Advertisement

Cycloheximide and Other Glutarimide Antibiotics

  • Hugh D. Sisler
  • Malcolm R. Siegel
Part of the Antibiotics book series (ANTIBIOTICS, volume 1)

Abstract

A number of biologically active glutarimide derivatives have been isolated from various streptomycetes. The derivatives for which chemical structures have been determined include cycloheximide, naramycin B, isocycloheximide, streptimidone, acetoxycycloheximide, inactone and the streptovitacins. All have in common the β (2-hydroxyethyl) glutarimide moiety attached to a cyclic or acyclic ketone. Although the antibiotics are noted particularly for their antifungal properties, they are toxic to a broad spectrum of organisms. Yet, a highly interesting characteristic of these antibiotics is the marked difference in their activity toward closely related organisms.

Keywords

Culture Filtrate Streptomyces Griseus Resistant Yeast Benzoyl Ester Cyclohexanone Ring 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Arnow, P., S. H. Brindle, N. A. Giuffre, and D. Perlman: Effects of antibiotics, antitumor agents, and antimetabolites on the metabolism of mammalian cells in tissue culture. Antimicrobial Agents and Chemotherapy 1962, 731–739 (1963).Google Scholar
  2. Bennett, JR., L. L., D. Smithers, and C. T. Ward: Inhibition of DNA synthesis in mammalian cells by actidione. Biochim. et Biophys. Acta 87, 60–69 (1964).Google Scholar
  3. Bennett, JR., L. L., V. L. Ward, and R. W. Brockman: Inhibition of protein synthesis in vitro by cycloheximide and related glutarimide antibiotics. Biochim. et Biophys. Acta 103, 478–485 (1965).Google Scholar
  4. Berliner, M. D., and L. S. Olive: Meiosis in Gymnosporangium and the cytological effects of certain antibiotic substances. Science 117, 652–653 (1953).PubMedCrossRefGoogle Scholar
  5. Blumauerovä, M., and J. Starka: Reversal of antibiotic action of cycloheximide (actidione) by bivalent metal ions. Nature 183, 261 (1959).PubMedCrossRefGoogle Scholar
  6. Bradley, S. G.: Relationship between sugar utilization and the action of cycloheximide on diverse fungi. Nature 194, 315–316 (1962).PubMedCrossRefGoogle Scholar
  7. Colombo, B., L. Felicetti, and C. Baglioni: Inhibition of protein synthesis by cycloheximide in rabbit reticulocytes. Biochem. Biophys. Research Commun 18, 389–395 (1965).CrossRefGoogle Scholar
  8. Cooney, W. J., and S. G. Bradley: Action of cycloheximide on animal cells. Antimicrobial Agents and Chemotherapy. 1961, 237–244 (1962).Google Scholar
  9. Cooney, W. J., and S. G. Bradley: Effect of cycloheximide on the immune response. Antimicrobial Agents and Chemotherapy. 1962, 1–9 (1963).Google Scholar
  10. Coursen, B. W.: Effect of the antibiotic, cycloheximide, on the growth and metabolism of Saccharomyces pastorianus. Ph.D. Thesis, University of Maryland 1959.Google Scholar
  11. Coursen, B. W., and H. D. Sisler: Effect of the antibiotic, cycloheximide, on the metabolism and growth of Saccharomyces pastorianus. Am. J. Botany 47, 541–549 (1960).CrossRefGoogle Scholar
  12. De Kloet, S. R.: Accumulation of RNA with DNA like base composition in Saccharomyces carlsbergiensis in the presence of cycloheximide. Biochem. Biophys. Research Commun 19, 582–586 (1965).CrossRefGoogle Scholar
  13. Eble, T. E., M. E. Bergy, C. M. Large, R. R. Herr, and W. G. Jackson: Isolation, purification and properties of streptovitacins A and B. Antibiotics Ann. 1958/59, 555–559 (1959).Google Scholar
  14. Ennis, H. L., and M. Lubin: Cycloheximide: Aspects of inhibition of protein synthesis in mammalian cells. Science 146, 1474–1476 (1964).PubMedCrossRefGoogle Scholar
  15. Evans, J. S., J. Ceru, and G. D. Mengel: The in vivo antitumor activity of streptovitacins A, B, C2 and D. Antibiotics Ann. 1959/60, 962–965 (1960).Google Scholar
  16. Evans, J. S., G. D. Mengel, J. Ceru, and R. L. Johnston: Biological studies on streptovitacin A, a new antitumor agent. Antibiotics Ann. 1958/59, 565–571 (1959).Google Scholar
  17. Fiala, E. S., and F. F. Davis: Preferential inhibition of synthesis and methylation of ribosomal RNA in Neurospora crassa by actidione. Biochem. Biophys. Research Commun 18, 115–118 (1965).CrossRefGoogle Scholar
  18. Fiala, S., and E. Fiala: Hormonal dependence of actidione (cycloheximide) action. Biochim. et Biophys. Acta 103, 699–701 (1965).Google Scholar
  19. Ford, J. H., and W. Klomparens: Cycloheximide (acti-dione) and its nonagricultural uses. Antibiotics & Chemotherapy 10, 682–687 (1960).Google Scholar
  20. Ford, J. H., W. Klomparens, and C. L. Hamner: Cycloheximide (actidione) and its agricultural uses. Plant Disease Reptr. 42, 680–695 (1958).Google Scholar
  21. Frohardt, R. P., H. W. Dion, Z. L. Jakubowski, A. Ryder, J. C. French, and Q. R. Bartz: Chemistry of streptimidone, a new antibiotic. J. Am. Chem. Soc. 81, 5500–5506 (1959).CrossRefGoogle Scholar
  22. Fukuhara, H.: RNA synthesis of yeast in the presence of cycloheximide. Biochem. Biophys. Research Commun 18, 297–301 (1965).CrossRefGoogle Scholar
  23. Gorski, J., and M. C. Axman: Cycloheximide (actidione) inhibition of protein synthesis and the uterine response to estrogen. Arch. Biochem. Biophys. 105, 517–520 (1964).PubMedCrossRefGoogle Scholar
  24. Greig, M. E., R. A. Walk, and A. J. Gibbons: Effect of actidione (cycloheximide) on yeast fermentation. J. Bacteriol. 75, 489–491 (1958).PubMedGoogle Scholar
  25. Grover, R. K., and J. D. Moore: Toximetric studies of fungicides against the brown rot organisms, Sclerotinia fructicola and S. laxa. Phytopathology 52, 876–880 (1962).Google Scholar
  26. Gundersen, K.: Cycloheximide, the active substance in Streptomyces griseus antagonism against Fomes annosus. Acta Horti Gotoburgensis 24, 1–24 (1961).Google Scholar
  27. Gundersen, K.: Induced resistance in Fomes annosus to the antibiotic cycloheximide. Acta Horti Gotoburgensis 25, 1–32 (1962a).Google Scholar
  28. Gundersen, K.: The action mechanism of cycloheximide in Fomes annosus. Acta Horti Gotoburgensis 25, 33–63 (1962b).Google Scholar
  29. Gundersen, K., and T. Wadstein: Morphological changes and resistance induced in Saccharomyces pastorianus by the antibiotic cycloheximide. J. Gen. Microbiol. 28, 325–332 (1962).PubMedGoogle Scholar
  30. Hadder, J. C., and G. B. Wilson: Cytological assay of c-mitotic and prophase poison actions. Chromosoma 9, 91–104 (1958).PubMedCrossRefGoogle Scholar
  31. Hawthorne, M. E., and G. B. Wilson: The cytological effects of the antibiotic actidione. Cytologia (Tokyo) 17, 71–85 (1952).CrossRefGoogle Scholar
  32. Herr, R. R.: Structure studies on streptovitacins A and B. Antibiotics Ann. 1958/59, 560–564 (1959a).Google Scholar
  33. Herr, R. R.: Structures of the streptovitacins. J. Am. Chem. Soc. 81, 2595–2596 (1959b).CrossRefGoogle Scholar
  34. Hewitt, E. J., and M. M. R. K. Afridi: Adaptive synthesis of nitrate reductase in higher plants. Nature 183, 57–58 (1959).CrossRefGoogle Scholar
  35. Highet, R. J., u. V. Prelog: Stoffwechselprodukte von Actinomyceten. Helv. Chim. Acta 42, 1523–1526 (1959).CrossRefGoogle Scholar
  36. Hirabayashi, A.: Studies on the antiamebic effect of protomycin, a new antibiotic isolated from the culture filtrate of a species of streptomycetes. J. Antibiotics (Japan), Ser. A 12, 298–309 (1959).Google Scholar
  37. Hsu, K. S.: The genetic basis of actidione resistance in Neurospora. J. Gen. Microbiol. 32, 341–347 (1963).PubMedGoogle Scholar
  38. Igarashi, S., and S. Wada: Fermicidin, an new antibiotic active against yeasts and trichomonas. [In Japanese] J. Antibiotics (Japan), Ser. B 7, 221–225 (1954).Google Scholar
  39. Johnson, F.: Glutarimide antibiotics. I. The synthesis of actiphenol. J. Org. Chem. 27, 3658–3660 (1962).CrossRefGoogle Scholar
  40. Johnson, F., and A.A. Carlson: Glutarimide antibiotics. Part VIII. A stereoselective synthesis of dl-α-epi-isocycloheximide. Tetrahedron Letters 14, 885–889 (1965).PubMedCrossRefGoogle Scholar
  41. Johnson, F., W. D. Gurowitz, and N. A. Starkovsky: Glutarimide antibiotics. Part II. The synthesis and stereochemistry of dl-neocycloheximide, a new isomer of cycloheximide. Tetrahedron Letters 25, 1167–1171 (1962).CrossRefGoogle Scholar
  42. Johnson, F., N. A. Starkovsky, and W. D. Gurowitz: Glutarimide antibiotics. VII. The synthesis of dl-neocycloheximide and the determination of the cyclohexanone ring stereochemistry of cycloheximide, its isomers, and inactone. J. Am. Chem. Soc. 87, 3492–3500 (1965).PubMedCrossRefGoogle Scholar
  43. Johnson, F., N. A. Starkovsky, A.C. Paton, and A.A. Carlson: Glutarimide antibiotics. IV. The total synthesis of dl-and l-cycloheximide. J. Am. Chem. Soc. 86, 118–119 (1964).CrossRefGoogle Scholar
  44. Kerridge, D.: The effect of actidione and other antifungal agents on nucleic acid and protein synthesis in Saccharomyces carlsbergensis. J. Gen. Microbiol. 19, 497–506 (1958).PubMedGoogle Scholar
  45. Kielhöfer, E., u. H. Aumann: Untersuchungen über die Wirkung des Antibioticums Actidion auf Hefe im Vergleich mit anderen fungitoxischen Substanzen. Z. Lebensm.-Untersuch, u. Forsch. 105, 283–296 (1957).CrossRefGoogle Scholar
  46. Kjellin-STRABY, K., and H. G. Boman: Studies on microbial RNA. III. Formation of submethylated sRNA in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. U.S. 53, 1346–1352 (1965).CrossRefGoogle Scholar
  47. Kohberger, D. L., M. W. Fisher, M. M. Galbraith, A. B. Hillegas, P. E. Thompson, and J. Ehrlich: Biological studies of streptimidone, a new antibiotic. Antibiotics & Chemotherapy 10, 9–16 (1960).Google Scholar
  48. Kornfeld, E. C., R. G. Jones, and T. V. Parke: The structure and chemistry of actidione an antibiotic from Streptomyces griseus. J. Am. Chem. Soc. 71, 150–159 (1949).PubMedCrossRefGoogle Scholar
  49. Lardy, H. A., D. Johnson, and W. C. Mcmurray: Antibiotics as tools for metabolic studies. I. A survey of toxic antibiotics in respiratory, phosphorylating and glycolytic systems. Arch. Biochem. Biophys. 78, 587–597 (1958).PubMedCrossRefGoogle Scholar
  50. Latuasan, H. E., and W. Berends: The action mechanism of actidione. Rec. trav. chim. 77, 416–422 (1958).CrossRefGoogle Scholar
  51. Leach, B. E., J. H. Ford, and A. J. Whiffen: Actidione, an antibiotic of Streptomyces griseus. J. Am. Chem. Soc. 69, 474 (1947).PubMedCrossRefGoogle Scholar
  52. Lee, B. K., and D. Wilkie: Sensitivity and resistance of yeast strains to actidione and actidione derivatives. Nature 206, 90–92 (1965).PubMedCrossRefGoogle Scholar
  53. Lemin, A. J., and J. H. Ford: Isocycloheximide. J. Org. Chem. 25, 344–346 (1960).CrossRefGoogle Scholar
  54. Lemin, A. J., and W. E. Magee: Degradation of cycloheximide derivatives in plants. Plant Disease Reptr. 41, 447–448 (1957).Google Scholar
  55. Lindner, R. C., H. C. Kirkpatrick, and T. E. Weeks: Comparative inhibition of virus multiplication by certain types of chemicals. Phytopathology 49, 802–807 (1959).Google Scholar
  56. Loefer, J. B., and T. S. Matney: Growth inhibition of free-living protozoa by actidione. Physiol. Zoöl. 25, 272–276 (1952).Google Scholar
  57. Mccallan, S. E. A., L. P. Miller, and R. M. Weed: Comparative effect of fungicides on oxygen uptake and germination of spores. Contrib. Boyce Thompson Inst. 18, 39–68 (1954).Google Scholar
  58. Mefferd, Jr., R. B., and J. B. Loefer: Inhibition of respiration in Tetrahymena pyriformis S by actidione. Physiol. Zoöl. 27, 115–118 (1954).Google Scholar
  59. Middlekauf, J. E., S. Hino, S. P. Yang, C. C. Lindegren, and G. Lindegren: Gene control of resistance vs. sensitivity to actidione in Saccharomyces. Genetics 42, 66–71 (1957).Google Scholar
  60. Monreal, K.: Die Wirkung von Actidion auf Saccharomyces cerevisiae var elipsoideus. Angew. Botan. 35, 24–60 (1961).Google Scholar
  61. Okuda, T.: Studies on streptomyces antibiotic, cycloheximide. VI. The absolute configuration of naramycin-A (cycloheximide) and its isomeric naramycin-B. Chem. Pharm. Bull. 7, 671–679 (1959).CrossRefGoogle Scholar
  62. Okuda, T., and M. Suzuki: Absolute configuration of cycloheximide. Chem. Pharm. Bull. 9, 1014–1016 (1961).CrossRefGoogle Scholar
  63. Okuda, T., M. Suzuki, Y. Egawa, and K. Ashino: Studies on streptomyces antibiotic, cycloheximide. II. Naramycin-B, an isomer of cycloheximide. Chem. Pharm. Bull. 7, 27–30 (1959).CrossRefGoogle Scholar
  64. Okuda, T., M. Suzuki, T. Furumai, and H. Takahashi: Studies on streptomyces antibiotic, cycloheximide. XVIII. Isomerization study of cycloheximides and thermal degradation of naramycin-B. Chemical support of the proposed absolute configuration of cycloheximides. Chem. Pharm. Bull. 11, 730–736 (1963).PubMedCrossRefGoogle Scholar
  65. Osato, T., Y. Morikubo, S. Yamazaki, T. Hikiji, K. Yano, M. Kanao, T. Osono, and H. Umezawa: Screening studies of antiviral substances produced by actinomycetes and new antiviral substances, niromycins. J. Antibiotics (Japan), Ser. A 13, 97–109 (1960a).Google Scholar
  66. Osato, T., Y. Morikubo, and H. Umezawa: Production and extraction of niromycins, antiviral antibiotics. J. Antibiotics (Japan), Ser. A 13, 110–113 (1960b).Google Scholar
  67. Palmer, C., and T. E. Maloney: Preliminary screening for potential algicides. Ohio J. Sci. 55, 1–8 (1955).Google Scholar
  68. Paul, R., et S. Tchelitcheff: Constitution chimique de l’inactone. Synthèse partielle de trois isomères de l’actidione. Bull. soc. chim. France 1316 (1955).Google Scholar
  69. Rao, K. V.: C-73: A metabolic product of Streptomyces albulus. J. Org. Chem. 25, 661–662 (1960a).CrossRefGoogle Scholar
  70. Rao, K. V.: E-73: An antitumor substance. Part II. Structure. J. Am. Chem. Soc. 82, 1129–1132 (1960b).CrossRefGoogle Scholar
  71. Rao, K. V.: E-73: An antitumor substance. Part III. Some derivatives. Antibiotics & Chemotherapy 12, 123–127 (1962).Google Scholar
  72. Rao, K. V., and W. P. Cullen: E-73: An antitumor substance. Part I. Isolation and characterization. J. Am. Chem. Soc. 82, 1127–1128 (1960).CrossRefGoogle Scholar
  73. Roush, A. H., and T. R. Shieh: The inhibition of purine transport and the induced biosynthesis of enzymes in yeasts by actidione. Federation Proc. 21, 147 (1962).Google Scholar
  74. Seydoux, J., et G. Turian: Accumulation d’acide pyruvique et d’acide α-ceto-glutarique et reversion partielle par l’aneurine chez neurospora traité à l’actidione. Path. Microbiol. 25, 752–765 (1962).Google Scholar
  75. Shepherd, C. J.: Inhibition of protein and nucleic acid synthesis in Aspergillus nidulans. J. Gen. Microbiol. 18, IV (1958).Google Scholar
  76. Siegel, M. R., and H. D. Sisler: Inhibition of protein synthesis in vitro by cycloheximide. Nature 200, 675–676 (1963).PubMedCrossRefGoogle Scholar
  77. Siegel, M. R., and H. D. Sisler: Site of action of cycloheximide in cells of Saccharomyces pastorianus. I. Effect of the antibiotic on cellular metabolism. Biochim. et Biophys. Acta 87, 70–82 (1964a).Google Scholar
  78. Siegel, M. R., and H. D. Sisler: Site of action of cycloheximide in cells of Saccharomyces pastorianus. II. The nature of inhibition of protein synthesis in a cell-free system. Biochim. et Biophys. Acta 87, 83–89 (1964b).Google Scholar
  79. Siegel, M. R., and H. D. Sisler: Site of action of cycloheximide in cells of Saccharomyces pastorianus. III. Further studies on the mechanism of action and the mechanism of resistance in saccharomyces species. Biochim. et Biophys. Acta 103, 558–567 (1965).Google Scholar
  80. Siegel, M. R., H. D. Sisler, and F. Johnson: Relationship of structure to fungitoxicity of cycloheximide and related glutarimide derivatives. Biochem. Pharmacol. 15, 1218–1223 (1966).CrossRefGoogle Scholar
  81. Sisler, H. D., and N. L. Marshall: Physiological effects of certain fungitoxic compounds on fungus cells. J. Wash. Acad. Sci. 47, 321–329 (1957).Google Scholar
  82. Sisler, H. D., and M. R. Siegel: Factors affecting toxicity of cycloheximide derivatives. Manuscript in preparation 1966.Google Scholar
  83. Smith, C. G.: Tissue culture. Bioassay methods for streptovitacin A. Proc. Soc. Exptl. Biol. Med. 100, 757–759 (1959).Google Scholar
  84. Smith, C. G., W. L. Lummis, and J. E. Grady: An improved tissue culture assay. I. Methodology and cytotoxicity of anti-tumor agents. Cancer Research 19, 843–846 (1959).Google Scholar
  85. Smith, C. G., W. L. Lummis, and J. E. Grady: Studies on the mode of action of streptovitacin A. Cancer Research 20, 1394–1398 (1960).Google Scholar
  86. Sokolski, W. T., N. J. Eilers, and G. M. Savage: Paper chromatography and microbiological assay of the streptovitacins. Antibiotics Ann. 1958/59, 551–554 (1959).Google Scholar
  87. Starzyk, M. J.: The effect of cycloheximide on the germination of conidia of Coccomyces hiemalis. Phytopathology 53, 235 (1963).Google Scholar
  88. Sugawara, R.: Protomycin, a new antibiotic of cycloheximide group. II. Production and properties. J. Antibiotics (Japan), Ser. A 16, 115–120 (1963a).Google Scholar
  89. Sugawara, R.: Protomycin, a new antibiotic of cycloheximide group. III. Degradation products. J. Antibiotics (Japan), Ser. A 16, 167–171 (1963b).Google Scholar
  90. Suzuki, M.: Studies on streptomyces antibiotic, cycloheximide. X. Structure-antimicrobial activity relationship of cycloheximide and related compounds. [In Japanese.] Yakugaku Zasshi 80, 1217–1222 (1960).Google Scholar
  91. Suzuki, M., Y. Egawa, and T. Okuda: Studies on streptomyces antibiotic, cycloheximide. XV. Hydroxycarbonylation of optically active 2, 4-dimethylcyclohexanones with glutarimide-β-acetaldehyde. (Synthesis of isocycloheximide and its isomers.) Chem. Pharm. Bull. 11, 582–588 (1963).CrossRefGoogle Scholar
  92. Trakatellis, A. C., M. Montjar, and A. E. Axelrod: Effect of cycloheximide on polysomes and protein synthesis in the mouse liver. Biochemistry 4, 2065–2071 (1965).CrossRefGoogle Scholar
  93. Tsukada, Y., T. Sugimori, K. Imai, and H. Katagiri: Action of cycloheximide on Zygosaccharomyces soja. J. Bacteriol. 83, 70–75 (1962).PubMedGoogle Scholar
  94. Van Tamelen, E. E., and V. Haarstad: Structure of the antibiotic streptimidone. J. Am. Chem. Soc. 82, 2974–2975 (1960).CrossRefGoogle Scholar
  95. Walker, A. T., and F. G. Smith: Effect of actidione on growth and respiration of Myrothecium verrucaria. Proc. Soc. Exptl. Biol. Med. 81, 556–559 (1952).Google Scholar
  96. Welch, J. J.: Rodent control. A review of chemical repellents for rodents. J. Agr. Food Chem. 2, 142–149 (1954).CrossRefGoogle Scholar
  97. Wescott, E. W.: Uptake of cycloheximide by a sensitive and a resistant yeast and effect of the antibiotic on alcohol dehydrogenase. Ph.D. Thesis, University of Maryland 1962.Google Scholar
  98. Wescott, E. W., and H. D. Sisler: Uptake of cycloheximide by a sensitive and a resistant yeast. Phytopathology 54, 1261–1264 (1964).Google Scholar
  99. Wettstein, F. O., H. Noll, and S. Penman: Effect of cycloheximide on ribosomal aggregates engaged in protein synthesis in vitro. Biochim. et Biophys. Acta 87, 525–528 (1964).Google Scholar
  100. Whiffen, A. J.: The production, assay, and antibiotic activity of actidione, an antibiotic from Streptomyces griseus. J. Bacteriol. 56, 283–291 (1948).Google Scholar
  101. Whiffen, A. J.: The activity in vitro of cycloheximide (actidione) against fungi pathogenic to plants. Mycologia 42, 253–258 (1950).CrossRefGoogle Scholar
  102. Whiffen, A. J., N. Bohonos, and R. L. Emerson: The production of an antifungal antibiotic by Streptomyces griseus. J. Bacteriol. 52, 610–611 (1946).PubMedGoogle Scholar
  103. Widuczynski, I. and A. O. M. Stoppani: Action of cycloheximide on amino acid metabolism in Saccharomyces ellipsoideus. Biochim. et Biophys. Acta 104, 413–426 (1965).CrossRefGoogle Scholar
  104. Wilkie, D., and B. K. Lee: Genetic analysis of actidione resistance in Saccharomyces cerevisiae. Genet. Res. Camb. 6, 130–138 (1965).CrossRefGoogle Scholar
  105. Williamson, A. R., and R. Schweet: Role of the genetic message in polyribosome function. J. Mol. Biol. 11, 358–372 (1965).PubMedCrossRefGoogle Scholar
  106. Wilson, G. B.: Cytological effects of some antibiotics. J. Heredity 41, 227–231 (1950).Google Scholar
  107. Wilson, G. B.: The assay of antimitotics. Chromosoma 16, 133–143 (1965).PubMedCrossRefGoogle Scholar
  108. Woo, P. W. K., H. W. Dion, and Q. R. Bartz: The structure of streptimidone. J. Am. Chem. Soc. 83, 3085–3087 (1961).CrossRefGoogle Scholar
  109. Young, C. W., P. F. Robinson, and B. Sackton: Inhibition of the synthesis of protein in intact animals by acetoxycycloheximide and a metabolic derangement concomitant with this blockage. Biochem. Pharmacol. 12, 855–865 (1963).PubMedCrossRefGoogle Scholar
  110. Zehnder, A., and E. O. Hughes: The antialgal activity of actidione. Can. J.Microbiol. 4, 399–408 (1958).PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1967

Authors and Affiliations

  • Hugh D. Sisler
  • Malcolm R. Siegel

There are no affiliations available

Personalised recommendations