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A REVIEW

Zinc and Immunity

Implications for Growth, Survival and Function of Lymphoid Cells

Pages 39-101 | Published online: 22 Oct 2008

References

  • Todd , W. R. , Elvejheim , C. A. and Hart , E. B. 1934 . Zinc in the nutrition of the rat . Am. J. Physiol. , 107 : 146 – 156 .
  • Prasad , A. S. 1991 . Discovery of human zinc deficiency and studies in an experimental human model . Am. J. Clin. Nutr. , 53 : 403 – 412 .
  • Kay , R. G. and Tasman-Jones , C. 1975 . Acute zinc deficiency in man during intravenous alimentation . Aust. N. Z. J. of Surg. , 45 : 325 – 30 .
  • Fraker , P. J. , Haas , S. M. and Luecke , R. W. 1977 . Effect of zinc deficiency on the immune response of young adult A/J mice . J. Nutr. , 107 : 1889 – 1895 .
  • Frost , P. , Chen , J. C. , Rabbani , I. , Smith , J. and Prasad , A. S. 1977 . “ The effect of Zn deficiency on the immune response ” . In Zinc Metabolism: Current Aspects in Health and Disease , 143 – 153 . NY Alan R Liss Inc .
  • Luecke , R. W. , Simonel , C. E. and Fraker , P. J. 1978 . The effect of restricted dietary intake on the antibody mediated response of the zinc deficient A/J mouse . J. Nutr. , 108 : 881 – 887 .
  • Fernades , G. , Nair , M. , Onoe , K. , Tanaka , T. , Floyd , R. and Good , R. A. 1979 . Impairment of cell mediated immunity functions by dietary Zn deficiency in mice . Proc. Natl. Acad. Sci. U. S. A. , 76 : 457 – 461 .
  • Oleske , J. M. , Westphal , M. L. , Shore , S. , Gorden , D. , Bogden , J. D. and Nahmias , A. 1979 . Zinc therapy of depressed cellular immunity in acrodermatitis enteropathica . Am. J. Dis. Child. , 133 : 915 – 918 .
  • Good , R. A. 1981 . Nutrition and Immunity . J. Clin. Immunol. , 1 : 3 – 11 .
  • Bach , J. F. 1981 . The multi-faceted zinc dependency of the immune system . Immunol Today. , 2 : 225 – 227 .
  • Prasad , A. S. , Meftah , S. , Abdallah , J. , Kaplan , J. , Brewer , G. J. , Bach , J. F. and Dardenne , M. 1988 . Serum thymulin in human zinc deficiency . J. Clin. Invest. , 82 : 1202 – 1210 .
  • Moulder , K. and Steward , M. W. 1989 . Experimental zinc deficiency: effects on cellular responses and the unity of humoral antibody . Clin. Exp. Immunol. , 77 : 269 – 274 .
  • Williams , R. B. and Mills , C. F. 1970 . The experimental production of zinc deficiency in the rat . Br. J. Nutr. , 24 : 989 – 1003 .
  • Gershwin , M. E. , Lentz , D. R. , Beach , R. S. and Hurley , L. S. 1984 . Nutritional factors and autoimmunity. IV. Dietary vitamin A deprivation induces a selective increase in IgM autoantibodies and hypergammaglobulinemia in New Zealand Black mice . J. Immunol. , 133 : 222 – 226 .
  • Williams , R. J. P. 1984 . Zinc: what is its role in biology? . Endeavour, New Series , 8 : 65 – 70 .
  • Coleman , J. E. 1992 . Zinc proteins: enzymes, storage proteins, transcription factors and replication proteins . Ann. Rev. Biochem. , 61 : 897 – 946 .
  • Phillips , J. L. and Azari , P. 1974 . Zinc transferrin. Enhancement of nucleic acid synthesis in phytohemagglutinin-stimulated human lymphocytes . Cell. Immunol. , 10 : 31 – 37 .
  • Blazsek , I. and Mathe , G. 1984 . Zinc and immunity . Biomed. Pharma-cother. , 38 : 187 – 193 .
  • Cousins , R. J. 1985 . Absorption, transport, and hepatic metabolism of copper and zinc: special reference to metallothionein and ceruloplasmin . Physiol. Rev. , 65 : 238 – 309 .
  • Ackland , M. L. and McArdle , H. J. 1990 . Significance of extracellular zinc-binding ligands in the uptake of zinc by human fibroblasts . J. Cell. Physiol. , 145 : 409 – 413 .
  • Kalfakakou , V. and Simons , T. J. B. 1990 . Anionic mechanisms of zinc uptake across the human red cell membrane . J. Physiol. , 421 : 485 – 497 .
  • Cousins , R. J. and Lee-Ambrose , L. M. 1992 . Nuclear zinc uptake and interactions and metallothionein gene expression are influenced by dietary zinc in rats . J. Nutr. , 122 : 56 – 64 .
  • Zalewski , P. D. , Forbes , I. J. and Betts , W. H. 1993 . Correlation of apopto-sis with change in intracellular labile Zn, using Zinquin, a new specific fluorescent probe for Zn . Biochem. J. , 296 : 403 – 408 .
  • Zalewski , P. D. , Forbes , I. J. , Seamark , R. F. , Borlinghaus , R. , Betts , W. H. , Lincoln , S. F. and Ward , A. D. 1994 . Flux of intracellular labile zinc during apop-tosis (gene-directed cell death) by a specific chemical probe, Zinquin . Chemise & Biology , 1 : 153 – 161 .
  • Cheek , D. B. , Hay , H. J. , Lattanzio , L. , Ness , D. , Ludwigsen , N. and Spargo , R. 1984 . Zinc content of red and white blood cells in aboriginal children . Aust. N. Z. J. Med. , 14 : 638 – 642 .
  • Prasad , L. H. and Prasad , A. S. 1988 . Cellular zinc in patients with diabetes melli-tus . Nutr. Res. , 8 : 889 – 897 .
  • Prasad , A. S. , Rabbani , P. , Abbasii , A. , Bowersox , E. and Fox , M. R. S. 1978 . Experimental zinc deficiency in humans . Ann. Int. Med. , 89 : 483 – 490 .
  • Kanter , R. J. , Rai , K. R. , Muniz , F. , Michael , B. , Balkon , J. and Sawitsky , A. 1982 . Intracellular zinc in chronic lymphocytic leukemia . Clin. Immunol. Immu-nopathol. , 24 : 26 – 32 .
  • Rosner , F. and Gorfien , P. C. 1968 . Erythrocyte and plasma zinc and magnesium levels in health and disease . J. lab. Clin. Med. , 72 : 213 – 219 .
  • Sandstead , H. H. 1994 . Understanding zinc: Recent observations and interpretations . J. Lab. Clin. Med. , 124 : 322 – 327 .
  • Barnes , P. M. and Moynahan , E. J. 1973 . Zinc deficiency in acrodermatitis enteropathica: multiple dietary intolerance treated with synthetic diet . Proc. Roy. Soc. Med. , 66 : 327 – 329 .
  • Neldner , K. H. and Hambidge , K. M. 1975 . Zinc therapy of acrodermatitis enteropathica . New Eng. J Med. , 292 : 879 – 882 .
  • Solomons , N. W. 1988 . “ Zinc and copper ” . In Modem Nutrition in Health and Disease, , 7th Edition , Edited by: Shils , M. E. and Young , V. R. 238 – 262 . Philadelphia : Lea and Febiger .
  • Udomkesmalee , E. , Dhanamitta , S. , Sirisinha , S. , Charoenkiatkul , S. , Tuntipopipat , S. , Banjong , O. , Rojroongwasinkul , N. , Kramer , T. R. and Smith , J. C. 1992 . Effect of vitamin A and zinc supplementation on the nutriture of children in Northeast Thailand . Am. J. Clin. Nutr. , 56 : 50 – 57 .
  • Xue-Cun , C. , Tai-An , Y. , Jin-Sheng , H. , Qiu-Yan , M. , Zhi-Min , H. and Li-Xiang , L. 1985 . Low levels of zinc in hair and blood, pica, anorexia, and poor growth in Chinese preschool children . Am. J. Clin. Nutr. , 42 : 694 – 700 .
  • Prasad , A. S. , Fitzgerald , J. T. , Hess , J. W. , Kaplan , J. , Pelen , F. and Dardenne , M. 1993 . Zinc deficiency in elderly patients . Nutrition , 9 : 218 – 224 .
  • Clegg , M. S. , Keen , C. L. and Hurley , L. S. 1989 . “ Biochemical pathologies of zinc deficiency ” . In Zinc in Human Biology , Edited by: Mills , C. R. 129 – 145 . Springer-Verlag .
  • Moynahan , E. 1975 . Zinc deficiency and cellular immune deficiency in acrodermatitis enteropathica in man and zinc deficiency with thymic hypoplasia in fresian calves: a possible genetic link . Lancet , ii : 710
  • Perryman , L. E. 1982 . Mechanisms of immune deficiency diseases of animals . J. Am. Vet. Med. Assoc. , 181 : 1097 – 101 .
  • Pekarek , R. S. , Hoagland , A. M. and Powanda , M. C. 1977 . Humoral and cellular immune responses in zinc-deficient rats . Nutr. Rep. Int. , 16 : 267 – 276 .
  • Feiler , L. S. , Smolin , G. , Okumoto , M. and Condon , D. 1982 . Herpetic keratitis in zinc deficient rabbits . Invest. Ophthalmol. Visual Sci. , 22 : 788 – 795 .
  • Fraker , P. J. , Caruso , R. and Kierszenbaum , F. 1982 . Alteration in the immune and nutritional status of mice by synergy between Zn deficiency and infection with Typanosoma cruzi . J. Nutr. , 112 : 1224 – 1229 .
  • Lee , C. M. , Humphrey , P. A. and Aboko-Cole , G. F. 1983 . Interaction of nutrition and infection: effect of zinc deficiency on resistance to Trypanosoma musculi . Int. J. Biochem. , 15 : 841 – 847 .
  • Salvin , S. B. , Horecker , B. L. , Pa , L-X and Rabin , B. S. 1987 . The effect of dietary zinc and prothymosin a on cellular immune responses of RF/J mice C . Lin Immunol Immunopathol , 43 : 281 – 288 .
  • Keen , C. L. and Gershwin , M. E. 1990 . Zinc deficiency and immune function . Ann. Rev. Nutr. , 10 : 415 – 431 .
  • Nawar , O. , Akridge , R. E. , Hassan , E. , el-Gazar , R. , Doughty , B. L. and Kemp , W. M. 1992 . The effect of zinc deficiency on granuloma formation, liver fibrosis, and antibody responses in experimental schistosomiasis . Am. J. Trop. Med. Hyg. , 47 : 383 – 389 .
  • Good , R. A. 1989 . “ A note on zinc and immunocompetence ” . In Zinc in Human Biology , Edited by: Mills , C. F. 221 – 223 . Springer-Verlag .
  • Hambridge , K. M. , Walravens , P. A. and Neldner , K. H. 1977 . “ The role of zinc in the pathogenesis and treatment of acrodermatitis enteropathica ” . In Zinc Metabolism Current Aspects in Health and Disease Edited by: Brewer , G. J. and Prasad , A. S. 329 – 340 . Liss, NY
  • Aggett , P. J. 1989 . “ Severe zinc deficiency ” . In Zinc in Human Biology , Edited by: Mills , C. R. 259 – 279 . Springer-Verlag .
  • Singh , K. P. , Zaidi , S. I. , Raisuddin , S. , Saxena , A. K. , Murthy , R. C. and Ray , P. K. 1992 . Effect of zinc on immune functions and host resistance against infection and tumor challenge . Immunopharmacol. Immunotoxicol. , 14 : 813 – 840 .
  • Eby , G. A. , Davis , D. R. and Halcomb , W. W. 1984 . Reduction in duration of common colds by zinc gluconate lozenges in a double blind study . Antimicrob. Agents Chemother. , 25 : 20 – 24 .
  • Brody , I. 1977 . Treatment of recurrent furunculosis with oral zinc . Lancet , ii : 1358
  • Fair , W. R. and Heston , W. D. W. 1977 . “ The relationship of bacterial pros-tatitis and zinc ” . In Zinc Metabolism Current Aspects in Health and Disease Edited by: Brewer , G. J. and Prasad , A. S. 129 – 140 . Liss, NY
  • Sugarma , B. , Epps , L. R. and Stenback , W. A. 1982 . Zinc and bacterial adherence . Infect. Immun. , 37 : 1191 – 1199 .
  • Raulin , J. 1869 . Etudes cliniques sur la vegetation . Ann. Sci. Nat. Bot. Biol. Veg. , 11 : 93 – 299 .
  • Bess , J. W. , Powell , P. J. , Issaq , H. J. , Schumack , L. J. , Grimes , M. K. , Henderson , L. E. and Arthur , L. O. 1992 . Tightly bound zinc in human immunodeficiency virus type I, human T cell leukaemia virus type I and other retroviruses . J. Virol. , 66 : 840 – 847 .
  • Fraker , P. J. , Gershwin , M. E. , Good , R. A. and Prasad , A. 1986 . Interrelationships between zinc and immune function . FedProc. , 45 : 1474 – 1479 .
  • Good , R. A. , Lorenz , E. , Engelman , R. and Day , N. K. 1990 . Experimental approaches to nutrition and cancer: fats, calories, vitamins and minerals . Med. Oncol. Tumor Pharmacother. , 7 : 183 – 192 .
  • Shelley , W. B. 1982 . Malignant melanoma and dermatofibrosarcoma in a 60-year-old patient with lifelong acrodermatitis enteropathica . J. Am. Acad Der-matol. , 6 : 63 – 66 .
  • Fong , L. Y. , Sivak , A. and Newberne , P. M. 1978 . Zinc deficiency and me-thylbenzylnitrosamine-induced esophageal cancer in rats . J. Natl. Cancer. Inst. , 61 : 145 – 150 .
  • Kasprzak , K. S. and Waalkes , M. P. 1986 . The role of calcium, magnesium, and zinc in carcinogenesis . Adv. Exp. Med. Biol. , 206 : 497 – 515 .
  • Stocks , P. and Davies , R. I. 1964 . Zinc and copper content of soils associated with incidence of cancer of the stomach and other organs . Br. J. Cancer , 18 : 14 – 24 .
  • McGlashan , N. D. 1967 . Zinc and oesophageal cancer . Lancet , i : 578
  • Poswillo , D. E. and Cohen , B. 1971 . Inhibition of carcinogenesis by dietary zinc . Nature , 231 : 447 – 448 .
  • Song , M. K. , Heng , M. C. , Rolandelli , R. , Ament , M. E. and Heng , M. K. 1993 . Possible link between zinc intake and colon cancer . J. Natl. Cancer Inst. , 85 : 667 – 66 .
  • Hadden , J. W. , Endicott , J. , Baekey , P. , Skipper , P. and Hadden , E. M. 1994 . Interleukins and contrasuppression induce immune regression of head and neck cancer . Arch. Otolaryngol Head Neck Surg. , 120 : 395 – 403 .
  • McQuitty , J. T. , DeWys , W. D. , Monaco , L. , Strain , W. H. , Rob , C. G. , Apgar , J. and Pories , W. J. 1970 . Inhibition of tumour growth by dietary zinc deficiency . Cancer Res. , 30 : 1387 – 1390 .
  • DeWys , W. D. and Pories , W. J. 1972 . Inhibition of a spectrum of human tumours by dietary zinc deficiency . J. Nat. Cancer Inst. , 48 : 375 – 381 .
  • Beach , R. S. , Gershwin , M. E. and Hurley , L S . 1981 . Dietary zinc modulation of moloney sarcoma virus oncogenesis . Cancer Res. , 41 : 552 – 559 .
  • Perkins , D. M. and Duncan , J. R. 1991 . The effect of ?-linolenic acid and zinc supplementation on the growth of normal and tumour cells in vitro . Prosta-glandins. Leukot Essent. Fatty Acids , 43 : 43 – 48 .
  • Falchuk , K. H. and Krishan , A. 1977 . 1, 10-Phenanthroline inhibition of lymphoblast cell cycle . Cancer Res. , 37 : 2050 – 2056 .
  • Allen , J. I. , Perri , R. T. , McClain , C. J. and Kay , N. E. 1983 . Alterations in human natural killer cell activity and monocyte cytotoxicity induced by zinc deficiency . J. Lab. Clin. Med. , 102 : 577 – 58 .
  • Chandra , R. K. and Au , B. 1980 . Single nutrient deficiency and cell mediated immune responses . Am. J. Clin. Nutr. , 33 : 736 – 738 .
  • Weston , W. L. , Huff , J. C. , Humbert , J. R. , Hambridge , K. N. , Neldner , K. H. and Walravens , P. A. 1977 . Zinc correction of defective chemotaxis in acrodermatitis enteropathica . Arc. Dermatol. , 13 : 422 – 425 .
  • Briggs , W. A. , Pedersen , M. , Mahajan , S. , Sillix , D. H. , Prasad , A. S. and McDonald , F. D. 1982 . Lymphocyte and granulocyte function in zinc treated and zinc deficient hemodialysis patients . Kidney Int. , 21 : 827 – 832 .
  • Singh , A. , Failla , M. L. and Deuster , P. A. 1994 . Exercise-induced changes in immune function: effects of zinc supplementation . J. Appl. Physiol. , 76 : 2298 – 2303 .
  • Miller , E. R. , Luecke , R. W. , Ullrey , D. E. , Baltzer , B. V. , Bradley , B. L. and Hoefer , J. A. 1968 . Biochemical, skeletal and allometric changes due to zinc deficiency in the baby pig . J. Nutr. , 95 : 278 – 286 .
  • Shanklin , S. H. , Miller , E. R. , Ullrey , D. E. , Hoefer , J. A. and Leucke , R. W. 1968 . Zinc requirement of baby pigs on casein diets . J. Nutr. , 96 : 101 – 108 .
  • Quarterman , J. 1974 . “ The effects of zinc deficiency or excess on the adrenals and the thymus in the rat ” . In Trace Element metabolism in Animals Vol 2 , Edited by: Hoekstra , W. G. , Suttie , J. W. , Gather , H. E. and Mentz , W. 742 – 748 . Baltimore : University Park Press .
  • His , S. , Fraker , P. J. and Luecke , R. W. 1976 . The effect of zinc deficiency on the immune response of A/J mice . Fed Proc. , 35 : 659
  • Fraker , P. J. , DePasquale-Jardieu , P. , Zwickl , C. M. and Luecke , R. W. 1978 . Regeneration of T-cell helper function in zinc-deficient adult mice . Proc. Natl. Acad. Sci. U. S. A. , 75 : 5660 – 5664 .
  • Beach , R. S. , Gershwin , M. E. and Hurley , L. S. 1979 . Altered thymic structure and mitogen responsiveness in postnatally zinc-deprived mice . Developmental and Comp Immunology , 3 : 725 – 738 .
  • Brummerstedt , E. , Flagstad , T. , Basse , A. and Anderson , E. 1971 . The effect of zinc on calves with hereditary thymic hypoplasia (lethal trait A 46) . Acta Pathol. Microbiol. Scand. , 79 : 686 – 687 .
  • Brummerstedt , E. 1977 . Animal model of human disease. Acrodermatitis enteropathica, zinc malabsorption . Am. J. Pathol. , 87 : 725 – 8 .
  • Julius , R. , Schilkind , M. , Sprinkle , T. and Rennert , O. 1973 . Acrodermati-tis enteropathica with immune deficiency . J. Pediat. , 83 : 1007 – 1011 .
  • Moynahan , E. J. 1974 . Acrodermatitis enteropathica: a lethal inherited human zinc-deficiency disorder . Lancet , ii : 399 – 400 .
  • Golden , M. H. N. , Jackson , A. A. and Golden , B. E. 1977 . Effect of zinc on thymus of recently malnourished children . Lancet , ii : 1057 – 1059 .
  • Golden , M. H. N. , Golden , B. E. , Harland , P. S. E. G. and Jackson , A. A. 1978 . Zinc and immunocompetence in protein-energy malnutrition . Lancet , i : 1226 – 1228 .
  • Fraker , P. J. , King , L. E. , Garvy , B. A. and Medina , C. A. 1993 . “ The immu-nopathology of zinc deficiency in humans and rodents A possible role for programmed cell death ” . In Human Nutrition A Comprehensive Treatise Vol 8: Nutrition and Immunology , Edited by: Klurfeld , D. M. 267 – 283 . Plenum Press NY .
  • Fraker , P. J. , Osatiashtiani , F. , Wagner , M. A. and King , L. E. 1995 . Possible roles for glucocorticoids and apoptosis in the suppression of lymphopoiesis during zinc deficiency: A review . J. Am. College Nutr. , 14 : 11 – 17 .
  • McMurray , D. N. , Bartow , R. A. , Mintzer , C. L. and Hernandez-Frontera , E. 1990 . Micronutrient status and immune function in tuberculosis . Ann. NY Acad. Sci. , 587 : 59 – 69 .
  • King , L. E. and Fraker , P. J. 1991 . Flow cytometric analysis of the pheno-typic distribution of splenic lymphocytes in zinc-deficient adult mice . J. Nutr. , 121 : 1433 – 1438 .
  • Pekarek , R. S. , Sandstead , H. H. , Jacob , R. A. and Barcome , D. F. 1979 . Abnormal cellular immune responses during acquired zinc deficiency . Am. J. Clin. Nutr. , 32 : 1466 – 1471 .
  • Allen , J. I. , Kay , N. E. and McClain , C. J. 1981 . Severe zinc deficiency in humans: association with a reversible T-lymphocyte dysfunction . Ann. Int. Med. , 95 : 154 – 157 .
  • Nash , L. , Iwata , T. , Fernandes , G. , Good , R. A. and Incefy , G. S. 1979 . Effect of zinc deficiency on autologous rosette forming cells . Cell Immunol. , 48 : 238 – 243 .
  • Compton , M. M. and Cidlowski , J. A. 1992 . Thymocyte apoptosis. A model of programmed cell death . Trends Endocrinol Metab. , 3 : 17 – 23 .
  • Concordet , J. P. and Ferry , A. 1993 . Physiological programmed cell death in thymocytes is induced by physical stress (exercise) . Am. J. Physiol. , 265 : C626 – C629 .
  • Zhang , Y. H. , Takahashi , K. , Jiang , G. Z. , Kawai , M. , Fukada , M. and Yokochi , T. 1993 . In vivo Induction of Apoptosis (Programmed Cell Death) in Mouse Thymus by Administration of Lipopolysaccharide . Infection and Immunity , 61 : 5044 – 504 .
  • Quarterman , J. and Humphries , W. R. 1979 . Effect of zinc deficiency and zinc supplementation on adrenals, plasma steroids and thymus in rats . Life Sci. , 24 : 177 – 183 .
  • DePasquale-Jardieu , P. and Fraker , P. J. 1979 . The role of corticosterone in the loss of immune function in the zinc deficient A/J mice . J. Nutr. , 109 : 1847 – 1855 .
  • DePasquale-Jardieu , P. and Fraker , P. J. 1980 . Further characterization of the role of corticosterone in the loss of humoral immunity in zinc deficient A/J mice as determined by adrenalectomy . J. Immunol. , 124 : 2650 – 265 .
  • Garvy , B. A. , King , L. E. , Telford , W. G. , Morford , L. A. and Fraker , P. J. 1993 . Chronic elevation of plasma corticosterone causes reductions in the number of cycling cells of the B lineage in murine bone marrow and induces apopto-sis . Immunology , 80 : 587 – 592 .
  • Good , R. A. , Fernades , G. , Yunis , E. J. , Cooper , W. C. , Jose , D. C. , Kramer , T. R. and Hansen , M. A. 1976 . Nutritional deficiency, immunologic function, and disease . Am. J. Pathol. , 84 : 599 – 614 .
  • Cunningham-Rundles , C. , Cunningham-Rundles , S. , Iwata , T. , Incefy , G. , Garofalo-JA Menendez-Botet , C. , Lewis , V. , Twomey , J. J. and Good , R. A. 1981 . Zinc deficiency, depressed thymic hormones, and T lymphocyte dysfunction in patients with hypogammaglobulinemia . Clin. Immunol. Immunopathol. , 21 : 387 – 96 .
  • Dowd , P. S. , Kelleher , J. and Guillou , P. J. 1986 . T lymphocyte subsets and interleukin 2 production in zinc deficient rats . B r. J. Nutr. , 55 : 59 – 69 .
  • Williams , J. R. , Little , J. B. and Shipley , W. U. 1974 . Association of mammalian cell death with a specific endonucleolytic degradation of DNA . Nature , 252 : 754 – 755 .
  • Mendelsohn , J. , Dorian , R. , Castagnola and Bernheim , J. 1977 . “ Is there gene amplification or other nonduplicative DHA synthesis in human lymphocyte activation? ” . In Regulatory Mechanisms of Lymphocyte Activation , Edited by: Lucas , D. O. 467 – 469 . Academic Press NY .
  • Bell , D. A. and Morrison , B. 1991 . The spontaneous apoptotic cell death of normal hum: lymphocytes in vitro: the release of, and immunoproliferative response to, nucleosomes in vitro . Clin. Immunol.Immunopathol. , 60 : 13 – 26 .
  • Kramer , T. R. 1984 . Reevaluation of zinc deficiency on concanavalin-A-induced rat spleen lymphocyte proliferation . J. Nutr. , 114 : 953 – 963 .
  • Cook-Mills , J. M. and Fraker , P. J. 1993 . Functional capacity of the residual lymphocytes in zinc deficient mice . B r. J. Nutr. , 69 : 835 – 848 .
  • Gross , R. L. , Osdin , N. , Fong , L. and Newberne , P. M. 1979 . Depressed im-munological function in zinc-deprived rats as measured by mitogen response of spleen, thymus and peripheral blood . Am. J. Clin. Nutr. , 32 : 1260 – 1265 .
  • Fraker , P. J. and Zwickl , C. M. 1981 . Immune repair capacity of zinc deficient young adult and neonatal mice . Fed Proc. , 40 : 918
  • Gross , R. L. , Osdin , N. , Fong , L. and Newberne , P. M. 1979 . In vitro restoration by levamisole of mitogen responsiveness in zinc-deprived rats . Am. J. Clin. Nutr. , 32 : 1267 – 1271 .
  • Gol'dberg , E. D. , Eshchenko , V. A. , Bovt , V. D. and Tolok , A. Y. 1993 . Effect of immunosuppressives on the zinc content of cells . Bull. Exp. Biol. Med. , 116 : 1274 – 1275 .
  • Fraker , P. J. , Zwickl , C. M. and Luecke , R. W. 1982 . Delayed type hypersen-sitivity in zinc deficient adult mice: impairment and restoration of response to di-nitrofluorobenzene . J. Nutr. , 112 : 309 – 313 .
  • Schlesinger , L. , Arevalo , M. , Arredondo , S. , Diaz , M. , Lonnerdal , B. and Stekel , A. 1992 . Effect of a zinc-fortified formula on immunocompetence and growth of malnourished infants . Am. J. Clin. Nutr. , 56 : 491 – 498 .
  • Smith , D. K. 1989 . Topical zinc and delayed hypersensitivity responsiveness . Nutr. Clin. Pract. , 4 : 206 – 210 .
  • Fraker , P. J. , Hildebrandt , K. and Luecke , R. W. 1984 . Alteration of antibody-mediated responses of suckling mice to T-cell dependent and independent antigens by maternal marginal zinc deficiency: restoration of responsivity by nutritional repletion . J. Nutr. , 114 : 170 – 179 .
  • Kukral , H. W. , Kirchgessner , M. and Roth , H. P. 1988 . Effect of marginal zinc deficiency on humoral immunity in rats . Z. Ernahrungswiss , 27 : 126 – 136 .
  • DePasquale-Jardieu , P. and Fraker , P. J. 1984 . Interference in the development of a secondary immune response in mice by zinc deprivation: persistence of effects . J. Nutr. , 114 : 1762 – 1769 .
  • Fraker , P. J. 1983 . Zinc deficiency: a common immunodeficiency state . Surv. Immunol. Res. , 2 : 155 – 163 .
  • Wirth , J. J. , Fraker , P. J. and Kierszenbaum , F. 1989 . Zinc requirements for macrophage function: effect of zinc deficiency on uptake and killing of a protozoa parasite . Immunol. , 68 : 114 – 119 .
  • Wirth , J. J. , Fraker , P. J. and Kierszenbaum , F. 1984 . Changes in the level of marker expression by mononuclear phagocytes in zinc deficient mice . J. Nutr. , 114 : 1826 – 1833 .
  • Cook-Mills , J. M. , Wirth , J. J. and Fraker , P. J. 1990 . Possible roles for zinc in destruction of Trypanosoma cruzi by toxic oxygen metabolites produced by mononuclear phagocytes . Adv. Exp. Med. Biol. , 262 : 111 – 121 .
  • James , S. J. , Swendseid , M. and Makinodan , T. 1987 . Macrophage-me-diated depression of T-cell proliferation in zinc-deficient mice . J. Nutr. , 117 : 1982 – 1988 .
  • Beach , R. S. , Gershwin , M. E. and Hurley , L. S. 1982 . Gestational zinc deprivation in mice:persistence of immunodeficiency for three generations . Science , 218 : 469 – 471 .
  • Beach , R. S. , Gershwin , M. E. and Hurley , L. S. 1982 . Reversibility of developmental retardation following murine fetal zinc deprivation . J. Nutr. , 112 : 1169 – 1181 .
  • Beach , R. S. , Gershwin , M. E. and Hurley , L. S. 1983 . Persistent immuno-logical consequences of gestational zinc deprivation . Am. J. Clin. Nutr. , 38 : 579 – 590 .
  • Keller , P. R. and Fraker , P. J. 1986 . Gestational zinc requirement of the A/J mouse: effects of a marginal zinc deficiency on in utero B cell development . Nutr. Res. , 6 : 41 – 50 .
  • Vruwink , K. G. , Hurley , L. S. , Gershwin , M. E. and Keen , C. L. 1988 . Gestational zinc deficiency amplifies the regulation of metallothionein induction in adult mice . Proc. Soc. Exp. Biol. Med. , 188 : 30 – 34 .
  • Meadows , N. J. , Smith , M. F. , Keeling , P. W. N. , Ruse , W. , Day , J. , Scopes , J. W. , Thompson , R. P. H. and Bloxham , D. L. 1981 . Zinc and small babies . Lancet , ii : 1135 – 1137 .
  • Dutz , W. , Rossipal , E. , Ghavami , H. , Vessal , K. , Kohout , E. and Post , C. 1976 . Persistent cell mediated immune deficiency following infantile stress during the first six months of life . Eur. J. Pediatr. , 122 : 117 – 130 .
  • Ferguson , A. C. 1978 . Prolonged impairment of cellular immunity in children with intrauterine growth retardation . J. Pediatr. , 93 : 52 – 56 .
  • McFarlane , H. 1976 . Malnutrition and impaired immune response to infection . Proc. Nutr. Soc. , 35 : 263 – 272 .
  • Haynes , D. C. , Gershwin , M. E. , Golub , M. S. , Cheung , A. T. , Hurley , L. S. and Hendricks , A. G. 1985 . Studies of marginal zinc deprivation in rhesus monkeys: VI. Influence on the immunohematology of infants in the first year . Am. J. Clin. Nutr. , 42 : 252 – 62 .
  • Vallee , B. L. and Falchuk , K. H. 1993 . The biochemical basis of zinc physiology . Physiol. Rev. , 73 : 79 – 118 .
  • Zalewski , P. D. and Forbes , I. J. 1993 . “ Intracellular zinc and the regulation of apoptosis ” . In Programmed Cell Death: The Cellular And Molecular Biology Of Apoptosis , Edited by: Lavin , M. and Watters , D. 73 – 86 . Melbourne : Harwood Academic Publishers .
  • Coto , J. A. , Hadden , E. M. , Sauro , M. , Zorn , N. and Hadden , J. W. 1992 . Interleukin 1. regulates secretion of zinc-thymulin by human thymic epithelial cells and its action on T-lymphocyte proliferation and nuclear protein kinase C . Proc. Natl. Acad Sci. U. S. A. , 89 : 7752 – 7756 .
  • Iwata , T. , Incefy , G. S. , Tanaka , T. , Fernades , G. , Menendez-Botet , C. J. , Pih , K. and Good , R. A. 1979 . Circulating thymic hormone levels in zinc deficiency . Cell Immunol. , 47 : 100 – 105 .
  • Cunningham-Rundles , C. , Cunningham-Rundles , S. , Garofalo , J. , Iwata , T. , Incefy , G. , Twomey , J. and Good , R. A. 1979 . Increased T-lymphocyte function and thymopoietin following zinc repletion in man . Fed Proc. , 38 : 1222
  • Iwata , T. , Inceh , G. S. , Cunningham-Rundles , S. , Cunningham-Rundles , C. , Smithwich , E. , Geller , N. , O'Reilly , R. and Good , R. A. 1981 . Circulating thymic hormone activity in patients with primary and secondary immunodeficiency diseases . Am. J. Med. , 71 : 385 – 394 .
  • Bendtzen , K. 1980 . Differential role of Zn2+ in antigen- and mitogen-in-duced lymphokine production . Scand. J. Immunol. , 12 : 489 – 492 .
  • Flynn , A. , Loftus , M. A. and Finke , J H . 1984 . Production of interleukin-1 and interleukin-2 in allogeneic mixed lymphocyte cultures under copper, magnesium and zinc deficient conditions . Nutr. Res. , 4 : 673 – 679 .
  • Salas , M. and Kirchner , H. 1987 . Induction of interferon gamma in human leukocyte cultures stimulated by Zn2+ . Clin. Immunol. Immunopathol. , 45 : 139 – 142 .
  • Winchurch , R. A. , Togo , J. and Adler , W. H. 1988 . Supplemental zinc restores antibody formation in cultures of aged spleen cells. III. Impairment of IL-2 mediated responses . Clin. Immunol. Immunopathol. , 49 : 215 – 222 .
  • Smit , V. , van Veelen , P. A. , Tjaden , U. R. , van der Greef , J. and Haaijman , J. J. 1992 . Human interleukin-3 contains a discontinuous zinc-binding domain . Biochem. Biophys. Res. Commun. , 187 : 859 – 866 .
  • Dessaint , J. P. , Katz , S. P. and Waksman , B. H. 1979 . Catheptic carboxypep-tidase B as a major component in “T-cell activating factor” of macrophages . J. Immuno. Pharmacol. , 1 : 399 – 414 .
  • Fosmire , G. J. 1990 . Zinc toxicity . Am. J. Clin. Nutr. , 51 : 225 – 227 .
  • Porter , K. G. , McMaster , D. , Elmes , M. E. and Love , A. H. 1977 . Anaemia and low serum-copper during zinc therapy . Lancet , ii : 774
  • Prasad , A. S. , Brewer , G. J. , Schoomaker , E. B. and Rabbani , P. 1978 . Hypo-cupremia induced by zinc therapy in adults . J. Am. Med. Assoc. , 240 : 2166 – 2168 .
  • Mulhern , S. A. , Vessey , A. R. , Taylor , G. L. and Magruder , L. E. 1985 . Suppression of antibody response by excess dietary zinc exposure during certain stages of ontogeny . Proc. Soc. Exp. Biol. Med. , 180 : 453 – 461 .
  • Chvapil , M. , Zukoski , C. F. , Hattler , B. G. , Stankova , L. , Montgomery , D. , Carlson , E. C. and Ludwig , J. C. 1976 . “ Zinc and cells ” . In Human Health and Disease Vol I. Zinc and Copper , Edited by: Prasad , A. S. and Oberleas , D. 269 – 281 . Acad Press NY .
  • Chandra , R. K. 1984 . Excessive intake of zinc impairs immune response . J. Am. Med. Assoc. , 252 : 1443 – 1446 .
  • Karl , L. , Chvapil , M. and Zukoski , C. F. 1973 . Effect of zinc on the viability and phagocytic capacity of peritoneal macrophages . Proc. Soc. Exp. Biol. Med. , 142 : 1123 – 1127 .
  • Chvapil , M. , Stankova , L. , Bernard , D. S. , Weldy , P. L. , Carlson , E. V. C. and Campbell , J. B. 1977 . Effect of zinc on peritoneal macrophages in vitro . Infect. Immun. , 16 : 367 – 373 .
  • Montgomery , D. W. , Chvapil , M. and Zukoski , C. F. 1979 . Effects of zinc chloride on guinea pig complement component activity in vitro: concentration-dependent inhibition and enhancement . Infect. Immun. , 23 : 424 – 431 .
  • Walsh , C. T. , Sandstead , H. H. , Prasad , A. S. , Newberne , P. M. and Fraker , P. J. 1994 . Zinc: health effects and research priorities for the 1990s . Environ. Health Perfect. , 102 : 5 – 46 .
  • Chesters , J. K. 1972 . The role of zinc ions in the transformation of lymphocytes by phytohaemagglutinin . Biochem. J. , 130 : 133 – 139 .
  • Williams , R. O. and Loeb , L. A. 1973 . Zinc requirement for DNA replication in stimulated human lymphocytes . J. Cell Biol. , 58 : 594 – 601 .
  • Alford , R. H. 1970 . Metal cation requirements for phytohaemagglutinin-induced transformation of human peripheral blood lymphocytes . J. Immunol. , 104 : 698 – 703 .
  • Zalewski , P. D. , Forbes , I. J. and Giannakis , C. 1991 . Physiological role for zinc in prevention of apoptosis (gene-directed death) . Biochem. Inter. , 24 : 1093 – 1101 .
  • Messer , H. H. , Murray , E. J. and Goebel , N. K. 1982 . Removal of trace metals from culture media and sera for in vitro deficiency studies . J. Nutr. , 112 : 652 – 657 .
  • Chesters , J. K. 1989 . “ Biochemistry of zinc in cell division and tissue growth ” . In Zinc in Human Biology , Edited by: Mills , C. R. 109 – 118 . Springer-Verlag .
  • Zazonico , P. , Fernandes , G. and Good , R. A. 1981 . The differential sensitivity of T cell and B cell mitogenesis to in vitro Zn deficiency . Cell. Immunol. , 60 : 203 – 211 .
  • Flynn , A. 1984 . Control of in vitro lymphocyte proliferation by copper, magnesium and zinc deficiency . J. Nutr. , 114 : 2034 – 2042 .
  • Townsend , S. F. , Briggs , K. K. , Krebs , N. F. and Hambidge , K. F. 1994 . Zinc Supplementation Selectively Decreases Fetal Hepatocyte DNA Synthesis and Insulin-Like Growth Factor II Gene Expression in Primary Culture . Pediatric Research , 35 : 404 – 408 .
  • Hart , D. A. 1978 . Effect of zinc chloride on hamster lymphoid cells: mito-genicity and differential enhancement of lipopolysaccharide stimulation of lymphocytes . Infect. Immun. , 19 : 457 – 461 .
  • Reardon , C. L. and Lucas , D. O. 1987 . Heavy-metal mitogenesis: thymo-cyte activation by Zn++ requires 2-mercaptoethanol and lipopolysaccharide as co-factors . Immunobiol. , 174 : 233 – 243 .
  • Winchurch , R. A. 1988 . Activation of thymocyte responses to interleu-kin-1 by zinc . Clin. Immunol. Immunopathol. , 47 : 174 – 180 .
  • Chvapil , M. 1976 . Effect of zinc on cells and biomembranes . Med. Clinics Nth. America , 60 : 799 – 812 .
  • Malave , I. , Rodriguez , J. , Araujo , Z. and Rojas , I. 1990 . Effect of zinc on the proliferative response of human lymphocytes: mechanism of its mitogenic action . Immunopharmacol , 20 : 1 – 10 .
  • Tanaka , Y. , Shiozawa , S. , Morimoto , I. and Fujita , T. 1990 . Role of zinc in interleukin 2 (IL-2)-mediated T-cell activation . Scand. J. Immunol. , 31 : 547 – 552 .
  • Malave , I. and Rondon-Benaim , I. 1984 . Modulatory effect of zinc on the proliferative response of murine spleen cells to polyclonal T cell mitogens . Cell. Immunol. , 89 : 322 – 330 .
  • Csermely , P. , Fodor , P. and Somogyi , J. 1987 . The tumor promoter tetra-decanoylphorbol-13-acetate elicits the redistribution of heavy metals in subcellu-lar fractions of rabbit thymocytes as measured by plasma emission spectroscopy . Carcinogenesis , 8 : 1663 – 1666 .
  • Ochi , T. , Sato , K. and Ohsawa , M. 1983 . Suppression of the proliferative response of human lymphocytes to cultured allogeneic HeLa cells by zinc . Toxicol. Lett. , 15 : 225 – 230 .
  • Kirchner , H. and Salas , M. 1987 . Stimulation of lymphocytes with zinc ions . Methods in Enzymology , 150 : 112 – 117 .
  • Rühl , H. and Kirchner , H. 1978 . Monocyte-dependent stimulation of human T cells by zinc . Clin. Exp. Immunol. , 32 : 484 – 488 .
  • Harrer , T. , Wolf , B. , Nager , W. , Schwarz , W. , Bergner , D. and Kalden , J. R. 1992 . In vitro activation of peripheral mononuclear cells by zinc in HIV-infected patients and healthy controls . Clin. Exp. Immunol. , 89 : 285 – 289 .
  • Tanaka , Y. , Shiozawa , S. , Morimoto , I. and Fujita , T. 1989 . Zinc inhibits pokeweed mitogen-induced development of immunoglobulin-secreting cells through augmentation of both CD4 and CD8 cells . Int. J. Immunopharmacol. , 11 : 673 – 679 .
  • Miller , G. G. and Strittmatter , W. J. 1992 . Identification of human T cells that require zinc for growth . Scand. J. Immunol. , 36 : 269 – 277 .
  • Cunningham-Rundles , S. , Cunningham-Rundles , C. , Dupont , B. and Good , R. A. 1980 . Zinc-induced activation of human B lymphocytes . Clin. Immunol. Immunopathol. , 16 : 115 – 122 .
  • McMahon , L. J. , Montgomery , D. W. , Guschewsky , A. , Woods , A. H. and Zukoski , C. F. 1976 . In vitro effects of zinc chloride on spontaneous sheep red blood cell (E) rosette formation by lymphocytes from cancer patients and normal subjects . Immunol. Commun. , 15 : 53 – 67 .
  • Forbes , I. J. , Zalewski , P. D. and Giannakis , C. 1991 . Role for zinc in a cellular response mediated by protein kinase C in human B lymphocytes . Exp. Cell Res. , 195 : 224 – 229 .
  • Ferry , F. and Donner , M. 1984 . In vitro modulation of murine natural killer cytotoxicity by zinc . Scand. J. Immunol. , 19 : 435 – 445 .
  • Flieger , D. , Riethmuller , G. and Ziegler-Heitbrock , H. W. L. 1989 . Zn2+ inhibits both tumor necrosis factor-mediated DNA fragmentation and cytolysis . Int. J. Cancer , 44 : 315 – 319 .
  • Bendtzen , K. and Mayland , L. 1982 . Role of Zn2+ and other divalent metal ions in human lymphokine production in vitro . Scand. J. Immunol. , 15 : 81 – 86 .
  • Winchurch , R. A. , Togo , J. and Adler , W. H. 1987 . Supplemental zinc (Zn2+) restores antibody formation in cultures of aged spleen cells. II. Effects on mediator production . Eur. J. Immunol. , 17 : 127 – 132 .
  • Scuderi , P. 1990 . Differential effects of copper and zinc on human peripheral blood monocyte cytokine secretion . Cell Immunol. , 126 : 127 – 132 .
  • Driessen , C. , Hirv , K. , Rind , L. and Kirchner , H. 1994 . Induction of cyto-kines by zinc ions in human peripheral blood mononuclear cells and separated monocytes . Lymphokine Cytokine. Res. , 13 : 15 – 20 .
  • Grummt , F. , Weinmann-Dorsch , C. , Schneider-Schaulies , J. and Lux , A. 1986 . Zinc as a second messenger of mitogenic induction. Effects on diadenosine tetraphosphate (Ap4A) and DNA synthesis . Exp. Cell Res. , 163 : 191 – 200 .
  • Chausmer , A. B. , Chausmer , A. L. and Dajani , N. 1991 . Effect of mitogen-ic and hormonal stimulation on zinc transport in mixed lymphocyte cultures . J. Am. College Nutr. , 10 : 205 – 208 .
  • Chesters , J. K. , Petrie , L. and Lipson , H. E. 1993 . Two zinc-dependent steps during G1 to S phase transition . J. Cell. Physiol. , 155 : 445 – 51 .
  • Abdallah , J. M. , Kukuruga , M. , Nakeff , A. and Prasad , A. S. 1988 . Cell cycle distribution defect in PHA-stimulated T lymphocytes of sickle cell disease patients . Am. J. Hematol. , 28 : 279 – 81 .
  • Serrano , L. , Dominguez , J. E. and Avila , J. 1988 . Identification of zinc-binding sites of proteins: zinc binds to the amino terminal region of tubulin . Anal. Biochem. , 172 : 210 – 218 .
  • Hesketh , J. E. 1981 . Impaired microtubule assembly in brain from zinc-deficient pigs and rats . Int. J. Biochem. , 13 : 921 – 926 .
  • Wyllie , A. H. 1980 . Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation . Nature , 284 : 555 – 556 .
  • Kerr , J. F. R. , Searie , J. , Harmon , B. V. and Bishop , C. J. 1987 . “ Apoptosis ” . In Perspectives of Mammalia Cell Death , Edited by: Potten , C. S. 94 – 238 . Oxford : Oxford Uni Press .
  • Cohen , J. J. , Duke , R. C. , Fadok , V. A. and Sellins , K. S. 1992 . Apoptosis and programmed cell death in immunity . Annu. Rev. Immunol. , 10 : 267 – 293 .
  • Newell , M. K. , Haughn , L. J. , Maroun , C. R. and Julius , M. H. 1990 . Death of mature T cells by separate ligation of CD4 and the T-cell receptor for antigen . Nature , 347 : 286 – 289 .
  • Liu , Y-J , Joshua , D. E. , Williams , G. T. , Smith , C. A. , Gordon , J. and Mac-Lennan , I. C. M. 1991 . Mechanism of antigen-driven selection in germinal centres . Nature , 342 : 929 – 931 .
  • Benhamou , L. E. , Cazenave , P. A. and Sarthou , P. 1990 . Anti-immunoglo-bulins induce death by apoptosis in WEHI-231 B lymphoma cells . Eur. J. Immunol. , 20 : 1405 – 1407 .
  • Nagata , S. and Golstein , P. 1995 . The Fas death factor . Science , 267 : 1449 – 1456 .
  • Dinsdale , D. and Williams , R. B. 1977 . The enhancement by dietary zinc deficiency of the susceptibility of the rat duodenum to colchicine . B r. J. Nutr. , 37 : 135 – 142 .
  • Waring , P. , Egan , M. , Braithwaite , A. , Mullbacher , A. and Sjaarda , A. 1990 . Apoptosis induced in macrophages and T blasts by the mycotoxin sporidesmin and protection by Zn2+ salts . Int. J. Immunopharmac. , 12 : 445 – 457 .
  • Thomas , D. J. and Caffrey , T. C. 1991 . Lipopolysaccharide induces double-stranded DNA fragmentation in mouse thymus: protective effect of zinc pretreat-ment . Toxicol. , 68 : 327 – 337 .
  • Cohen , J. J. and Duke , R. C. 1984 . Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death . J. Immunol. , 132 : 38 – 42 .
  • Elmes , M. E. 1977 . Apoptosis in the small intestine of zinc-deficient and fasted rats . J. Pathol. , 123 : 219 – 224 .
  • Elmes , M. E. and Jones , J. G. 1980 . Ultrastructural changes in the small intestine of zinc-deficient rats . J. Pathol. , 130 : 37 – 43 .
  • Elmes , M. E. and Jones , J. G. 1980 . Ultrastructural studies on Paneth cell apoptosis in zinc deficient rats . Cell. Tissue. Res. , 208 : 57 – 63 .
  • Martin , S. J. , Mazdai , G. , Strain , J. J. , Cotter , T. G. and Hannigan , B. M. 1991 . Programmed cell death (apoptosis) in lymphoid and myeloid cell lines dur ing zinc deficiency . Clin. Exp. Immunol. , 83 : 338 – 343 .
  • McCabe , M. J. , Jiang , S. A. and Orrenius , S. 1993 . Chelation of intracellu-lar zinc triggers apoptosis in mature thymocytes . Lab. Invest. , 69 : 101 – 109 .
  • Treves , S. , Trentini , P. L. , Ascanelli , M. , Bucci , G. and Divirgilio , F. 1994 . Apoptosis Is Dependent on Intracellular Zinc and Independent of Intracellular Calcium in Lymphocytes . Exp. Cell Res. , 211 : 339 – 343 .
  • Veis , D. J. , Sorenson , C. M. , Shutter , J. R. and Korsmeyer , S. J. 1993 . Bcl-2 deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair . Cell , 75 : 229 – 240 .
  • Hockenbery , D. M. , Oltvai , Z. N. , Yin , X.-M. , Millman , C. L. and Korsmeyer , S. J. 1993 . Bcl-2 functions in an anti-oxidant pathway to prevent apoptosis . Cell , 75 : 241 – 251 .
  • Giannakis , C. , Forbes , I. J. and Zalewski , P. D. 1991 . Ca2+/Mg2+-depen-dent nuclease: tissue distribution, relationship to inter-nucleosomal DNA fragmentation and inhibition by Zn2+ . Biochem. Biophys. Res. Commun. , 181 : 915 – 920 .
  • Cohen , G. M. , Sun , X-M. , Snowden , R. T. , Dinsdale , D. and Skilleter , D. N. 1992 . Key morphological features of apoptosis may occur in the absence of internucleosomal DNA fragmentation . Biochem. J. , 286 : 331 – 334 .
  • Flynn , A. 1983 . Effects of antigen stimulation and interleukin-1 on in vivo splenic zinc in the A/J mouse . J. Am. CoIl. Nutr. , 2 : 205 – 213 .
  • Tufft , L. S. , Nockels , C. F. and Fettma , M. J. 1988 . Effects of Escherichia coli on iron, copper, and zinc metabolism in chicks . Av i an Dis. , 32 : 779 – 786 .
  • Schroeder , J. J. and Cousins , R. J. 1990 . Interleukin 6 regulates metallo-thionein gene expression and zinc metabolism in hepatocyte monolayer cultures . Proc. Natl. Acad Sci. USA , 87 : 3137 – 3141 .
  • Slater , J. P. , Mildvan , A. S. and Loeb , L. A. 1971 . Zinc in DNA polymer-ases. Biochem . Biophys. Res. Commun. , 44 : 37 – 43 .
  • Falchuk , K. H. , Krishan , A. and Vallee , B. L. 1975 . DNA distribution in cell-cycle of Euglena-Gracilis cytofluorometry of zinc-deficient cells . Biochem. , 14 : 3439 – 3444 .
  • Kirchgessner , M. , Roth , H. P. and Weigand , E. 1976 . “ Biochemical changes in zinc deficiency in Trace Elements ” . In Human Health and Disease Vol 1 Zinc and Copper , Edited by: Prasad , A. S. and Oberleas , D. 189 – 225 . Acad Press NY .
  • Brudzynska , K. , Ploszajska , A. , Roszczyk , R. and Walter , Z. 1982 . Interaction of zinc ions with DNA-dependent RNA polymerases-A,B,C isolated from calf thymus . Molec. Biol. Reports , 8 : 77 – 83 .
  • Good , R. A. , West , A. , Day , N. K. , Dong , Z. W. and Fernandes , G. 1982 . Effects of undernutrition on host cell and organ function . Cancer Res. , 42 : 737 – 746 .
  • Da Silva , J. J. R. F. and Williams , R. J. P. 1991 . “ Zinc: Lewis acid catalysis and regulation ” . In The Biological Chemistry of the Elements Clarendon , 299 – 318 . Press Oxford .
  • Morimoto , S. , Shiraishi , T. , Fukuo , K. , Koh , E. , Kitano , S. , Yasuda , O. , Tamatani , M. and Ogihara , T. 1992 . EDTA induces differentiation and suppresses proliferation of promyelocytic leukaemia cell line HL60 -possible participation of zinc . Biochem. Inter. , 28 : 313 – 321 .
  • Flamigni , F. , Campana , G. , Carboni , L. , Guarnieri , C. and Spampinato , S. 1994 . Zinc Is Required for the Expression of Ornithine Decarboxylase in a Di-fluoromethylornithine-Resistant Cell Line . Biochemical Journal , 299 : 515 – 519 .
  • Csermely , P. and Somogyi , J. 1989 . Zinc as a possible mediator of signal transduction in T lymphocytes . Acta Physiol. Hung. , 74 : 195 – 199 .
  • Zalewski , P. D. , Forbes , I. J. , Giannakis , C. , Cowled , P. A. and Betts , W. H. 1990 . Synergy between zinc and phorbol ester in translocation of protein kinase C to cytoskeleton . Febs. Letts. , 273 : 131 – 134 .
  • Zalewski , P. D. , Forbes , I. J. , Giannakis , C. and Betts , W. H. 1991 . Regulation of protein kinase C by Zn2+-dependent interaction with actin . Biochem. Inter. , 24 : 1103 – 1110 .
  • Turner , J. M. , Brodsky , M. H. , Irving , B. A. , Levin , S. D. , Perlmutter , R. M. and Littman , D. R. 1990 . Interaction of the unique N-terminal region of tyrosine kinase p561ck with cytoplasmic domains of CD4 and CD8 is mediated by cysteine motifs . Cell , 60 : 755 – 765 .
  • Pernelle , J. J. , Creuzet , C. , Loeb , J. and Gacon , G. 1991 . Phosphorylation of the lymphoid cell kinase p561ck is stimulated by micromolar concentrations of Zn2+ . FEBSLett. , 281 : 278 – 282 .
  • Borrego , F. , Lopez-Beltran , A. , Pena , J. and Solana , R. 1994 . Downre-gulation of Fc ? receptor IIIA a(CD16-II) on natural killer cells induced by anti-CD16 mAb is independent of protein tyrosine kinases and protein kinase C . Cell Immunol. , 158 : 208 – 17 .
  • Chvapil , M. , Elias , S. L. , Ryan , J. N. and Zukoski , C. F. 1972 . “ Pathophy-siology of zinc ” . In Int. Rev. Neurobiol , 105 – 124 . NY Acad Press . Suppl 1
  • Alexander , J. , Forre , O. , Aaseth , J. , Dobloug , J. and Ovrebo , S. 1982 . Induction of a metallothionein-like protein in human lymphocytes . Scand. J. Immunol. , 15 : 217 – 220 .
  • Chvapil , M. 1973 . New aspects in the biological role of zinc: a stabilizer of macromolecules and biological membranes . Life Sci. , 13 : 1041 – 9 .
  • Bettger , W. J. and O'Dell , B. L. 1981 . A critical physiological role of zinc in the structure and function of biomembranes . Life Sci. , 28 : 1425 – 1438 .
  • Vallee , B. L. and Galdes , A. 1984 . The metallobiochemistry of zinc enzymes . Adv. Enzymol. , 56 : 283 – 430 .
  • Aleksandrowicz , J. , Astaldi , G. , Bodzon , A. , Lisiewicz , J. , Mysliwiec , D. , Sasiadek , U. , Strycharska , M. and Walewska-Czyzewska , M. 1976 . Trace elements and immunologic defects. Zinc deficiency and activity of lysosomal acid phosphatase in lymphocyte of mice . Boll. Ist. Sierote. Milan. , 55 : 195 – 200 .
  • Beletsky , I. P. , Matyasova , J. , Nikonova , L. V. , Skalka , M. and Umansky , S. R. 1989 . On the role of Ca, Mg-dependent nuclease in the postirradiation degradation of chromatin in lymphoid tissues . Gen. Physiol. Biophys. , 8 : 381 – 388 .
  • Lohmann , R. D. and Beyersmann , D. 1993 . Cadmium and zinc mediated changes of the Ca(2+)-dependent endonuclease in apoptosis . Biochem. Biophys. Res. Commun. , 190 : 1097 – 1103 .
  • Ballester , O. F. and Prasad , A. S. 1983 . Anergy, zinc deficiency, and decreased nucleoside phosphorylase activity in patients with sickle cell anemia . Ann. Intern. Med. , 98 : 180 – 182 .
  • Cossack , Z. T. 1989 . T-lymphocyte dysfunction in the elderly associated with zinc deficiency and subnormal nucleoside phosphorylase activity: effect of zinc supplementation . Eur. Cancer. Clin. Oncol. , 25 : 973 – 976 .
  • Meftah , S. and Prasad , A. S. 1989 . Nucleotides in lymphocytes from human subjects with zinc deficiency . J. Lab. Clin. Med. , 114 : 114 – 119 .
  • Seres , D. S. , Bunk , M. J. , Osborne , M. P. , Rivlin , R. S. and Tiwari , R. K. 1991 . Effects of marginal dietary zinc deficiency and vitamin E supplementation on hepatic adenine dinucleotide phosphoribosyl transferase activity in female Sprague Dawley rats . Nutr. Res. , 11 : 337 – 345 .
  • Rice , W. G. , Hillyer , C. D. , Harten , B. , Schaeffer , C. A. , Dorminy , M. , Lackey , D. A. , Kirsten , E. , Mendeleyev , J. , Buki , K. G. , Hakam , A. and Kun , E. 1992 . Induction of endonuclease-mediated apoptosis in tumour cells by C-nitroso-substituted ligands of poly(ADP-ribose) polymerase . Proc. Natl. Acad. Sci.(USA) , 89 : 7703 – 7707 .
  • Rice , W. G. , Schaeffer , C. A. , Harten , B. , Villenger , F. , South , T. L. , Summers , M. F. , Henderson , L. E. , Bess , J. W. Jr. , Arthur , L. O. McDougal , J. S. 1993 . Inhibition of HIV-1 infectivity by zinc-ejecting aromatic C-nitroso compounds . Nature , 361 : 473 – 475 .
  • Sherman , A. R. 1992 . Zinc, copper, and iron nutriture and immunity . J. Nutr. , 122 : 604 – 609 .
  • Brock , J. H. 1993 . Iron and immunity . J. Nutr. Immunol. , 2 : 47 – 106 .
  • Lukasewycz , O. A. and Prohaska , J. R. 1983 . Lymphocytes from copper-deficient mice exhibit decreased mitogen reactivity . Nutr. Res. , 3 : 335 – 341 .
  • Lukasewycz , O. A. , Prohaska , J. R. , Meyer , S. G. , Schmidtke , J. R. , Hatfield , S. M. and Marder , P. 1985 . Alterations in lymphocytes subpopulations in copper-deficient mice . Infect. Immunol. , 48 : 644 – 647 .
  • Bala , S. and Failla , M. L. 1992 . Copper deficiency reversibly impairs DNA synthesis in activated T lymphocytes by limiting interleukin 2 activity . Proc. Natl. Acad Sci. U. S. A. , 89 : 6794 – 6797 .
  • Kishore , V. , Latman , N. , Roberts , D. W. , Barnett , J. B. and Sorenson , J. R. 1984 . Effect of nutritional copper deficiency on adjuvant arthritis and immuno-competence in the rat . Agents Actions , 14 : 274 – 282 .
  • Lukasewycz , O. A. and Prohaska , J. R. 1982 . Immunization against trans-plantable leukemia impaired in copper-deficient mice . J. Natl. Cancer. Inst. , 69 : 489 – 493 .
  • Prohaska , J. R. , Downing , S. W. and Lukasewycz , O. A. 1983 . Chronic dietary copper deficiency alters biochemical and morphological properties of mouse lymphoid tissues . J. Nutr. , 113 : 1583 – 1590 .
  • Kishimoto , S. , Iwamoto , S. , Masutani , S. , Yamamoto , R. , Jo , T. , Saji , F. , Teranda , N. , Sasaki , Y. , Imaoka , S. and Sugiyama , T. 1993/1994 . Apoptosis of Acinar Cells in the Pancreas of Rats Fed on a Copper-Depleted Diet . Exp. Toxicol. Pathol. , 45 : 489 – 495 .
  • Rao , M. S. , Yeldandi , A. V. , Subbarao , Y. and Reddy , J. K. 1993 . Role of apoptosis in copper deficiency-induced pancreatic involution in the rat . Am. J. Pathol. , 142 : 1952 – 1957 .
  • Ide , H. , Yeldandi , A. V. , Reddy , J. K. and Rao , M. S. 1994 . Increased expression of sulfated glycoprotein-2 and DNA fragmentation in the pancreas of copper-deficient rats . Toxicol. Appl. Pharmacol. , 126 : 174 – 177 .
  • Pocino , M. , Malave , I. and Baute , L. 1990 . Zinc administration restores the impaired immune response observed in mice receiving excess copper by oral route . Immunopharmacol. Immunotoxicol. , 12 : 697 – 713 .
  • Hileti , D. , Panayiotidis , P. and Hoffbrand , A. V. 1995 . Iron chelators induce apoptosis in proliferating cells . Brit J. Hematol , 89 : 181 – 187 .
  • Shippee , R. L. , Burgess , D. H. , Ciavarra , P. , DiCapua , R. A. and Stake , P. E. 1983 . Cadmium-induced suppression of the primary immune response and acute toxicity in mice: differential interaction of zinc . Toxicol. Appl. Pharmacol. , 71 : 303 – 306 .
  • Hong Bin , Q. and Garfinkel , D. 1994 . The cadmium toxicity hypothesis of aging: a possible explanation for the zinc deficiency hypothesis of aging . Medical Hypotheses , 42 : 380 – 384 .
  • Chowdhury , B. A. and Chandra , R. K. 1989 . Effect of zinc administration on cadmium-induced suppression of natural killer cell activity in mice . Immunol. Lett. , 22 : 287 – 91 .
  • Otsuka , F. and Ohsawa , M. 1991 . Differential susceptibility of T and B lymphocyte proliferation to cadmium: relevance to zinc requirement in T lymphocyte proliferation . Chem. Biol. Interact. , 78 : 193 – 205 .
  • Ohsawa , M. , Otsuka , M. and Sugizaki , S. 1992 . Zinc status in prolifera-tive response of T lymphocytes . J. Nutr. Sci. Vitaminol. Tokyo. , : 518 – 521 . Spec No
  • El Azzouzi , B. , Tsangaris , G. T. , Pellegrini , O. , Manuel , Y. , Benveniste , J. and Thomas , Y. 1994 . Cadmium induces apoptosis in a human T cell line . Toxicol. , 88 : 127 – 139 .
  • Beach , R. S. , Gershwin , M. E. and Hurley , L. S. 1981 . Nutritional factors and autoimmunity. I. Immunopathology of zinc deprivation in New Zealand mice . J. Immunol. , 126 : 1999 – 2006 .
  • Beach , R. S. , Gershwin , M. E. and Hurley , L. S. 1982 . Nutritional factors and autoimmunity II. Prolongation of survival in zinc-deprived NZB/W mice . J. Immunol. , 128 : 308 – 313 .
  • Beach , R. S. , Gershwin , M. E. and Hurley , L. S. 1982 . Nutritional factors and autoimmunity III. Zinc deprivation versus restricted food intake in MRL/1 mice -the distinction between interacting dietary influences . J. Immunol. , 129 : 2686 – 2692 .
  • Vruwink , K. , Keen , C. L. , Gershwin , M. E. and Hurley , L. S. 1987 . Studies of nutrition and autoimmunity. Failure of zinc deprivation to alter autoantibody production when initiated in disease-established mice . J. Nutr. , 117 : 177 – 182 .
  • Tapazoglou , E. , Prasad , A. S. , Hill , G. , Brewer , G. J. and Kaplan , J. 1985 . Decreased natural killer cell activity in zinc deficient subjects with sickle cell disease . J. Lab. Clin. Med. , 105 : 19 – 22 .
  • Prasad , A. S. , Kaplan , J. , Brewer , G. J. and Dardenne , M. 1989 . Immuno-logical effects of zinc deficiency in sickle cell anemia (SCA) . Prog. Clin. Biol. Res. , 319 : 629 – 649 .
  • Bjorksten , B. , Black , O. , Gustavson , K. H. , Hallmans , G. , Hagloff , B. and Tarvik , A. 1980 . Zinc and immune function in Down's syndrome . Acta Pediatr. Scand. , 69 : 183 – 187 .
  • Licastro , F. , Chiricolo , M. , Mocchegiani , E. , Fabris , N. , Zannoti , M. , Beltrandi , E. , Mancini , R. , Parente , R. , Arena , G. and Masi , M. 1994 . Oral zinc supplementation in Down's syndrome subjects decreased infections and normalized some humoral and cellular immune parameters . J. Intellect. Disabil. Res. , 38 : 149 – 162 .
  • Allen , J. L. , Bell , E. , Boosalis , M. G. , Oken , M. M. , McClain , C. J. , Levine , A. S. and Morley , J. E. 1985 . Association between urinary zinc excretion and lymphocyte dysfunction in patients with lung cancer . Am. J. Med. , 79 : 209 – 215 .
  • Labadie , H. , Verneau , A. , Trinchet , J. C. and Beaugrand , M. 1986 . Does oral zinc improve the cellular immunity of patients with alcoholic cirrhosis? . Gas-troenterol Clin. Biol. , 10 : 799 – 803 .
  • Niewoehner , C. B. , Allen , J. I. , Boosalis , M. G. , Levine , A. S. and Morley , J. E. 1986 . The role of zinc supplementation in type II diabetes mellitus . Am. J. Med. , 81 : 63 – 8 .
  • Raz , I. , Karsai , D. and Katz , M. 1989 . The influence of zinc supplementation on glucose homeostasis in NIDDM . Diabetes Res. , 11 : 73 – 79 .
  • Mocchegiani , E. , Boemi , M. , Fumelli , P. and Fabris , N. 1989 . Zinc-dependent low thymic hormone level in type I diabetes . Diabetes , 38 : 932 – 937 .
  • Mooradian , A. D. , Norma , D. C. and Morley , J. E. 1988 . The effect of zinc status on the immune function of diabetic rats . Diabetologia , 31 : 703 – 707 .
  • Bogden , J. D. , Baker , H. and Frank , O. 1990 . Micronutrient status and human immunodeficiency virus (HIV) infection . Ann. NY Acad Sci. , 587 : 189 – 195 .
  • Wang , Y. , Liang , B. and Watson , R. R. 1994 . The effect of alcohol consumption on nutritional status during murine AIDS . Alcohol , 11 : 273 – 278 .
  • Pifer , L. L. , Wang , Y. F. , Chiang , T. M. , Ahokas , R. , Woods , D. R. and Joyner , R. E. 1987 . Borderline immunodeficiency in male homosexuals: is life-style contributory? . South. Med. J. , 80 : 687 – 91 . 697
  • Falutz , J. , Tsoukas , C. and Gold , P. 1988 . Zinc as a cofactor in human immunodeficiency virus-induced immunosuppression . J. Am. Med. Assoc. , 259 : 2850 – 2851 .
  • Ameisen , J. C. and Capron , A. 1991 . Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis . Immunol. Today. , 12 : 102 – 105 .
  • Janeway , C. A. 1992 . The case of the missing CD4s . Curr. Opin. Immunol. , 2 : 359 – 361 .
  • Santos-Neto , L. , Tosta , C. E. and Dorea , J. G. 1992 . Zinc reverses the increased sensitivity of lymphocytes from aged subjects to the antiproliferative effect of prostaglandin E2 . Clin. Immunol. Immunopathol. , 64 : 184 – 187 .
  • Garfinkel , D. 1986 . Is aging inevitable? The intracellular zinc deficiency hypothesis of aging . Medical Hypotheses , 19 : 117 – 137 .
  • Kaplan , J. , Hess , J. W. and Prasad , A. S. 1988 . Impaired interleukin 2 production in the elderly: Association with mild zinc deficiency . J. Trace Elem. Exp. Med. , 1 : 3 – 8 .
  • Payette , H. , Rola-Pleszczynski , M. and Ghadirian , P. 1990 . Nutrition factors in relation to cellular and regulatory immune variables in a free-living elderly population . Am. J. Clin. Nutr. , 52 : 927 – 932 .
  • Dardenne , M. , Boukaiba , N. , Gagnerault , M. C. , Homo-Delarche , F. , Chappuis , P. , Lemonnier , D. and Savino , W. 1993 . Restoration of the thymus in aging mice by in vivo zinc supplementation . Clin. Immunol. Immunopathol. , 66 : 127 – 135 .
  • Turnlund , J. R. , Durvin , N. , Costa , F. and Margen , S. 1986 . Stable isotope studies of zinc absorption and retention in young and elderly men . J. Nutr. , 116 : 1239 – 1247 .
  • Bunker , V. W. , Hinks , L. J. , Stansfield , M. F. , Lason , M. S. and Clayton , B. E. 1987 . Metabolic balance studies for zinc and copper in housebound elderly people and the relationship between zinc balance and leukocyte zinc concentration . Am. J. Clin. Nutr. , 46 : 343 – 349 .
  • Couzy , F. , Kastenmayer , P. , Mansourian , R. , Guinchard , S. , Munoz-Box , R. and Dirren , H. 1993 . Zinc absorption in healthy elderly humans and the effect of diet . Am. J. Clin. Nutr. , 58 : 690 – 694 .
  • Yamaguchi , M. and Ozaki , K. 1990 . Effect of the new zinc compound β-alanyl-L-histidinato zinc on bone metabolism in elderly rats . Pharmacology , 41 : 345 – 349 .
  • Oldereid , N. B. , Thomassen , Y. , Attramadal , A. , Olaisen , B. and Purvis , K. 1993 . Concentrations of lead, cadmium and zinc in the tissues of reproductive organs of men . J. Reprod. Fertil. , 99 : 421 – 425 .
  • Morita , A. , Kimura , M. and Itokawa , Y. 1994 . The effect of aging on the mineral status of female mice . Biol. Trace. Elem. Res. , 42 : 165 – 177 .
  • Bergman , B. , Sjostrom , R. and Wing , K. R. 1974 . The variation with age of tissue zinc concentrations in albino rats determined by atomic absorption spec-trophotometry . Acta Physiol. Scand. , 92 : 440 – 450 .
  • Congy , F. , Clavel , J. P. , Devillechabrolle , A. , Gerbet , D. , Marescot , M. R. and Moulias , R. 1983 . Plasma zinc levels in elderly hospitalized subjects. Correlation with other nutritional and immunological markers and survival . Sem. Hop. , 59 : 3105 – 3108 .
  • Wostmann , B. S. , Wong , F. R. and Snyder , D. L. 1992 . Serum zinc in aging germ-free and conventional rats . Proc. Soc. Exp. Biol. Med. , 199 : 218 – 221 .
  • Fabris , N. 1994 . Neuroendocrine-immune aging: a integrative view on the role of zinc . Ann. N. Y. Acad. Sei. , 719 : 353 – 368 .
  • Duchateau , J. , Delepesse , G. , Vrijens , R. and Collet , H. 1981 . Beneficial effects of zinc supplementation on the immune response of old people . Am. J. Med. , 70 : 1001 – 1004 .
  • Wagner , P. A. , Jernigan , J. J. A. , Bailey , L. B. , Nickens , C. and Brazzi , G. A. 1983 . Zinc nutriture and cell mediated immunity in the aged . Int. J. Vitam. Nutr. Res. , 53 : 94 – 101 .
  • Mocchegiani , E. , Bulian , D. , Santarelli , L. , Tibaldi , A. , Muzzioli , M. , Pierpaoli , W. and Fabris , N. 1994 . The immuno-reconstituting effect of melatonin or pineal grafting and its relation to zinc pool in aging mice . J. Neuroimmunol. , 53 : 189 – 201 .
  • Bogden , J. D. , Oleske , J. M. , Lavenhar , M. A. , Munves , E. M. , Kemp , F. W. , Bruening , K. S. , Holding , K. J. , Denny , T. N. , Guaino , M. A. , Krieger , L. M. and Holland , B. K. 1988 . Zinc and immunocompetence in elderly people: effects of zinc supplementation for 3 months . Am. Clin J. Nutr. , 48 : 655 – 663 .
  • Bogden , J. D. , Oleske , J. M. , Lavenhar , M. A. , Munves , E. M. , Kemp , F. W. , Bruening , K. S. , Holding , K. J. , Denny , T. N. , Guaino , M. A. and Holland , B. K. 1990 . Effects of one year of supplementation with zinc and other micronutrients on cellular immunity in the elderly . J. Am. Coll. Nutr. , 9 : 214 – 25 .
  • Goodwin , J. S. and Garry , P. J. 1988 . Lack of correlation between indices of nutritional status and immunologic function in elderly humans . J. Gerontol. , 43 : M46 – M49 .
  • Winchurch , R. A. , Thomas , D. J. , Adler , W. H. and Lindsay , T. J. 1984 . Supplemental zinc restores antibody formation in cultures of aged spleen cells . J. Immunol. , 133 : 569 – 571 .
  • Burnet , F. M. 1981 . A possible role of zinc in the pathology of dementia . Lancet , i : 186 – 188 .
  • Constantinidis , J. 1992 . Treatment of Alzheimer's disease by zinc compounds . Drug Development Research , 27 : 1 – 14 .
  • Chazot , G. and Broussolle , E. 1993 . Alterations in trace elements during brain aging and in Alzheimer's dementia . Prog. Clin. Biol. Res. , 380 : 269 – 28 .
  • Pavletich , N. P. and Pabo , C. O. 1991 . Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1Å . Science , 252 : 809 – 817 .
  • Vallee , B. L. and Auld , D. S. 1990 . Active-site zinc ligands and activated H2O of zinc enzymes . Proc. Natl. Acad Sci. USA , 87 : 220 – 224 .
  • Vulpe , C. , Levinson , B. , Whitney , S. , Packman , S. and Gitschier , J. 1993 . Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase . Nature Genet. , 3 : 7 – 13 .

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