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Volumn 38, Issue 2, 2003, Pages 190-197

Capsular polysaccharide from Actinobacillus actinomycetemcomitans inhibits IL-6 and IL-8 production in human gingival fibroblast

Author keywords

Actinobacillus actinomycetemcomitans; Human gingival fibroblasts; Interleukin 6; Interleukin 8

Indexed keywords

BACTERIAL POLYSACCHARIDE; INTERLEUKIN 6; INTERLEUKIN 8; AUTACOID; LIPOPOLYSACCHARIDE; MONOCLONAL ANTIBODY;

EID: 0344010578     PISSN: 00223484     EISSN: None     Source Type: Journal    
DOI: 10.1034/j.1600-0765.2003.00656.x     Document Type: Article
Times cited : (15)

References (42)
  • 1
    • 0021004470 scopus 로고
    • Actinobacillus actinomycetemcomitans in human periodontal disease. Prevalence in patient groups and distribution of biotypes and serotype within families
    • Zambon JJ, Christersson LA, Slots J. Actinobacillus actinomycetemcomitans in human periodontal disease. Prevalence in patient groups and distribution of biotypes and serotype within families. J Periodontol 1983;54:707-711.
    • (1983) J Periodontol , vol.54 , pp. 707-711
    • Zambon, J.J.1    Christersson, L.A.2    Slots, J.3
  • 2
    • 0021403590 scopus 로고
    • Black-pigmented Bacteroides species, Capnocytophaga species, and Actinobacillus actinomycetemcomitans in human periodontal disease: Virulence factors in colonization, survival, and tissue destruction
    • Slots J, Genco RJ. Black-pigmented Bacteroides species, Capnocytophaga species, and Actinobacillus actinomycetemcomitans in human periodontal disease: virulence factors in colonization, survival, and tissue destruction. J Dent Res 1984;63:412-421.
    • (1984) J Dent Res , vol.63 , pp. 412-421
    • Slots, J.1    Genco, R.J.2
  • 3
    • 0021911144 scopus 로고
    • Actinobacillus actinomycetemcomitans in human periodontal disease
    • Zambon JJ. Actinobacillus actinomycetemcomitans in human periodontal disease. J Clin Periodontol 1985;12:1-20.
    • (1985) J Clin Periodontol , vol.12 , pp. 1-20
    • Zambon, J.J.1
  • 4
    • 0018827360 scopus 로고
    • Biochemical and morphological characterization of the killing of human monocytes by a leukotoxin derived from Actinobacillus actinomycetemcomitans
    • Taichman NS, Dean RT, Sanderson CJ. Biochemical and morphological characterization of the killing of human monocytes by a leukotoxin derived from Actinobacillus actinomycetemcomitans. Infect Immun 1980;28:258-268.
    • (1980) Infect Immun , vol.28 , pp. 258-268
    • Taichman, N.S.1    Dean, R.T.2    Sanderson, C.J.3
  • 5
    • 0021349420 scopus 로고
    • Extraction and isolation of a leukotoxin from Actinobacillus actinomycetemcomitans with polymyxin B
    • Tsai CC, Shenker BJ, DiRienzo JM, Malamud D, Taichman NS. Extraction and isolation of a leukotoxin from Actinobacillus actinomycetemcomitans with polymyxin B. Infect Immun 1984;43:700-705.
    • (1984) Infect Immun , vol.43 , pp. 700-705
    • Tsai, C.C.1    Shenker, B.J.2    DiRienzo, J.M.3    Malamud, D.4    Taichman, N.S.5
  • 7
    • 0021303413 scopus 로고
    • The bone-resorbing activities in tissue culture of lipopolysaccharides from the bacteria Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Capnocytophaga ochracea isolated from human mouths
    • Iino Y, Hopps RM. The bone-resorbing activities in tissue culture of lipopolysaccharides from the bacteria Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Capnocytophaga ochracea isolated from human mouths. Arch Oral Biol 1984;29:59-63.
    • (1984) Arch Oral Biol , vol.29 , pp. 59-63
    • Iino, Y.1    Hopps, R.M.2
  • 8
    • 0019215819 scopus 로고
    • Characterization of the lipopolysaccharide from Actinobacillus actinomycetemcomitans Y4 and N27
    • Kiley P, Holt SC. Characterization of the lipopolysaccharide from Actinobacillus actinomycetemcomitans Y4 and N27. Infect Immun 1980;30:862-873.
    • (1980) Infect Immun , vol.30 , pp. 862-873
    • Kiley, P.1    Holt, S.C.2
  • 9
    • 0022123511 scopus 로고
    • Bone resorbing activity of purified capsular material from Actinobacillus actinomycetemcomitans
    • Wilson M, Kamin S, Harvey W. Bone resorbing activity of purified capsular material from Actinobacillus actinomycetemcomitans. J Periodontal Res 1985;20: 484-491.
    • (1985) J Periodontal Res , vol.20 , pp. 484-491
    • Wilson, M.1    Kamin, S.2    Harvey, W.3
  • 10
    • 0027587443 scopus 로고
    • Seroclassification of hitherto non-typeable Actinobacillus actinomycetemcomitans strains: Evidence for a new serotype e
    • Gmür R, McNabb H, van Steenbergen TJ, et al. Seroclassification of hitherto non-typeable Actinobacillus actinomycetemcomitans strains: evidence for a new serotype e. Oral Microbiol Immunol 1993; 8:116-120.
    • (1993) Oral Microbiol Immunol , vol.8 , pp. 116-120
    • Gmür, R.1    McNabb, H.2    Van Steenbergen, T.J.3
  • 11
    • 0026935456 scopus 로고
    • Frequency and stability of mono- Or poly-infection by Actinobacillus actinomycetemcomitans serotypes a, b, c, d or e
    • Saarela M, Asikainen S, Alaluusua S, Pyhala L, Lai CH, Jousimies-Somer H. Frequency and stability of mono-or poly-infection by Actinobacillus actinomycetemcomitans serotypes a, b, c, d or e. Oral Microbiol Immunol 1992;7:277-279.
    • (1992) Oral Microbiol Immunol , vol.7 , pp. 277-279
    • Saarela, M.1    Asikainen, S.2    Alaluusua, S.3    Pyhala, L.4    Lai, C.H.5    Jousimies-Somer, H.6
  • 12
    • 0020620385 scopus 로고
    • Serology of oral Actinobacillus actinomycetemcomitans and serotype distribution in human periodontal disease
    • Zambon JJ, Slots J, Genco RJ. Serology of oral Actinobacillus actinomycetemcomitans and serotype distribution in human periodontal disease. Infect Immun 1983; 41:19-27.
    • (1983) Infect Immun , vol.41 , pp. 19-27
    • Zambon, J.J.1    Slots, J.2    Genco, R.J.3
  • 13
    • 0024464573 scopus 로고
    • Immunochemical and structural characterization of a serotype-specific polysaccharide antigen from Actinobacillus actinomycetemcomitans Y4 (serotype b)
    • Amano K, Nishihara T, Shibuya N, Noguchi T, Koga T. Immunochemical and structural characterization of a serotype-specific polysaccharide antigen from Actinobacillus actinomycetemcomitans Y4 (serotype b). Infect Immun 1989;57:2942-2946.
    • (1989) Infect Immun , vol.57 , pp. 2942-2946
    • Amano, K.1    Nishihara, T.2    Shibuya, N.3    Noguchi, T.4    Koga, T.5
  • 14
    • 0030088140 scopus 로고    scopus 로고
    • Production of inflammatory mediators and cytokines by human gingival fibroblasts following bacterial challenge
    • Dongari-Bagtzoglou AI, Ebersole JL. Production of inflammatory mediators and cytokines by human gingival fibroblasts following bacterial challenge. J Periodontal Res 1996;31:90-98.
    • (1996) J Periodontal Res , vol.31 , pp. 90-98
    • Dongari-Bagtzoglou, A.I.1    Ebersole, J.L.2
  • 15
    • 0031243399 scopus 로고    scopus 로고
    • Interleukin-6 production in human fibroblasts derived from periodontal tissues is differentially regulated by cytokines and a glucocorticoid
    • Okada N, Kobayashi M, Mugikura K et al. Interleukin-6 production in human fibroblasts derived from periodontal tissues is differentially regulated by cytokines and a glucocorticoid. J Periodont Res 1997;32:559-569.
    • (1997) J Periodont Res , vol.32 , pp. 559-569
    • Okada, N.1    Kobayashi, M.2    Mugikura, K.3
  • 16
    • 0032133297 scopus 로고    scopus 로고
    • Increased presence of interleukin-6 (IL-6) and IL-8 secreting fibroblast subpopulations in adult periodontitis
    • Dongari-Bagtzoglou AI, Ebersole JL. Increased presence of interleukin-6 (IL-6) and IL-8 secreting fibroblast subpopulations in adult periodontitis. J Periodontol 1998;69:899-910.
    • (1998) J Periodontol , vol.69 , pp. 899-910
    • Dongari-Bagtzoglou, A.I.1    Ebersole, J.L.2
  • 17
    • 0034320704 scopus 로고    scopus 로고
    • Relationship between interleukin-6 levels in gingival crevicular fluid and periodontal status in patients with rheumatoid arthritis and adult periodontitis
    • Bozkurt FY, Berker E, Akkus S, Bulut S. Relationship between interleukin-6 levels in gingival crevicular fluid and periodontal status in patients with rheumatoid arthritis and adult periodontitis. J Periodontol 2000;71:1756-1760.
    • (2000) J Periodontol , vol.71 , pp. 1756-1760
    • Bozkurt, F.Y.1    Berker, E.2    Akkus, S.3    Bulut, S.4
  • 18
    • 0033152740 scopus 로고    scopus 로고
    • Interleukin 1 beta, interleukin 6, beta 2-microglobulin, and transforming growth factor-alpha in gingival crevicular fluid from human periodontal disease
    • Mogi M, Otogoto J, Ota N, Inagaki H, Minami M, Kojima K. Interleukin 1 beta, interleukin 6, beta 2-microglobulin, and transforming growth factor-alpha in gingival crevicular fluid from human periodontal disease. Arch Oral Biol 1999;44: 535-539.
    • (1999) Arch Oral Biol , vol.44 , pp. 535-539
    • Mogi, M.1    Otogoto, J.2    Ota, N.3    Inagaki, H.4    Minami, M.5    Kojima, K.6
  • 19
    • 0035380371 scopus 로고    scopus 로고
    • Characterization of cellular infiltrate, detection of chemokine receptor CCR5 and interleukin-8 and RANTES chemokines in adult periodontitis
    • Gamonal J, Acevedo A, Bascones A, Jorge O, Silva A. Characterization of cellular infiltrate, detection of chemokine receptor CCR5 and interleukin-8 and RANTES chemokines in adult periodontitis. J Periodont Res 2001;36:194-203.
    • (2001) J Periodont Res , vol.36 , pp. 194-203
    • Gamonal, J.1    Acevedo, A.2    Bascones, A.3    Jorge, O.4    Silva, A.5
  • 20
    • 0026011186 scopus 로고
    • Murine macrophage interleukin-1 release by capsular-like serotype-specific polysaccharide antigens of Actinobacillus actinomycetemcomitans
    • Takahashi T, Nishihara T, Ishihara Y et al. Murine macrophage interleukin-1 release by capsular-like serotype-specific polysaccharide antigens of Actinobacillus actinomycetemcomitans. Infect Immun 1991;59:18-23.
    • (1991) Infect Immun , vol.59 , pp. 18-23
    • Takahashi, T.1    Nishihara, T.2    Ishihara, Y.3
  • 21
    • 0029278801 scopus 로고
    • Role of prostaglandin in the formation of osteoclasts induced by capsular-like polysaccharide antigen of Actinobacillus actinomycetemcomitans strain Y4
    • Ueda N, Nishihara T, Ishihara Y, Amano K, Kuroyanagi T, Noguchi T. Role of prostaglandin in the formation of osteoclasts induced by capsular-like polysaccharide antigen of Actinobacillus actinomycetemcomitans strain Y4. Oral Microbiol Immunol 1995;10:69-75.
    • (1995) Oral Microbiol Immunol , vol.10 , pp. 69-75
    • Ueda, N.1    Nishihara, T.2    Ishihara, Y.3    Amano, K.4    Kuroyanagi, T.5    Noguchi, T.6
  • 22
    • 0028942439 scopus 로고
    • Actinobacillus actinomycetemcomitans Y4 capsular-polysaccharide-like polysaccharide promotes osteoclast-like cell formation by interleukin-1 alpha production in mouse marrow cultures
    • Nishihara T, Ueda N, Amano K et al. Actinobacillus actinomycetemcomitans Y4 capsular-polysaccharide-like polysaccharide promotes osteoclast-like cell formation by interleukin-1 alpha production in mouse marrow cultures. Infect Immun 1995;63:1893-1898.
    • (1995) Infect Immun , vol.63 , pp. 1893-1898
    • Nishihara, T.1    Ueda, N.2    Amano, K.3
  • 23
    • 0033278131 scopus 로고    scopus 로고
    • Intracellular interleukin-1 alpha production in human gingival fibroblasts is differentially regulated by various cytokines
    • Kobayashi M, Okada N, Okamatsu Y et al. Intracellular interleukin-1 alpha production in human gingival fibroblasts is differentially regulated by various cytokines. J Dent Res 1999;78:840-849.
    • (1999) J Dent Res , vol.78 , pp. 840-849
    • Kobayashi, M.1    Okada, N.2    Okamatsu, Y.3
  • 24
    • 0023853738 scopus 로고
    • Suppression of murine macrophage interleukin-1 release by the polysaccharide portion of Haemophilus actinomycetemcomitans lipopolysaccharide
    • Nishihara T, Koga T, Hamada S. Suppression of murine macrophage interleukin-1 release by the polysaccharide portion of Haemophilus actinomycetemcomitans lipopolysaccharide. Infect Immun 1988;56:619-625.
    • (1988) Infect Immun , vol.56 , pp. 619-625
    • Nishihara, T.1    Koga, T.2    Hamada, S.3
  • 25
    • 0006731628 scopus 로고
    • Use of autoclaved extracts of hemolytic streptococci for serological grouping
    • Rantz LA, Randall E. Use of autoclaved extracts of hemolytic streptococci for serological grouping. Stanford Med Bull 1955;13:290-291.
    • (1955) Stanford Med Bull , vol.13 , pp. 290-291
    • Rantz, L.A.1    Randall, E.2
  • 26
    • 0025008205 scopus 로고
    • Monoclonal antibody-coated latex agglutination assay for identification of Actinobacillus actinomycetemcomitans
    • Koga T, Senpuku H, Nakashima K, Ishihara Y, Nishihara T. Monoclonal antibody-coated latex agglutination assay for identification of Actinobacillus actinomycetemcomitans. Zentralbl Bakteriol 1990;274:91-99.
    • (1990) Zentralbl Bakteriol , vol.274 , pp. 91-99
    • Koga, T.1    Senpuku, H.2    Nakashima, K.3    Ishihara, Y.4    Nishihara, T.5
  • 27
    • 0002447206 scopus 로고
    • Bacterial Lipopolysaccharides. Extraction with phenol-water and further application of the procedure
    • Westphal O, Jann K. Bacterial Lipopolysaccharides. Extraction with phenol-water and further application of the procedure. Methods Carbohydr Chem 1965;5:83-91.
    • (1965) Methods Carbohydr Chem , vol.5 , pp. 83-91
    • Westphal, O.1    Jann, K.2
  • 28
    • 0021303413 scopus 로고
    • The bone-resorbing activities in tissue culture of lipopolysaccharides from the bacteria Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Capnocytophaga ochracea isolated from human mouths
    • Iino Y, Hopps RM. The bone-resorbing activities in tissue culture of lipopolysaccharides from the bacteria Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Capnocytophaga ochracea isolated from human mouths. Arch Oral Biol 1984;29:59-63.
    • (1984) Arch Oral Biol , vol.29 , pp. 59-63
    • Iino, Y.1    Hopps, R.M.2
  • 29
    • 0025851760 scopus 로고
    • Role of interleukin-1 and prostaglandin in in vitro bone resorption induced by Actinobacillus actinomycetemcomitans lipopolysaccharide
    • Ishihara Y, Nishihara T, Maki E, Noguchi T, Koga T. Role of interleukin-1 and prostaglandin in in vitro bone resorption induced by Actinobacillus actinomycetemcomitans lipopolysaccharide. J Periodont Res 1991;26:155-160.
    • (1991) J Periodont Res , vol.26 , pp. 155-160
    • Ishihara, Y.1    Nishihara, T.2    Maki, E.3    Noguchi, T.4    Koga, T.5
  • 30
    • 0032201122 scopus 로고    scopus 로고
    • Involvement of prostaglandin E2 and interleukin-1 alpha in the differentiation and survival of osteoclasts induced by lipopolysaccharide from Actinobacillus actinomycetemcomitans Y4
    • Ueda N, Koide M, Ohguchi M et al. Involvement of prostaglandin E2 and interleukin-1 alpha in the differentiation and survival of osteoclasts induced by lipopolysaccharide from Actinobacillus actinomycetemcomitans Y4. J Periodont Res 1998;33:509-516.
    • (1998) J Periodont Res , vol.33 , pp. 509-516
    • Ueda, N.1    Koide, M.2    Ohguchi, M.3
  • 31
    • 0031879472 scopus 로고    scopus 로고
    • Activin a regulates the production of mature interleukin-1beta and interleukin-1 receptor antagonist in human monocytic cells
    • Ohguchi M, Yamato K, Ishihara Y et al. Activin A regulates the production of mature interleukin-1beta and interleukin-1 receptor antagonist in human monocytic cells. J Interferon Cytokine Res 1998;18: 491-498.
    • (1998) J Interferon Cytokine Res , vol.18 , pp. 491-498
    • Ohguchi, M.1    Yamato, K.2    Ishihara, Y.3
  • 32
    • 0030228984 scopus 로고    scopus 로고
    • Gingival fibroblast cytokine profiles in Actinobacillus actinomycetemcomitans-associated periodontitis
    • Dongari-Bagtzoglou AI, Ebersole JL. Gingival fibroblast cytokine profiles in Actinobacillus actinomycetemcomitans-associated periodontitis. J Periodontol 1996;67:871-878.
    • (1996) J Periodontol , vol.67 , pp. 871-878
    • Dongari-Bagtzoglou, A.I.1    Ebersole, J.L.2
  • 33
    • 0031882523 scopus 로고    scopus 로고
    • Effect of lipopolysaccharide and inflammatory cytokines on interleukin-6 production by healthy human gingival fibroblasts
    • Kent LW, Rahemtulla F, Hockett RD Jr, Gilleland RC, Michalek SM. Effect of lipopolysaccharide and inflammatory cytokines on interleukin-6 production by healthy human gingival fibroblasts. Infect Immun 1998;66:608-614.
    • (1998) Infect Immun , vol.66 , pp. 608-614
    • Kent, L.W.1    Rahemtulla, F.2    Hockett Jr., R.D.3    Gilleland, R.C.4    Michalek, S.M.5
  • 34
    • 0033090239 scopus 로고    scopus 로고
    • Interleukin (IL)-1 and Porphyromonas gingivalis lipopolysaccharide stimulation of IL-6 production by fibroblasts derived from healthy or periodontally diseased human gingival tissue
    • Kent LW, Rahemtulla F, Michalek SM. Interleukin (IL)-1 and Porphyromonas gingivalis lipopolysaccharide stimulation of IL-6 production by fibroblasts derived from healthy or periodontally diseased human gingival tissue. J Periodontol 1999;70:274-282.
    • (1999) J Periodontol , vol.70 , pp. 274-282
    • Kent, L.W.1    Rahemtulla, F.2    Michalek, S.M.3
  • 35
    • 0029283278 scopus 로고
    • Differential expression of IL-1 beta, TNF-alpha, IL-6, and IL-8 in human monocytes in response to lipopolysaccharides from different microbes
    • Agarwal S, Piesco NP, Johns LP, Riccelli AE. Differential expression of IL-1 beta, TNF-alpha, IL-6, and IL-8 in human monocytes in response to lipopolysaccharides from different microbes. J Dent Res 1995;74:1057-1065.
    • (1995) J Dent Res , vol.74 , pp. 1057-1065
    • Agarwal, S.1    Piesco, N.P.2    Johns, L.P.3    Riccelli, A.E.4
  • 36
    • 0025952112 scopus 로고
    • 6-Deoxy-D-talan and 6-deoxy-1-talan. Novel serotype-specific polysaccharide antigens from Actinobacillus actinomycetemcomitans
    • Shibuya N, Amano K, Azuma J, et al. 6-Deoxy-D-talan and 6-deoxy-1-talan. Novel serotype-specific polysaccharide antigens from Actinobacillus actinomycetemcomitans. J Biol Chem 1991;266: 16318-16323.
    • (1991) J Biol Chem , vol.266 , pp. 16318-16323
    • Shibuya, N.1    Amano, K.2    Azuma, J.3
  • 37
    • 0020032275 scopus 로고
    • Relationship between attachment loss and precipitating serum antibody to Actinobacillus actinomycetemcomitans in adolescents and young adults having severe periodontal destruction
    • Ranney RR, Yanni NR, Burmeister JA, Tew JG. Relationship between attachment loss and precipitating serum antibody to Actinobacillus actinomycetemcomitans in adolescents and young adults having severe periodontal destruction. J Periodontol 1982;53:1-7.
    • (1982) J Periodontol , vol.53 , pp. 1-7
    • Ranney, R.R.1    Yanni, N.R.2    Burmeister, J.A.3    Tew, J.G.4
  • 38
    • 0023337254 scopus 로고
    • Relationship of serum antibody to attachment level patterns in young adults with juvenile periodontitis or generalized severe periodontitis
    • Gunsolley JC, Burmeister JA, Tew JG, Best AM, Ranney RR. Relationship of serum antibody to attachment level patterns in young adults with juvenile periodontitis or generalized severe periodontitis. J Periodontol 1987;58:314-320.
    • (1987) J Periodontol , vol.58 , pp. 314-320
    • Gunsolley, J.C.1    Burmeister, J.A.2    Tew, J.G.3    Best, A.M.4    Ranney, R.R.5
  • 39
    • 0029773617 scopus 로고    scopus 로고
    • Influence of anti-Actinobacillus actinomycetemcomitans Y4 (serotype b) lipopolysaccharide on severity of generalized early-onset periodontitis
    • Califano JV, Gunsolley JC, Nakashima K, Schenkein HA, Wilson ME, Tew JG. Influence of anti-Actinobacillus actinomycetemcomitans Y4 (serotype b) lipopolysaccharide on severity of generalized early-onset periodontitis. Infect Immun 1996;64:3908-3910.
    • (1996) Infect Immun , vol.64 , pp. 3908-3910
    • Califano, J.V.1    Gunsolley, J.C.2    Nakashima, K.3    Schenkein, H.A.4    Wilson, M.E.5    Tew, J.G.6
  • 40
    • 0026082056 scopus 로고
    • Interleukin-8 (IL-8): The major neutrophil chemotactic factor in the lung
    • Kunkel SL, Standiford T, Kasahara K, Stricter RM. Interleukin-8 (IL-8): the major neutrophil chemotactic factor in the lung. Exp Lung Res 1991;17:17-23.
    • (1991) Exp Lung Res , vol.17 , pp. 17-23
    • Kunkel, S.L.1    Standiford, T.2    Kasahara, K.3    Stricter, R.M.4
  • 41
    • 0030043948 scopus 로고    scopus 로고
    • Compartmentalized IL-8 and elastase release within the human lung in unilateral pneumonia
    • Boutten A, Dehoux MS, Seta N et al. Compartmentalized IL-8 and elastase release within the human lung in unilateral pneumonia. Am J Respir Crit Care Med 1996;153:336-342.
    • (1996) Am J Respir Crit Care Med , vol.153 , pp. 336-342
    • Boutten, A.1    Dehoux, M.S.2    Seta, N.3
  • 42
    • 0030022763 scopus 로고    scopus 로고
    • Neutralization of macrophage inflammatory protein-2 attenuates neutrophil recruitment and bacterial clearance in murine Klebsiella pneumonia
    • Greenberger MJ, Strieter RM, Kunkel SL et al. Neutralization of macrophage inflammatory protein-2 attenuates neutrophil recruitment and bacterial clearance in murine Klebsiella pneumonia. J Infect Dis 1996;173:159-165.
    • (1996) J Infect Dis , vol.173 , pp. 159-165
    • Greenberger, M.J.1    Strieter, R.M.2    Kunkel, S.L.3


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