Literature for peptidase S28.001: lysosomal Pro-Xaa carboxypeptidase

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Substrates Pharma

(Topics flags: S Structure, A Assay, T Target, P Specificity, K Knockout, E Expression, V Review, M Mutation, I Inhibitor. To select only the references relevant to a single topic, click the link above. See explanation.)

    2026
  1. Kaiser-Graf,D., Domenig,O., Poglitsch,M., Kreutz,R. and Bolbrinker,J.
    Upregulation of angiotensin-(1-7) formation in human podocytes - enzyme activity assay upon fluid flow shear stress
    PLoS ONE (2026) 21, e0339874-e0339874. PubMed  Europe PubMed DOI  PMC  EPMC
  2. 2022
  3. Baharin,A., Ting,T.Y. and Goh,H.H.
    Post-Proline Cleaving Enzymes (PPCEs): Classification, Structure, Molecular Properties, and Applications
    Plants (Basel) (2022) 11 PubMed  Europe PubMed DOI  PMC  EPMC  V
  4. 2020
  5. Dunaevsky,Y.E., Tereshchenkova,V.F., Oppert,B., Belozersky,M.A., Filippova,I.Y. and Elpidina,E.N.
    Human proline specific peptidases: a comprehensive analysis
    Biochim Biophys Acta Gen Subj (2020) 1864, 129636-129636. PubMed  Europe PubMed DOI  V
  6. Hao,P., Liu,Y., Guo,H., Zhang,Z., Chen,Q., Hao,G., Zhang,C. and Zhang,Y.
    Prolylcarboxypeptidase Mitigates Myocardial Ischemia/Reperfusion Injury by Stabilizing Mitophagy
    Front Cell Dev Biol (2020) 8, 584933-584933. PubMed  Europe PubMed DOI  PMC  EPMC  K
  7. Wu,Y., Yang,H. and Xiao,C.
    Genetic association study of prolylcarboxypeptidase polymorphisms with susceptibility to essential hypertension in the Yi minority of China: A case-control study based on an isolated population
    J Renin Angiotensin Aldosterone Syst (2020) 21, 1470320320919586-1470320320919586. PubMed  Europe PubMed DOI  M
  8. Wu,Y., Pan,X. and Jin,X.
    Haplotype-based association study between PRCP gene polymorphisms and essential hypertension in Hani minority group from a remote region of China
    J Renin Angiotensin Aldosterone Syst (2020) 21, 1470320320981316-1470320320981316. PubMed  Europe PubMed DOI  M
  9. 2018
  10. Bruschetta,G., Jin,S., Kim,J.D. and Diano,S.
    Prolyl carboxypeptidase in Agouti-related peptide neurons modulates food intake and body weight
    Mol Metab (2018) 10, 28-38. PubMed  Europe PubMed DOI  K
  11. 2017
  12. Graham,T.H.
    Prolylcarboxypeptidase (PrCP) inhibitors and the therapeutic uses thereof: a patent review
    Expert Opin Ther Pat (2017) 27, 1077-1088. PubMed  Europe PubMed DOI  I
  13. Luft,F.C.
    The renin-angiotensin system and prolylcarboxypeptidase
    J Mol Med (Berl) (2017) 95, 461-463. PubMed  Europe PubMed DOI
  14. Maier,C., Schadock,I., Haber,P.K., Wysocki,J., Ye,M., Kanwar,Y., Flask,C.A., Yu,X., Hoit,B.D., Adams,G.N., Schmaier,A.H., Bader,M. and Batlle,D.
    Prolylcarboxypeptidase deficiency is associated with increased blood pressure, glomerular lesions, and cardiac dysfunction independent of altered circulating and cardiac angiotensin II
    J Mol Med (Berl) (2017) 95, 473-486. PubMed  Europe PubMed DOI  M
  15. 2016
  16. Gittleman,H.R., Merkulova,A., Alhalabi,O., Stavrou,E.X., Veigl,M.L., Barnholtz-Sloan,J.S. and Schmaier,A.H.
    A cross-sectional study of KLKB1 and PRCP polymorphisms in patient samples with cardiovascular disease
    Front Med (Lausanne) (2016) 3, 17-17. PubMed  Europe PubMed DOI  PMC  EPMC  M
  17. Kehoe,K., Van Elzen,R., Verkerk,R., Sim,Y., Van der Veken,P., Lambeir,A.M. and De Meester,I.
    Prolyl carboxypeptidase purified from human placenta: Its characterization and identification as an apelin-cleaving enzyme
    Biochim Biophys Acta (2016) 1864, 1481-1488. PubMed  Europe PubMed DOI
  18. 2015
  19. Waumans,Y., Baerts,L., Kehoe,K., Lambeir,A.M. and De Meester,I.
    The dipeptidyl peptidase family, prolyl oligopeptidase, and prolyl carboxypeptidase in the immune system and inflammatory disease, including atherosclerosis
    Front Immunol (2015) 6, 387-387. PubMed  Europe PubMed DOI  PMC  EPMC
  20. 2014
  21. Graham,T.H., Shu,M., Verras,A., Chen,Q., Garcia-Calvo,M., Li,X., Lisnock,J., Tong,X., Tung,E.C., Wiltsie,J., Hale,J.J., Pinto,S. and Shen,D.M.
    Pyrazoles as non-classical bioisosteres in prolylcarboxypeptidase (PrCP) inhibitors
    Bioorg Med Chem Lett (2014) 24, 1657-1660. PubMed  Europe PubMed DOI  I
  22. Marangoni,R.A., Santos,R.A. and Piccolo,C.
    Deficient prolylcarboxypeptidase gene and protein expression in left ventricles of spontaneously hypertensive rats (SHR)
    Peptides (2014) 61, 69-74. PubMed  Europe PubMed DOI
  23. Wang,J., Matafonov,A., Madkhali,H., Mahdi,F., Watson,D., Schmaier,A.H., Gailani,D. and Shariat-Madar,Z.
    Prolylcarboxypeptidase independently activates plasma prekallikrein (Fletcher factor)
    Curr Mol Med (2014) 14, 1173-1185. PubMed  Europe PubMed
  24. 2013
  25. Adams,G.N., Stavrou,E.X., Fang,C., Merkulova,A., Alaiti,M.A., Nakajima,K., Morooka,T., Merkulov,S., LaRusch,G.A., Simon,D.I., Jain,M.K. and Schmaier,A.H.
    Prolylcarboxypeptidase promotes angiogenesis and vascular repair
    Blood (2013) 122, 1522-1531. PubMed  Europe PubMed DOI  K
  26. Debenham,J.S., Graham,T.H., Verras,A., Zhang,Y., Clements,M.J., Kuethe,J.T., Madsen-Duggan,C., Liu,W., Bhatt,U.R., Chen,D., Chen,Q., Garcia-Calvo,M., Geissler,W.M., He,H., Li,X., Lisnock,J., Shen,Z., Tong,X., Tung,E.C., Wiltsie,J., Xu,S., Hale,J.J., Pinto,S. and Shen,D.M.
    Discovery and optimization of orally active cyclohexane-based prolylcarboxypeptidase (PrCP) inhibitors
    Bioorg Med Chem Lett (2013) 23, 6228-6233. PubMed  Europe PubMed DOI  I
  27. Goptar,I.A., Shagin,D.A., Shagina,I.A., Mudrik,E.S., Smirnova,Y.A., Zhuzhikov,D.P., Belozersky,M.A., Dunaevsky,Y.E., Oppert,B., Filippova,I.Y. and Elpidina,E.N.
    A digestive prolyl carboxypeptidase in Tenebrio molitor larvae
    Insect Biochem Mol Biol (2013) 43, 501-509. PubMed  Europe PubMed DOI
  28. Grobe,N., Weir,N.M., Leiva,O., Ong,F.S., Bernstein,K.E., Schmaier,A.H., Morris,M. and Elased,K.M.
    Identification of prolyl carboxypeptidase as an alternative enzyme for processing of renal angiotensin II using mass spectrometry
    Am J Physiol Cell Physiol (2013) 304, C945-C953. PubMed  Europe PubMed DOI
  29. Jeong,J.K. and Diano,S.
    Prolyl carboxypeptidase and its inhibitors in metabolism
    Trends Endocrinol Metab (2013) 24, 61-67. PubMed  Europe PubMed DOI  I
  30. Kehoe,K., Verkerk,R., Sim,Y., Waumans,Y., Van der Veken,P., Lambeir,A.M. and De Meester,I.
    Validation of a specific prolylcarboxypeptidase activity assay and its suitability for plasma and serum measurements
    Anal Biochem (2013) 443, 232-239. PubMed  Europe PubMed DOI  A
  31. Wu,Y., Yang,H., Yang,B., Yang,K. and Xiao,C.
    Association of polymorphisms in prolylcarboxypeptidase and chymase genes with essential hypertension in the Chinese Han population
    J Renin Angiotensin Aldosterone Syst (2013) 14, 263-270. PubMed  Europe PubMed DOI  M
  32. 2012
  33. Graham,T.H., Liu,W., Verras,A., Reibarkh,M., Bleasby,K., Bhatt,U.R., Chen,Q., Garcia-Calvo,M., Geissler,W.M., Gorski,J.N., He,H., Lassman,M.E., Lisnock,J., Li,X., Shen,Z., Tong,X., Tung,E.C., Wiltsie,J., Xie,D., Xu,S., Xiao,J., Hale,J.J., Pinto,S. and Shen,D.M.
    A new class of prolylcarboxypeptidase inhibitors, part 2: the aminocyclopentanes
    Bioorg Med Chem Lett (2012) 22, 2818-2822. PubMed  Europe PubMed DOI  I
  34. Graham,T.H., Liu,W., Verras,A., Sebhat,I.K., Xiong,Y., Bleasby,K., Bhatt,U.R., Chen,Q., Garcia-Calvo,M., Geissler,W.M., Gorski,J.N., He,H., Lassman,M.E., Lisnock,J., Li,X., Shen,Z., Tong,X., Tung,E.C., Wiltsie,J., Xiao,J., Xie,D., Xu,S., Hale,J.J., Pinto,S. and Shen,D.M.
    A new class of prolylcarboxypeptidase inhibitors, part 1: discovery and evaluation
    Bioorg Med Chem Lett (2012) 22, 2811-2817. PubMed  Europe PubMed DOI  I
  35. Graham,T.H., Shen,H.C., Liu,W., Xiong,Y., Verras,A., Bleasby,K., Bhatt,U.R., Chabin,R.M., Chen,D., Chen,Q., Garcia-Calvo,M., Geissler,W.M., He,H., Lassman,M.E., Shen,Z., Tong,X., Tung,E.C., Xie,D., Xu,S., Colletti,S.L., Tata,J.R., Hale,J.J., Pinto,S. and Shen,D.M.
    The discovery of non-benzimidazole and brain-penetrant prolylcarboxypeptidase inhibitors
    Bioorg Med Chem Lett (2012) 22, 658-665. PubMed  Europe PubMed DOI  I
  36. Jeong,J.K., Szabo,G., Raso,G.M., Meli,R. and Diano,S.
    Deletion of prolyl carboxypeptidase attenuates the metabolic effects of diet-induced obesity
    Am J Physiol Endocrinol Metab (2012) 302, E1502-E1510. PubMed  Europe PubMed DOI  K
  37. Tan,F., Skidgel,R.A. and Erdos,E.G.
    Lysosomal Pro-Xaa carboxypeptidase
    [ISSN:978-0-12-407742-3] (2012) 3, 3425-3432. DOI
  38. Wu,Z., Yang,C., Graham,T.H., Verras,A., Chabin,R.M., Xu,S., Tong,X., Xie,D., Lassman,M.E., Bhatt,U.R., Garcia-Calvo,M.M., Shen,Z., Chen,Q., Bleasby,K., SinhaRoy,R., Hale,J.J., Tata,J.R., Pinto,S., Colletti,S.L. and Shen,D.M.
    Discovery of aminoheterocycles as potent and brain penetrant prolylcarboxypeptidase inhibitors
    Bioorg Med Chem Lett (2012) 22, 1727-1730. PubMed  Europe PubMed DOI  I
  39. Wu,Z., Yang,C., Xiong,Y., Feng,Z., Lombardo,M., Verras,A., Chabin,R.M., Xu,S., Tong,X., Xie,D., Lassman,M.E., Bhatt,U.R., Garcia-Calvo,M.M., Geissler,W., Shen,Z., Chen,Q., SinhaRoy,R., Hale,J.J., Tata,J.R., Pinto,S., Shen,D.M. and Colletti,S.L.
    Discovery of a new class of potent prolylcarboxypeptidase inhibitors derived from alanine
    Bioorg Med Chem Lett (2012) 22, 1774-1778. PubMed  Europe PubMed DOI  I
  40. 2011
  41. Adams,G.N., LaRusch,G.A., Stavrou,E., Zhou,Y., Nieman,M.T., Jacobs,G.H., Cui,Y., Lu,Y., Jain,M.K., Mahdi,F., Shariat-Madar,Z., Okada,Y., D'Alecy,L.G. and Schmaier,A.H.
    Murine prolylcarboxypeptidase depletion induces vascular dysfunction with hypertension and faster arterial thrombosis
    Blood (2011) 117, 3929-3937. PubMed  Europe PubMed DOI  PMC  EPMC  K
  42. Chajkowski,S.M., Mallela,J., Watson,D.E., Wang,J., McCurdy,C.R., Rimoldi,J.M. and Shariat-Madar,Z.
    Highly selective hydrolysis of kinins by recombinant prolylcarboxypeptidase
    Biochem Biophys Res Commun (2011) 405, 338-343. PubMed  Europe PubMed DOI  E  P
  43. Diano,S.
    New aspects of melanocortin signaling: a role for PRCP in alpha-MSH degradation
    Front Neuroendocrinol (2011) 32, 70-83. PubMed  Europe PubMed DOI
  44. Duan,L., Motchoulski,N., Danzer,B., Davidovich,I., Shariat-Madar,Z. and Levenson,V.V.
    Prolylcarboxypeptidase regulates proliferation, autophagy, and resistance to 4-hydroxytamoxifen-induced cytotoxicity in estrogen receptor-positive breast cancer cells
    J Biol Chem (2011) 286, 2864-2876. PubMed  Europe PubMed DOI  PMC  EPMC
  45. Shen,H.C., Ding,F.X., Zhou,C., Xiong,Y., Verras,A., Chabin,R.M., Xu,S., Tong,X., Xie,D., Lassman,M.E., Bhatt,U.R., Garcia-Calvo,M.M., Geissler,W., Shen,Z., Chen,D., SinhaRoy,R., Hale,J.J., Tata,J.R., Pinto,S., Shen,D.M. and Colletti,S.L.
    Discovery of benzimidazole pyrrolidinyl amides as prolylcarboxypeptidase inhibitors
    Bioorg Med Chem Lett (2011) 21, 1299-1305. PubMed  Europe PubMed DOI  I
  46. 2010
  47. Abeywickrema,P.D., Patel,S.B., Byrne,N.J., Diehl,R.E., Hall,D.L., Ford,R.E., Rickert,K.W., Reid,J.C., Shipman,J.M., Geissler,W.M., Pryor,K.D., SinhaRoy,R., Soisson,S.M., Lumb,K.J. and Sharma,S.
    Expression, purification and crystallization of human prolylcarboxypeptidase
    Acta Crystallogr Sect F Struct Biol Cryst Commun (2010) 66, 702-705. PubMed  Europe PubMed DOI  PMC  EPMC  E
  48. Soisson,S.M., Patel,S.B., Abeywickrema,P.D., Bryne,N.J., Diehl,R.E., Hall,D.L., Ford,R.E., Reid,J.C., Rickert,K.W., Shipman,J.M., Sharma,S. and Lumb,K.J.
    Structural definition and substrate specificity of the S28 protease family: the crystal structure of human prolylcarboxypeptidase
    BMC Struct Biol (2010) 10, 16-16. PubMed  Europe PubMed DOI  S
  49. Zhao,X., Southwick,K., Cardasis,H.L., Du,Y., Lassman,M.E., Xie,D., El-Sherbeini,M., Geissler,W.M., Pryor,K.D., Verras,A., Garcia-Calvo,M., Shen,D.M., Yates,N.A., Pinto,S. and Hendrickon,R.C.
    Peptidomic profiling of human cerebrospinal fluid identifies YPRPIHPA as a novel substrate for prolylcarboxypeptidase
    Proteomics (2010) 10, 2882-2886. PubMed  Europe PubMed DOI  P
  50. Zhou,C., Garcia-Calvo,M., Pinto,S., Lombardo,M., Feng,Z., Bender,K., Pryor,K.D., Bhatt,U.R., Chabin,R.M., Geissler,W.M., Shen,Z., Tong,X., Zhang,Z., Wong,K.K., Roy,R.S., Chapman,K.T., Yang,L. and Xiong,Y.
    Design and synthesis of prolylcarboxypeptidase (PrCP) inhibitors to validate PrCP as a potential target for obesity
    J Med Chem (2010) 53, 7251-7263. PubMed  Europe PubMed DOI  T  I
  51. Zhu,L., Carretero,O.A., Liao,T.D., Harding,P., Li,H., Sumners,C. and Yang,X.P.
    Role of prolylcarboxypeptidase in angiotensin II type 2 receptor-mediated bradykinin release in mouse coronary artery endothelial cells
    Hypertension (2010) 56, 384-390. PubMed  Europe PubMed DOI  PMC  EPMC
  52. 2009
  53. Ngo,M.L., Mahdi,F., Kolte,D. and Shariat-Madar,Z.
    Upregulation of prolylcarboxypeptidase (PRCP) in lipopolysaccharide (LPS) treated endothelium promotes inflammation
    J Inflamm (Lond) (2009) 6, 3-3. PubMed  Europe PubMed DOI  PMC  EPMC
  54. Palmiter,R.D.
    Reduced levels of neurotransmitter-degrading enzyme PRCP promote a lean phenotype
    J Clin Invest (2009) 119, 2130-2133. PubMed  Europe PubMed DOI  PMC  EPMC
  55. Wallingford,N., Perroud,B., Gao,Q., Coppola,A., Gyengesi,E., Liu,Z.W., Gao,X.B., Diament,A., Haus,K.A., Shariat-Madar,Z., Mahdi,F., Wardlaw,S.L., Schmaier,A.H., Warden,C.H. and Diano,S.
    Prolylcarboxypeptidase regulates food intake by inactivating alpha-MSH in rodents
    J Clin Invest (2009) 119, 2291-2303. PubMed  Europe PubMed DOI  PMC  EPMC
  56. Zhang,Y., Hong,X.M., Xing,H.X., Li,J.P., Huo,Y. and Xu,X.P.
    E112D polymorphism in the prolylcarboxypeptidase gene is associated with blood pressure response to benazepril in Chinese hypertensive patients
    Chin Med J (Engl) (2009) 122, 2461-2465. PubMed  Europe PubMed DOI  M
  57. 2006
  58. Wang,L., Feng,Y., Zhang,Y., Zhou,H., Jiang,S., Niu,T., Wei,L.J., Xu,X., Xu,X. and Wang,X.
    Prolylcarboxypeptidase gene, chronic hypertension, and risk of preeclampsia
    Am J Obstet Gynecol (2006) 195, 162-171. PubMed  Europe PubMed DOI
  59. 2005
  60. Shariat-Madar,Z., Rahimy,E., Mahdi,F. and Schmaier,A.H.
    Overexpression of prolylcarboxypeptidase enhances plasma prekallikrein activation on Chinese hamster ovary cells
    Am J Physiol Heart Circ Physiol (2005) 289, H2697-H2703. PubMed  Europe PubMed DOI
  61. 2004
  62. [YEAR:12-2-2004]Maryanoff,B.E.
    Inhibitors of serine proteases as potential therapeutic agents: the road from thrombin to tryptase to cathepsin G
    J Med Chem (12-2-2004) 47, 769-787. PubMed  Europe PubMed DOI  I
  63. [YEAR:2-3-2004]Shariat-Madar,Z., Mahdi,F. and Schmaier,A.H.
    Recombinant prolylcarboxypeptidase activates plasma prekallikrein
    Blood (2-3-2004) 103, 4554-4561. PubMed  Europe PubMed DOI  I
  64. Tan,F. and Erdos,E.G.
    Lysosomal Pro-X carboxypeptidase
    [ISSN:0-12-079610-4] (2004) 2, 1936-1938.  V
  65. 2002
  66. [YEAR:17-7-2002]Moreira,C.R., Schmaier,A.H., Mahdi,F., da Motta,G., Nader,H.B. and Shariat-Madar,Z.
    Identification of prolylcarboxypeptidase as the cell matrix-associated prekallikrein activator
    FEBS Lett (17-7-2002) 523, 167-170. PubMed  Europe PubMed DOI
  67. [YEAR:17-5-2002]Shariat-Madar,Z., Mahdi,F. and Schmaier,A.H.
    Identification and characterization of prolylcarboxypeptidase as an endothelial cell prekallikrein activator
    J Biol Chem (17-5-2002) 277, 17962-17969. PubMed  Europe PubMed DOI
  68. Shariat-Madar,Z., Mahdi,F. and Schmaier,A.H.
    Assembly and activation of the plasma kallikrein/kinin system: a new interpretation
    Int Immunopharmacol (2002) 2, 1841-1849. PubMed  Europe PubMed DOI
  69. 1998
  70. Skidgel,R.A. and Erdos,E.G.
    Cellular carboxypeptidases
    Immunol Rev (1998) 161, 129-141. PubMed  Europe PubMed DOI
  71. 1997
  72. [YEAR:15-9-1997]Watson,B., Jr., Nowak,N.J., Myracle,A.D., Shows,T.B. and Warnock,D.G.
    The human angiotensinase C gene (HUMPCP) maps to 11q14 within 700 kb of D11S901: a candidate gene for essential hypertension
    Genomics (15-9-1997) 44, 365-367. PubMed  Europe PubMed DOI
  73. 1995
  74. Suzawa,Y., Hiraoka,B.Y., Harada,M. and Deguchi,T.
    High-performance liquid chromatographic determination of prolylcarboxypeptidase activity in monkey kidney
    J Chromatogr B Biomed Appl (1995) 670, 152-156. PubMed  Europe PubMed DOI
  75. 1993
  76. [YEAR:5-8-1993]Tan,F., Morris,P.W., Skidgel,R.A. and Erdos,E.G.
    Sequencing and cloning of human prolylcarboxypeptidase (angiotensinase C). Similarity to both serine carboxypeptidase and prolylendopeptidase families
    J Biol Chem (5-8-1993) 268, 16631-16638. PubMed  Europe PubMed
  77. 1981
  78. Kumamoto,K., Stewart,T.A., Johnson,A.R. and Erdos,E.G.
    Prolylcarboxypeptidase (angiotensinase C) in human lung and cultured cells
    J Clin Invest (1981) 67, 210-215. PubMed  Europe PubMed DOI  PMC  EPMC
  79. Odya,C.E. and Erdos,E.G.
    Human prolylcarboxypeptidase
    Methods Enzymol (1981) 80, 460-466. PubMed  Europe PubMed DOI  V
  80. [YEAR:15-11-1981]Skidgel,R.A., Wickstrom,E., Kumamoto,K. and Erdos,E.G.
    Rapid radioassay for prolylcarboxypeptidase (angiotensinase C)
    Anal Biochem (15-11-1981) 118, 113-119. PubMed  Europe PubMed
  81. 1978
  82. Odya,C.E., Marinkovic,D.V., Hammon,K.J., Stewart,T.A. and Erdos,E.G.
    Purification and properties of prolylcarboxypeptidase (angiotensinase C) from human kidney
    J Biol Chem (1978) 253, 5927-5931. PubMed  Europe PubMed
  83. 1973
  84. [YEAR:15-3-1973]Kakimoto,T., Oshima,G., Yeh,H.S. and Erdos,E.G.
    Purification of lysosomal prolycarboxypeptidase angiotensinase C
    Biochim Biophys Acta (15-3-1973) 302, 178-182. PubMed  Europe PubMed
  85. 1971
  86. Matsunaga,M.
    Nature of lysosomal angiotensinase activity
    Jpn Circ J (1971) 35, 333-338. PubMed  Europe PubMed
  87. 1969
  88. Matsunaga,M., Saito,N., Kira,J., Ogino,K. and Takayasu,M.
    Acid angiotensinase as a lysosomal enzyme
    Jpn Circ J (1969) 33, 545-551. PubMed  Europe PubMed
  89. 1968
  90. [YEAR:26-6-1968]Johnson,D.C. and Ryan,J.W.
    Degradation of angiotensin II by a carboxypeptidase of rabbit liver
    Biochim Biophys Acta (26-6-1968) 160, 196-203. PubMed  Europe PubMed
  91. Yang,H.Y., Erdos,E.G. and Chiang,T.S.
    New enzymatic route for the inactivation of angiotensin
    Nature (1968) 218, 1224-1226. PubMed  Europe PubMed DOI