Physiology pp 379-400 | Cite as

Lead and Cadmium Effect on Host Defense Mechanisms and Toxic Interactions with Bacterial Endotoxin

  • James A. Cook
  • W. C. Wise
  • W. J. Dougherty
  • P. V. Halushka


There is growing concern over the presence of significant quantities of non-biodegradable pollutants, such as lead and cadmium, in the environment (Wessel and Dominski, 1977; Goyer and Rhyne, 1973; Webb, 1979). Widespread environmental contamination with lead and cadmium occurs from many sources ranging from industrial or automobile emissions (Haley, 1968; Beliles, 1975; Cox, 1974) to consumable items and appliances in the home (Chisolm, 1973; Cox, 1974). Understanding of the interaction of these toxic trace metals with biologic systems is thus becoming increasingly important. Such interactions may result from accidental overt intoxication or potential toxic effects of subclinical body burdens of these heavy metals manifested in the presence of costressors. The impact on host defense mechanisms is an important variable in toxicity assessment of these environmental contaminants. Selye et al. (1966) reported that a single injection of lead acetate increased the sensitivity of rats to various endotoxins from gram-negative bacteria by approximately 100,000-fold. This initial observation of an extreme toxic synergism between lead and endotoxin has inspired a number of studies of environmental significance as well as an understanding of the fundamental mechanisms of endotoxic shock. This chapter reviews some toxicologic effects of lead and cadmium on phagocyte function and host resistance to infection and examines potential mechanisms by which these heavy metals render animals hypersensitive to bacterial endotoxin.


Alveolar Macrophage Lead Acetate Cadmium Chloride Bacterial Endotoxin Endotoxic Shock 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Allen, R. C., and Loose, L. D., 1976, Phagocytic activation of luminal-dependent chemiluminescence in rabbit alveolar and peritoneal macrophages, Biochem. Biophys. Res. Commun. 69:245.PubMedCrossRefGoogle Scholar
  2. Aranyi, C., Miller, F. J., Andres, S., Ehrlich, R., Fenters, J., Gardner, D.E., and Waters M. D., 1979, Cytotoxicity to alveolar macrophages of trace metals absorbed on fly ash, Environ. Res. 20:14.PubMedCrossRefGoogle Scholar
  3. Beliles, R. P., 1975, Lead and cadmium: Effect on host defense mechanisms and toxic interactions with bacterial endotoxin, in: Toxicology, the Basic Science of Poisons (L. J. Cassarett and J. Doull, eds.), p. 454, Macmillan Co., New York.Google Scholar
  4. Bell, S. W., Masters, S. K., Ingram, P., Waters, M., and Shelburne, J. D., 1979, Ultrastructure and X-ray microanalysis of macrophages exposed to cadmium chloride, Scan. Electron Microsc. 3:111.PubMedGoogle Scholar
  5. Bertok, L., 1968, Effect of sulfhydryl compound on the lead acetate-induced endotoxin hypersensitivity of rats, J. Bacteriol. 95:1974.PubMedGoogle Scholar
  6. Bingham, E., Pfitzer, E. A., Barkley, W., and Radford, E., 1968, Alveolar macrophages: Reduced number in rats after prolonged inhalation of lead sesquioxide, Science 162:1297.PubMedCrossRefGoogle Scholar
  7. Bingham, E., Barkley, W., Zerwas, M., Stemmer, K., and Taylor, P., 1972, Responses of alveolar macrophages to metals. I. Inhalation of lead and nickel, Arch. Environ. Health 25:406.PubMedGoogle Scholar
  8. Bouley, G., Dubreuil, A., Despaux, N., and Boudene, C., 1977, Toxic effects of cadmium microparticles on the respiratory system, Scand. J. Work Environ. Health 3:116.PubMedCrossRefGoogle Scholar
  9. Bozelka, B. E., and Burkholder, P. M., 1979, Increased mortality of cadmium-intoxicated mice with the BCG strain of Mycobacterium bovis, J. Reticuloendothelial Soc. 26:229.Google Scholar
  10. Braude, A. L., 1964, Absorption distribution and elimination of endotoxins and their derivatives, in: Bacterial Endotoxins (M. Landy and W. Braun, eds.), Rutgers University Press, New Brunswick, N.J.Google Scholar
  11. Bult, H., Beetens, J., Vercrysse, P., and Herman, A. G., 1978, Blood levels of 6-keto-PGF, the stable metabolite of prostacyclin, during endotoxin induced hypotension, Arch. Int. Pharmacodyn. Ther. 236:285.PubMedGoogle Scholar
  12. Burch, R. M., Knapp, D. R., and Halushka, P. V., 1979, Vasopressin stimulates thromboxane synthesis in the toad urinary bladder: Effects of imidazole, J. Pharmacol. Exp. Ther. 210:344.PubMedGoogle Scholar
  13. Cain, K., and Skilleter, D., 1980, Selective uptake of cadmium by parenchymal cells of liver, Biochem. J. 188:285.PubMedGoogle Scholar
  14. Caldwell, K. C., Taddeini, L., Woodburn, R. L., Anderson, G. L., and Lobell, M., 1979, Induction of myeloperoxidase deficiency in granulocytes in lead-intoxicated dogs, Blood 53:588.PubMedGoogle Scholar
  15. Caprio, R. J., Margulis, H. L., and Joselow, M. M., 1974, Lead absorption in children and its relationship to urban traffic densities, Arch. Environ. Health 28:195.PubMedGoogle Scholar
  16. Chisolm, J., Jr., 1973, Management of increased lead absorption and lead poisoning in children, N. Engl. J. Med. 289:1016.PubMedCrossRefGoogle Scholar
  17. Cook, J. A., and DiLuzio, N. R., 1973, Protective effect of cysteine and methylprednisolone in leadendotoxin induced shock, Exp. Mol. Pathol. 19:127.PubMedCrossRefGoogle Scholar
  18. Cook, J. A., Marconi, E. A., and DiLuzio, N. R., 1974, Lead, cadmium, endotoxin interaction: Effect on mortality and hepatic function, Toxicol. Appl. Pharmacol. 28:292.PubMedCrossRefGoogle Scholar
  19. Cook, J. A., Hoffmann, E. O., and DiLuzio, N. R., 1975a, Factors modifying susceptibility to bacterial endotoxin: The effect of lead and cadmium, Critical Reviews in Toxicology, pp. 201–229, CRC Press, Cleveland, January.Google Scholar
  20. Cook, J. A., Hoffmann, E. O., and DiLuzio, N. R., 1975b, Influence of lead and cadmium on the susceptibility of rats to bacterial challenge, Proc. Soc. Exp. Biol. Med. 150:741.PubMedGoogle Scholar
  21. Cook, J. A., Wise, W. C., and Halushka, P. V., 1980, Elevated thromboxane levels in the rat during shock: Protective effects of imidazole 13-azaprostanoic acid, or essential fatty acid deficiency, J. Clin. Invest. 65:227.PubMedCrossRefGoogle Scholar
  22. Cook, J. A. Dougherty, W. J., and Holt, T., 1981, Distribution of 203Pb during lead potentiated endotoxic shock, Exp. Mol Path. 34:253.CrossRefGoogle Scholar
  23. Cornell, R. P., and Filkins, J. P., 1974, Depression of hepatic gluconeogenesis by acute lead administration. Proc. Soc. Exp. Biol. Med. 147:371.PubMedGoogle Scholar
  24. Cox, C. C., and Waters, M. D., 1978, Isolation of a soluble cadmium binding protein from pulmonary macrophages, Toxicol. Appl. Pharmacol. 46:385.PubMedCrossRefGoogle Scholar
  25. Cox, D. B., 1974, Cadmium; trace element of concern in mining and manufacturing, J. Environ. Health 36:361.Google Scholar
  26. deBruin, A., 1971, Certain biological effects of lead upon the animal organism, Arch. Environ. Health 23:249.PubMedGoogle Scholar
  27. Decker, C. G., Byerrum, R. U., and Hoppert, C. A., 1957, A study of the distribution and retention of cadmium-115 in the albino rat, Arch. Biochem. Biophys. 66:140.PubMedCrossRefGoogle Scholar
  28. DeClerq, E., and Merigan, T. C., 1969, An active interferon inducer obtained from Hemophilus influenza type B, J. Immunol. 103:889.Google Scholar
  29. Exon, J. H., Patton, N. M., and Koller, L. D., 1975, Hexamitias in cadmium exposed mice, Arch. Environ. Health 30:463.PubMedGoogle Scholar
  30. Exon, J. H., Koller, L. D., and Kerkvliet, N. I., 1979, Lead-cadmium interactions: Effects on viralinduced mortality and tissue residue in mice, Arch. Environ. Health 34:469.PubMedGoogle Scholar
  31. Faith, R. E., Luster, M. I., and Kimmel, C. A., 1979, Effect of chronic developmental lead exposure on cell mediated immune functions, Exp. Immunol. 35:413.Google Scholar
  32. Filkins, J. P., 1973, Hypoglycemia and depressed hepatic gluconeogenesis during endotoxicosis in lead sensitized rats, Proc. Soc. Exp. Biol. Med. 142:915.PubMedGoogle Scholar
  33. Filkins, J. P., and Buchanan, B. J., 1973, Effects of lead acetate on sensitivity to shock, intravascular carbon and endotoxin clearances, and hepatic endotoxin detoxification, Proc. Soc. Exp. Biol. Med. 142:471.PubMedGoogle Scholar
  34. Freiberg, R., Piscator, M., and Nordberg, M. B., 1971, Cadmium in the Environment, Chemical Rubber Co., Cleveland.Google Scholar
  35. Gaafer, H. A., and Doyle, J., 1971, Specificity of macrophage receptors, Proc. Soc. Exp. Biol.Med. 136:121.Google Scholar
  36. Gainer, J. H., 1973, Activation of the Rauscher leukemia virus by metals, J. Natl. Cancer Inst. 55:609.Google Scholar
  37. Gainer, J. H., 1974, Lead aggravates viral diseases and represses the antiviral activity of interferon inducers, Environ. Health Perspect. 7:113.PubMedCrossRefGoogle Scholar
  38. Gainer, J. H., 1977a, Effects of heavy metals and deficiency of zinc on mortality rates in mice infected with encephalomyocarditis virus, Am. J. Vet. Res. 38:87.Google Scholar
  39. Gainer, J. H., 1977b, Effects of interferon on heavy metals excess and zinc deficiency, Am. J. Vet. Res. 38:863.PubMedGoogle Scholar
  40. Galvin, M. J., Shupe, K., and Lefer, A. M., 1978, Antiendotoxin actions of methylprednisolone in isolated perfused cat liver, Pharmacology 17:181.PubMedCrossRefGoogle Scholar
  41. Gardner, D. E., Miller, F. J., Wing, J. W., and Kirtz, J. M., 1977, Alterations in bacterial defense mechanisms of lung induced by inhalation of cadmium, Bull. Eur. Physiopathol. Respir. 13:157.PubMedGoogle Scholar
  42. Gaworski, C. L., and Sharma, R. P., 1978, The effects of heavy metals on [3H] thymidine uptake in lymphocytes, Toxicol. Appl. Pharmacol. 46:305.PubMedCrossRefGoogle Scholar
  43. Goyer, R. A., and Rhyne, B. C., 1973, Pathological effects of lead, Int. Rev. Exp. Pathol. 12:2.Google Scholar
  44. Graham, J. A., Gardner, D. E., Waters, M. D., and Coffine, D. L., 1975, Effect of trace metals on phagocytosis by alveolar macrophages, Infect. Immun. 11:1278.PubMedGoogle Scholar
  45. Graham, J. A., Miller, F. J., Daniels, M. J., Payne, E. A., and Gardner, D. E., 1978, Influence of cadmium, nickel, and chromium on primary immunity in mice, Environ. Res. 16:77.PubMedCrossRefGoogle Scholar
  46. Greengard, J., 1966, Lead poisoning in childhood: Signs, symptoms, current therapy, clinical expressions, Clin. Pediatr. (Philadelphia) 5:268.CrossRefGoogle Scholar
  47. Hadbavny, A. M., Buchanan, B. J., and Filkins, J. P., 1978, Insulin and regulatory alterations of RES depression. J. Reticuloendothelial Soc. 24:57.Google Scholar
  48. Hadley, J. G., Gardner, D. E., Coffin, D. L., and Menzel, D. B., 1977, Inhibition of antibody-mediated rosette formation by alveolar macrophages: A sensitive assay for metal toxicity, J. Reticuloendothelial Soc. 22:417.Google Scholar
  49. Haley, T. J., 1968, A review of the toxicology of lead, Air Quality Monogr. 69(7):53.Google Scholar
  50. Harris, R. H., Zmudka, M., Maddox, Y., Ramwell, P. W., and Fletcher, J. R., 1980, Relationship of TxB2 and 6-keto-PGF1 to the hemodynamic changes during baboon endotoxic shock, in: Advances in Prostaglandin and Thromboxane Research (B. Samuelson, P. W. Ramwell, and R. Pavoletti, eds.), Vol. 7, pp. 843–849, Raven Press, New York.Google Scholar
  51. Hart, B. A., 1978, Transport of cadmium by alveolar macrophages, J. Reticuloendothelial Soc. 24:363.Google Scholar
  52. Hemphill, F. E., Kaeberle, M. L., and Buck, W. B., 1971, Lead suppression of mouse resistance to Salmonella typhimurium, Science 172:1031.PubMedCrossRefGoogle Scholar
  53. Hildebrand, C. E., and Cram, L. S., 1979, Distribution of cadmium in human blood cultured in low levels of CdCl: Accumulation of Cd in lymphocytes and preferential binding to metallothionin, Proc. Soc. Exp. Biol. Med. 161:438.PubMedGoogle Scholar
  54. Hoffmann, E. O., DiLuzio, N. R., Holper, K., Brettschneider, L., and Coover, J., 1974, Ultrastructural changes in the liver of baboons following lead and endotoxin administration, Lab. Invest. 30:311.PubMedGoogle Scholar
  55. Hoffmann, E. O., Cook, J. A., DiLuzio, N. R., and Coover, J., 1975, The effects of acute cadmium administration on the liver and kidney of the rat, Lab. Invest. 32:655.PubMedGoogle Scholar
  56. Holper, K., Trejo, R. A., Brettschneider, L., and DiLuzio, N. R., 1973, Enhancement of endotoxic shock in the lead sensitized subhuman primates, Surg. Gynecol. Obstet. 136:595.Google Scholar
  57. Jones, R. B., and Kiesow, L. A., 1974, Potentiation of endotoxin-induced consumptive coagulopathy by lead acetate administration, Infect. Immun. 10:1343.PubMedGoogle Scholar
  58. Jones, R. J., Williams, R. L., and Jones, A. M., 1971, Effect of heavy metals on the immune response and preliminary findings for cadmium in rats, Proc. Soc. Exp. Biol. Med. 137:1231.PubMedGoogle Scholar
  59. Jones, R. B., Wise, J. L., and Kiesow, L. A., 1974, Failure of methylprednisolone to protect lead sensitized rats against endotoxin, Infect. Immun. 8:683.Google Scholar
  60. Kaminski, K. J., Fischer, C. A., Kennedy, G. L., Jr., and Calandra, J. C., 1977, Response of pulmonary macrophages to lead, J. Exp. Pathol. 58:9.Google Scholar
  61. Karnovsky, M. L., Simmons, S., Glass, E. A., Gaafar, A. W., and Hart, P. D., 1970, Mononuclear Phagocytes (R. van Furth, ed.), p. 145, Davis, Philadelphia.Google Scholar
  62. Knutson, D. W., Vredevoe, D. L., Aoki, K. R., Esther, J., and Levy, L., 1980, Cadmium and the reticuloendothelial system (RES), a specific defect in blood clearance of soluble aggregates of IgG by the liver in mice given cadmium, Immunology 40:17.PubMedGoogle Scholar
  63. Koller, L. D., 1973, Immunosuppression produced by lead, cadmium and mercury, Am. J. Vet. Res. 34:1457.PubMedGoogle Scholar
  64. Koller, L. D., 1979, Effects of environmental contaminants on the immune system, Adv. Vet. Sci. Comp. Med. 23:267.PubMedGoogle Scholar
  65. Koller, L. D., and Brauner, J. A., 1977, Decreased B-lymphocyte response after exposure to lead and cadmium, Toxicol. Appl. Pharmacol. 42:621.PubMedCrossRefGoogle Scholar
  66. Koller, L. D., and Kovacic, S., 1974, Decreased antibody formation in mice exposed to lead, Nature (London) 250:148.CrossRefGoogle Scholar
  67. Koller, L. D., and Roan, J. G., 1977, Effects of lead and cadmium on mouse peritoneal macrophages, J. Reticuloendothelial Soc. 21:7.Google Scholar
  68. Koller, L. D., Exon, J. H., and Roan, J. G., 1975, Antibody suppression by cadmium, Arch. Environ. Health 30:598.PubMedGoogle Scholar
  69. Koller, L. D., Roan, J. G., and Exon, J. H., 1976, Humoral antibody response in mice after single dose exposure to lead or cadmium, Proc. Soc. Exp. Biol. Med. 151:339.PubMedGoogle Scholar
  70. Koller, L. D., Roan, J. G., Brauner, J. A., and Exon, J. H., 1977, Immune response in aged mice exposed to lead, J. Toxicol. Environ. Health 3:535.PubMedCrossRefGoogle Scholar
  71. Koller, L. D., Roan, J. G., and Kerkvliet, N. I., 1979, Mitogen stimulation of lymphocytes in CBA mice exposed to lead and cadmium, Environ. Res. 19:177.PubMedCrossRefGoogle Scholar
  72. Lazar, G., Serra, D., and Tuchweber, B., 1974, Effect on cadmium toxicity of substances influencing reticuloendothelial activity, Toxicol. Appl. Pharmacol. 29:367.PubMedCrossRefGoogle Scholar
  73. Loose, L. D., Silkworth, J. B., and Warrington, D., 1977, Cadmium-induced depression of respiratory burst in mouse pulmonary alveolar macrophages, peritoneal macrophages and polymorphonuclear neutrophils, Biochem. Biophys. Res. Commun. 79:326.PubMedCrossRefGoogle Scholar
  74. Loose, L. D., Silkworth, J. B., and Warrington, D., 1978, Cadmium induced phagocyte cytotoxicity, Bull. Environ. Contam. Toxicol. 20:582.PubMedCrossRefGoogle Scholar
  75. McLelland, D. B. L., and van Furth, R., 1975, In vitro synthesis of lysozyme by human and mouse tissues and leukocytes, Immunology 28:1099.Google Scholar
  76. Muller, T. E., Gilbert, K. E., Krause, C. H., Gross, U, Age-Stehr, J., and Diamantstein, T., 1977, Suppression of delayed type hypersensitivity of mice by lead, Experientia 33:667.PubMedCrossRefGoogle Scholar
  77. Mustafa, M. G., and Cross, C. E., 1971, Pulmonary alveolar macrophage-oxidative metabolism of isolated cells and mitochondria and effect of cadmium ion on electron and energy transfer reactions, Biochemistry 10:4176.PubMedCrossRefGoogle Scholar
  78. Mustafa, M. G., Cross, C. E., and Tyler, W. S., 1971a, Interfence of cadmium ion with oxidative metabolism of alveolar macrophages, Arch. Intern. Med. 127:1050.PubMedCrossRefGoogle Scholar
  79. Mustafa, M. G., Cross, C. E., Munn, R. J., and Hardie, J. A., 1971b, Effects of divalent metal cations on alveolar macrophage membrane adenosine triphosphatase activity, J. Lab. Clin. Med. 77:563.PubMedGoogle Scholar
  80. Natusch, D. F. S., Wallace, J. R., and Evans, C. N., 1973, Toxic trace elements; preferential concentration in respirable particles, Science, 183:202.CrossRefGoogle Scholar
  81. Neilan, B. A., Taddeini, L., McJilton, C. E., and Handwerger, B. S., 1980, Decreased T cell function in mice exposed to chronic low levels of lead, Clin. Exp. Immunol. 39:746.PubMedGoogle Scholar
  82. Palmer, K. C., Snider, G., and Hayes, J. A., 1975, Cellular proliferation induced in the lung by cadmium aerosol, Am. Rev. Respir. Dis. 112:173.PubMedGoogle Scholar
  83. Perry, H. M., Erlanger, M., Unice, A., Schoepfle, E., and Perry, E. F., 1970, Hypertension and tissue metals following intravenous cadmium, mercury and zinc, Am. J. Physiol. 219:755.PubMedGoogle Scholar
  84. Reichgott, M. J., and Engelman, K., 1975, Indomethacin: Lack of effect on lethality of endotoxin in rats, Circ. Shock 2:215.Google Scholar
  85. Rippe, D. F., and Berry, J. L., 1973, Metabolic manifestations of lead acetate sensitization to endotoxin in mice, J. Reticuloendothelial Soc. 13:527.Google Scholar
  86. Ruiter, N., Seemayer, N., and Manglovic, G., 1977, Einfluz von zindk-ionen auf die toxische Wirkung von bleichlord (PbCl) untersucht an mausemakrophagen in vitro, Zentralbl. Bakteriol. Parasitenkd. Infektionskr. Hyg. Abt. 1 Orig. Reihe B 164:90.Google Scholar
  87. Sbarra, A. J., and Karnovsky, M. L., 1959, The biochemical basis of phagocytosis. I. Metabolic changes during the ingestion of particles by polymorphonuclear leucocytes, J. Biol. Chem. 234:1355.PubMedGoogle Scholar
  88. Selye, H., Tuckweber, B., and Bertok, L., 1966, Effect of lead acetate on susceptibility of rats to bacterial endotoxins, J. Bacteriol. 91:884.PubMedGoogle Scholar
  89. Seyberth, H. W., Schmidt-Gayk, H., and Hackenthal, E., 1972, Toxicity clearance and distribution of endotoxin in mice as influenced by actinomycin D, cycloheximide, α-amanitin and lead acetate, Toxicology 10:491.Google Scholar
  90. Shuler, J. J., Erve, P. R., and Schumer, W., 1976, Glucocorticosteroid effect on hepatic carbohydrate metabolism in the endotoxin-shocked monkey, Ann. Surg. 183:345.CrossRefGoogle Scholar
  91. Shumer, W., and Erve, P. R., 1973, Endotoxin sensitivity of adrenalectomized rats treated with lead acetate, J. Reticuloendothelial Soc. 13:122.Google Scholar
  92. Strauss, R. H., Palmer, K. C., and Hayes, J. A., 1976, Acetate lung injury induced by cadmium aerosol, Am. J. Pathol. 84:561.PubMedGoogle Scholar
  93. Trejo, R. A., and DiLuzio, N. R., 1971, Impaired detoxification as a mechanism of lead acetateinduced hypersensitivity to endotoxin, Proc. Soc. Exp. Biol. Med. 136:889.PubMedGoogle Scholar
  94. Trejo, R. A., DiLuzio, N. R., and Hoffmann, E. O., 1972, Reticuloendothelial and hepatic function alterations following lead acetate administration, Exp. Mol. Pathol. 17:145.PubMedCrossRefGoogle Scholar
  95. Truscott, R. B., 1970, Endotoxin studies in chicks: Effect of leadacetate, Can. J. Comp. Med. 34:135.Google Scholar
  96. Vallee, B. L., and Ulmer, P. D., 1972, Biochemical effects of mercury, cadmium and lead, Annu. Rev. Biochem. 41:91.PubMedCrossRefGoogle Scholar
  97. Ward, P. A., Goldschmidt, P., Norbert, D., and Greene, J., 1975, Suppressive effects of metal salts on leukocyte and fibroblastic function, J. Reticuloendothelial Soc. 18:313.Google Scholar
  98. Waters, M. D., Gardner, D. W., Aranyi, C., and Coffin, D. L., 1975, Metal toxicity for rabbit alveolar macrophages in vitro, Environ. Res. 9:32.PubMedCrossRefGoogle Scholar
  99. Webb, M., 1979, Topics in Environmental Health, Vol. 2, The Chemistry and Biochemistry of Cadmium, Elsevier/North-Holland, Amsterdam.Google Scholar
  100. Wessel, M., and Dominski, A., 1977, Our children’s daily lead, Am. Sci. 65:294.PubMedGoogle Scholar
  101. White, D. J., Marshall, A. J., and McLeod, S., 1975, The influence of experimental distemper infarction on the distribution of lead in dogs previously subacutely intoxicated with lead carbonate, Br. J. Exp. Pathol. 56:544.PubMedGoogle Scholar
  102. Wise, W. C., Cook, J. A., Halushka, P. V., and Knapp, D. R., 1980, Protective effects of thromboxane synthetase inhibitors in rats with endotoxic shock, Circ. Res. 46:854.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • James A. Cook
    • 1
  • W. C. Wise
    • 1
  • W. J. Dougherty
    • 2
  • P. V. Halushka
    • 3
  1. 1.Department of PhysiologyMedical University of South CarolinaCharlestonUSA
  2. 2.Department of AnatomyMedical University of South CarolinaCharlestonUSA
  3. 3.Departments of Pharmacology and MedicineMedical University of South CarolinaCharlestonUSA

Personalised recommendations