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Heat-shock proteins and molecular chaperones: implications for pathogenesis, diagnostics, and therapeutics

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International Journal of Clinical and Laboratory Research

Summary

Cells react to physical (e.g., heat) or chemical (e.g., anoxia, low pH) stressors, mounting a stress (heat-shock) response. Most genes are turned down or off, while a few are activated. The latter encode the stress or heat-shock proteins (Hsps), whose levels increase in stressed cells. Various Hsps are molecular chaperones. These, and other molecular chaperones that are not Hsps, help the other cellular proteins to achieve their native state (correct folding or functional conformation), reach their final destination (e.g., the endoplasmic reticulum or the mitochondria), resist denaturing by stressors, and regain the native state after partial denaturation. Thus the Hsps and molecular chaperones occupy the stage's center whenever and wherever there is cellular and tissue injury caused by local or systemic stressors via protein damage. This feature, their participation in protein folding and transport, and their evolutionary conservation within the three phylogenetic domains, strongly suggest a vital role for Hsps and molecular chaperones. Their importance in pathogenesis, and as diagnostic markers and prognostic indicators, is beginning to be appreciated. The role of Hsps and molecular chaperones in cell recovery from injury by a variety of noxae of clinical and surgical relevance is also being assessed. Consequently, the potential of these molecules (and corresponding genes) as targets for treatment or as therapeutic tools is emerging and is being explored. Stroke, myocadial infarction, inflammatory syndromes, infectious and parasitic diseases, autoimmune disorders, cancer, and aging are but some examples of conditions in which Hsps and molecular chaperones are being scrutinized. The era of Hsps and molecular chaperone pathology has dawned. It is likely that genetic and acquired defects of Hsp and molecular chaperone structure and function will be identified, and will play a primary, or auxiliary but determinant, role in disease.

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References

  1. Woese CR, Kandler O, Wheelis ML. Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eucarya. Proc Natl Acad Sci USA 1990; 87: 4576.

    Article  PubMed  CAS  Google Scholar 

  2. Macario AJL, Conway de Macario E. A preview of the uses of monoclonal antibodies against methanogens in fermentation biotechnology: significance for public health: In: Macario AJL, Conway de Macario E, eds. Monoclonal antibodies against bacteria. Orlando, Florida: Academic Press, 1985:269–286.

    Google Scholar 

  3. Conway de Macario E, Macario AJL, Miller T, Wolin MJ, Antigenic diversity of methanogenic bacteria from intestinal tracts of animals. Syst Appl Microbiol 1987; 9:210.

    Google Scholar 

  4. Belay N, Johnson R, Rajagopal BS, Conway de Macario E, Daniels L. Methanogenic bacteria from human dental plaque. Appl Environ Microbiol 1988; 54:600.

    PubMed  CAS  Google Scholar 

  5. Belay N, Mukhopadhyay B, Conway de Macario E, Galask R, Daniels L. Methanogenic bacteria in human vaginal samples. J Clin Microbiol 1990; 28:1666.

    PubMed  CAS  Google Scholar 

  6. Neidhardt FC, Bogelen RA van, Vaughn V. The genetics and regulation of heat-shock proteins. Annu Rev Genet 1984; 18:295.

    Article  PubMed  CAS  Google Scholar 

  7. Tissiéres A, Mitchell HK, Tracy UM. Protein synthesis in salivary glands ofDrosophila melanogaster: relation to chromosome puffs. J Mol Biol 1974; 34:388.

    Google Scholar 

  8. Ellis J, Vies SM van der: Molecular chaperones. Annu Rev Biochem 1991; 60:321.

    Article  PubMed  CAS  Google Scholar 

  9. Georgopoulos C, Welch WJ. Role of the major heat shock proteins as molecular chaperones. Annu Rev Cell Biol 1993; 9:601.

    Article  PubMed  CAS  Google Scholar 

  10. Welch WJ. Mammalian stress response: cell physiology, structure/function of stress proteins, and implications for medicine and disease. Physiol Rev 1992; 72:1063.

    PubMed  CAS  Google Scholar 

  11. Ritossa F. A new puffing pattern induced by heat shock and DNP inDrosophila. Experientia 1962; 18:571.

    Article  CAS  Google Scholar 

  12. Sanders BM. Stress proteins in aquatic organisms: an environmental perspective. Crit Rev Toxicol 1993; 23:49.

    PubMed  CAS  Google Scholar 

  13. Subject JR, Shyy T-T. Stress protein systems of mammalian cells. Am J Physiol 1986; 250:C1.

    Google Scholar 

  14. Watson K. Microbial stress proteins. Adv Microbial Physiol 1990; 31:183.

    CAS  Google Scholar 

  15. Macario AJL, Dugan CB, Conway de Macario E. AdnaK homolog in the archaebacteriumMethanosarcina mazei S6. Gene 1991; 108:133.

    Article  PubMed  CAS  Google Scholar 

  16. Anfinsen CB. Principles that govern the folding of protein chains. Science 1973; 181:223.

    Article  PubMed  CAS  Google Scholar 

  17. Frydman J, Nimmesgern E, Ohtsuka K, Hartl FU. Folding of nascent polypeptide chains in a high molecular mass assembly with molecular chaperones. Nature 1994; 370:111.

    Article  PubMed  CAS  Google Scholar 

  18. Gething MJ, Sambrook J. Protein folding in the cell. Nature 1992; 355:33.

    Article  PubMed  CAS  Google Scholar 

  19. Parsell DA, Lindquist S. The function of heat shock proteins in stress tolerance: degradation and reactivation of damaged proteins. Annu Rev Genet 1993; 27:437.

    Article  PubMed  CAS  Google Scholar 

  20. Lin H-y, Masso-Welch P, Di Y-P, Cai J-w, Shen J-w, Subjeck JR. The 170-kDa glucose-regulated stress protein is an endoplasmic reticulum protein that binds immunoglobulin. Mol Biol Cell 1993; 4:1109.

    PubMed  CAS  Google Scholar 

  21. Parsell DA, Sanchez Y, Stitzel JD, Lindquist S. Hsp 104 is a highly conserved protein with two essential nucleotide binding sites. Nature 1991; 353:270.

    Article  PubMed  CAS  Google Scholar 

  22. Pratt WB, Welsh MJ. Chaperone functions of the heat shock proteins associated with steroid receptors. Semin Cell Biol 1994; 5:83.

    Article  PubMed  CAS  Google Scholar 

  23. Mazzarella RA, Green M. ERp99, an abundant conserved glycoprotein of the endoplasmic reticulum is homologous to the 90-kDa heat shock protein (hsp90) and the glucose regulated protein (grp94). J Biol Chem 1987; 262:8875.

    PubMed  CAS  Google Scholar 

  24. Craig EA, Gambill BD, Nelson RJ. Heat shock proteins: molecular chaperones of protein biogenesis. Microbiol Rev 1993; 57:402.

    PubMed  CAS  Google Scholar 

  25. Chappell TG, Konforti BB, Schmid SL, Rothman JE. The ATPase core of a clathrin uncoating protein. J Biol Chem 1987; 262:746.

    PubMed  CAS  Google Scholar 

  26. Munro S, Pelham HRB. An Hsp 70-like protein in the ER: identity with the 78kd glucose-regulated protein and immunoglobulin heavy chain binding protein. Cell 1986; 46:294.

    Article  Google Scholar 

  27. Craig EA. The heat-shock response ofSaccharomyces cervisiae. In: Jones EW, Pringle JR, Broach JR, eds The molecular and cellular biology of the yeastSaccharomyces: gene expression. Plainview, New York: Cold Spring Harbor Laboratory Press; 1992:501–581.

    Google Scholar 

  28. Georgeopoulos C, Liberek K, Zylicz M, Ang D. Properties of the heat shock proteins ofEscherichia coli and the autoregulation of the heat shock response. In: Morimoto TR, Tissiéres A, Georgopoulos G, eds. The biology of heat-shock proteins and molecular chaperones. Plainview, New York: Cold Spring Harbor Laboratory Press: 1994:209–249.

    Google Scholar 

  29. Gupta RS, Singh B. Cloning of the Hsp 70 gene fromHalobacterium marismortui: relatedness of archaebacterial Hsp70 to its eubacterial homologs and a model for the evolution of the Hsp70 gene. J Bacteriol 1992; 174:4594.

    PubMed  CAS  Google Scholar 

  30. Rensing SA, Maier U-G. Phylogenetic analysis of the stress-70 protein family. J Mol Evol 1994; 39:80.

    Article  PubMed  Google Scholar 

  31. Conway de Macario E, Macario AJL. Heat-shock response in Achaea. Trends Biotechnol, 1994; 12:512.

    Article  PubMed  CAS  Google Scholar 

  32. Willison KR, Kubota H. The structure, function, and genetics of the chaperonin containing TCP-1 (CCT) in eukaryotic cytosol. In: Morimoto RI, Tissiéres A, Georgopoulos C, eds. The biology of heat shock proteins and molecular chaperones. Plainview, New York: Cold Spring Harbor Laboratory Press; 1994:299–312.

    Google Scholar 

  33. Trent JD, Nimmesgern E, Wall JS, Hartl FU, Horwich AL. A molecular chaperone from a thermophilic archaebacterium is related to the eukaryotic proteint-complex polypeptide-1. Nature 1991; 354:490.

    Article  PubMed  CAS  Google Scholar 

  34. Chen X, Sullivan DS, Huffaker TC, Two yeast genes with similarity to TCP-1 are required for microtubule and actin function in vivo. Proc Natl Acad Sci USA 1994; 91:9111.

    Article  PubMed  CAS  Google Scholar 

  35. Li W-Z, Lin P, Frydman J, Boal TR, Cardillo TS, Richard LM, Toth D, Lichtman MA, Hartl F-U, Sherman F, Segel GB. Tcp20, a subunit of the eukaryotic TRiC chaperonin from humans and yeast. J Biol Chem 1994; 269:18616

    PubMed  CAS  Google Scholar 

  36. Chen JJ, McNealy DJ, Dalal S, Androphy EJ. Isolation, sequence analysis and characterization of a cDNA encoding human chaperonin 10. Biochim Biophys Acta 1994; 1219:189.

    PubMed  CAS  Google Scholar 

  37. Leung TKC, Rajendran MY, Monfries C, Hall C, Lim L. The human heat-shock protein family. Biochem J 1990; 267:125

    PubMed  CAS  Google Scholar 

  38. Caplan AJ, Cyr DM, Douglas MG. Eukaryotic homologues ofEscherichia coli dnaJ: a diverse protein family that functions with Hsp 70 stress proteins. Mol Biol Cell 1993; 4:555

    PubMed  CAS  Google Scholar 

  39. Cheetham ME, Brion J-P, Anderton BH, Human homologues of the bacterial heat-shock protein DnaJ are preferentially expressed in neurons. Biochem J 1992; 284:469.

    PubMed  CAS  Google Scholar 

  40. Oh S, Iwahori A, Kato S. Human cDNA encoding DnaJ protein homologue. Biochim Biophys Acta 1993; 1174:114.

    PubMed  CAS  Google Scholar 

  41. Ohtsuka K. Cloning of a cDNA for heat-shock protein hsp40, a human homologue of bacterial DnaJ. Biochem Biophys Res Commun 1993; 197:235.

    Article  PubMed  CAS  Google Scholar 

  42. Raabe T, Manley JL. A human homologue of theEscherichia coli DnaJ heat-shock protein. Nuclei Acids Res 1991; 19:6645.

    Article  CAS  Google Scholar 

  43. Macario AJL, Dugan CB, Clarens M, Conway de Macario E. dnaJ in Archaea. Nucleic Acids Res 1993; 21:2773.

    Article  PubMed  CAS  Google Scholar 

  44. Conway de Macario E, Dugan CB Macario AJL. Identification of agrpE heat-shock gene homolog in the archaeonMethanosarcina mazei. J Mol Biol 1994; 240:95.

    Article  PubMed  CAS  Google Scholar 

  45. Ikeda E, Yoshida S, Mitsuzawa H, Uno I, Toh-e A.YGE1 is a yeast homologue ofEscherichia coli grpE and is required for maintenance of mitochondrial functions. FEBS Lett 1994; 339:265.

    Article  PubMed  CAS  Google Scholar 

  46. Ashburner M, Bonner JJ. The induction of gene activity inDrosophila by heat-shock. Cell 1979; 17:241

    Article  PubMed  CAS  Google Scholar 

  47. Hlodan R, Hartl FU. How the protein folds in the cell. In: Pain RH, ed. Mechanisms of protein folding, Oxford: Oxford University Press: 1994:194–228.

    Google Scholar 

  48. Morimoto RE, Tissiéres A, Georgopoulos C. Progress and perspectives on the biology of heat shock proteins and molecular chaperones. In: Morimoto RI, Tissiéres A, Georgopoulos C, eds. The biology of heat shock proteins and molecular chaperones. Plainview, New York: Cold Spring Harbor Laboratory Press; 1994:1–30.

    Google Scholar 

  49. Bond U, Schlesinger MJ. Ubiquitin is a heat shock protein in chicken embryo fibroblasts. Mol Cell Biol 1986; 5:949.

    Google Scholar 

  50. Ou W-J, Cameron PH, Thomas DY, Bergeron JJM. Association of folding intermediates of glycoproteins with calnexin during protein maturation. Nature 1993; 364:771.

    Article  PubMed  CAS  Google Scholar 

  51. Kunz J, Hall MN. Cyclosporin A, FK506 and rapamycin: more than just immunosuppression. Trends Biochem Sci 1993; 18:334.

    Article  PubMed  CAS  Google Scholar 

  52. Compton LA, Davis JM, MacDonald JR, Bächinger HP. Structural and functional characterization ofEscherichia coli peptidyl-prolylcis-trans isomerase. Eur J Biochem 1992; 206:927.

    Article  PubMed  CAS  Google Scholar 

  53. Hacker J, Fischer G. Immunophilins: structure-function relationship and possible role in microbial pathogenicity. Mol Microbiol 1993; 10:445.

    Article  PubMed  CAS  Google Scholar 

  54. Noiva R, Lennarz WJ. Protein disulfide isomerase. J Biol Chem 1992; 267:3553.

    PubMed  CAS  Google Scholar 

  55. LaMantia M, Lennarz WJ. The essential function of yeast protein disulfide isomerase does not reside in its isomerase activity. Cell 1993; 74:899.

    Article  PubMed  CAS  Google Scholar 

  56. Bardwell JCA, Beckwith J. The bonds that tie: catalyzed disulfide bond formation. Cell 1993; 74:771.

    Article  Google Scholar 

  57. Creighton TE, Freedman RB. A model catalyst of protein disulphide bond formation. Curr Biol 1993; 3:790.

    Article  PubMed  CAS  Google Scholar 

  58. Vies SM van der, Gatenby AA, Viitanen PV, Lorimer GH. Molecular chaperones and their role in protein assembly. In: Cleland JL, ed. Protein folding in vivo and in vitro. Washington, D.C.: American Chemical Society; 1993:72–83.

    Google Scholar 

  59. Holbrook NJ, Udelsman R. Heat shock protein gene expression in response to physiologic stress and aging. In: Morimoto TR, Tissiéres A, Georgopoulos G, eds. The biology of heat-shock proteins and molecular chaperones. Plainview, New York: Cold Spring Harbor Laboratory Press: 1994:577–593.

    Google Scholar 

  60. Heydary AR, Wu B, Takahashi R, Strong R, Richardson A. Expression of heat shock protein 70 is altered by age and diet at the level of transcription. Mol Cell Biol 1993: 13:2909

    Google Scholar 

  61. Benjamin IJ, Williams RS. Expression and function of stress proteins in the ischemic heart. In: Morimoto TR, Tissiére A, Georgopoulos G, eds. The biology of heat-shock proteins and molecular chaperones. Plainview, New York: Cold Spring Harbor Laboratory Press; 1994:533–553.

    Google Scholar 

  62. Nowak TS Jr, Abe H. Postischemic stress response in brain. In: Morimoto TR, Tissiéres A, Georgopoulos G, eds. The biology of heat-shock proteins and molecular chaperones. Plainview, New York, Cold Spring Harbor Laboratory Press; 1994: 553–575.

    Google Scholar 

  63. Delcayre C, Samuel JL, Marotte F, Best-Belpomme M, Mercadier JJ, Rappaport L. Synthesis of stress proteins in rat cardiac myocytes 2–4 days after imposition of hemodynamic overload. J Clin Invest 1988; 83:460.

    Google Scholar 

  64. Dillmann W, Mehta H, Barrieux A, Gath BD, Neeley W, Ross J. Ischemia of the dog heart induces the appearance of a cardiac mRNA coding for a protein with migration characteristics similar to heat shock/stress proteins 71. Circ Res 1986; 59:110.

    PubMed  CAS  Google Scholar 

  65. Andres J, Sharma HS, Knöll R, Stahl J, Sassen LMA, Verdouw PD, Schaper W. Expression of heat shock proteins in the normal and stunned porcine myodarcium. Cardiovasc Res 1993; 27:1421.

    PubMed  CAS  Google Scholar 

  66. Mestril R, Chi S-H, Sayen MR, Dillmann WH. Isolation of a novel inducible rat heat-shock protein (Hsp 70) gene and its expression during ischaemia/hypoxia and heat shock. Biochem J 1994; 298:561.

    PubMed  CAS  Google Scholar 

  67. Dienel GA, Kiessling M, Jacewicz M, ulsinelli W. Synthesis of heat shock proteins in rat brain cortex after transient ischemia. J Cereb Blood Flow Metab 1986; 6:505.

    PubMed  CAS  Google Scholar 

  68. Nowak TS Jr, Bond U, Schlesinger MJ. Heat shock RNA levels in brain and other tissues after hyperthermia and transient ischemia. J Neurochem 1990; 54:451.

    Article  PubMed  CAS  Google Scholar 

  69. Vass K, Welch WJ, Nowak TS. Localization of 70 kDa stress protein induction in gerbil brain after ischemia. Acta Neuropathol (Berl) 1988; 77:413.

    Google Scholar 

  70. Barbe MF, Tytell M, Gower DJ, Welch WJ. Hyperthermic shock protects against light damage in the rat retina. Science 1988; 241:1817.

    Article  PubMed  CAS  Google Scholar 

  71. Uney JB, Kew JNC, Staley K, Tyers P, Sofroniew MV. Transfection-mediated expression of human Hsp70i protects rat dorsal root ganglian neurones and glia from severe heat stress. FEBS Lett 1993; 334:313

    Article  PubMed  CAS  Google Scholar 

  72. Kaufmann SHE, Schoel B. Heat shock proteins as antigens in immunity against infection and self. In: Morimoto TR, Tissiéres A, Georgopoulos G, eds. The biology of heat-shock proteins and molecular chaperones. Plainview, New York: Cold Spring Harbor Laboratory Press; 1994:495–531.

    Google Scholar 

  73. Hunt P, Colston A, Bujdoso R. Nomenclature of mycobacterial stress proteins (65 kDa antigens) and other members of the Hsp60 family. Trends Microbiol 1994; 2:298.

    Article  PubMed  CAS  Google Scholar 

  74. Young DB, Garbe TR. Heat shock proteins and antigens ofMycobacterium tuberculosis. Infect Immun 1991; 59:3086.

    PubMed  CAS  Google Scholar 

  75. Young D, Garbe T, Lathigra R, Abou-Zeid C, Zhang Y. Characterization of prominent protein antigens from mycobacteria. Bull Int Union Tuberc Lung Dis 1991; 66:47.

    PubMed  CAS  Google Scholar 

  76. Mistry Y, Young DB, Mukherjee R. Hsp70 synthesis in Schwann cells in response to heat shock and infection withMycobacterium leprae. Infect Immun 1992; 60:3105.

    PubMed  CAS  Google Scholar 

  77. Schwan WR, Goebel W. Host cell responses toListeria monocytogenes infection include differential transcription of host stress genes involved in signal transduction. Proc Natl Acad Sci USA 1994; 91:6428.

    Article  PubMed  CAS  Google Scholar 

  78. Hedstrom R, Culpepper J, Harrison RA, Agabian N, Newport G. A major immunogen inSchistosoma mansoni infections is homologous to the heat-shock protein Hsp70. J Exp Med 1987; 165:1430.

    Article  PubMed  CAS  Google Scholar 

  79. Hedstrom R, Culpepper J, Schinski V, Agabian N, Newport G. Schistosome heat-shock proteins are immunologically distinct host-like antigens. Mol Biochem Parasitol 1988; 29:275.

    Article  PubMed  CAS  Google Scholar 

  80. Rey-Ladino JA, Rainer NE. Expression of 65-and 67-kilodalton heat-regulated proteins and a 70-kilodalton heat shock cognate protein ofLeishmania donovani in macrophages. Infect Immun 1993; 61:3265.

    PubMed  CAS  Google Scholar 

  81. Olson CL, Nadeau KC, Sullivan MA, Winquist AG, Donelson JE, Walsh CT, Engman DM. Molecular and biochemical comparison of the 70-kDa heat shock proteins ofTrypanosoma cruzi. J Biol Chem 1994; 269:3868.

    PubMed  CAS  Google Scholar 

  82. Rocchi G, Pavesi A, Ferrari C, Bolchi A, Manara GC. A new insight into the suggestion of a possible antigenic role of a member of the 70 kD heat shock proteins. Cell Biol Int 1993; 17:83.

    Article  PubMed  CAS  Google Scholar 

  83. Barrios C, Lussow AR, Van Embden JDA, Van de Zee R, Rappuoli R, Costantino P, Louis JA, Lambert P-H, Del Giudice G. Mycobacterial heat-shock proteins as carrier molecules. II. The use of the 70-kDa mycobacterial heat-shock protein as carrier for conjugated vaccines can circumvent the need for adjuvants and Bacillus Calmette Guérin priming. Eur J Immunol 1992; 22:1365.

    Article  PubMed  CAS  Google Scholar 

  84. Srivastava PK. Peptide-binding heat shock proteins in the endoplasmic reticulum: role in immune response to cancer and in antigen presentation. Adv Cancer Res 1993; 62:153.

    Article  PubMed  CAS  Google Scholar 

  85. Udono H, Srivastava PK. Heat shock protein 70-associated peptides elicit specific cancer immunity. J Exp Med 1993; 178: 1391.

    Article  PubMed  CAS  Google Scholar 

  86. Udono H, Levey DL, Srivastava PK, Cellular requirements for tumor-specific immunity elicited by heat shock proteins: tumor rejection antigen gp96 primes CD8+T cells in vivo. Proc. Natl Acad Sci USA 1994; 91:3077.

    Article  PubMed  CAS  Google Scholar 

  87. Jäättelä M, Wissing D, Bauer PA, Li GC. Major heat shock protein hsp70 protects tumor cells from tumor necrosis factor cytotoxicity. EMBO J 1992; 11:3507.

    PubMed  Google Scholar 

  88. Oesterreich S, Weng C-N, Qiu M, Hilsenbeck SG, Osborne CK, Fuqua SAW. The small heat shock protein hsp27 is correlated with growth and drug resistance in human breast cancer cell lines. Cancer Res 1993; 53:4443.

    PubMed  CAS  Google Scholar 

  89. Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM. Inhibition of heat shock protein HSP90-pp60v-src hetero-protein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci USA 1994; 91:8324.

    Article  PubMed  CAS  Google Scholar 

  90. Yehiely F, Oren M. The gene for the rat heat-shock cognate,hsc70, can suppress oncogene-mediated transformation. Cell Growth Different 1992; 3:803.

    CAS  Google Scholar 

  91. Yang Y, Janich S, Cohn JA, Wilson JM. The common variant of cystic fibrosis transmembrane conductance regulator is recognized by hsp70 and degraded in a pre-Golgi nonlysosomal compartment. Proc Natl Acad Sci USA 1993; 90:9480

    Article  PubMed  CAS  Google Scholar 

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  1. Wadsworth Center for Laboratories and Research, New York State Department of Health, Empire State Plaza, P.O. Box 509, 12201-0509, Albany, NY, USA

    A. J. L. Macario

  2. Department of Biomedical Sciences, School of Public Health, The University at Albany, Albany, New York, USA

    A. J. L. Macario

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Macario, A.J.L. Heat-shock proteins and molecular chaperones: implications for pathogenesis, diagnostics, and therapeutics. Int J Clin Lab Res 25, 59–70 (1995). https://doi.org/10.1007/BF02592359

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