Chemokines and chemokine receptors in the pathogenesis of multiple sclerosis

Abstract

In recent years we have seen growing evidence for the role of chemokines in the pathogenesis of several infectious and non-infectious inflammatory CNS disease states, including Multiple Sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE). An increase in proinflammatory chemokines has been associated with demyelinating lesions and clinical neurological dysfunction in patients with MS; these chemokines could be potential targets for MS therapy. Besides a clearly defined role in mediating leukocyte migration, these and other chemokines may act as immunoregulatory molecules in the driving to Th1/Th2 responses, switch of cytokine profiles, and the induction of tolerance. Since chemokine receptors have now been identified on macrophages, microglia, astrocytes, and endothelial cells as well as neurons in the CNS, chemokine/receptor interactions may mediate functional responses in a variety of CNS cell types during the course of inflammatory disease states. Therefore, clarification of the roles of chemokines and their receptors in the pathogenesis of EAE and MS will be useful in establishing immunotherapeutic strategies for these neurological autoimmune disorders.

Keywords

EAE MS chemokine inflammation

Get full access to this article

View all access options for this article.

References

Van Damme J. Interleukin-8 and related chemotactic cytokines: Thomson A (ed) The cytokine handbook. London: Academic Press ; 1994, 185-208.

Clark-Lewis I et al. (1995) Structure-activity relationships of chemokines . J Leuk Biol 57: 703-711 .

Garcia-Zepeda EA et al. (1996) Human monocytes chemoattractant protein (MCP)-4 is a novel CC chemokine with activities on monocytes, eosinophils, and basophils induced in allergic and nonallergic inflammation that signals through the CC chemokine receptors (CCR)-2 and -3 . J Immunol 157: 5613-5626 .

Luster AD. (1998) Chemokines-chemotactic cytokines that mediate inflammation . N Engl J Med 338: 436-445 .

Bazan JF et al. (1997) A new class of membrane-bound chemokine with a CX3C motif . Nature 385: 640-644 .

Mizoue LS , Bazan JF , Johnson EC , Handel TM. (1999) Solution structure and dynamics of the CX3C chemokine domain of fractalkine and its interaction with an N-terminal fragment of CX3CR1 . Biochemistry 38: 1402-1414 .

Pan Y et al. (1997) Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation . Nature 387: 611-617 .

Khan O et al. (1996) Interferon beta-1b serum levels in multiple sclerosis patients following subcutaneous administration . Neurology 46: 1639-1643 .

Oppenheim JJ , Zachariae COC , Mukaida N , Matsushima K. (1991) Properties of the novel proinflammatory supergene intercrine cytokine family . Annu Rev Immunol 9: 617-648 .

10.

Miller MD , Krangel MS. (1992) Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines . Crit Rev Immunol 12: 17-42 .

11.

Proost P , Wuyts A , Damme JV. (1996) The role of chemokines in inflammation . Int J Clin Lab Res 26: 211-223 .

12.

Baggiolini M. (1998) Chemokines and leukocyte traffic . Nature 392: 565-568 .

13.

Zlotnik A , Morales J , Hedrick JA. (1999) Recent advances in chemokines and chemokine receptors . Crit Rev Immunol 19: 1-47 .

14.

Karpus WJ et al. (1995) An important role for the chemokine macrophage inflammatory protein-1-a in the pathogenesis of the T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis . J Immunol 155: 5003-5010 .

15.

Gunn MD et al. (1999) Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization . J Exp Med 189: 451-460 .

16.

Proudfoot AEI , Wells TNC , Clapham PR. (1999) Chemokine receptors-Future targets for HIV ? Biochem Pharmacol 57: 451-463 .

17.

Sallusto F , Lanzavecchia A , Mackay CR. (1998) Chemokines and chemokine receptors in T-cell priming and Th1/Th2-mediated responses . Immunol Today 19: 568-574 .

18.

Annunziato F et al. (1999) Assessment of chemokine receptor expression by human Th1 and Th2 cells in vitro and in vivo . J Leukoc Biol 65: 691-699 .

19.

Lukacs NW et al. (1988) Production of monocyte chemoattractant protein-1 and macrophage inflamma-tory protein-1a by inflammatory granuloma fibroblasts . Am J Pathol 144: 711-718 .

20.

Hedrick JA and Zlotnik A. (1996) Chemokines and lymphocyte biology . Curr Opin Immunol 8: 343-347 .

21.

Lavi E et al. (1998) Chemokine receptors in the human brain and their relationship to HIV infection . J Neurovirol 4: 301-311 .

22.

Hesselgesser J et al. (1997) Functional chemokine receptor expression in human neuronal cells: evidence for a CD4 independent association between HIV-1 gp120 and the viral coreceptor CXCR4 . Curr Biol 7: 112-121 .

23.

Hesselgesser J etal. (1998) Neuronalapoptosisinducedby HIV-1 gp120 and the chemokine SDF-1α is mediated by the chemokine receptor CXCR4 . Curr Biol 8: 595-598 .

24.

Hesselgesser J , Horuk R. (1999) Chemokines and chemokine receptor expression in the central nervous system . J Neurovirol 5: 13-26 .

25.

Sorensen T et al. (1999) Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients . JClin Invest 103: 807-815 .

26.

Bleul CC et al. (1997) The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes . Proc Natl Acad Sci USA 94: 1925-1930 .

27.

Wu LJ et al. (1997) CCR5 levels and expression pattern correlate with infectability by macrophage-tropic HIV- 1, in vitro . J Exp Med 185: 1681-1691 .

28.

Sica A et al. (1997) Bacterial lipopolysaccharide rapidly inhibits expression of C-C chemokine receptors in human monocytes . J Exp Med 185: 969-974 .

29.

He J et al. (1997) CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia . Nature 385: 645-649 .

30.

Berger EA. (1997) HIV entry and tropism: the chemokine receptor connection . AIDS 11: S3-S16 .

31.

Clapham PR , Weiss RA. (1997) Spoilt for choice of coreceptors . Nature 388: 230-231 .

32.

D'Souza MP , Harden VA. (1996) Chemokines and HIV-1 second receptors . Nature Med 2: 1293-1300 .

33.

Spanaus KS et al. (1997) C-X-C and C-C chemokines are expressed in the cerebrospinal fluid in bacterial meningitis and mediate chemotactic activity on peripheral blood-derived polymorphonuclear and mononuc-lear cells in vitro . J Immunol 158: 1956-1964 .

34.

Schmidtmayerova H et al. (1996) Human immunodeficiency virus type 1 infection alters chemokine β peptide expression in human monocytes: implications for recruitment of leukocytes into brain and lymph nodes . Proc Natl Acad Sci USA 93: 700-704 .

35.

Rollins B , Walz A , Baggiolini M. (1991) Recombinant human MCP-1/JE induces chemotaxis, calcium flux, and the respiratory burst in human monocytes . Blood 78: 1112-1116 .

36.

Randolph GJ , Furie MB. (1995) A soluble gradient of endogenous monocyte chemoattractant protein-1 promotes the transendothelial migration of monocytes in vitro . J Immunol 155: 3610-3618 .

37.

Yi J et al. (1997) CXCR-4 is expressed by primary macrophages and supports CCR5-independent infection by dual-tropic but not T-tropic isolates of HIV-1 . JVirol 72: 772-777 .

38.

Heesen M et al. (1996) Mouse astrocytes respond to the chemokines MCP-1 and KC, but reverse transcriptasepolymerase chain reaction does not detect mRNA for the KC or new MCP-1 receptor . J Neurosci Res 45: 382-391 .

39.

Heesen ML et al. (1997) Alternate splicing of mouse fusin/CXC chemokine receptor-4 . J Immunol 158: 3561-3564 .

40.

Tanabe S et al. (1997) Functional expression of the CXC-chemokine receptor-4/fusin on mouse microglial cells and astrocytes . J Immunol 159: 905-911 .

41.

Westmoreland SV et al. (1998) Chemokine receptor expression on resident and inflammatory cells in the brain of macaques with simian immunodeficiency virus encephalitis . Am J Pathol 152: 659-665 .

42.

Meucci O et al. (1998) Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity . Proc Natl Acad Sci USA 95: 14500-14505 .

43.

Horuk R et al. (1996) The duffy antigen receptor for chemokines: structural analysis and expression in the brain . J Leukocyte Biol 59: 29-38 .

44.

Horuk R et al. (1997) Expression of chemokine receptors by subsets of neurons in the central nervous system . J Immunol 158: 2882-2890 .

45.

Tani M et al. (1996) Neutrophil infiltration, glial reaction, and neurological disease in transgenic mice expressing the chemokine N51/KC in oligodendrocytes . J Clin Invest 98: 529-539 .

46.

Eng LF , Ghirnikar RS , Lee YL. (1995) Inflammation in EAE: role of chemokine/cytokine expression by resident and infiltrating cells . Neurochem Res 21: 511-525 .

47.

Constantinescu CS et al. (1998) Pathogenesis of Neuroimmunologic Diseases . Immunol Res 171: 217-227 .

48.

Arnason BG. (1983) Relevance of experimental allergic encephalomyelitis to multiple sclerosis . Neurol Clin 1: 765-782 .

49.

Wekerle H. (1991) Immunopathogenesis of multiple sclerosis . Acta Neurol 13: 197-204 .

50.

Traugott U , McFarlin DE , Raine CS. (1986) Immuno-pathology of the lesion in chronic relapsing experimental autoimmune encephalomyelitis in the mouse . Cell Immunol 99: 395-410 .

51.

Suen WE , Bergman CM , Hjelmstrom P , Ruddle NH. (1997) A critical role for lymphotoxin in experimental allergic encephalomyelitis . J Exp Med 186: 1233-1240 .

52.

Navikas V , Link H. (1996) Review: cytokines and the pathogenesis of multiple sclerosis . J Neurosci Res 45: 322-333 .

53.

Lublin FD. Experimental models of autoimmune demyelination; In: Cook SD (ed): Handbook of multiple sclerosis. 2nd ed. New York, Marcel Dekker , 1996, pp. 119-143.

54.

Unanue ER , Allen PM. (1987) The basis for the immunoregulatory role of macrophages and other accessory cells . Science 236: 551-557 .

55.

Wolpe SD et al. (1988) Macrophages secrete a novel heparin-binding protein with inflammatory and neutrophil chemokinetic properties . J Exp Med 167: 570-581 .

56.

Bacon KB , Premack BA , Gardner P , Schall TJ. (1995) Activation of dual T cell signaling pathways by the chemokine RANTES . Science 269: 1727-1730 .

57.

Karpus WJ , Kennedy KJ. (1997) MIP-1α and MCP-1 differentially regulate acute and relapsing autoimmune encephalomyelitis as well as Th1/Th2 lymphocyte differentiation . J Leuk Biol 62: 681-687 .

58.

Taub DD et al. (1996) Chemokines and T lymphocyte activation. I. Chemokines costimulate human T lymphocyte activation in vitro . J Immunol 156: 2095-2103 .

59.

Duijevtijn AM. Schreiber AB , Butcher EC. (1986) Interferon-g regulates an antigen specific for endothelial cells involved in lymphocyte traffic . Proc Natl Acad Sci USA 83: 9114-9118 .

60.

Davatelis G et al. (1988) Cloning and characterization of a cDNA for murine macrophage inflammatory protein (MIP), a novel monokine with inflammatory and chemokine properties . J Exp Med 167: 1939-1944 .

61.

Farber JM. (1997) MIG and IP-10: CXC chemokines that target lymphocytes . J Leuk Biol 61: 246-257 .

62.

McRae BL et al. (1992) Induction of active and adoptive chronic-relapsing experimental autoimmune encephalomyelitis (EAE) using an encephalitogenic epitope of proteolipid protein . J Neuroimmunol 38: 229-240 .

63.

Bernard CC et al. (1997) Myelin oligodendrocyte glycoprotein: a novel candidate autoantigen in multiple sclerosis . J Mol Med 75: 77-88 .

64.

Kojima K et al. (1994) Experimental autoimmune panencephalitis and uveoretinitis transferred to the Lewis rat by T lymphocytes specific for the S100 beta molecule, a calcium binding protein of astroglia . JExp Med 180: 817-829 .

65.

Tuohy VK et al. (1992) Myelin proteolipid protein: minimum sequence requirements for active induction of autoimmune encephalomyelitis in SWR/J and SJL/J mice . J Neuroimmunol 39: 67-74 .

66.

Ransohoff R. (1997) Chemokines in neurologic disease models: correlation between chemokine expression patterns and inflammatory pathology . J Leuk Biol 62: 645-652 .

67.

Godiska R , Chantry D , Dietsch GN , Gray PW. (1995) Chemokine expression in murine experimental allergic encephalomyelitis . J Neuroimmunol 58: 167-176 .

68.

Glabinski AR et al. (1999) Chemokine expression in GKO mice (lacking interferon-gamma) with experiental autoimmune encephalomyelitis . Neurovirol 5: 95-101 .

69.

Miyagishi R et al. (1996) Identificationofcelltypes producing RANTES, MIP-1a and MIP-1b in rat experimental autoimmune encephalomyelitis by in situ hybridization . J Neuroimmunol 77: 17-26 .

70.

Kuchroo VK et al. (1993) Cytokines and adhesion molecules contribute to the ability of myelin proteolipid protein-specific T cell clones to mediate experimental allergic encephalomyelitis . J Immunol 151: 4371-4382 .

71.

Glabinski AR et al. (1997) Synchronous synthesis of a- and b- chemokines by cells of diverse lineage in the central nervous system of mice with relapses of chronic experimental autoimmune encephalomyelitis . Am J Path 150: 617-630 .

72.

Karpus WI et al. (1997) Differential CC chemokine-induced enhancement of T helper cell cytokine production . J Immunol 158: 4129-4136 .

73.

Lukacs NW et al. (1997) C-C chemokines differentially alter interleukin-4 production from lymphocytes . Am J Pathol 150: 1861-1868 .

74.

Ransohoff RM et al. (1993) Astrocyte expression of mRNA encoding cytokines IP-10 and JE/MCP-1 in experimental autoimmune encephalomyelitis . FASEB J 7: 592-600 .

75.

Tani M et al. (1996) In situ hybridization analysis of glial fibrillary acidic protein mRNA reveals evidence of biphasic astrocyte activation during acute experimental autoimmune encephalomyelitis . Am J Pathol 148: 889-896 .

76.

Karpus WJ , Lukacs NW. (1996) The role of chemokines in oral tolerance. Abrogation of nonresponsiveness by treatment with antimonocyte chemotactic protein-1 . Ann NY Acad Sci 778: 133-144 .

77.

Karpus WJ , Kennedy KJ , Kunkel SL , Lukacs NW. (1998) Monocyte chemotactic protein 1 regulates oral tolerance induction by inhibition of T helper cell 1-related cytokines . J Exp Med 187: 733-741 .

78.

Vanguri P , Cho SY , Chi CM. (1996) Role of muIP-10 in interferon-gamma induction of Ia in rat astrocytes . Mol Immunol 33: 1079-1087 .

79.

Rossi DL et al. (1998) Cloning and characterization of a new type of mouse chemokine . Genomics 47: 163-170 .

80.

Raport CJ et al. (1995) The orphan G-protein-coupled receptor-encoding gene V28 is closely related to genes for chemokine receptors and is expressed in lymphoid and neural tissues . Gene 163: 295-299 .

81.

Nishiyori A et al. (1998) Localization of fractalkine and CX3CR1 mRNAs in rat brain: does fractalkine play a role in signaling from neuron to microglia ? FEBS Lett 429: 167-172 .

82.

Asensio VC et al. (1999) C10 is a novel chemokine expressed in experimental inflammatory demyelinating disorders that promotes recruitment of macrophages to the central nervous system . Am J Pathol 154: 1181-1191 .

83.

McKhann GM. (1990) Guillain-Barré syndrome: clinical and therapeutic observations . Ann Neurol 27: S13-S16 .

84.

Merrill JE. (1992) Proinflammatory and antiinflamma-tory cytokines in multiple sclerosis and central nervous system acquired immunodeficiency syndrome . J Immunother 12: 167-170 .

85.

McFarland HF. (1996) Complexities in the treatment of autoimmune disease . Science 274: 2037-2038 .

86.

Whitham RH et al. (1991) Lymphocytes from SJL/J mice immunized with spinal cord respond selectively to a peptide of proteolipid protein and transfer relapsing demyelinating experimental autoimmune encephalomyelitis . J Immunol 146: 101-107 .

87.

van Noort JM et al. (1995) The small heat-shock protein, a B-crystallin as candidate autoantigen in multiple sclerosis . Nature 375: 798-801 .

88.

Kerlero de Rosbo N et al. (1997) Predominance of the autoimmune response to myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis: reactivity to the extracellular domain of MOG is directed against three main regions . Eur J Immunol 27: 3059-3069 .

89.

Hafler DA et al. (1985) In vivo activated T lymphocytes in the peripheral blood and cerebrospinal fluid of patients with multiple sclerosis . N Engl J Med 312: 1405-1411 .

90.

Hohlfeld R , Londei M , Massacesi L , Salvetti M. (1995) T-cell autoimmunity in multiple sclerosis . Immunol Today 16: 259-261 .

91.

Voskuhl RR et al. (1993) T helper 1(Th1) functional phenotype of human myelin basic protein-specific T lymphocytes . Autoimmunity 15: 137-143 .

92.

Van Der Voorn P et al. (1999) Expression of MCP-1 by reactive astrocytes in demyelinating multiple sclerosis lesions . Am J Pathol 154: 45-51 .

93.

Simpson JE , Newcombe J , Cuzner ML , Woodroofe MN. (1998) Expression of monocyte chemoattractant protein-1 and other beta-chemokines by resident glia and inflammatory cells in multiple sclerosis lesions . J Neuroimmunol 84: 238-249 .

94.

McManus C et al. (1998) MCP-1, MCP-2 and MCP-3 expression in multiple sclerosis lesions: an immunohistochemical and in situ hybridization study . J Neuroimmunol 86: 20-29 .

95.

Fiten P et al. (1999) Microsatellite polymorphisms in the gene promoter of MCP-3 alleles and multiple sclerosis development . J Neuroimmunol 95: 195-201 .

96.

Luo Y et al. (1998) The CXC-chemokine, H174: expression in the central nervous system . J Neurovirol 4: 575-585 .

97.

Biddison WE et al. (1997) Chemokine and matrix metalloproteinase secretion by myelin proteolipid protein-specific CD8+ T cells: potential roles in inflammation . J Immunol 158: 3046-3053 .

98.

Barnes DA et al. (1996) Induction of RANTES expression by astrocytes and astrocytoma cell lines . J Neuroimmunol 71: 207-214 .

99.

Miyagishi R , Kikuchi S , Fukazawa T , Tashiro K. (1995) Macrophage inflammatory protein-1alpha in the cerebrospinal fluid of patients with multiple sclerosis and other inflammatory neurological diseases . J Neurol Sci 129: 223-227 .

100.

Muller-Ladner U et al. (1996) Enhanced expression of chemtactic receptors in multiple sclerosis lesions . J Neurol Sci 144: 135-141 .

101.

Balashov KE et al. (1999) CCR5+ and CXCR3+ T cells are increased in multiple sclerosis and their ligands MIP-1alpha and IP-10 are expressed in demyelinating brain lesions . Proc Nat Acad Sci USA 96: 6873-6878 .

102.

Bennetts BH et al. (1997) The CCR5 deletion mutation fails to protect against multiple sclerosis . Human Immunol 58: 52-59 .

103.

Liu R et al. (1996) Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection . Cell 86: 367-377 .

104.

Hesselgesser J et al. (1998) Identifcation and characterization of small molecule functional antagonists of the CCR1 chemokine receptor . Journal of Biological Chemistry 273: 15687-15692 .

105.

Tani M , Ransohoff RM. (1994) Do chemokines mediate inflammatory cell invasion of the central nervous system parenchyma ? Brain Pathol 4: 135-143 .

106.

Masuyama J , Minato N , Kano S. (1986) Mechanisms of lymphocyte adhesion of human vascular endothelial cells in culture: T lymphocyte adhesion to endothelial cells through endothelial HLA-DR antigens induced by gamma interferon . J Clin Invest 77: 1596-1605 .

107.

Tanaka Y et al. (1993) T-cell adhesion induced by proteoglycan-immobilized cytokine MIP-1 beta . Nature 361: 79-82 .

108.

Gerszten RE et al. (1999) MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions . Nature 398: 718-723 .

109.

Tanaka Y et al. (1998) Heparan sulfate proteoglycan on endothelium efficiently induces integrin-mediated T cell adhesion by immobilizing chemokines in patients with rheumatoid synovitis . Arthr Rheum 41: 1365-1377 .

110.

Shaw LM , Mercurio AM. (1989) Interferon-g and lipopolysaccharide promote macrophage adherence to basement membrane glycoproteins . J Exp Med 169: 303-308 .

111.

Cannella B , Cross AH , Raine CS. (1990) Upregulation and coexpression of adhesion molecules correlate with relapsing autoimmune demyelination in the central nervous system . J Exp Med 172: 1521-1524 .

112.

Yednock TA et al. (1993) Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin . Nature 356: 63-66 .

113.

Lukacs NW et al. (1994) Intercellular adhesion molecule-1 mediates the expression of monocyte-derived MIP-1 alpha during monocyte-endothelial cell interactions . Blood 83: 1174-1178 .

114.

Archelos JJ , Previtali SC , Hartung HP. (1999) The role of integrins in immune-mediated diseases of the nervous system . Trend Neurosci 22: 30-38 .

115.

Pinkstaff JK , Detterich J , Lynch G , Gall C. (1999) Integrin subunit gene expression is regionally differentiated in adult brain . JNeurosci 19: 1541-1556 .

116.

Opdenakker G , Van Damme J. (1994) Cytokine-regulated proteases in autoimmune diseases . Immunol Today 15: 103-107 .

117.

Proost P , Van Damme J , Opdenakker G. (1993) Leukocyte gelatinase B cleavage releases encephalitogens from human myelin basic protein . Biochem Biophys Res Commun 192: 1175-1181 .

118.

Gijbels K et al. (1993) Gelatinase B is present in the cerebrospinal fluid during experimental autoimmune encephalomyelitis and cleaves myelin basic protein . J Neurosci Res 36: 432-440 .

119.

Dubois B , Opdenakker G , Carton H. (1999) Gelatinase B in multiple sclerosis and experimental autoimmune encephalomyelitis . Acta Neurol Belg 99: 53-56 .

120.

Youssef S et al. (1998) Long-lasting protective immunity to experimental autoimmune encephalomyelitis following vaccination with naked DNA encoding C-C chemokines . J Immunol 161: 3870-3879 .

121.

Stuve O et al. (1997) Chemokine-enhanced migration of human peripheral blood mononuclear cells is antagonized by interferon beta-1b through an effect on matrix metalloproteinase-9 . J Neuroimmunol 80: 38-46 .

122.

Foxman EF , Campbell JJ , Butcher EC. (1997) Multistep navigation and the combinatorial control of leukocyte chemotaxis . J Cell Biol 139: 1349-1360 .

123.

Strieter RM et al. (1996) “ The good, the bad, and the ugly”. The role of chemokines in models of human disease . J Immunol 156: 3583-3586 .

124.

Utans-Schneitz U et al. (1998) A novel rat CC chemokine identified by targeted differential display, is upregulated in brain inflammation . J Neuroimmunol 92: 179-190 .

125.

Reiseter BS , Miller GT , Happ MP , Kasaian MT. (1998) Treatment of murine experimental autoimmune encephalomyelitis with a myelin basic protein peptide analog alters the cellular composition of leukocytes infiltrating the cerebrospinal fluid . J Neuroimmunol 91: 156-170 .

126.

Smeltz RB , Wolf NA , Swanborg RH. (1999) Inhibition of autoimmune T cell responses in the DA rat by bone marrow-derived NK cells in vitro: implications for autoimmunity . J Immunol 163: 1390-1397 .