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Volumn 9, Issue 2, 1996, Pages 193-204

Analysis of function, specificity and T cell receptor expression of cloned mucosal T cell lines in Crohn's disease

Author keywords

Crohn's disease; Inflammatory bower disease; Mucosal T cells; T cell receptors

Indexed keywords

CD3 ANTIGEN; CD4 ANTIGEN; CD45 ANTIGEN; INTERLEUKIN 2; MUCIN; T LYMPHOCYTE RECEPTOR;

EID: 0029956261     PISSN: 08968411     EISSN: None     Source Type: Journal    
DOI: 10.1006/jaut.1996.0023     Document Type: Article
Times cited : (17)

References (60)
  • 1
    • 0022474707 scopus 로고
    • HLA-A and B antigens in inflammatory bowel disease
    • Biemond I., Burnham W.R., D'Amaro J., Langman M.J. 1986. HLA-A and B antigens in inflammatory bowel disease. Gut 27: 934-941
    • (1986) Gut , vol.27 , pp. 934-941
    • Biemond, I.1    Burnham, W.R.2    D'Amaro, J.3    Langman, M.J.4
  • 5
    • 0024390798 scopus 로고
    • Pleiotropy and redundancy: T cell-derived lymphokines in the immune response
    • Paul W.E. 1989. Pleiotropy and redundancy: T cell-derived lymphokines in the immune response. Cell 57: 521-524
    • (1989) Cell , vol.57 , pp. 521-524
    • Paul, W.E.1
  • 6
    • 0023620343 scopus 로고
    • Are the focal microscopic jejunal lesions in Crohn's disease produced by a T-cell-mediated immune response?
    • Entrican J.H., Busuttil A., Ferguson A. 1987. Are the focal microscopic jejunal lesions in Crohn's disease produced by a T-cell-mediated immune response? Scand. J. Gastroenterol. 22: 1071-1075
    • (1987) Scand. J. Gastroenterol. , vol.22 , pp. 1071-1075
    • Entrican, J.H.1    Busuttil, A.2    Ferguson, A.3
  • 7
    • 0020677329 scopus 로고
    • T lymphocyte subsets in inflammatory bowel disease: Peripheral blood
    • Selby W., Jewell D. 1983. T lymphocyte subsets in inflammatory bowel disease: peripheral blood. Gut 24: 99-105
    • (1983) Gut , vol.24 , pp. 99-105
    • Selby, W.1    Jewell, D.2
  • 9
    • 0025062193 scopus 로고
    • The role of activated T cells in transformed intestinal mucosa
    • MacDonald T., Spencer J. 1990. The role of activated T cells in transformed intestinal mucosa. Digestion 46(Suppl. 2): 290-296
    • (1990) Digestion , vol.46 , Issue.SUPPL. 2 , pp. 290-296
    • MacDonald, T.1    Spencer, J.2
  • 10
    • 0024413527 scopus 로고
    • T lymphocytes in human gut epithelium preferentially express the α/β antigen receptor and are of the CD45/UCHL1-positive
    • Brandtzaeg P.V., Bosnes V., Halstensen T.S., Scott H., Sollid L.M., Valnes N. 1989. T lymphocytes in human gut epithelium preferentially express the α/β antigen receptor and are of the CD45/UCHL1-positive. Scand. J. Immunol. 30: 123-128
    • (1989) Scand. J. Immunol. , vol.30 , pp. 123-128
    • Brandtzaeg, P.V.1    Bosnes, V.2    Halstensen, T.S.3    Scott, H.4    Sollid, L.M.5    Valnes, N.6
  • 11
    • 0023677452 scopus 로고
    • Alterations of the immune system in ulcerative colitis and Crohn's disease
    • MacDermott R.P., Stenson W.F. 1988. Alterations of the immune system in ulcerative colitis and Crohn's disease. Adv. Immunol. 42: 285-338
    • (1988) Adv. Immunol. , vol.42 , pp. 285-338
    • MacDermott, R.P.1    Stenson, W.F.2
  • 13
    • 0023871935 scopus 로고
    • Lymphocytes isolated from the intestinal lamina propria of normal nonhuman primates have increased expression of genes associated with T-cell activation
    • Zeitz M., Greene W.C., Peffer N.J., James S.P. 1988. Lymphocytes isolated from the intestinal lamina propria of normal nonhuman primates have increased expression of genes associated with T-cell activation. Gastroenterol. 94: 647-655
    • (1988) Gastroenterol. , vol.94 , pp. 647-655
    • Zeitz, M.1    Greene, W.C.2    Peffer, N.J.3    James, S.P.4
  • 15
    • 0022545059 scopus 로고
    • Spontaneous secretion of IgG subclasses by intestinal mononuclear cells: Differences between ulcerative colitis, Crohn's disease, and controls
    • Scott M.G., Nahm M.H., Macke K., Nash G.S., Bertovich M.J., MacDermott R.P. 1986. Spontaneous secretion of IgG subclasses by intestinal mononuclear cells: differences between ulcerative colitis, Crohn's disease, and controls. Clin. Exp. Immunol. 66: 209-215
    • (1986) Clin. Exp. Immunol. , vol.66 , pp. 209-215
    • Scott, M.G.1    Nahm, M.H.2    Macke, K.3    Nash, G.S.4    Bertovich, M.J.5    MacDermott, R.P.6
  • 16
    • 0026552488 scopus 로고
    • Increased interleukin-2 messenger RNA in the intestinal mucosal lesions of Crohn's disease but not ulcerative colitis
    • Mullin G.E., Lazenby A.J., Harris M.L., Bayless T.M., James S.P. 1992. Increased interleukin-2 messenger RNA in the intestinal mucosal lesions of Crohn's disease but not ulcerative colitis. Gastroenterol. 102: 1620-1627
    • (1992) Gastroenterol. , vol.102 , pp. 1620-1627
    • Mullin, G.E.1    Lazenby, A.J.2    Harris, M.L.3    Bayless, T.M.4    James, S.P.5
  • 17
    • 0021253159 scopus 로고
    • Serum-free medium for the generation and the propagation of functional human cytotoxic and helper T cell clones
    • Yssel H., DeVries J.E., Koken M., van Blitterswijk W., Spits H. 1984. Serum-free medium for the generation and the propagation of functional human cytotoxic and helper T cell clones. J. Immunol. Methods 72: 219-227
    • (1984) J. Immunol. Methods , vol.72 , pp. 219-227
    • Yssel, H.1    DeVries, J.E.2    Koken, M.3    Van Blitterswijk, W.4    Spits, H.5
  • 18
    • 0022548615 scopus 로고
    • Detection of somatic mutations in man: Evaluation of the microtiter cloning assay for T-lymphocytes
    • Henderson L., Cole H., Cole J., James S.E., Green M. 1986. Detection of somatic mutations in man: evaluation of the microtiter cloning assay for T-lymphocytes. Mutagenesis 1: 195-200
    • (1986) Mutagenesis , vol.1 , pp. 195-200
    • Henderson, L.1    Cole, H.2    Cole, J.3    James, S.E.4    Green, M.5
  • 19
    • 0025010810 scopus 로고
    • Autoantibodies to colonic cells and subcellular fractions in inflammatory bowel disease: Do they exist?
    • Cantrell M., Prindiville T., Gershwin M.E. 1990. Autoantibodies to colonic cells and subcellular fractions in inflammatory bowel disease: Do they exist? Journal of Autoimmunity 3: 307-320
    • (1990) Journal of Autoimmunity , vol.3 , pp. 307-320
    • Cantrell, M.1    Prindiville, T.2    Gershwin, M.E.3
  • 20
    • 0019498699 scopus 로고
    • Folate transport in isolated brush border membrane vesicles from rat intestine
    • Selhub J., Rosenburg I.H. 1981. Folate transport in isolated brush border membrane vesicles from rat intestine. J. Biol. Chem. 256: 4489-4493
    • (1981) J. Biol. Chem. , vol.256 , pp. 4489-4493
    • Selhub, J.1    Rosenburg, I.H.2
  • 21
    • 0016750245 scopus 로고
    • Human intestinal sucrase-isomaltase and cleavage of the hybrid into active distinct subunits
    • Conklin K.A., Yamashiro K.M., Gray G.M. 1975. Human intestinal sucrase-isomaltase and cleavage of the hybrid into active distinct subunits. J. Biol. Chem. 250: 5735-5741
    • (1975) J. Biol. Chem. , vol.250 , pp. 5735-5741
    • Conklin, K.A.1    Yamashiro, K.M.2    Gray, G.M.3
  • 22
    • 0022466160 scopus 로고
    • Sodium-proton exchange in colon brush-border membranes
    • Gastrointest. Liver Physiol. 14
    • Binder H.J., Stange G., Murer H., Stieger B., Hauri H.P. 1986. Sodium-proton exchange in colon brush-border membranes. Am. J. Physiol. 251: G382-389 (Gastrointest. Liver Physiol. 14).
    • (1986) Am. J. Physiol. , vol.251
    • Binder, H.J.1    Stange, G.2    Murer, H.3    Stieger, B.4    Hauri, H.P.5
  • 23
    • 0025308139 scopus 로고
    • Characterization of monoclonal antihuman small bowel and colon specific mucin antibodies
    • Prindiville T.P., Cantrell M.C., Gershwin M.E., Ruebner B.H. 1990. Characterization of monoclonal antihuman small bowel and colon specific mucin antibodies. Am. J. Clin. Pathol. 93: 621-630
    • (1990) Am. J. Clin. Pathol. , vol.93 , pp. 621-630
    • Prindiville, T.P.1    Cantrell, M.C.2    Gershwin, M.E.3    Ruebner, B.H.4
  • 24
    • 33749946901 scopus 로고
    • Colorimetric method for determination of sugars and related substances
    • Dubois M., Gilles K.A., Hamilton J.K., Rebers P.A., Smith F. 1956. Colorimetric method for determination of sugars and related substances. Anal. Chem. 28: 350-356
    • (1956) Anal. Chem. , vol.28 , pp. 350-356
    • Dubois, M.1    Gilles, K.A.2    Hamilton, J.K.3    Rebers, P.A.4    Smith, F.5
  • 25
    • 0018149399 scopus 로고
    • The isolation and characterization of high-molecular weight glycoprotein from pig colonic mucus
    • Marshall T., Allen A. 1978. The isolation and characterization of high-molecular weight glycoprotein from pig colonic mucus. Biochem. J. 173: 569-578
    • (1978) Biochem. J. , vol.173 , pp. 569-578
    • Marshall, T.1    Allen, A.2
  • 26
    • 0025310787 scopus 로고
    • Is T cell memory maintained by crossreactive stimulation?
    • Beverley P.C. 1990. Is T cell memory maintained by crossreactive stimulation? Immunol. Today 11: 203-205
    • (1990) Immunol. Today , vol.11 , pp. 203-205
    • Beverley, P.C.1
  • 27
    • 0024361550 scopus 로고
    • Leukocyte cell surface enzymology: CD45 (LCA, T200) is a protein tyrosine phosphatase
    • Clark E.A., Ledbetter J.A. 1989. Leukocyte cell surface enzymology: CD45 (LCA, T200) is a protein tyrosine phosphatase. Immunol. Today 10: 225-228
    • (1989) Immunol. Today , vol.10 , pp. 225-228
    • Clark, E.A.1    Ledbetter, J.A.2
  • 29
    • 0018639079 scopus 로고
    • Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease
    • Chirgwin J.M., Przybyla A.E., MacDonald R.J., Rutter W.J. 1979. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18: 5294-5299
    • (1979) Biochemistry , vol.18 , pp. 5294-5299
    • Chirgwin, J.M.1    Przybyla, A.E.2    MacDonald, R.J.3    Rutter, W.J.4
  • 30
    • 0023905495 scopus 로고
    • Transcription of the dystrophin gene in human muscle and non-muscle tissue
    • Chelly J., Kaplan J.C., Maire P., Gautron S., Kahn A. 1988. Transcription of the dystrophin gene in human muscle and non-muscle tissue. Nature 333: 858-860
    • (1988) Nature , vol.333 , pp. 858-860
    • Chelly, J.1    Kaplan, J.C.2    Maire, P.3    Gautron, S.4    Kahn, A.5
  • 31
    • 0024500344 scopus 로고
    • Correlation between the biologic functions and the generation of lymphokines in T cell clones
    • Tartakovsky B., Axelrod O., Blankenstein T., Mozes E. 1989. Correlation between the biologic functions and the generation of lymphokines in T cell clones. J. Immunol. 142: 2695-2701
    • (1989) J. Immunol. , vol.142 , pp. 2695-2701
    • Tartakovsky, B.1    Axelrod, O.2    Blankenstein, T.3    Mozes, E.4
  • 32
    • 0027170328 scopus 로고
    • Skewed T-cell receptor repertoire in genetically identical twins correlates with multiple sclerosis
    • Utz U., Biddison W.E., McFarland H.F., McFarlin D.E., Flerlage M., Martin R. 1993. Skewed T-cell receptor repertoire in genetically identical twins correlates with multiple sclerosis. Nature 364: 243-247
    • (1993) Nature , vol.364 , pp. 243-247
    • Utz, U.1    Biddison, W.E.2    McFarland, H.F.3    McFarlin, D.E.4    Flerlage, M.5    Martin, R.6
  • 33
    • 0026604656 scopus 로고
    • Evidence for selective accumulation of intrathyroidal T lymphocytes in human autoimmune thyroid disease based on T cell receptor V gene usage
    • Davies T.F., Martin A., Concepcion E.S., Graves P., Lahat N., Cohen W., Ben-Nun A. 1992. Evidence for selective accumulation of intrathyroidal T lymphocytes in human autoimmune thyroid disease based on T cell receptor V gene usage. J. Clin. Invest. 89: 157-162
    • (1992) J. Clin. Invest. , vol.89 , pp. 157-162
    • Davies, T.F.1    Martin, A.2    Concepcion, E.S.3    Graves, P.4    Lahat, N.5    Cohen, W.6    Ben-Nun, A.7
  • 34
    • 0025779157 scopus 로고
    • Evidence of limited variability of antigen receptors on intrathyroidal T cells in autoimmune thyroid disease
    • Davies T.F., Martin A., Concepcion E.S., Graves P., Cohen L., Ben-Nun A. 1991. Evidence of limited variability of antigen receptors on intrathyroidal T cells in autoimmune thyroid disease. New Eng. J. Med. 325: 238-244
    • (1991) New Eng. J. Med. , vol.325 , pp. 238-244
    • Davies, T.F.1    Martin, A.2    Concepcion, E.S.3    Graves, P.4    Cohen, L.5    Ben-Nun, A.6
  • 36
    • 0026471746 scopus 로고
    • Autoaggressive myocytotoxic T lymphocytes expressing an unusual γ/δ T cell receptor
    • Pluschke G., Rüegg D., Hohlfeld R., Engel A.G. 1992. Autoaggressive myocytotoxic T lymphocytes expressing an unusual γ/δ T cell receptor. J. Exp. Med. 176: 1785-1789
    • (1992) J. Exp. Med. , vol.176 , pp. 1785-1789
    • Pluschke, G.1    Rüegg, D.2    Hohlfeld, R.3    Engel, A.G.4
  • 39
    • 0023751365 scopus 로고
    • Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy
    • Urban J.L., Kumar V., Kono D.H., Gomez C., Horvath S.J., Clayton J., Ando D.G., Sercarz E.E., Hood L. 1988. Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy. Cell 54: 577-592
    • (1988) Cell , vol.54 , pp. 577-592
    • Urban, J.L.1    Kumar, V.2    Kono, D.H.3    Gomez, C.4    Horvath, S.J.5    Clayton, J.6    Ando, D.G.7    Sercarz, E.E.8    Hood, L.9
  • 40
    • 0023121484 scopus 로고
    • Kinetics and specificity of T and B cell responses in relapsing experimental allergic encephalomyelitis
    • Perry L.L., Barzaga M.E. 1987. Kinetics and specificity of T and B cell responses in relapsing experimental allergic encephalomyelitis. J. Immunol. 138: 1434-1441
    • (1987) J. Immunol. , vol.138 , pp. 1434-1441
    • Perry, L.L.1    Barzaga, M.E.2
  • 43
    • 0023690334 scopus 로고
    • Polyclonal nature of the intestinal mucosal lymphocyte populations in inflammatory bowel disease
    • Kaulfersch W., Fiocchi C., Waldmann T.A. 1988. Polyclonal nature of the intestinal mucosal lymphocyte populations in inflammatory bowel disease. Gastroenterol. 95: 364-370
    • (1988) Gastroenterol. , vol.95 , pp. 364-370
    • Kaulfersch, W.1    Fiocchi, C.2    Waldmann, T.A.3
  • 44
    • 0343057547 scopus 로고
    • Polyclonal activation of B lymphocytes and its role in self discrimination
    • J.R. Inglis, ed. Elsevier, Amsterdam
    • Goodman M., Weigle W. 1982. Polyclonal activation of B lymphocytes and its role in self discrimination. In B Lymphocytes Today. J.R. Inglis, ed. Elsevier, Amsterdam, pp. 63-69
    • (1982) B Lymphocytes Today , pp. 63-69
    • Goodman, M.1    Weigle, W.2
  • 47
    • 0024325672 scopus 로고
    • Antigen recognition in autoimmune encephalomyelitis and the potential for peptide mediated immunotherapy
    • Wraith D.C., Smilek D.E., Mitchell D.J., Steinman L., McDevitt H.O. 1989. Antigen recognition in autoimmune encephalomyelitis and the potential for peptide mediated immunotherapy Cell 59: 247-255
    • (1989) Cell , vol.59 , pp. 247-255
    • Wraith, D.C.1    Smilek, D.E.2    Mitchell, D.J.3    Steinman, L.4    McDevitt, H.O.5
  • 49
    • 0027454052 scopus 로고
    • Induction of relapsing paralysis in experimental autoimmune encephalomyelitis by bacterial superantigen
    • Brocke S., Gaur A., Piercy C., Gautam A., Gijbels K., Fathman C.G., Steinman L. 1993. Induction of relapsing paralysis in experimental autoimmune encephalomyelitis by bacterial superantigen. Nature 365: 642-649
    • (1993) Nature , vol.365 , pp. 642-649
    • Brocke, S.1    Gaur, A.2    Piercy, C.3    Gautam, A.4    Gijbels, K.5    Fathman, C.G.6    Steinman, L.7
  • 50
    • 0026329183 scopus 로고
    • Selective depletion in HIV infection of T cells that bear specific T cell receptor Vβ sequences
    • Imberti L., Sottini A., Bettinardi A., Puoti M., Primi D. 1991. Selective depletion in HIV infection of T cells that bear specific T cell receptor Vβ sequences. Science 254: 860-862
    • (1991) Science , vol.254 , pp. 860-862
    • Imberti, L.1    Sottini, A.2    Bettinardi, A.3    Puoti, M.4    Primi, D.5
  • 51
    • 0026694943 scopus 로고
    • Superantigen implicated in dependence of HIV-1 replication in T-cells and TCR Vβ expression
    • Laurence J., Hodtsev A.S., Posnett D.N. 1992. Superantigen implicated in dependence of HIV-1 replication in T-cells and TCR Vβ expression. Nature 358: 255-259
    • (1992) Nature , vol.358 , pp. 255-259
    • Laurence, J.1    Hodtsev, A.S.2    Posnett, D.N.3
  • 52
    • 0023024787 scopus 로고
    • Phenotypic analysis of lamina propria lymphocytes. Predominance of helper-inducer and cytolytic T-cell phenotypes and deficiency of suppressor-inducer phenotypes in Crohn's disease and control patients
    • James S.P., Fiocci C., Graeff A.S., Strober W. 1986. Phenotypic analysis of lamina propria lymphocytes. Predominance of helper-inducer and cytolytic T-cell phenotypes and deficiency of suppressor-inducer phenotypes in Crohn's disease and control patients. Gastroenterol. 91: 1483-1489
    • (1986) Gastroenterol. , vol.91 , pp. 1483-1489
    • James, S.P.1    Fiocci, C.2    Graeff, A.S.3    Strober, W.4
  • 53
    • 0026095235 scopus 로고
    • Increased activation of isolated intestinal lamina propria mononuclear cells in inflammatory bowel disease
    • Schreiber S., MacDermott R.P., Raedler A., Pinnau R., Bertovich M.J., Nash G.S. 1991. Increased activation of isolated intestinal lamina propria mononuclear cells in inflammatory bowel disease. Gastroenterol. 101: 1020-1030
    • (1991) Gastroenterol. , vol.101 , pp. 1020-1030
    • Schreiber, S.1    MacDermott, R.P.2    Raedler, A.3    Pinnau, R.4    Bertovich, M.J.5    Nash, G.S.6
  • 54
    • 0025615020 scopus 로고
    • Differential expression of CD25 (interleukin-2 receptor) on lamina propria T cells and macrophages in the intestinal lesions in Crohn's disease and ulcerative colitis
    • Choy M.Y., Walker-Smith J.A., Williams, C.B., MacDonald T.T. 1990. Differential expression of CD25 (interleukin-2 receptor) on lamina propria T cells and macrophages in the intestinal lesions in Crohn's disease and ulcerative colitis. Gut 31: 1365-1370
    • (1990) Gut , vol.31 , pp. 1365-1370
    • Choy, M.Y.1    Walker-Smith, J.A.2    Williams, C.B.3    MacDonald, T.T.4
  • 55
    • 0025807511 scopus 로고
    • Immunohistochemical characterization, distribution, and ultrastructure of lymphocytes bearing T-cell receptor γ/δ in inflammatory bowel disease
    • Fukushima K., Masuda T., Ohtani H., Sasaki O., Funayama Y., Matsuno S., Nagura H. 1991. Immunohistochemical characterization, distribution, and ultrastructure of lymphocytes bearing T-cell receptor γ/δ in inflammatory bowel disease. Gastroenterol. 101: 670-678
    • (1991) Gastroenterol. , vol.101 , pp. 670-678
    • Fukushima, K.1    Masuda, T.2    Ohtani, H.3    Sasaki, O.4    Funayama, Y.5    Matsuno, S.6    Nagura, H.7
  • 56
    • 0025165778 scopus 로고
    • Lack of induction of suppressor T cells by intestinal epithelial cells from patients with inflammatory bowel disease
    • Mayer L., Eisenhardt D. 1990. Lack of induction of suppressor T cells by intestinal epithelial cells from patients with inflammatory bowel disease. Clin. Invest. 86: 1255-1260
    • (1990) Clin. Invest. , vol.86 , pp. 1255-1260
    • Mayer, L.1    Eisenhardt, D.2
  • 57
    • 84958732143 scopus 로고
    • Synthesis and regulation of accessory cytokines in human intestinal epithelial cells: Comparison between normal and IBD
    • Panja A., Siden E., Goldberg S., Mayer L. 1993. Synthesis and regulation of accessory cytokines in human intestinal epithelial cells: comparison between normal and IBD. Gastroenterol. 104(Suppl. 2): A759
    • (1993) Gastroenterol. , vol.104 , Issue.SUPPL. 2
    • Panja, A.1    Siden, E.2    Goldberg, S.3    Mayer, L.4
  • 59
    • 0027293755 scopus 로고
    • Where, when, and how to detect biased expression of disease-relevant Vβ genes in rats with experimental autoimmune encephalomyelitis
    • Offner H., Buenafe A.C., Vainiene M., Celnik B., Weinberg A.D., Gold D.P., Hashim G., Vandenbark A.A. 1993. Where, when, and how to detect biased expression of disease-relevant Vβ genes in rats with experimental autoimmune encephalomyelitis. J. Immunol. 151(1): 506-517
    • (1993) J. Immunol. , vol.151 , Issue.1 , pp. 506-517
    • Offner, H.1    Buenafe, A.C.2    Vainiene, M.3    Celnik, B.4    Weinberg, A.D.5    Gold, D.P.6    Hashim, G.7    Vandenbark, A.A.8
  • 60
    • 0027290414 scopus 로고
    • Characterization of the primary structure of the T cell receptor β chains in cells infiltrating the salivary gland in the sicca syndrome of HIV-1 infection
    • Dwyer E., Itescu S., Winchester R. 1993. Characterization of the primary structure of the T cell receptor β chains in cells infiltrating the salivary gland in the sicca syndrome of HIV-1 infection. J. Clin. Invest. 92: 495-502
    • (1993) J. Clin. Invest. , vol.92 , pp. 495-502
    • Dwyer, E.1    Itescu, S.2    Winchester, R.3


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