Iron Homeostasis and the Assessment of Iron Status

Jacobs A. Non-haematological effects of iron deficiency. Clin Haematol 1982; 11: 353–64.

DeMaeyer E Adiels-Tegman M. The prevalence of anaemia in the world. World Health Stat Q 1985; 38: 302.

Hoffbrand AV Ganeshaguru K Hooton JWL Tattersall MHN Effect of iron deficiency and desferrioxamine on DNA synthesis in human cells. Br J Haematol 1976; 33: 517–26.

Peters TJ Raja KB Simpson RJ Snape S. Mechanisms and regulation of intestinal iron absorption. Ann NY Acad Sci. 1988; 526: 141–7.

McCance RA Widdowson EM. Absorption and excretion of iron. Lancet 1937; ii: 680–4.

Cooke JD Skikne BS. Intestinal regulation of body iron. Blood Rev. 1987; 1: 167–272.

Bothwell TH Charlton RW Cook JD Finch CA. Iron Metabolism in Man. Oxford: Blackwell Scientific Publications, 1979.

Forth W Rummel W. Iron absorption. Physiol Rev. 1973; 53: 724–92.

Peters TJ Raja KB Simpson RJ. Speciation of trace metals, with special reference to intestinal iron absorption. Food Chem 1992; 43: 315–20.

Peters TJ Pippard MJ. Disorders of iron metabolism. In: Weatherall DY Ledingham JGG Warrell DA , eds. Oxford Textbook of Medicine. Oxford: Oxford Medical Publications, 1996.

Raja KB Bjarnason I Simpson RJ Peters TJ. In vitro measurement and adaptive response of Fe³⁺ uptake by mouse intestine. Cell Biochem Func 1987; 5: 69–76.

Raja KB Simpson RJ Peters TJ. Investigation of a role for reduction in ferric iron uptake by mouse duodenum. Biochim Biophys Acta 1992; 1135: 141–6.

Simpson RJ Peters TJ. Iron-binding lipids of rabbit duodenal brush-border membrane. Biochim Biophys Acta 1987; 898: 181–6.

Huebers HA Huebers E Csiba E Rummel W Finch CA. The significance of transferrin for intestinal iron absorption. Blood 1983; 61: 283–90.

Osterloh KRS Simpson RJ Peters TJ. The role of mucosal transferrin in intestinal iron absorption. Br J Haematol 1987; 65: 1–3.

Bezwoda WR MacPhail AP Bothwell TH Baynes RD Derman DP Torrance JD. Failure of transferrin to enhance iron absorption in achlorhydric human subjects. Br J Haematol 1986; 63: 749–52.

Goya N Miyazaki S Kodate S Ushio B. A family of congenital atransferrinemia. Blood 1972; 40: 239–45.

Raja KB Pippard MJ Simpson RJ Peters TJ. Relationship between erythropoiesis and the enhanced intestinal uptake of ferric iron in hypoxia in the mouse. Br J Haematol 1986; 64: 587–93.

Raja KB Simpson RJ Pippard MJ Peters TJ. In vivo studies on the relationship between intestinal iron (Fe³⁺) absorption and erythropoiesis in the mouse. Br J Haematol 1988; 68: 373–8.

Finch CA Huebers HA Eng M Miller L. Effect of transfused reticulocytes on iron exchange. Blood 1982; 59: 364–9.

Huebers HA Finch CA. Transferrin. Biologic behaviour and clinical implications. Blood 1984; 61: 763–7.

Kino K Tsunoo H Higa Y Takami M Hamaguchi H. Nakajima H. Hemoglobin—haptoglobin receptor in rat liver plasma membrane. J Biol Chem 1980; 255: 9616–20.

Hershko C Cook JD Finch CA. Storage iron kinetics II. The uptake of hemoglobin iron by hepatic parenchymal cells. J Lab Clin Med. 1972; 80: 624–34.

Morgan EH Baker E. Iron uptake and metabolism by hepatocytes. Fed Proc 1986; 45: 2810–6.

Hershko C Graham G Bates GW Rachmilewitz A. Non-specific serum iron in thalassaemia: an abnormal scrum iron fraction of potential toxicity. Br J Haematol 1978; 40: 255–63.

Fawwaz RA Winchell HS Pollycove M Sargent T. Hepatic iron disposition in humans. 1. First-pass hepatic deposition of intestinally absorbed iron in patients with low latent iron-binding capacity. Blood 1967; 30: 417–24.

Sciot R Paterson AC Van den Oord JJ Desmet VJ. Lack of hepatic transferrin receptor expression in hemochromatosis. Hepatology 1987; 7: 831–7.

Trowbridge IS Newman RA Domingo DL Sauvage S. Transferrin receptors: structure and function. Biochem Pharmacol 1984; 33: 925–32.

Sutherland R. Delia D Schneider C Newman R Kemshead J Greaves M. Ubiquitous cell-surface glycoprotein on tumour cells in proliferation-associated receptor for transferrin. Proc Natl Acad Sci USA 1981; 78: 4515–9.

Rao K Harford JB Rouault TA McClelland A Ruddle FH Klausner RD. Transcriptional regulation by iron of the gene for the transferrin receptor. Mol Cell Biol 1986; 6: 236–40.

Rouault TA Haile DJ Downey WE Philpott CC Tang C Samaniego F An iron sulfur cluster plays a novel regulatory role in the iron-responsive element binding protein. Biometals 1992; 5: 131–40.

Arosio P Adelman TG Drysdale JW. On ferritin heterogeneity. J Biol Chem 1978; 253: 4451–8.

Cragg SJ Wagstaff M Worwood M. Detection of a glycosylated subunit in human serum ferritin. Biochem J 1981; 199: 565–71.

Harrison PM Ford GC Rice DW Smith JMA Treffry A White JL. Structural and functional studies on ferritins. Biochem Soc Trans 1987; 15: 744–8.

Pippard MJ Tikaepae J Peters TJ. Ferritin iron metabolism in the rat liver. Br J Haematol 1986; 64: 839.

Zahringer J Baliga BS Munro HN. The mechanism for translational control in ferritin synthesis by iron. Proc Natl Acad Sci USA 1976; 76: 857–61.

Rogers J Munro HN. Translation of ferritin light and heavy subunit mRNAs is regulated by intracellular chelatable iron levels in rat hepatoma cells. Proc Natl Acad Sci USA 1987; 84: 2277–81.

Worwood M Cragg SJ Williams AM Wagner N Jacobs A. The clearance of ¹³¹I-human ferritin in man. Blood 1982; 60: 827–33.

Cragg SJ Covell AM Burch A Owen GM Jacobs A Worwood M. Turnover of ¹³¹I-human spleen ferritin in plasma. Br J Haematol 1983; 55: 83–92.

Ward RJ O'Connell MJ Mann S Wade V Dickson DPE Reid N Heterogeneity of iron cores in hepatic haemosiderins from primary and secondary haemochromatosis. Biochem Soc Trans 1988; 16: 830–1.

O'Connell MJ Ward RJ Baum H Treffry A Peters TJ. Evidence of a biosynthetic link between ferritin and haemosiderins. Biochem Soc Trans 1988; 16: 828–9.

Weir MP Gibson JF Peters TJ. Haemosiderin and tissue damage. Cell Biochem Func 1984; 2: 186–94.

O'Connell MJ Peters TJ. Ferritin and haemosiderin in free radical generation, lipid peroxidation and protein damage. Chem Phys Lipids 1987; 45: 241–9.

Pippard MJ Johnson DK Finch CA. Hepatocyte iron kinetics in the rat explored with an iron chelator. Br J Haematol 1982; 52: 211–24.

Bassett ML Halliday JW Powell LW. Value of hepatic iron measurements in early hemochromatosis and determination of the critical iron level associated with fibrosis. Hepatology 1986; 6: 24–9.

Bacon BR Britton RS. The pathology of hepatic iron overload: A free radical mediated process? Hepatology 1990; 11: 127–37.

Seymour CA Peters TJ. Organelle pathology in primary and secondary haemochromatosis with special reference to lysosomal changes. Br J Haematol 1978; 40: 239–53.

Myers BM Prendergast FG Holman R Kunty SM La Russo NF Alterations in the structure, physicochemical properties and pH of hepatocyte lysosomes in experimental iron overload. J Clin Invest 1991; 88: 1207–15.

Britton RS Ramm GA Olynyk J Singh R O'Neill R Bacon BR. Pathophysiology of iron toxicity. In: Hershko C Konijn AM Aisen P , eds. Progress in Iron Research. New York: Plenum Press, 1994: 239–53.

Bothwell TH Charlton RW. A general approach to the problems of iron deficiency and iron overload in the population at large. Semin Hematol 1982; 19: 54–67.

Cook JD Skikne BS Lynch SR Reusser ME. Estimates of iron sufficiency in the US population. Blood 1986; 68: 726–31.

Cook JD Skikne BS. Iron deficiency: definition and diagnosis. J Int Med. 1989; 226: 349–55.

Cook JD Lynch SR. The liabilities of iron deficiency. Blood 1986; 68: 803–9.

Cartier L-J Ohira Y Chen M Cuddihee RW Holloszy JO. Perturbation of mitochondrial composition in muscle by iron deficiency. J Biol Chem 1986; 261: 13827–32.

Rowland TW Deisroth MB Green GM Kelleher JF. The effect of iron therapy on the exercise capacity of nonanaemic iron-deficient adolescent runners. Am J Dis Child 1988; 142: 165–9.

Finch CA Miller LR Inamdar AR Person R Seiler K Mackler B. Iron deficiency in the rat. Physiological and biochemical studies of muscle dysfunction. J Clin Invest 1976; 58: 447–53.

Lozoff B Brittenham GM. Behavioural alterations in iron deficiency. Hematol Oncol Clin North Am 1987; 1: 449–64.

Aukett MA Parks YA Scott PH Wharton BA. Treatment with iron increases weight gain and psychomotor development. Arch Dis Child 1986; 61: 849–57.

Soemantri AG Pollitt E Kim I. Iron deficiency anaemia and educational achievement. Am J Clin Nutr 1985; 42: 1221–8.

Beard J. Feed efficiency and norepinephrine turnover in iron deficiency. Proc Soc Exp Biol Med. 1987; 184: 337–44.

Dallman PR. Iron deficiency and the immune response. Am J Clin Nutr 1987; 46: 329–34.

Walter T Arredondo S Arevalo M Stekel A. Effect of iron therapy on phagocytosis and bactericidal activity in neutrophils of iron-deficient infants. Am J Clin Nutr 1986; 44: 877–82.

Goepel E Ulmer RD Neth RD. Premature labour contractions and the value of serum ferritin during pregnancy. Gynecol Obstet Invest 1988; 26: 265–73.

Lieberman E Ryan KJ Monson RR Schoenbaum SC. Association of maternal haematocrit with premature labor. Am J Obstet Gynecol 1988; 159: 107–14.

Hallberg L. Iron nutrition and food iron fortification. Semin Hematol 1982; 19: 31–41.

Moyo VM Mandishona E Hasstedt SJ Gangaidzo IT Gomo ZAR Khumalo H Evidence of genetic transmission in African iron overload. Blood 1998; 91: 1076–82.

Worwood M. Genetics of haemochromatosis. Baillière's Clin Haematol 1994; 7: 903–18.

Menahem S Salmon AP Dennett X. Hemochromatosis presenting as severe cardiac failure in a young adolescent. Int J Cardiol 1990; 29: 86–9.

Knisely AS. Iron and pediatric liver disease. Semin Liver Dis. 1994; 14: 229–35.

Sheldon JH. Haemochromatosis. Oxford: Oxford University Press, 1935.

Powell LW Summers KM Board PC Axelsen E Webb S Halliday JW. Expression of haemochromatosis in homozygous subjects: implications for early diagnosis and prevention. Gastroenterology 1990; 98: 1625–32.

Niederau C Strohmeyer G Stremmel W. Epidemiology, clinical spectrum and prognosis of hemochromatosis. In: Hershko C Konijn AM Aisen P , eds. Progress in Iron Research. New York: Plenum Press, 1994: 293–302.

Niederau C Fischer R Sonnenberg A Stremmel W Trampisch HJ Strohmeyer G. Survival and causes of death in cirrhotic and noncirrhotic patients with primary hemochromatosis. N Engl J Med. 1985; 313: 1256–8.

MacDonald RA. Hemochromatosis and hemosiderosis: study of 211 autopsied cases. Arch Int Med. 1960; 105: 686–700.

Simon M. Secondary iron overload and the haemochromatosis allele. Br J Haematol 1985; 60: 1–5.

Iron: Nutritional and Physiological Significance. Report of the British Nutrition Foundation's Task Force, 1995. London: Chapman & Hall, 1995.

Tietz NW Rinker AD Morrison SR. When is a serum iron really a serum iron? The status of serum iron measurements. Clin Chem 1994; 40: 546–51.

Sherwood RA. Iron and haemoglobins: determination in biological samples. In: Encyclopaedia of Analytical Science. London: Academic Press, 1995: Vol 4; 2382–8.

Iron Panel of the International Committee for Standardization in Haematology Revised recommendations for the measurements of serum iron in human blood. Br J Haematol 1990; 75: 615–6.

Wiams FH Plickert NJ Heald JI. The modified ‘ACA’ method for serum iron quantification eliminates desferrioxamine interference. Clin Chem 1988; 34: 1513–4.

McIntosh M Lynn J Meyerricks N Constant I. Serum iron determination in patients receiving therapy with iron chelation (‘Imferon’). Clin Chem 1976; 22: 524–7.

Jacobs JC Alexander NM. Colorimetry and constant-potential colorimetry determinations of transferrin-bound iron, total iron-binding capacity and total iron in serum containing iron-dextran. with use of sodium dithionite and alumina columns. Clin Chem 1990; 36: 1803–7.

Worwood M. The laboratory assessment of iron status—an update. Clin Chim Acta 1997; 259: 3–23.

MacGillivray RTA Mendez E Shewal JG Sinha SK Lineback-Zins J Brew K. The primary structure of human transferrin. The structures of seven cyanogen bromide fragments and the assembly of the complete structure. J Biol Chem 1983; 258: 3543–53.

Park I Schaeffer E Sidoli A Baralle FE Cohen GN Zakin MM. Organization of the human transferrin gene: direct evidence that it originated by gene duplication. Proc Natl Acad Sci USA 1985; 82: 3149–53.

Morton AG Tavill AS. The role of iron in the regulation of hepatic transferrin synthesis. Br J Haematol 1977; 36: 383–94.

Huebers HA Huebers E Csiba E Rummel W Finch CA. The significance of transferrin for intestinal iron transport. Blood 1983; 61: 283–90.

Beilby J Olynyk J Ching S Prins A Swanson N Reed W Transferrin index: An alternative method for calculating the iron saturation of transferrin. Clin Chem 1992; 38: 2078–81.

Cook JD Lipschitz DA Miles CEM Finch CA. Serum ferritin as a marker of iron stores in normal subjects. Am J Clin Nutr 1974; 27: 681–7.

Addison GM Beamish MR Hales CN Hodgkins M Jacobs AD Llewellin P. An immunoradiometric assay for ferritin in the serum of normal subjects and patients with iron deficiency and iron overload. J Clin Path 1972; 25: 326–9.

Jacobs A Miller F Worwood M Beamish MR Wardrop CA. Ferritin in the scrum of normal subjects and patients with iron deficiency and iron overload. BMJ 1972; 4: 206–8.

Worwood M. Serum ferritin. Clin Sci. 1986; 70: 215–20.

Saarinen UM Siimes MA. Serum ferritin in assessment of iron nutrition in healthy infants. Acta Paediatr Scand 1978; 67: 741–51.

Bentley DP. Iron metabolism and anaemia in pregnancy. Clin Haematol 1985; 14: 613–28.

Witte DL. Can scrum ferritin be effectively interpreted in the presence of the acute-phase response. Clin Chem 1991; 37: 484–5.

Lipschitz DA Cook JD Finch CA. A clinical evaluation of serum ferritin as an index of iron stores. N Engl J Med. 1974; 290: 1213–6.

Milder MS Cook JD Stray S Finch C.A. Idiopathic haemochromatosis, an interim report. Medicine (Baltimore) 1980; 59: 34–49.

Kohgo Y Nishisato T Kondo H Tsushima N Niitsu Y Urushizaki I. Circulating transferrin receptor in human serum. Br J Haematol 1986; 64: 277–81.

Flowers CH Skikne BS Covell AM Cook JD. The clinical measurement of scrum transferrin receptor. J Lab Clin Med. 1989; 114: 368–77.

Huebers HA Beguin Y Pootrakul P Einspahr D Finch CA. Intact transferrin receptors in human plasma and their relation to erythropoiesis. Blood 1990; 75: 102–7.

Shih YJ Baynes RD Hudson BG Flowers CH Skikne BS Cook JD. Serum transferrin receptor is a truncated form of tissue receptor. J Biol Chem 1990; 265: 19077–81.

Cook JD Skikne BS Baynes RD. Scrum transferrin receptor. Ann Rev Med. 1993; 44: 63–74.

Baynes RD. Assessment of iron status. Clin Biochem 1996; 29: 209–15.

Skikne BS Flowers CH Cook JD. Serum transferrin receptor. A quantitative measure of tissue iron deficiency. Blood 1990; 75: 1870–6.

Carriaga MT Skikne BS Finley B Cutler B Cook JD. Serum transferrin receptor for the detection of iron deficiency in pregnancy. Am J Clin Nutr 1991; 54: 1077–81.

Klemow D Einsphar D Brown T Flowers CH Skikne BS. Serum transferrin receptor measurements in hematologic malignancies. Am J Hematol 1990; 34: 193–8.

Kohgo Y Niitsu Y Kondo H Kato J Tsushima N Sasaki K Serum transferrin receptor as a new index of erythropoiesis. Blood 1987; 70: 1955–8.

Kuiper-Kramer EPA Huisman CMS van Raan J van Eijk HG. Analytical and clinical implications of soluble transferrin receptor in serum. Eur J Clin Chem Clin Biochem 1996; 34: 645–9.

Colton C Geraci K Tahsildar H Serum transferrin receptor/ferritin ratio is a reliable predictor of iron deficiency anaemia in inflammatory bowel disease patients. Am J Gastroenterol 1995; 108: A800.

Simmons WK Cook JD Bingham KC Thomas M Jackson J Jackson M Evaluation of a gastric delivery system for iron supplementation in pregnancy. Am J Clin Nutr 1993; 58: 622–6.

Labbe RF Rettmer RL. Zinc protoporphyrin: a product of iron-deficient erythropoiesis. Semin Hematol 1989; 26: 40–6.

Yip R. Changes in iron metabolism with age. In: Brock JH Halliday JW Pippard MJ Powell LW , eds. Iron Metabolism in Health and Disease. London: W. B. Saunders, 1994: 427–8.

Garrett S Worwood M. Zinc protoporphyrin and iron deficient erythropoiesis. Acta Haematol 1994; 91: 21–5.

Wong SS Qutishat AS Lange J Gornet TG Buja LM. Detection of iron-deficiency anemia in hospitalized patients by zinc protoporphyrin. Clin Chim Acta 1996; 244: 91–101.

Hastka J Lasserre J-J Schwarzbeck A Reiter A Hehlmann R. Laboratory tests of iron status: correlations or common sense? Clin Chem 1996; 42: 718–24.

Cazzola M Huebers HA Sayers MH MacPhail AP Eng M Finch CA. Transferrin saturation, plasma iron turnover, and transferrin uptake in normal humans. Blood 1985; 66: 935–9.

Cook JD Marsaglia G Eschbach JW Funk DD Finch CA. Ferrokinetics: a biologic model for plasma iron exchange in man. J Clin Invest 1970; 49: 197–205.

Cazzola M Pootrakul P Huebers HA Eng M Eschbach J Finch CA. Erythroid marrow function in anaemic patients. Blood 1987; 69: 296–301.

Peters TJ Duane P Raja K. Use of liver volume determination in the assessment of iron overload in patients with haemochromatosis. Eur J Gastroenterol Hepatol 1991; 3: 137–41.

Raja KB Duane P Snape SD Simpson RJ Papasavvas G Peters TJ. In vitro duodenal iron uptake and serum and mucosal iron protein levels, with special reference to rheumatoid arthritis. Br J Rheumatol 1995; 34: 1041–7.

Konijn AM Hershko C. Ferritin synthesis in inflammation I. Pathogenesis of impaired iron release. Br J Haematol 1977; 37: 7–16.

Goldblum SE Cohen DA Jay M McClain CJ. Interleukin 1 induced depression of iron and zinc: role of granulocytes and lactoferrin. Am J Physiol 1987; 252: E27–32.

Hastka J Lasserre J-J Schwarzbeck A Strauch M Hehlmann R. Zinc protoporphyrin in anemia of chronic disorders. Blood 1993; 81: 1200–4.

Ferguson BJ Skikne BS Simpson KM Baynes RD Cook JD. Serum transferrin receptor distinguishes the anaemia of chronic disease from iron deficiency anaemia. J Lab Clin Med. 1992; 119: 385–90.

Burns ER Goldberg SN Lawrence C Wenz B. Clinical utility of serum tests for iron deficiency in hospitalized patients. Am J Clin Pathol 1990; 93: 240–5.

Pettersson T Kivivuori SM Siimes MA. Is serum transferrin receptor useful for detecting iron-deficiency in anaemic patients with chronic inflammatory diseases? Br J Rheumatol 1994; 33: 740–4.

Simon M Bourel M Fauchet R Genetet B. Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis. Gut 1976; 17: 332–4.

Campbell RD Trowsdale J. Map of the human MHC. Immunol Today 1993; 14: 349–52.

Jazwinska EC Lee SC Webb SI Halliday JW Powell L. Localisation of the hemochromatosis gene close to D6S105. Am J Hum Genet 1993; 53: 347–52.

Worwood M Raha-Chowdhury R Dorak MT Darke C Bowen DJ Burnett AK. Alleles at D6S265 and D6S105 define a haemochromatosis-specific genotype. Br J Haematol 1994; 86: 863–6.

Raha-Chowdhury R Bowen DJ Stone C Pointon JJ Terwilliger JD Shearman JD New polymorphic microsatellite markers place the haemochromatosis gene telometric to D6S105. Human Mol Genet 1995; 4: 1869–74.

Feder JN Gnirke A Thomas W Tsuchihashi Z Ruddy DA Basava A A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature Genet 1996; 13: 399–408.

Roberts AG Whatley SD Morgan RR Worwood M Elder GH. Increased frequency of the haemochromatosis Cys 282 Tyr mutation in sporadic porphyria cutanea tarda. Lancet 1997; 349: 321–3.