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. 1990 May;85(5):1497–1506. doi: 10.1172/JCI114596

Neutrophil adherence to isolated adult canine myocytes. Evidence for a CD18-dependent mechanism.

M L Entman 1, K Youker 1, S B Shappell 1, C Siegel 1, R Rothlein 1, W J Dreyer 1, F C Schmalstieg 1, C W Smith 1
PMCID: PMC296597  PMID: 1970581

Abstract

Cardiac myocytes were isolated from adult dogs and incubated with isolated canine neutrophils (PMN). Intercellular adhesion was low and unchanged by stimulation of the PMN with zymosan activated serum or platelet activating factor (PAF) at concentrations that significantly enhance PMN adhesion to protein-coated glass and canine endothelial cell monolayers. Intercellular adhesion was significantly increased only when both myocytes and PMN were stimulated (e.g., myocytes incubated with IL-1, tumor necrosis factor, or phorbol myristate acetate, and PMN were chemotactically stimulated). Inhibitors of protein synthesis diminished the IL-1 beta-induced effect by greater than 80%. The IL-1 beta, PAF-stimulated PMN-myocyte adhesion was associated with substantial H2O2 production. Under conditions with low PMN-myocyte adhesion (i.e., IL-1 beta alone, PAF alone, or no stimulus) H2O2 production was generally less than 5% of that occurring with high adhesion. An anti-CD18 monoclonal antibody (R15.7) inhibited stimulated PMN-myocyte adhesion by greater than 95% and reduced H2O2 production by greater than 90%. Control isotype-matched, binding, and nonbinding antibodies were without effect on adherence or H2O2 production. The results indicate that cytokine stimulation of adult myocytes induces expression of a ligand involved in CD18-dependent adherence of canine neutrophils.

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  1. Altieri D. C., Edgington T. S. The saturable high affinity association of factor X to ADP-stimulated monocytes defines a novel function of the Mac-1 receptor. J Biol Chem. 1988 May 25;263(15):7007–7015. [PubMed] [Google Scholar]
  2. Anderson D. C., Freeman K. L., Heerdt B., Hughes B. J., Jack R. M., Smith C. W. Abnormal stimulated adherence of neonatal granulocytes: impaired induction of surface Mac-1 by chemotactic factors or secretagogues. Blood. 1987 Sep;70(3):740–750. [PubMed] [Google Scholar]
  3. Anderson D. C., Miller L. J., Schmalstieg F. C., Rothlein R., Springer T. A. Contributions of the Mac-1 glycoprotein family to adherence-dependent granulocyte functions: structure-function assessments employing subunit-specific monoclonal antibodies. J Immunol. 1986 Jul 1;137(1):15–27. [PubMed] [Google Scholar]
  4. Anderson D. C., Schmalstieg F. C., Shearer W., Becker-Freeman K., Kohl S., Smith C. W., Tosi M. F., Springer T. Leukocyte LFA-1, OKM1, p150,95 deficiency syndrome: functional and biosynthetic studies of three kindreds. Fed Proc. 1985 Jul;44(10):2671–2677. [PubMed] [Google Scholar]
  5. Arfors K. E., Lundberg C., Lindbom L., Lundberg K., Beatty P. G., Harlan J. M. A monoclonal antibody to the membrane glycoprotein complex CD18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo. Blood. 1987 Jan;69(1):338–340. [PubMed] [Google Scholar]
  6. Bednar M., Smith B., Pinto A., Mullane K. M. Nafazatrom-induced salvage of ischemic myocardium in anesthetized dogs is mediated through inhibition of neutrophil function. Circ Res. 1985 Jul;57(1):131–141. doi: 10.1161/01.res.57.1.131. [DOI] [PubMed] [Google Scholar]
  7. Beesley J. E., Pearson J. D., Hutchings A., Carleton J. S., Gordon J. L. Granulocyte migration through endothelium in culture. J Cell Sci. 1979 Aug;38:237–248. doi: 10.1242/jcs.38.1.237. [DOI] [PubMed] [Google Scholar]
  8. Bevilacqua M. P., Pober J. S., Mendrick D. L., Cotran R. S., Gimbrone M. A., Jr Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238–9242. doi: 10.1073/pnas.84.24.9238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Breviario F., Bertocchi F., Dejana E., Bussolino F. IL-1-induced adhesion of polymorphonuclear leukocytes to cultured human endothelial cells. Role of platelet-activating factor. J Immunol. 1988 Nov 15;141(10):3391–3397. [PubMed] [Google Scholar]
  10. Brown A. F. Neutrophil granulocytes: adhesion and locomotion on collagen substrata and in collagen matrices. J Cell Sci. 1982 Dec;58:455–467. doi: 10.1242/jcs.58.1.455. [DOI] [PubMed] [Google Scholar]
  11. Brown E. J., Goodwin J. L. Fibronectin receptors of phagocytes. Characterization of the Arg-Gly-Asp binding proteins of human monocytes and polymorphonuclear leukocytes. J Exp Med. 1988 Mar 1;167(3):777–793. doi: 10.1084/jem.167.3.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Charo I. F., Yuen C., Perez H. D., Goldstein I. M. Chemotactic peptides modulate adherence of human polymorphonuclear leukocytes to monolayers of cultured endothelial cells. J Immunol. 1986 May 1;136(9):3412–3419. [PubMed] [Google Scholar]
  13. Detmers P. A., Wright S. D., Olsen E., Kimball B., Cohn Z. A. Aggregation of complement receptors on human neutrophils in the absence of ligand. J Cell Biol. 1987 Sep;105(3):1137–1145. doi: 10.1083/jcb.105.3.1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dreyer W. J., Smith C. W., Michael L. H., Rossen R. D., Hughes B. J., Entman M. L., Anderson D. C. Canine neutrophil activation by cardiac lymph obtained during reperfusion of ischemic myocardium. Circ Res. 1989 Dec;65(6):1751–1762. doi: 10.1161/01.res.65.6.1751. [DOI] [PubMed] [Google Scholar]
  15. Dunn C. J., Fleming W. E. Increased adhesion of polymorphonuclear leukocytes to vascular endothelium by specific interaction of endogenous (interleukin-1) and exogenous (lipopolysaccharide) substances with endothelial cells 'in vitro'. Eur J Rheumatol Inflamm. 1984;7(3):80–86. [PubMed] [Google Scholar]
  16. Dustin M. L., Rothlein R., Bhan A. K., Dinarello C. A., Springer T. A. Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol. 1986 Jul 1;137(1):245–254. [PubMed] [Google Scholar]
  17. Engler R. L., Dahlgren M. D., Morris D. D., Peterson M. A., Schmid-Schönbein G. W. Role of leukocytes in response to acute myocardial ischemia and reflow in dogs. Am J Physiol. 1986 Aug;251(2 Pt 2):H314–H323. doi: 10.1152/ajpheart.1986.251.2.H314. [DOI] [PubMed] [Google Scholar]
  18. Engler R. L., Dahlgren M. D., Peterson M. A., Dobbs A., Schmid-Schönbein G. W. Accumulation of polymorphonuclear leukocytes during 3-h experimental myocardial ischemia. Am J Physiol. 1986 Jul;251(1 Pt 2):H93–100. doi: 10.1152/ajpheart.1986.251.1.H93. [DOI] [PubMed] [Google Scholar]
  19. Engler R. L., Schmid-Schönbein G. W., Pavelec R. S. Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog. Am J Pathol. 1983 Apr;111(1):98–111. [PMC free article] [PubMed] [Google Scholar]
  20. Farmer B. B., Mancina M., Williams E. S., Watanabe A. M. Isolation of calcium tolerant myocytes from adult rat hearts: review of the literature and description of a method. Life Sci. 1983 Jul 4;33(1):1–18. doi: 10.1016/0024-3205(83)90706-3. [DOI] [PubMed] [Google Scholar]
  21. Forman M. B., Bingham S., Kopelman H. A., Wehr C., Sandler M. P., Kolodgie F., Vaughn W. K., Friesinger G. C., Virmani R. Reduction of infarct size with intracoronary perfluorochemical in a canine preparation of reperfusion. Circulation. 1985 May;71(5):1060–1068. doi: 10.1161/01.cir.71.5.1060. [DOI] [PubMed] [Google Scholar]
  22. Furie M. B., Naprstek B. L., Silverstein S. C. Migration of neutrophils across monolayers of cultured microvascular endothelial cells. An in vitro model of leucocyte extravasation. J Cell Sci. 1987 Sep;88(Pt 2):161–175. doi: 10.1242/jcs.88.2.161. [DOI] [PubMed] [Google Scholar]
  23. Galfre G., Howe S. C., Milstein C., Butcher G. W., Howard J. C. Antibodies to major histocompatibility antigens produced by hybrid cell lines. Nature. 1977 Apr 7;266(5602):550–552. doi: 10.1038/266550a0. [DOI] [PubMed] [Google Scholar]
  24. Gamble J. R., Harlan J. M., Klebanoff S. J., Vadas M. A. Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8667–8671. doi: 10.1073/pnas.82.24.8667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Giger U., Boxer L. A., Simpson P. J., Lucchesi B. R., Todd R. F., 3rd Deficiency of leukocyte surface glycoproteins Mo1, LFA-1, and Leu M5 in a dog with recurrent bacterial infections: an animal model. Blood. 1987 Jun;69(6):1622–1630. [PubMed] [Google Scholar]
  26. Gimbrone M. A., Jr, Brock A. F., Schafer A. I. Leukotriene B4 stimulates polymorphonuclear leukocyte adhesion to cultured vascular endothelial cells. J Clin Invest. 1984 Oct;74(4):1552–1555. doi: 10.1172/JCI111570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Gresham H. D., Goodwin J. L., Allen P. M., Anderson D. C., Brown E. J. A novel member of the integrin receptor family mediates Arg-Gly-Asp-stimulated neutrophil phagocytosis. J Cell Biol. 1989 May;108(5):1935–1943. doi: 10.1083/jcb.108.5.1935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Harlan J. M., Killen P. D., Senecal F. M., Schwartz B. R., Yee E. K., Taylor R. F., Beatty P. G., Price T. H., Ochs H. D. The role of neutrophil membrane glycoprotein GP-150 in neutrophil adherence to endothelium in vitro. Blood. 1985 Jul;66(1):167–178. [PubMed] [Google Scholar]
  29. Harlan J. M. Leukocyte-endothelial interactions. Blood. 1985 Mar;65(3):513–525. [PubMed] [Google Scholar]
  30. House S. D., Lipowsky H. H. Leukocyte-endothelium adhesion: microhemodynamics in mesentery of the cat. Microvasc Res. 1987 Nov;34(3):363–379. doi: 10.1016/0026-2862(87)90068-9. [DOI] [PubMed] [Google Scholar]
  31. Jolly S. R., Kane W. J., Hook B. G., Abrams G. D., Kunkel S. L., Lucchesi B. R. Reduction of myocardial infarct size by neutrophil depletion: effect of duration of occlusion. Am Heart J. 1986 Oct;112(4):682–690. doi: 10.1016/0002-8703(86)90461-8. [DOI] [PubMed] [Google Scholar]
  32. Lo S. K., Detmers P. A., Levin S. M., Wright S. D. Transient adhesion of neutrophils to endothelium. J Exp Med. 1989 May 1;169(5):1779–1793. doi: 10.1084/jem.169.5.1779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Luscinskas F. W., Brock A. F., Arnaout M. A., Gimbrone M. A., Jr Endothelial-leukocyte adhesion molecule-1-dependent and leukocyte (CD11/CD18)-dependent mechanisms contribute to polymorphonuclear leukocyte adhesion to cytokine-activated human vascular endothelium. J Immunol. 1989 Apr 1;142(7):2257–2263. [PubMed] [Google Scholar]
  34. Marlin S. D., Morton C. C., Anderson D. C., Springer T. A. LFA-1 immunodeficiency disease. Definition of the genetic defect and chromosomal mapping of alpha and beta subunits of the lymphocyte function-associated antigen 1 (LFA-1) by complementation in hybrid cells. J Exp Med. 1986 Sep 1;164(3):855–867. doi: 10.1084/jem.164.3.855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Mehta J. L., Nichols W. W., Mehta P. Neutrophils as potential participants in acute myocardial ischemia: relevance to reperfusion. J Am Coll Cardiol. 1988 Jun;11(6):1309–1316. doi: 10.1016/0735-1097(88)90297-5. [DOI] [PubMed] [Google Scholar]
  36. Mullane K. M., Kraemer R., Smith B. Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium. J Pharmacol Methods. 1985 Nov;14(3):157–167. doi: 10.1016/0160-5402(85)90029-4. [DOI] [PubMed] [Google Scholar]
  37. Mullane K. M., Read N., Salmon J. A., Moncada S. Role of leukocytes in acute myocardial infarction in anesthetized dogs: relationship to myocardial salvage by anti-inflammatory drugs. J Pharmacol Exp Ther. 1984 Feb;228(2):510–522. [PubMed] [Google Scholar]
  38. Nathan C. F. Neutrophil activation on biological surfaces. Massive secretion of hydrogen peroxide in response to products of macrophages and lymphocytes. J Clin Invest. 1987 Dec;80(6):1550–1560. doi: 10.1172/JCI113241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Nathan C. F. Respiratory burst in adherent human neutrophils: triggering by colony-stimulating factors CSF-GM and CSF-G. Blood. 1989 Jan;73(1):301–306. [PubMed] [Google Scholar]
  40. O'Shea J. J., Brown E. J., Seligmann B. E., Metcalf J. A., Frank M. M., Gallin J. I. Evidence for distinct intracellular pools of receptors for C3b and C3bi in human neutrophils. J Immunol. 1985 Apr;134(4):2580–2587. [PubMed] [Google Scholar]
  41. Olafsson B., Forman M. B., Puett D. W., Pou A., Cates C. U., Friesinger G. C., Virmani R. Reduction of reperfusion injury in the canine preparation by intracoronary adenosine: importance of the endothelium and the no-reflow phenomenon. Circulation. 1987 Nov;76(5):1135–1145. doi: 10.1161/01.cir.76.5.1135. [DOI] [PubMed] [Google Scholar]
  42. Petty H. R., Francis J. W., Todd R. F., 3rd, Petrequin P., Boxer L. A. Neutrophil C3bi receptors: formation of membrane clusters during cell triggering requires intracellular granules. J Cell Physiol. 1987 Nov;133(2):235-42, 256. doi: 10.1002/jcp.1041330206. [DOI] [PubMed] [Google Scholar]
  43. Philips M. R., Buyon J. P., Winchester R., Weissmann G., Abramson S. B. Up-regulation of the iC3b receptor (CR3) is neither necessary nor sufficient to promote neutrophil aggregation. J Clin Invest. 1988 Aug;82(2):495–501. doi: 10.1172/JCI113623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Pober J. S., Gimbrone M. A., Jr, Lapierre L. A., Mendrick D. L., Fiers W., Rothlein R., Springer T. A. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol. 1986 Sep 15;137(6):1893–1896. [PubMed] [Google Scholar]
  45. Pober J. S., Lapierre L. A., Stolpen A. H., Brock T. A., Springer T. A., Fiers W., Bevilacqua M. P., Mendrick D. L., Gimbrone M. A., Jr Activation of cultured human endothelial cells by recombinant lymphotoxin: comparison with tumor necrosis factor and interleukin 1 species. J Immunol. 1987 May 15;138(10):3319–3324. [PubMed] [Google Scholar]
  46. Pohlman T. H., Stanness K. A., Beatty P. G., Ochs H. D., Harlan J. M. An endothelial cell surface factor(s) induced in vitro by lipopolysaccharide, interleukin 1, and tumor necrosis factor-alpha increases neutrophil adherence by a CDw18-dependent mechanism. J Immunol. 1986 Jun 15;136(12):4548–4553. [PubMed] [Google Scholar]
  47. Romson J. L., Hook B. G., Kunkel S. L., Abrams G. D., Schork M. A., Lucchesi B. R. Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog. Circulation. 1983 May;67(5):1016–1023. doi: 10.1161/01.cir.67.5.1016. [DOI] [PubMed] [Google Scholar]
  48. Romson J. L., Hook B. G., Rigot V. H., Schork M. A., Swanson D. P., Lucchesi B. R. The effect of ibuprofen on accumulation of indium-111-labeled platelets and leukocytes in experimental myocardial infarction. Circulation. 1982 Nov;66(5):1002–1011. doi: 10.1161/01.cir.66.5.1002. [DOI] [PubMed] [Google Scholar]
  49. Rothlein R., Dustin M. L., Marlin S. D., Springer T. A. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol. 1986 Aug 15;137(4):1270–1274. [PubMed] [Google Scholar]
  50. Rowe G. T., Manson N. H., Caplan M., Hess M. L. Hydrogen peroxide and hydroxyl radical mediation of activated leukocyte depression of cardiac sarcoplasmic reticulum. Participation of the cyclooxygenase pathway. Circ Res. 1983 Nov;53(5):584–591. doi: 10.1161/01.res.53.5.584. [DOI] [PubMed] [Google Scholar]
  51. Schmid-Schönbein G. W., Engler R. L. Granulocytes as active participants in acute myocardial ischemia and infarction. Am J Cardiovasc Pathol. 1987 Jan;1(1):15–30. [PubMed] [Google Scholar]
  52. Sen S., Petscher C., Ratliff N. A factor that initiates myocardial hypertrophy in hypertension. Hypertension. 1987 Mar;9(3):261–267. doi: 10.1161/01.hyp.9.3.261. [DOI] [PubMed] [Google Scholar]
  53. Simpson P. J., Mickelson J., Fantone J. C., Gallagher K. P., Lucchesi B. R. Iloprost inhibits neutrophil function in vitro and in vivo and limits experimental infarct size in canine heart. Circ Res. 1987 May;60(5):666–673. doi: 10.1161/01.res.60.5.666. [DOI] [PubMed] [Google Scholar]
  54. Simpson P. J., Todd R. F., 3rd, Fantone J. C., Mickelson J. K., Griffin J. D., Lucchesi B. R. Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mo1, anti-CD11b) that inhibits leukocyte adhesion. J Clin Invest. 1988 Feb;81(2):624–629. doi: 10.1172/JCI113364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Smith C. W., Hollers J. C., Patrick R. A., Hassett C. Motility and adhesiveness in human neutrophils. Effects of chemotactic factors. J Clin Invest. 1979 Feb;63(2):221–229. doi: 10.1172/JCI109293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Smith C. W., Marlin S. D., Rothlein R., Toman C., Anderson D. C. Cooperative interactions of LFA-1 and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophils in vitro. J Clin Invest. 1989 Jun;83(6):2008–2017. doi: 10.1172/JCI114111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Smith C. W., Rothlein R., Hughes B. J., Mariscalco M. M., Rudloff H. E., Schmalstieg F. C., Anderson D. C. Recognition of an endothelial determinant for CD 18-dependent human neutrophil adherence and transendothelial migration. J Clin Invest. 1988 Nov;82(5):1746–1756. doi: 10.1172/JCI113788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Staunton D. E., Dustin M. L., Springer T. A. Functional cloning of ICAM-2, a cell adhesion ligand for LFA-1 homologous to ICAM-1. Nature. 1989 May 4;339(6219):61–64. doi: 10.1038/339061a0. [DOI] [PubMed] [Google Scholar]
  59. Tonnesen M. G., Anderson D. C., Springer T. A., Knedler A., Avdi N., Henson P. M. Adherence of neutrophils to cultured human microvascular endothelial cells. Stimulation by chemotactic peptides and lipid mediators and dependence upon the Mac-1, LFA-1, p150,95 glycoprotein family. J Clin Invest. 1989 Feb;83(2):637–646. doi: 10.1172/JCI113928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Tonnesen M. G., Smedly L. A., Henson P. M. Neutrophil-endothelial cell interactions. Modulation of neutrophil adhesiveness induced by complement fragments C5a and C5a des arg and formyl-methionyl-leucyl-phenylalanine in vitro. J Clin Invest. 1984 Nov;74(5):1581–1592. doi: 10.1172/JCI111574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Vedder N. B., Harlan J. M. Increased surface expression of CD11b/CD18 (Mac-1) is not required for stimulated neutrophil adherence to cultured endothelium. J Clin Invest. 1988 Mar;81(3):676–682. doi: 10.1172/JCI113372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Werns S. W., Simpson P. J., Mickelson J. K., Shea M. J., Pitt B., Lucchesi B. R. Sustained limitation by superoxide dismutase of canine myocardial injury due to regional ischemia followed by reperfusion. J Cardiovasc Pharmacol. 1988 Jan;11(1):36–44. doi: 10.1097/00005344-198801000-00006. [DOI] [PubMed] [Google Scholar]
  63. Wright S. D., Levin S. M., Jong M. T., Chad Z., Kabbash L. G. CR3 (CD11b/CD18) expresses one binding site for Arg-Gly-Asp-containing peptides and a second site for bacterial lipopolysaccharide. J Exp Med. 1989 Jan 1;169(1):175–183. doi: 10.1084/jem.169.1.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Wright S. D., Meyer B. C. Fibronectin receptor of human macrophages recognizes the sequence Arg-Gly-Asp-Ser. J Exp Med. 1985 Aug 1;162(2):762–767. doi: 10.1084/jem.162.2.762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Zimmerman G. A., McIntyre T. M. Neutrophil adherence to human endothelium in vitro occurs by CDw18 (Mo1, MAC-1/LFA-1/GP 150,95) glycoprotein-dependent and -independent mechanisms. J Clin Invest. 1988 Feb;81(2):531–537. doi: 10.1172/JCI113351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Zimmerman G. A., McIntyre T. M., Prescott S. M. Thrombin stimulates the adherence of neutrophils to human endothelial cells in vitro. J Clin Invest. 1985 Dec;76(6):2235–2246. doi: 10.1172/JCI112232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. de Lorgeril M., Basmadjian A., Lavallée M., Clément R., Millette D., Rousseau G., Latour J. G. Influence of leukopenia on collateral flow, reperfusion flow, reflow ventricular fibrillation, and infarct size in dogs. Am Heart J. 1989 Mar;117(3):523–532. doi: 10.1016/0002-8703(89)90724-2. [DOI] [PubMed] [Google Scholar]

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