缅北禁地

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Staff Profile

Emeritus Professor Barry Hirst

Emeritus Professor

  • Address: Biosciences Institute
    University of 缅北禁地
    Faculty of Medical Sciences
    缅北禁地 Upon Tyne
    NE2 4HH
Background

External services

Health Research Authority; 缅北禁地 & North Tyneside 2 Research Ethics Committee Chair  

Health Education England; Centre for Advancing Clinical Practice, External Panel Chair/Member 

Academy for Healthcare Science; Education, Training & Standards Committee Chair 


Qualifications

BSc Physiology, 缅北禁地 upon Tyne
PhD 缅北禁地 upon Tyne


Google Scholar web link:

ORCID:

Research

Research Interests

Epithelia form a barrier between the external world and the body. Epithelial barrier functions minimise access of toxic agents and pathogens, while providing for selective uptake of nutrients. Three inter-related areas, intestinal nutrient transport, intestinal drug transport and epithelial-bacterial pathogen interactions are the focus of research.

Intestinal nutrient transporters allow not only for nutrient supply from the diet to the body, but also fulfil specialist needs in maintaining enterocyte homeostasis. One example is the supply of glycine by the high-affinity glycine-specific GLYT1 transporter (SLC6A9 gene). GLYT1 demonstrates both apical and basal localisation, with at least five different transcripts identified, from the use of two promoters and with several differential splicing events. The laboratory investigated the role of these different transcripts of the GLYT1 in maintaining glycine supply to enterocytes during the fasting-fed cycle. This is coupled to studies of the role of glycine in maintaining enterocyte health in the face of oxidative and other challenges. The role of GLYT1 in maintaining cancer cell proliferation is a related area.

Oral drug bioavailability is a balance between passive and active absorptive mechanisms and the ability of the intestinal epithelium and hepatocytes to actively secrete drug molecules through a variety of ABC-transporters. Research focused on the role of these transporters and their potential for interaction with drug metabolism systems, thus enabling predictive in vitro methods for assessing oral bioavailability.

Many pathogenic bacteria have evolved to interact specifically with epithelial tissues, enabling them to gain access to the host. Research on human tonsils, in collaboration with Judith Hall and Janet Wilson (ENT Surgery), focused on the determinants for interaction of Streptococci with human tonsils, the expression and regulation of antimicrobial peptides in the tonsil and the influence of antimicrobial peptides on Streptococci-tonsil interactions.


Google Scholar web link:

ORCID

Teaching



Publications

  • Articles

    • Bierhals CG, Howard A, Hirst BH. . Biomedicines 2021, 9(12), 1770.
    • Boeynaems J-M, Canivet C, Chan A, Clark MJ, Cornu C, Daemen E, Demotes J, De Nys K, Hirst B, Hundt F, Kassai B, Kerpel-Fronius S, Kiessig L, Klech H, Kraehenbuhl J-P, Lafolie P, Lucht M, Niese D, Pauli-Magnus C, Peters B, Schaltenbrand R, Stockis A, Stykova M, Verheus N, Klingmann I. . Frontiers in Pharmacology 2013, 4, 112.
    • Bell S, Howard A, Wilson JA, Abbot EL, Smith WD, Townes CL, Hirst BH, Hall J. . Molecular Oral Microbiology 2012, 27(3), 160-171.
    • Smith WD, Pointon JA, Abbot E, Kang HJ, Baker EN, Hirst BH, Wilson JA, Banfield MJ, Kehoe MA. . Journal of Bacteriology 2010, 192(18), 4651-4659.
    • McLure S, Willis M, Fox A, Newton J, Hirst B. . Journal of Paramedic Practice 2010, 2(5), 230-232.
    • Howard A, Tahir I, Javed S, Waring SM, Ford D, Hirst BH. . Journal of Physiology 2010, 588(6), 995–1009.
    • Hirst BH, Howard A, Javed S. . Journal of Physiological Sciences 2009, 59(s1), 247.
    • Abbot EL, Smith WD, Siou GPS, Chiriboga C, Smith RJ, Wilson JA, Hirst BH, Kehoe MA. . Cellular Microbiology 2007, 9(7), 1822-1833.
    • Ball SL, Siou GP, Wilson JA, Howard A, Hirst BH, Hall J. . Journal of Laryngology and Otology 2007, 121(10), 973-978.
    • Nile CJ, Townes CL, Hirst BH, Hall J. . Molecular Immunology 2006, 43(4), 388-394.
    • Fearn RA, Hirst BH. . Environmental Toxicology and Pharmacology 2006, 21(2), 168-178.
    • Prime-Chapman H, Moore V, Hirst BH. . Journal of Drug Targeting 2005, 13(1), 1-6.
    • Chan LMS, Cooper AE, Dudley ALJ, Ford D, Hirst BH. . Journal of Drug Targeting 2004, 12(7), 405-413.
    • Howard A, Goodlad RA, Walters JRF, Ford D, Hirst BH. . Journal of Nutrition 2004, 134(11), 2957-2964.
    • Nile CJ, Townes CL, Michailidis G, Hirst BH, Hall J. . Cellular and Molecular Life Sciences 2004, 61(21), 2760-2766.
    • Prime-Chapman HM, Fearn RA, Cooper AE, Moore V, Hirst BH. . Journal of Pharmacology and Experimental Therapeutics 2004, 311(2), 476-484.
    • Ball SL, Siou GP, Howard A, Hall J, Wilson JA, Hirst BH. . Clinical Otolaryngology & Allied Sciences 2004, 29(4), 427.
    • Ford D, Howard A, Hirst BH. . Histochemistry and Cell Biology 2003, 119(1), 37-43.
    • Jepson MA, Simmons NL, O'Hagan DT, Hirst BH. . Journal of Drug Targeting 2003, 11(5), 269-272.
    • Reuss L, Hirst BH. . Journal of Physiology 2002, 542(1), 1-2.
    • Clark AM, Hirst BH. . Histochemistry and Cell Biology 2002, 118(2), 137-147.
    • Ann Clark M, Blair H, Liang L, Brey RN, Brayden D, Hirst BH. . Vaccine 2001, 20(1-2), 208-217.
    • Christie GR, Ford D, Howard A, Clark M Ann, Hirst BH. . Gastroenterology 2001, 120(2), 439-448.
    • Clark MA, Wilson C, Sama A, Wilson JA, Hirst BH. . Histochemistry and Cell Biology 2000, 114(4), 311-321.
    • Hirst BH. . American Journal of Physiology: Cell Physiology 1999, 277(3), C359-C360.
    • Fontes CMGA, Ali S, Gilbert HJ, Hazlewood GP, Hirst BH, Hall J. . Journal of Biotechnology 1999, 72(1-2), 95-101.
    • N. Foster,M. A. Clark,M. A. Jepson,B. H. Hirst. Ulex europaeus 1 lectin targets microspheres to mouse Peyer's patch M-cells in vivo. Vaccine 1998, 16(5), 536-41.
    • C. L. Scudamore,M. A. Jepson,B. H. Hirst,H. R. Miller. The rat mucosal mast cell chymase, RMCP-II, alters epithelial cell monolayer permeability in association with altered distribution of the tight junction proteins ZO-1 and occludin. Eur J Cell Biol 1998, 75(4), 321-30.
    • Ford D, Thwaites D, Simmons N, Gilbert H, Hirst B. . Journal of Physiology 1998, 507(3), 697-706.
    • M. A. Clark,B. H. Hirst,M. A. Jepson. M-cell surface beta1 integrin expression and invasin-mediated targeting of Yersinia pseudotuberculosis to mouse Peyer's patch M cells. Infect Immun 1998, 66(3), 1237-43.
    • M. A. Clark,B. H. Hirst,M. A. Jepson. Inoculum composition and Salmonella pathogenicity island 1 regulate M-cell invasion and epithelial destruction by Salmonella typhimurium. Infect Immun 1998, 66(2), 724-31.
    • C. B. Collares-Buzato,M. A. Jepson,N. L. Simmons,B. H. Hirst. Increased tyrosine phosphorylation causes redistribution of adherens junction and tight junction proteins and perturbs paracellular barrier function in MDCK epithelia. Eur J Cell Biol 1998, 76(2), 85-92.
    • C. B. Collares-Buzato,M. A. Jepson,G. T. McEwan,B. H. Hirst,N. L. Simmons. Co-culture of two MDCK strains with distinct junctional protein expression: a model for intercellular junction rearrangement and cell sorting. Cell Tissue Res 1998, 291(2), 267-76.
    • K. A. Reed,M. A. Clark,T. A. Booth,C. J. Hueck,S. I. Miller,B. H. Hirst,M. A. Jepson. Cell-contact-stimulated formation of filamentous appendages by Salmonella typhimurium does not depend on the type III secretion system encoded by Salmonella pathogenicity island 1. Infect Immun 1998, 66(5), 2007-17.
    • Matthews, C.J., McEwan, G.T.A., Redfern, C.P.F., Thomas, E.J., Hirst, B.H. . Journal of Physiology 1998, 513(2), 443-452.
    • S. Ali,C. M. Fontes,G. P. Hazlewood,B. H. Hirst,A. J. Clark,H. J. Gilbert,J. Hall. Co-integration and expression of bacterial and genomic transgenes in the pancreatic and intestinal tissues of transgenic mice. Gene 1997, 202(1-2), 203-8.
    • M. A. Jepson,M. A. Clark,N. Foster,C. M. Mason,M. K. Bennett,N. L. Simmons,B. H. Hirst. Targeting to intestinal M cells. J Anat 1996, 189 ( Pt 3), 507-16.
    • K. A. Reed,T. A. Booth,B. H. Hirst,M. A. Jepson. Promotion of Salmonella typhimurium adherence and membrane ruffling in MDCK epithelia by staurosporine. FEMS Microbiol Lett 1996, 145(2), 233-8.
    • M. A. Clark,K. A. Reed,J. Lodge,J. Stephen,B. H. Hirst,M. A. Jepson. Invasion of murine intestinal M cells by Salmonella typhimurium inv mutants severely deficient for invasion of cultured cells. Infect Immun 1996, 64(10), 4363-8.
    • S. Ali,J. Hall,G. P. Hazlewood,B. H. Hirst,H. J. Gilbert. A protein targeting signal that functions in polarized epithelial cells in vivo. Biochem J 1996, 315 ( Pt 3), 857-62.
    • Ali S, Hall J, Hazelwood GP, Hirst BH et al. A protein targeting signal that functions in polarized epithelial cells in vivo. Biochemical Journal 1996, 315, 857-862.
    • Thwaites DT, McEwan GTA, Hirst BH, Simmons NL. . Biochimica et Biophysica Acta: Biomembranes 1995, 1234(1), 111-118.
    • Thwaites DT, Armstrong G, Hirst BH, Simmons NL. . British Journal of Pharmacology 1995, 115(5), 761-766.
    • Thwaites DT, Cavet M, Hirst BH, Simmons NL. . British Journal of Pharmacology 1995, 114(5), 981-986.
    • Thwaites DT, Hirst BH, Simmons NL. . British Journal of Pharmacology 1994, 113(3), 1050-1056.
    • Thwaites DT, McEwan GTA, Brown CDA, Hirst BH, Simmons NL. . Journal of Membrane Biology 1994, 140(2), 143-151.
    • Thwaites DT, Brown CDA, Hirst BH, Simmons NL. . Journal of Biological Chemistry 1993, 268(11), 7640-7642.
    • Thwaites DT, McEwan GTA, Hirst BH, Simmons NL. . Pfluegers Archiv: European Journal of Physiology 1993, 425(1-2), 178-180.
    • Thwaites DT, Simmons NL, Hirst BH. . Pharmaceutical Research 1993, 10(5), 667-673.
    • Thwaites DT, Hirst BH, Simmons NL. . Pharmaceutical Research 1993, 10(5), 674-681.
    • Thwaites DT, McEwan GTA, Brown CDA, Hirst BH, Simmons NL. . Journal of Biological Chemistry 1993, 268, 18438-18441.
    • Matthews CJ, Thomas EJ, Redfern CPF, Hirst BH. . Human Reproduction 1993, 8(10), 1570-1575.
    • JEPSON MA, SIMMONS NL, HIRST GL, HIRST BH. IDENTIFICATION OF M-CELLS AND THEIR DISTRIBUTION IN RABBIT INTESTINAL PEYER PATCHES AND APPENDIX. CELL AND TISSUE RESEARCH 1993, 273(1), 127-136.
    • Thwaites DT, Brown CDA, Hirst BH, Simmons NL. . Biochimica et Biophysica Acta: Biomembranes 1993, 1151(2), 237-245.
    • Thwaites DT, McEwan GTA, Cook MJ, Hirst BH, Simmons NL. . FEBS Letters 1993, 333(1-2), 78-82.
    • Thwaites DT, Hirst BH, Simmons NL. . Biochemical and Biophysical Research Communications 1993, 194(1), 432-438.
    • Matthews CJ, McEwan GTA, Redfern CPF, Thomas EJ, Hirst BH. . Pflügers Archiv European Journal of Physiology 1993, 422(4), 401-403.
    • Matthews CJ, Redfern CPF, Thomas EJ, Hirst BH. . Experimental Physiology 1993, 78(5), 715-718.
    • Matthews CJ, Redfern CPF, Hirst BH, Thomas EJ. . Fertility and Sterility 1992, 57(5), 990-997.
    • HIRST BH, COY DH. STRUCTURE-ACTIVITY STUDIES WITH SOMATOSTATIN - ROLE OF LYSINE IN POSITION-4 AND POSITION-9 FOR GASTRIC ACTIVITY. REGULATORY PEPTIDES 1984, 8(4), 267-271.
    • GASCOIGNE AD, HIRST BH. PROSTAGLANDINS ALTER THE RELATIONSHIP BETWEEN GASTRIC HYDROGEN-ION CONCENTRATION AND FLOW - EVIDENCE FOR STIMULATION OF NON-PARIETAL SECRETION IN THE CAT. JOURNAL OF PHYSIOLOGY-LONDON 1981, 316(JUL), 427-438.
    • HIRST BH, LUND PK, REED JD, SANDERS DJ, SHAW B, TAYLOR W. EFFECTS OF A COMBINED ESTROGEN-PROGESTIN PREPARATION ON GASTRIC-ACID AND PEPSIN SECRETION, SERUM GASTRIN CONCENTRATION AND BILIARY-SECRETION OF BILE-ACIDS, PHOSPHOLIPIDS, AND CHOLESTEROL IN THE CAT. BRITISH JOURNAL OF PHARMACOLOGY 1979, 65(1), 87-95.
    • HIRST BH, REED JD, SHAW B, CQY DH, SCHALLY AV. QUANTITATION OF SOMATOSTATIN INHIBITION OF INSULIN-STIMULATED GASTRIC-ACID AND PEPSIN SECRETION IN CAT. ACTA HEPATO-GASTROENTEROLOGICA 1978, 25(3), 208-212.
    • ALBINUS M, BLAIR EL, HIRST BH, REED JD. EFFECT OF ANESTHESIA ON PENTAGASTRIN STIMULATED GASTRIC-ACID SECRETION IN CAT. JOURNAL OF PHYSIOLOGY-LONDON 1978, 274(JAN), 1-8.
    • HIRST BH, LABIB LA, REED JD. CHARACTERISTICS AND TACHYPHYLAXIS OF GASTRIN-STIMULATED GASTRIC-ACID SECRETION IN CAT. JOURNAL OF PHYSIOLOGY-LONDON 1978, 276(MAR), 1-11.
    • ALBINUS M, BLAIR EL, HIRST BH, REED JD, SCHALLY AV, SHAW B. EFFECTS OF SOMATOSTATIN AND METIAMIDE ON TACHYPHYLAXIS OF PENTAGASTRIN STIMULATED GASTRIC-ACID AND PEPSIN SECRETION IN CONSCIOUS CAT. JOURNAL OF PHYSIOLOGY-LONDON 1977, 266(3), 801-817.

  • Book Chapter

    • Thwaites DT, Hirst BH, Simmons NL. . In: Molecular and Cellular Mechanisms of H<sup>+</sup> Transport. Heidelberg: Springer-Verlag, 1994, pp.283-296.

  • Conference Proceedings (inc. Abstracts)

    • Dismore L, Taylor L, Aujayeb A, Swainston K. . In: British Thoracic Society. 2023, London, UK: BMJ Group.
    • Fultang L, Howard A, Hirst B. . In: Experimental Biology 2014. 2014, San Diego: Federation of American Societies for Experimental Biology.
    • Clapp A, Tullo E, Carrick-Sen D, Newton J, Hirst B. . In: British Geriatrics Society Spring Meeting. 2013, Belfast, Ireland: Oxford University Press.
    • Howard A, Hirst BH. . In: Experimental Biology Meeting 2011. 2011, Walter E Washington Convention Center, Washington, DC: Federation of American Societies for Experimental Biology.
    • Mowbray CA, Howard A, Morsman J, Hirst BH. Differentiation of HepG2 and Huh7 cells using dimethyl sulfoxide. In: FASEB JOURNAL. 2010, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA: FEDERATION AMER SOC EXP BIOL.
    • Javed S, Howard A, Hirst B. . In: Mutagenesis: 31st Annual Meeting of the United Kingdom Environmental Mutagen Society. 2009, University of Northumbria, 缅北禁地 upon Tyne, UK: Oxford University Press.
    • Tahir I, Howard A, Ford D, Hirst BH. . In: FASEB Journal: Experimental Biology 2005 Meeting. 2005, San Diego, California, USA: Federation of American Societies for Experimental Biology.
    • Aldridge PD, Gray MA, Hirst BH, Khan CMA. . In: International Symposium on Epithelial-Bacterial Pathogen Interactions. 2004, 缅北禁地 upon Tyne, UK: Molecular Microbiology: Wiley-Blackwell.
    • Howard A, Goodlad RA, Ford D, Walters JRF, Hirst BH. . In: Journal of Physiology: Conference of the Physiological Society. 2002, Liverpool: Wiley-Blackwell Publishing Ltd.
    • Wilson V, Howard A, Ford D, Hirst BH. . In: Journal of Physiology: Conference of the Physiological Society. 2002, Liverpool: Wiley-Blackwell Publishing Ltd.
    • Howard A, Rugg-Gunn P, Goodlad RL, Walters JRF, Ford D, Hirst BH. . In: FASEB Journal. 2001, Federation of American Societies for Experimental Biology.
    • Chan L, Dudley A, Keating K, Cooper AE, Ford D, Hirst BH. . In: Meeting of the Physiological Society. 2001, Sheffield, UK: Wiley-Blackwell Publishing Ltd.
    • Prime-Chapman HM, Moore V, Hirst BH. . In: Meeting of the Physiological Society. 2001, Sheffield, UK: Wiley-Blackwell Publishing Ltd.
    • Howard A, Gray PA, Ford D, Hirst BH. . In: JOURNAL OF PHYSIOLOGY-LONDON. 2000.
    • Gray PA, Ford D, Hirst BH. Regulation of the amino acid transporter hEAAC1 in human intestinal Caco-2 cells. In: FASEB JOURNAL. 2000.
    • Chan L, Dudley A, Ford D, Hirst BH. MDR1- and MRP2-mediated secretion of rhodamine dyes. In: JOURNAL OF PHYSIOLOGY-LONDON. 2000.
    • Howard A, Jordinson M, Goodlad RA, Walters JR, Ford D, Hirst BH. Changes in expression of intestinal peptide and amino acid transporters in rats fed by total parenteral nutrition. In: GASTROENTEROLOGY. 2000.
    • Logan KA, Matthews CJ, Hirst BH. . In: 26th Annual Meeting of the Physiological Society of New Zealand. 1999, Wellington, New Zealand.
    • Anderson KG, Taylor IH, Hirst BH. . In: FASEB Journal. 1999, Federation of American Societies for Experimental Biology.
    • Matthews CJ, Ford D, Hirst BH. . In: FASEB Journal. 1999, Federation of American Societies for Experimental Biology.
    • MATTHEWS CJ, MCEWAN GTA, REDFERN CPF, THOMAS EJ, HIRST BH. ISOLATION, CULTURE AND FUNCTIONAL-ANALYSIS OF GLANDS FROM HUMAN ENDOMETRIUM. In: JOURNAL OF PHYSIOLOGY-LONDON. 1992.
    • MATTHEWS CJ, REDFERN CPF, THOMAS EJ, HIRST BH. ELECTROLYTE TRANSPORT BY PRIMARY MONOLAYER-CULTURES OF HUMAN ENDOMETRIAL GLANDULAR EPITHELIAL-CELLS. In: JOURNAL OF PHYSIOLOGY-LONDON. 1992.
    • MATTHEWS CJ, MCEWAN GTA, REDFERN CPF, THOMAS EJ, HIRST BH. ELECTRICAL-PROPERTIES OF PRIMARY MONOLAYER-CULTURES OF HUMAN ENDOMETRIAL GLANDULAR EPITHELIAL-CELLS. In: JOURNAL OF PHYSIOLOGY-LONDON. 1992.
    • HIRST BH, HOLLAND J. GASTRIC-MUCOSAL BLOOD-FLOW AND ACID-SECRETION IN THE CONSCIOUS CAT. In: JOURNAL OF PHYSIOLOGY-LONDON. 1981.
    • HIRST BH, LABIB LA, REED JD, STEPHEN JG. EFFECT OF INHIBITORS ON THE RELATIONSHIP BETWEEN HISTAMINE-STIMULATED AND INSULIN-STIMULATED GASTRIC HYDROGEN-ION CONCENTRATION AND FLOW IN THE CAT. In: JOURNAL OF PHYSIOLOGY-LONDON. 1979.
    • HIRST BH, BLAIR EL, LABIB LA, REED JD, STEPHEN JG. EFFECT OF INHIBITORS ON RELATIONSHIP BETWEEN HYDROGEN-ION CONCENTRATION AND FLOW OF GASTRIC-JUICE IN CAT. In: GUT. 1978.
    • COY DH, HIRST BH, MEYERS CA, REED JD, SCHALLY AV. DIFFERENTIATION OF SOMATOSTATIN RECEPTORS INVOLVED IN INHIBITION OF GASTRIC-ACID AND GROWTH-HORMONE SECRETION WITH HALOGENATED TRP8 ANALOGS. In: JOURNAL OF PHYSIOLOGY-LONDON. 1978.
    • HIRST BH, REED JD, SHAW B. GASTRIC-ACID AND PEPSIN STIMULATING ACTIVITY OF GASTRIN FRAGMENTS IN CAT. In: JOURNAL OF PHYSIOLOGY-LONDON. 1977.

  • Editorials

    • Brayden DJ, Hirst BH. . Current Opinion in Pharmacology 2017, 36, iv-vii.
    • Siou GPS, Smith W, Kehoe MA, Hirst BH, Wilson JA. . Annals of the Royal College of Surgeons of England 2005, 87(6), 482-482.
    • Hirst BH. . American Journal of Physiology: Cell Physiology 1999, 277(3), C359-C360.

  • Letters

    • Matthews CJ, Redfern CPF, Hirst BH, Thomas EJ. . Fertility and Sterility 1992, 58(6), 1267-1268.
    • HIRST BH, LUND PK, REED JD, SANDERS DJ. BROMOCRIPTINE, GASTRIC-ACID OUTPUT, AND GASTRIN SECRETION. LANCET 1977, 1(8017), 902-903.

  • Notes

    • Hirst BH. . Journal of Physiology 2004, 560(2), 339-339.
    • Hirst BH. . Journal of Physiology 2002, 540(1), 1.
    • HIRST BH, REED JD, GOMEZPAN A, LABIB LA. BROMOCRIPTINE POTENTIATION OF GASTRIC-ACID SECRETION IN CATS. CLINICAL ENDOCRINOLOGY 1976, 5(6), 723-729.

  • Report

    • Hirst B, Padfield P, Corner L, Down K, Williams H, Williams S, Stubbs M. . Birmingham, UK: Health Education England, 2015.

  • Reviews

    • Mowbray C, Howard A, Hirst BH. . European Pharmaceutical Review 2015, 20(3), 8-14.
    • Howard A, Hirst BH. . Biological and Pharmaceutical Bulletin 2011, 34(6), 784-788.
    • Foster N, Hirst BH. . Advanced Drug Delivery Reviews 2005, 57(3), 431-450.
    • Chan LMS, Lowes S, Hirst BH. . European Journal of Pharmaceutical Sciences 2004, 21(1), 25-51.
    • Jepson MA, Clark MA, Hirst BH. . Advanced Drug Delivery Reviews 2004, 56(4), 511-525.
    • Clark MA, Jepson MA, Hirst BH. . Advanced Drug Delivery Reviews 2001, 50(1-2), 81-106.
    • Clark MA, Hirst BH, Jepson MA. . Advanced Drug Delivery Reviews 2000, 43(2-3), 207-223.
    • Notarianni E, Hirst BH. . Placenta 1999, 20(2-3), 149-154.