
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    • v.38 no.4
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    • pp.278-284
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    • 2011
  • The CCR4-CAF1-NOT complex-mediated degradation of mRNA is a fundamental aspect of gene regulation in eukaryotes. We herein examined the role of AtCAF1 in the innate immune and wound responses of plants. Our results showed that overexpression of AtCAF1 significantly downregulated the transcript level of EFR but not FLS2 and BRI1, as well as abolished up-regulated expression pattern of EFR in response to wounding. Consistently, Agrobacteriummediated transient expression of GUS was highly enhanced in the transgenic plants overexpressing AtCAF. Furthermore, JA responsive genes were down-regulated by overexpression of AtCAF, causing the transgenic plants overexpressing AtCAF more susceptible to necrotrophic fungal pathogen, Botrytis cinerea. These results suggest that The CCR4-CAF1-NOT complex-mediated degradation of mRNA negatively regulates wounding-mediated disease resistance in Arabidopsis thaliana.

Cloning of cDNA Encoding Putative Cellular Receptor Interacting with E2 protein of Hepatitis C Virus (C형 간염바이러스 E2 단백질에 결합하는 추정 세포수용체 cDNA의 클로닝)

  • 이성락;백재은;석대현;박세광;최인학
    • Journal of Life Science
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    • v.13 no.4
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    • pp.541-550
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    • 2003
  • E2 glycoprotein of hepatitis C virus (HCV) comprises a surface of viral particle together with E1 glycoprotein, and is thought to be involved in the attachment of HCV viral particle to receptor (s) on the permissible cells including hepatocytes, B cells, T cells, and monocytes. We constructed a phage library expressing cellular proteins of hepatocytes on the phage surface, which turned out to be 8.8${\times}$$10^5$ cfu of diversity and carried inserts in 95% of library. We screened both cDNA phage library and 12-mer peptide library to identify the cellular proteins binding to E2 protein. Some intracellular proteins including tensin and membrane band 4.1 which are involved in signal transduction of survival and cytoskeleton organization, were selected from cDNA phage library through several rounds of panning and screening. On the contrary, membrane proteins such as CCR7, CKR-L2, and insulin-like growth factor-1 receptor were identified through screening of peptide library. Phages expressing peptides corresponding to those membrane proteins were bound to E2 protein specifically as determined by neutralization of binding assay. Since it is well known that HCV can infect T cells as well as hepatocytes, we examined to see if E2 protein can bind to CCR7, a member of C-protein coupled receptor family expressed on T cells, using CCR7 transfected tells. Human CCR7 cDNA was cloned into pcDNA3.1(-) vector and transfected into human embryonic kidney cell, 293T, and expressed on the surface of the cell as shown by flow cytometer. Binding assay of E2 protein using CCR7 transfected cells indicated that E2 protein bound to CCR7 by dose-dependent mode, giving rise to the possibility that CCR7 might be a putative cellular receptor for HCV.

High Frequencies of the CCR2b-64I and SDF1-3'A Mutations with HIV Infection in Koreans

  • Choi, Byeong-Sun;Cha, Seung-Hun;Kim, Sung Soon;Park, Yong-Keun;Lee, Joo-Shil
    • IMMUNE NETWORK
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    • v.2 no.2
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    • pp.86-90
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    • 2002
  • Background: Host genetic polymorphisms in the HIV-1 co-receptor CCR5 and CCR2b and SDF-1, ligand for co-receptor CXCR4, have been known to be associated with the resistance of HIV infection and/or the delayed disease progression in HIV-infected patients. Methods: We examined the frequencies of SDF1-3'A and CCR2b-64I alleles of 354 Koreans including 100 HIV-uninfected persons, 13 discordant spouses of HIV-infected persons, and 241 HIV-infected persons. The genotyping assays of SDF1 and CCR2b genes were carried out by polymerase chain reaction-restriction fragment length polymorphism. Results: The frequencies of CCR2b-64I and SDF1-3'A alleles in Koreans were very high compared with Caucasians and blacks. Observed frequencies of CCR2b-64I and SDF1-3'A allelic variants were 25.1% and 28.7%, respectively. The frequency of the CCR2b-64I allele in Koreans was 2~4 times higher than those of other ethnic groups with the exception of Asian. The frequencies of CCR2b-64I and SDF1-3'A genotypes did not show the significant difference between HIV-infected and uninfected Koreans. However, the prevalence of CCR2b-64I genotype of the LTNP group was about two times higher than that of the remainder group (P< 0.05). Four (45%) out of 9 LTNPs (long-term nonprogressors) showed having the SDF1-3'A allele and 7 (78%) out of 9 LTNPs carried the CCR2b-64I allele. 3 (33%) out of 9 LTNPs had both SDF1-3'A and CCR2b-64I alleles. But none of 5 RPs (rapid progressors) appeared to have both SDF1-3'A and CCR2b-64I alleles. Conclusion: The different genetic backgrounds in study populations may affect the disease progression and the AIDS epidemic in each country. Further studies need to define whether high frequencies of CCR2b-64I and SDF1-3'A allelic variants may affect the HIV disease progression.