Skip to main content
SpringerLink
Log in

Aminopterin toxicity reversal by a hemopoietic fraction of microbial “animal protein factor”: Some similarities of streptomyces fermentation residue to pituitary erythropoietin

  • Original contribution
  • Published:
The American Journal of Digestive Diseases

Summary

From a crude streptomyces griseus “animal protein factor” feed supplement in which a corticotropin had been found, an acid eluate of charcoal adsorbate was prepared. In 2 milligram oral daily doses this eluate not only reversed the myeloplastic and cholinergic effects of aminopterin poisoning in weanling rats, but evoked accelerated growth and hemopoiesis in the face of aminopterin administration. It is concluded that the original fermentation broth contained an erythropoietin and a somatotropin in addition to the corticotropin.

Since intestinal commensal organisms including those classified among the enterobacteriacae have been shown to be a source of corticotropin, it is postulated that microbial sources, including the intestinal flora can engender somatotropic and erythropoietic factors similar to those, or precursors to those produced by the adenohypophysis. It is further postulated that pituitary erythropoietin precursor arises from the intestinal flora, is a transient constituent of intestinal mucosa and liver and reaches the anterior pituitary where it is modified to its final elaborate; erythropoietic hormone, EPH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Barnard, R. D. and Appel, A.: Scleroderma Associated with Malignant Estrapenie Leukoblastosis (“Leukemia”); Case Report Illustrating Therapeutic Response to Orally Administered Crude “B12” Fermentation Concentrates. Urol. & Cutan. Rev., 54:345, 1950.

    CAS  Google Scholar 

  2. Barnard, R. D. and Fox, H. L.: Innocuity of Protracted Administration of Crude, B12-Containing Fermentation Concentrates as Demonstrated in a Patient with Acute Leukemia. Ohio State M. J., 46:784, 1950.

    CAS  Google Scholar 

  3. Waksman, S. A.: Actinomyein. Antibioties and Chemother.,4:504, 1954; see also Hackmann, C.: Experimental Investigation of the Action of Actinomyein C on Malignant Tumors. Z. Krebsforsch,58. 500, 1952.

    Google Scholar 

  4. Barnard, R. D., Kopet, S. J. and Stahl, A. E.: Erythremia (“Polycythemia”) During Massive, Oral, Strepto-myces-Derived B12 Therapy: A Report of Two Cases with Further Observations on the Anti-Allergic Effects of Streptomyces Fermentation Antibiotics. Ann. Allergy, 9:360, 1951.

    PubMed  CAS  Google Scholar 

  5. Barnard, R. D.: Management of Hodgkin’s Disease, Hawaii M. J., 11:57, 1952.

    Google Scholar 

  6. Rokujo, M., Ukita, T., Tamura, T., Tsumita, T. and Kos-aka, S.: Screening Tests of the Chemical Compounds which Inhibit the Yoshida Ascites Tumor (In Japanese), cited by Umezawa et al., Sarkomyein and Antineoplastic Agents from Streptomyces. Antibiotics and Chemother. 4:514, 1954.

    Google Scholar 

  7. Nelson, J. W., O’Connell, P. W. and Haines, W. J.: Ad-renocortieotropins from Non-mammalian Sources. Science, 119:379, 1954.

    Article  PubMed  CAS  Google Scholar 

  8. Takeda, K., et al: Bacterial Adrenocorticotropin. Japanese J. Exp. Med., 21:337, 1951, 22:423, 1952.

    Google Scholar 

  9. Barnard, R. D.: Cortieotherapeutie Equivalence of Ter-ramycin. N. Y. State J. Med., 50:1852, 1950 Idem., Salt Retention: An Adrenoeortieomimetie Effect of Certain Antibioties, Ibid., 51:517, 1951.

    Google Scholar 

  10. Coren, O. J. and Barnard, R. D.: Probable Mechanism of Bowel Content Deodorization by Chloresium; A Confirmatory Bacteriologic Study. N. Y. State J. Med., 54, 445, 1954.

    Google Scholar 

  11. Barnard, R. D.: Administration of Fermentation Residues of Antibiotic-Producing Streptomyces Strains in Human Neoplastie Disease. Proc. VIth Int. Cancer Congress. Read at San Paulo, Brazil, July 27, 1954. Barnard, R. D., Kessler, L. N. and Kershner, D.: APF Therapy in Advanced Cancer, Int. Rec. Med. In Press.

    Google Scholar 

  12. Barnard, R. D.: Oncolytic Effects of Antibiotic-Containing Animal Feed Supplements. Lancet ii, 677, 1954.

    Google Scholar 

  13. Barnard, R. D. and Freeman, M. D.: Reversal of Aminop-terin Toxicity by Water-Soluble Cupridihydroporphyrina (Chloresium) Am. J. Dig. Dis., 21:163, 1954.

    Article  PubMed  CAS  Google Scholar 

  14. Evans, H. M.: Cited in Handbook of Endocrinology, 1937, American Medical Association, Chicago, III.

    Google Scholar 

  15. Van Dyke, D. C, Contopoulos, A. N., Williams, S. B., Simpson, M. E., Lawrence, J. H. and Evans, H. M.: Hormonal Factors Influencing Erythropoiesis. Acta He-matologiea. 11:1203. 1954. Contopoulos, A. N., Evans, E. S., Ellis, S. and Simpson, M. E.: Increased Metabolic Bate without Thyroid Partieipation on Injection of Rats with Pituitary Erythropoietic Fractions. Proc. Soc. Exp. Biol. and Med., 86:729, 1954.

    Google Scholar 

  16. Sayers, W. A., Sayers, G. and Woodbury, L. A.: Assay of Adrenocorticotropin by Adrenal Ascorbic Acid Depletion, Endocrinology, 42:379, 1948.

    Article  CAS  PubMed  Google Scholar 

  17. Weyer, E. B.: Personal Communication. Kleinberg, W.: Personal Communication. Mayer, E. R.: Increased 17-ketosteroid Excretion by Patients Ingesting Crude Strep-tomyces Griseus Residue. Unpublished Communication.

  18. Solomon, C, Barnard, B. D. and Golan, H. G.: Clinical Significance of Blood Cholinesterase Determinations. N. Y. State J. Med., 49, 1949. Barnard, B. D.: Marrow Aplasia and Estrapenia in Pemphigus Vulgaris; Case Report with Autopsy Findings and Notes on Relationship of Erythroid Marrow Function to Atopic-Exudative Skin Lesions. Urel & Cutan Rev.51:586, 1947.

    Google Scholar 

  19. Barnard, B. D., Mentha, J. W. and LaForgia, C.: Belationship of Blood Cholinesterase Level to Duration of Life in Leukemia with Notes on Elevation of Blood Cholinesterase in Some “Leukemoid” States. Med. Rec. 162:19, 1949.

    Google Scholar 

  20. Barnard, B. D.: Cholinergic Porphyria Laerymation and Paradoxical Mydriasis in the Rat: Possible Heme Nature of Cholinesterase. Proc. Soc. Exp. Biol. & Med. 54:357, 1943.

    Google Scholar 

  21. Mendel, B., Mundell, D. B. and Hawkins, B. D.: Removal of Acetyleholine by Cholinesterase Injections and the Effect of These on Nerve Impulse Transmission. J. Neurophysiol. 6:431, 1943.

    CAS  Google Scholar 

  22. Barnard, R. D. and Mentha, J. W.: Effect of Cholinesterase-Containing Fraction of Human Plasma Globulin Fraction in Macrocytic Anemia. Science,107:571, 1948.

    Article  PubMed  Google Scholar 

  23. Goldstein, D. B. and Goldstein, A.: An Adaptive Bacterial Cholinesterase from a Pseudomonas Species. J. Gen. Microbiol. 8:8, 1953.

    PubMed  CAS  Google Scholar 

  24. Williams, B. J.: Personal Communication, cit. 17.

  25. Barnard, R. D. and Orens, L. B.: Antibiotic Administration During Radiation Therapy. N. Y. State J. Med., 51:2535, 1952; Barnard, E. D., Caracappa, J. M., Gordon, G. B., Schwartz, M. and Moldover, A.: Further Observations on the Besponse of Erythroblastie, Megaloblastic and Badiation Anemia to Streptomyces-Derived Animal Protein Factor and Antibiotics, Ibid., 51:1739, 1951.

    Google Scholar 

  26. Menge, H., Renton, C. A., Sizemore, J. B., Lillie, B. J. and Bird, H. R.: Poultry Nutrition II. Properties and Fractionation of a Growth Factor in Condensed Fish Solubles, Poultry Sci.,32:863, 1953.

    CAS  Google Scholar 

  27. Saechetti, C. and Bianchini, E.: STH and Hemopoiesis; Hemopoiesis in the Splenectomized Rat. Arch. Sci. med., 95:587, 1953. See also Gemzell, C. A. and Sjostrand, T.:Effect of Hypophysectomy, ACTHand growth hormone on the Total Amount of Hemoglobin and Blood Volume of the Rat. Acta Endocrinol. 16:6, 1954.

    Google Scholar 

  28. Barnard, R. D.: Therapeutic Applications of Human Plasma Cholinesterase, Lancet, ii:1229, 1952.

    Google Scholar 

  29. Evans, F. T., Gray, P. W. S., Lehmann, H. and Silk, E.: Succinylcholine, Ibid, ii:1038, 1952.

    Google Scholar 

  30. Barnard, R. D. and Fox, H. L.: The Effect of Cholase Administration on Some Dermatologic Conditions, N. Y. State J. Med., 53:2826, 1953.

    PubMed  CAS  Google Scholar 

  31. Mian, E. U.: Effect of Corticotrophie Hormone on Acetyl-cholinesterase Activity of Blood Serum. Boll. ital. soe. biol. sper. 27:108, 1951.

    CAS  Google Scholar 

  32. Davis, J. E.: Antianemic Agents and Cholinesterase Activity. Am. J. Dig. Dis. 17:339, 1950.

    PubMed  CAS  Google Scholar 

  33. Conard, R. A.: Cholinesterase Activity, Weight, Water Content and Pathology of Small Intestines of Rats Subjected to X-irradition. Am. J. Physiol. 170:418, 1952.

    PubMed  CAS  Google Scholar 

  34. Bum, J. H., Kordik, P. and Mole, R. M.: Effect of X-irradiation on Besponse of Intestine to Acetyleholine and on Its Content of “Pseudo” Cholinesterase. Brit. J. Pharm. 7:58, 1952.

    Google Scholar 

  35. Lüthy, H.: Effect of Radiation on the Plasma Cholinesterase of the Mouse, Radiol. Clin., 22:491, 1953.

    Google Scholar 

  36. Barnard, R. D.: Depression of Blood Cholinesterase Level Following X-Ray Therapy and Its Bearing on the Mechanism of Radiation Sickness. Med. Rec. 161:350, 1948.

    CAS  Google Scholar 

  37. Langley, L. L.: Extra-Adrenal Adaptation to Stress. Int. Physiol. Congress, Montreal, Sept. 3, 1953.

  38. Barnard, R. D.: The Nature of Acute Leukemia and the Interrelationships of the Malignant Dyscrasias. N. Y. State J. Med., 47:2703, 1947. Barnard, R. D. and Fried-land, S.: The Atopic Nature of Amyotrophie Lateral Sclerosis: Evidence Afforded by Results with Adrenal Cortex Therapy, Ibid. 50:1365, 1950.

    PubMed  CAS  Google Scholar 

  39. Tintera, J. J.: Hypoadrenocorticism. N. Y. State J. Med., In Press.

  40. Everett, J. W. and Sawyer, C. H.: Pituitary Regulation of Cholinesterase. Anat. Bee, 94:336, 1946. Acknowledgements: The Streptomyces Fraction was prepared and furnished by Dr. I. A. Solomons of Charles Pfizer & Co., Brooklyn. Valuable Technical advice was rendered by Dr. Solomons and Dr. Elliott R. Weyer of Pfizer. Chlorophyl-lin derivatives were furnished by the Rystan Company, Mt. Vernon, N. Y.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Professional Pathological Laboratories, 1 W. 34 Street, New York City, New York

    Robert D. Barnard & Mark D. Freeman

Authors
  1. Robert D. Barnard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark D. Freeman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barnard, R.D., Freeman, M.D. Aminopterin toxicity reversal by a hemopoietic fraction of microbial “animal protein factor”: Some similarities of streptomyces fermentation residue to pituitary erythropoietin. Amer. Jour. Dig. Dis. 22, 76–82 (1955). https://doi.org/10.1007/BF02886454

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02886454

Keywords

Search

Navigation