Skip to main content
SpringerLink
Log in

Tierexperimentelle Untersuchungen zur medikamentös-allergischen Agranulocytose Schultz

  • Published:
Zeitschrift für die gesamte experimentelle Medizin einschließlich experimentelle Chirurgie

Zusammenfassung

Mit Hilfe isologer 4-Aminophenazonserum- bzw. -leukocytenkonjugate wurden Kaninchen sensibilisiert. Die gewonnenen Hyperimmunseren ergaben eine serologische Spezifität für das Hapten (4-Aminophenazon); spezifisch gegen die entsprechenden Trägerproteine, vor allem gegen leukocytäre Antigene, gerichtete Antikörper lie\en sich in diesen Seren nicht nachweisen. Die unkonjugierten Haptene (4-Aminophenazon, Aminopyrin) zeigten weder in vitro noch in vivo eine sicher objektivierbare, direkte immunologische Aktivität. Immunhämatologische Untersuchungen auf zellspezifische Leukocytolysine bzw. Leukocytenagglutinine in den gewonnenen Hyperimmunseren verliefen negativ. Im Leukocytenagglutinationstest konnten aber Spenderzellen zur Agglutination gebracht werden, wenn im Versuchsansatz neben den Hyperimmunseren das Konjugatantigen bzw. ein in vitro hergestellter Antigen-Antikörperkomplex vorhanden war. An Hand von Belastungsversuchen lie\ sich experimentell ein vom Sensibilisierungsgrad der Tiere und der Menge des verabfolgten Vollantigens abhängiger Granulocytensturz herbeiführen, der in der Regel rasch reversibel war. Hämatologisch der menschlichen Agranulocytose vergleichbare Zustandsbilder traten dagegen nicht auf. Lösliche Immunkomplexe aus 4-Aminophenazonkonjugat und hochtitrigen Hyperimmunseren lie\en sich quantitativ an angereicherte Blutleukocyten bzw. Knochenmarkzellen absorbieren. Auf Grund der gewonnenen Versuchsergebnisse wird die Hypothese entwickelt, da\ für den granulocytopenischen Effekt am Versuchstier cytotrop aktive Immunkomplexe verantwortlich sind. Entsprechende Vorstellungen zur Immunpathogenese des Morbus Schultz sowie die daraus resultierenden Konsequenzen für eine sinnvolle Anwendung der Serodiagnostik bei dieser Erkrankung werden abschlie\end diskutiert.

Summary

Aminopyrin (ap), its metabolite 4-aminophenazone (4aph) and conjugates, produced by binding 4aph to isologous serum or homogenates of leukocytes were used as antigens in immunization experiments in rabbits. The hyperimmunsera exhibited a high grade specificity towards the haptenic group of the antigens. There was no evidence of any specificity to the protein carriers, especially to leukocytic antigens, as could be shown by precipitin tests, complement fixation, passive hemagglutination technic or passive cutaneous anaphylaxis. Immunohematological tests for agglutinins and cytolysins specific to leukocytes failed to give positive results. Leukocytes did agglutinate, however, when conjugate was added to the reaction system or when antigen-antibodycomplexes, formed in vitro in slight antigen excess, were used in the LAT. There was complete absorption of antigen-antibody-complexes in vitro by rabbit leukocytes, washed free of plasma. No comparable effect took place with thrombocytes or erythrocytes. When sensitized rabbits were challenged with 4aph or ap no granulocytopenia was observed. But a marked fall of the granulocyte count did occur, when highly sensitized animals were challenged with the homologous, conjugated antigens. Sometimes “granulocytoclasia” simulated agranulocytosis, but was compensated as a rule within one hour. Even after a treatment of several days a hematological state comparable to agranulocytosis-Schultz could not be elicited immunologically in animals sensitized to ap.

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

Literatur

  1. Achard, C., F. Coste etR. Cahe: Un cas de pure agranulocytose et un cas de purpura hémorrhagique avec agranulocytose terminale consécutif à un traitement aux sels d'or. Bull. Soc. méd. Paris3, 547 (1932); zit. von P.Miescher u. K. H.Vorlaender in: Immunpathologie in Klinik und Forschung. Stuttgart: Thieme 1961.

    Google Scholar 

  2. Ackroyd, J. F.: The cause of thrombocytopenia in Sedormid purpura. Clin. Sci.8, 269–290 (1949).

    PubMed  CAS  Google Scholar 

  3. Alexander, H. L.: Reactions with drug therapy. Philadelphia-London: Saunders 1955.

    Google Scholar 

  4. Andersen, M. S.: Lecture on recurrent agranulocytosis with note an dosage of Amidopyrin. Ugeskr. Laeg.96, 237 (1934); zit. in: J. Amer. med. Ass.102, 1822 (1934).

    Google Scholar 

  5. van Arsdel, P. P., E. Middleton, W. B. Sherman, andH. Buchwald: A quantitative study on the in vitro release of histamine from leukocytes of atopic persons. J. Allergy29, 429–437 (1958).

    Google Scholar 

  6. Barrett, J. T., M. M. Rigney, R. A. Guthrie, andD. S. Metcalfe: Characteristics of a hapten induced Leukoagglutinin. J. Immunol.90, 643–646 (1963).

    PubMed  CAS  Google Scholar 

  7. Benacerraf, B., andP. G. H. Gell: Immunological specifity of delayed and immediate hypersensitivity reactions. Mechanism of cell and tissue damage produced by immune reactions. IInd Intern. Sympos. Immunopathology Brook Lodge 1961, pp. 136–145. Basel-Stuttgart: Schwabe 1962.

    Google Scholar 

  8. Benacerraf, B., andB. B. Levine: Immunological specifity of delayed and immediate hypersensitivity reactions. J. exp. Med.115, 1023–1036 (1962).

    PubMed  CAS  Google Scholar 

  9. Benhamou, E., A. Albou etP. Griguer: Agranulocytose au Pyramidon avec nécroses maxillo-otitiques et surdité définitive. Sang.30, 214–216 (1959).

    PubMed  CAS  Google Scholar 

  10. Benjamin, J. E., andJ. B. Biedermann: Agranulocytic leukopenia induced by a drug related to Aminopyrine. J. Amer. med. Ass.107, 493–494 (1936).

    Google Scholar 

  11. Bernard, L. J., W. C. Jefferson, andP. F. Hahn: Failure to demonstrate in vitro lysis of sensitized guinea pig leukocytes by dog haemoglobin antigen. Proc. Soc. exp. Biol. (N. Y.)80, 58–60 (1952).

    CAS  Google Scholar 

  12. Bierman, H. R., R. L. Byron, K. H. Kelly, andN. L. Petraki: The lung removal mechanism for leukocytes. Blood6, 770–771 (1951).

    Google Scholar 

  13. Bock, H. E.: Über die nosologische Stellung der Agranulocytose, insbesondere der Aminopyrinagranulocytose. Verh. dtsch. Ges. inn. Med.47, 213–219 (1935).

    Google Scholar 

  14. —: Das Hämomyelogramm. Klin.Wschr.18, 1565–1568 (1939).

    Google Scholar 

  15. —: Agranulocytose. Stuttgart: Enke 1946.

    Google Scholar 

  16. —: Die Bedeutung der allergischen Pathogenese bei der Arteriitis. Verh. dtsch. Ges. inn. Med.60, 391–413 (1954).

    Google Scholar 

  17. —: Medikamentöse Agranulocytose. Regensburg. Jb. ärztl. Fortbild.5, 1–9 (1957).

    Google Scholar 

  18. — u.B. Schlegel: Nebenwirkungen von Arzneimitteln auf Blut und Knochenmark. Zit.: H.E.Bock: Allergie und Agranulocytose. In:R. Jürgens u.J. Waldenström, S. 89–113. Stuttgart: Schattauer 1957.

    Google Scholar 

  19. — u.K. Seidel: Nebenwirkungen von Arzneimitteln auf Blut und Knochenmark. Zit.: H.E.Bock: Allergie und Agranulocytose. In:R. Jürgens u.J. Waldenström, S. 89–113. Stuttgart: Schattauer 1957.

    Google Scholar 

  20. — u.K. Wiede: Über Agranulocytose, Aleukie, Amylhämie und andere Hämozytotoxikosen. Folia haemat. (Frankfurt)42, 7–74 (1930).

    Google Scholar 

  21. Bohn, S. S.: Agranulocytic angina following ingestion of Dinitrophenol. J. Amer. med. Ass.103, 249–251 (1934).

    CAS  Google Scholar 

  22. Bolton, V. L.: A laboratory study of Amidopyrine, Barbital, Phenylhydrazine and Benzene in relation to agranulocytic angina. J. Lab. clin. Med.20, 1199–1203 (1935).

    CAS  Google Scholar 

  23. Boyd, C.: Fundaments of Immunology. New York-London: Interscience Publishers 1947.

    Google Scholar 

  24. Bracco, M., P. C. Curti, andN. Masera: Experimental production of blood disorders in rat by injection of antierythroblastic, antileukoblastic and antimegakaryocytic sera. Acta haemat. (Basel)6, 91–105 (1951).

    CAS  Google Scholar 

  25. Braunsteiner, H.: Agranulocytose und Panzytopenie. Wien. Z. inn. Med.35, 470–477 (1954).

    PubMed  CAS  Google Scholar 

  26. Brodie, B. B., andJ. Axelrod: The fate of Aminopyrin (Pyramidon) in man and methods for the estimation of Aminopyrin and its metabolites in biological material. J. Pharmacol, exp. Ther.99, 171–184 (1950).

    CAS  Google Scholar 

  27. Bunting, C. H.: The effects of lymphotoxins and myelotoxins on the leukocytes of the blood and on the blood forming organs. Univ. Penns. med. Bull.16, 216–217 (1903); Zit. von P.Miescher u. K. O.Vorlaender in: Immunpathologie in Klinik und Forschung. Stuttgart: Thieme 1961.

    Google Scholar 

  28. Butt, E. M., A. M. Hoffmann, andS. N. Soll: Experimental production of neutropenia with Aminopyrin. Arch. intern. Med.64, 26–42 (1939).

    Google Scholar 

  29. Butzengeiger, K. H., u.M. Gartz: Zur Frage der Nachweisbarkeit eines Leukozyten zerstörenden Stoffes im Blut der Panmyelophthise. Klin. Wschr.58, 495–497 (1950).

    Google Scholar 

  30. Chew, W. B., D. J. Stephens, andJ. S. Lawrence: Antileukocytic serum. J. Immunol.30, 301–317 (1936).

    Google Scholar 

  31. Chudomel, V., Z. Jezkova, andJ. Libansky: Detection of leukocyte antibodies by the complement consumption test. Blood14, 920–930 (1959).

    PubMed  CAS  Google Scholar 

  32. Climenko, D. R.: The modification of the hematopietic function in the rabbit by certain cyclic compounds. J. Lab. clin. Med.21, 913–921 (1936).

    CAS  Google Scholar 

  33. Code, C. F.: Histamine in blood. Physiol. Rev.32, 47–65 (1952).

    PubMed  CAS  Google Scholar 

  34. Cohn, Z. A., andJ. G. Hirsch: The isolation and properties of the specific cytoplasmic granules of rabbit polymorphonuclear leukocytes. J. exp. Med.112, 983–1004 (1960).

    PubMed  CAS  Google Scholar 

  35. Craddock, C. G., W. S. Adams, S. Perry, W. A. Skoog, andJ. S. Lawrence: Studies of leukopoesis. J. Lab. clin. Med.45, 881–905 (1955).

    PubMed  Google Scholar 

  36. Dameshek, W.: Benzene poisoning and agranulocytosis. J. Amer. med. Ass.97, 712 (1929).

    Google Scholar 

  37. — andA. Colmes: The effect of drugs in the production of agranulocytosis with particular reference to amidopyrine hypersensitivity. J. clin. Invest.15, 85–97 (1936).

    PubMed  CAS  Google Scholar 

  38. — andM. Ingall: Agranulocytosis (malignant neutropenia). Amer. J. med. Sci.181, 502–521 (1931).

    Google Scholar 

  39. Dausset, J.: Immuno-Hématologie, Biologique et Clinique. Paris: Flammarion 1956.

    Google Scholar 

  40. —: The leukoagglutinins. Transfusion2, 209–215 (1962).

    Article  PubMed  CAS  Google Scholar 

  41. —: Serologie des immunogranulopénies. Proc. 8th Congr., Europ. Soc. Haemat. Vienna 1961, p. 207. Basel: Karger 1962.

    Google Scholar 

  42. —,A. Nenna, andH. Brecy: Leuko-agglutinins in chronic idiopathic or symptomatic pancytopenia and in paroxysmal nocturnal hemoglobinuria. Blood9, 696–720 (1954).

    PubMed  CAS  Google Scholar 

  43. Davidson, B. N., andM. Shapiro: Neutropenia following Dinitrophenol with improvement after Pentnucleotide and leukocyte cream. J. Amer. med. Ass.103, 480–482 (1934).

    Google Scholar 

  44. Davis, J. St., andL. F. Frissel: Amidopyrin Hypersensitivity. J. Lab. clin. Med.23, 122 (1937).

    Google Scholar 

  45. Discombe, G.: Agranulocytosis caused by Amidopyrin. Brit. med. J.1952/I, 1270–1273.

    Google Scholar 

  46. Dixon, F. J., J. J. Vazquez, W. O. Weigle, andC. G. Cochrane: Immunology and pathogenesis of experimental serum sickness. In: Cellular and humoral aspects of the hypersensitive states, p. 354–374. Ed.:H. S. Lawrence. New York: Hoeber-Harper 1961.

    Google Scholar 

  47. Eisen, H. N.: Hypersensitivity to simple chemicals. Cellular and humoral aspects of the hypersensitive states, p. 89–122. In:H. S. Lawrence, with 25 contributing authors. New York: Hoeber-Harper 1961.

    Google Scholar 

  48. —,S. Belman, andM. E. Carsten: The reaction of 2,4-Dinitrobenzenesulfonic acid with free aminogroups of proteins. J. Amer. chem. Soc.75, 4583–4585 (1953).

    CAS  Google Scholar 

  49. —,M. Kern, W. T. Newton, andE. Helmreich: A study of the distribution of 2,4-dinitrobenzene sensitizers between isolated lymphode cells and extracellularmedium in relation to induction of contact skin sensitivity. J. exp. Med.110, 187–206 (1959).

    PubMed  CAS  Google Scholar 

  50. — andM. Tabachnick: Elicitation of allergic contact dermatitis in the guinea pig. J. exp. Med.108, 773–796 (1958).

    PubMed  CAS  Google Scholar 

  51. Engelfriet, C. P., andJ. J. van Loghem: Studies on leukocyte isoand autoantibodies. Brit. J. Haemat.7, 223–238 (1961).

    PubMed  CAS  Google Scholar 

  52. Erlenmeyer, H., u.E. Berger: Über immunchemische Untersuchungen in der Pyrazolon-Reihe. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.177, 116–118 (1935).

    Google Scholar 

  53. Farah, F. S., M. Kern, andH. N. Eisen: The preparation and some properties of purified antibody specific for the 2,4-Dinitrophenyl group. J. exp. Med.112, 1195–1210 (1960).

    PubMed  CAS  Google Scholar 

  54. Favour, C. B.: In vitro effect of tuberculin on cells. Advanc. tuberc. Res.4, 219–235 (1951).

    Google Scholar 

  55. Filehne, W.: Über das Pyramidon, ein Antipyrinderivat. Berl. klin. Wschr.33, 1061–1063 (1896).

    Google Scholar 

  56. Filipp, G., F. Walter u.B. v.Boros: Zum Problem der experimentellen Knochenmarksanaphylaxie. Acta allerg. (Kbh.)14, 311–325, 296–310 (1959).

    Google Scholar 

  57. Finch, S. C., andJ. F. Ross: Leukocyte response to leukocyte nuclear and cytoplasmic antisera. J. Lab. clin. Med.46, 871–878 (1955).

    PubMed  CAS  Google Scholar 

  58. Fischer, K.: Die Spezifität von Serumantikörpern gegen Medikament-Eiwei\komplexe und deren biologische Bedeutung. Inauguraldissertation, Bern 1965.

  59. Fitzhugh, T.: Drug idiosyncrasy with special reference to Amidopyrin as a cause of agranulocytic angina. Ann. intern. Med.8, 148–155 (1934).

    CAS  Google Scholar 

  60. Freedman, A. L., P. S. Barr, andE. A. Brody: Haemolytic anemia due to quinidine — Observations on its mechanism. Amer. J. Med.20, 808–816 (1956).

    Google Scholar 

  61. Frenger, W., F. Sckeiffarth u.Th. Schricker: Zur Frage des Vorkommens sog. Anti-Leukocyten-Antikörper bei Agranulocytose. ärztl. Wschr.10, 1080–1083 (1955).

    CAS  Google Scholar 

  62. Fried, B. M., andW. Dameshek: Experimental agranulocytosis. Arch. intern. Med.49, 94–112 (1932).

    Google Scholar 

  63. Fritze, E.: Zum Wirkungsmechanismus der Leukozytenaggregation. Dtsch. Arch. inn. Med.196, 102–115 (1949).

    Google Scholar 

  64. Garvin, J. E.: Factors affecting the adhesiveness of human leukocytes and platelets in vitro. J. exp. Med.114, 51–73 (1961).

    PubMed  CAS  Google Scholar 

  65. Gell, P. G. H.: Studies on hypersensitivity. The relationship between contact and delayed sensitivity: A study on the specifity of cellular immune reactions. J. exp. Med.113, 511–585 (1961).

    Google Scholar 

  66. — andA. M. Silverstein: Delayed hypersensitivity to hapten-protein conjugates. J. exp. Med.115, 1037–1051 (1962).

    PubMed  CAS  Google Scholar 

  67. Goldberg, B.: Mechanisms of immune injury in mammalian cell systems. InP. Grabar, andP. A. Miescher: Immunpathology. III. Intern. Symp., La Jolla, p. 300–310. Basel-Stuttgart: Schwabe 1963.

    Google Scholar 

  68. Goudsmit, R., andJ. J. van Loghem: Studies on the occurrence of leukocyte antibodies. Vox sang. (Basel)3, 58–67 (1953);3, 89 (1953).

    Google Scholar 

  69. Gross, R., u.H. E. Bock: Erkrankungen der Leukopoese (Leukozytopathien) und des retikulohistiozytären Systems. Klin. Gegenwart10, 567–643 (1962).

    Google Scholar 

  70. Halberkann, J., u.F. Fretwurst: Die Stoffwechselprodukte des Pyramidons und verwandter Verbindungen beim Menschen. Hoppe-Seylers Z. physiol. Chem.285, 97 (1950).

    PubMed  CAS  Google Scholar 

  71. Halpern, B. N., A. Holtzer, P. Liacopoulos, andJ. Meyer: Allergy ty pyrazolone derivatives (Aminopyrine) with evidence of a reaginic type antibody. J. Allergy29, 1–12 (1958).

    CAS  Google Scholar 

  72. Hard, S.: Agranulocytosis in conjunction with neoarsphenamine treatment. Acta derm.-venereol. (Stockh.)30, 449–450 (1950).

    CAS  Google Scholar 

  73. Harrington, W. J., J. W. Hollingsworth, andC. V. Moore: Demonstration of a thrombocytopenic factor in the blood of patients with thrombocytopenic purpura. J. Lab. clin. Med.38, 1–21 (1951).

    PubMed  CAS  Google Scholar 

  74. Harris, J. W.: Studies on the mechanism of a drug-induced hemolytic anemia. J. Lab. clin. Med.47, 760–775 (1956).

    PubMed  CAS  Google Scholar 

  75. Harte, R. A.: Serological tests with Pyrazolon-compounds. J. Immunol.34, 433–439 (1938).

    CAS  Google Scholar 

  76. Hartl, W.: Zur Technik des Leukocyten-Agglutinationstests. Acta haemat. (Basel)28, 273–282 (1963).

    Google Scholar 

  77. —: Der fluoreszenzserologische Nachweis Leukocyten-spezifischer Antikörper. Acta haemat. (Basel)30, 288–304 (1963).

    CAS  Google Scholar 

  78. —: Möglichkeiten einer immunhaematologischen Serodiagnostik der medikamentös-allergischen Agranulocytose (Morbus Schultz). Dtsch. med. Wschr.88, 2375–2386 (1963).

    Google Scholar 

  79. —: Zur Serodiagnose der arzneimittelallergischen Agranulocytose. Arch. klin. Med.212, 191–215 (1966).

    PubMed  CAS  Google Scholar 

  80. —: Arzneimittelallergische Immunreaktionen. Dtsch. med. Wschr.91, 1498–1501 (1965).

    Google Scholar 

  81. — u.A. Puxeddu: Zur Frage der Spezifität arzneimittelallergischer Immunreaktionen durch aminophenazonhaltige Antirheumatica. Klin. Wschr.44, 30–32 (1966).

    PubMed  CAS  Google Scholar 

  82. Herz, L. F.: The role of Amidopyrine in the etiology of granulocytopenia with special reference to its chemical structure. J. Lab. clin. Med.20, 33–44 (1934).

    CAS  Google Scholar 

  83. Hoffmann, A. M., E. M. Butt, andN. G. Hickey: Neutropenia following amidopyrin. J. Amer. med. Ass.102, 1213–1214 (1934).

    Google Scholar 

  84. Hoigné, R.: über die Veränderungen von Blutgerinnungsfaktoren, Thrombozyten und Leukozyten im anaphylaktischen Schock, beim Arthusphänomen und beim Shwartzman-Sanarelli Phänomen. Inauguraldissertation, Zürich 1951.

  85. —: Arzneimittelallergien. Bern: Huber 1965.

    Google Scholar 

  86. Hollingsworth, J. W., andS. C. Finch: Leukocyte response to granuloeyte fraction antisera. J. Lab. clin. Med.46, 879–884 (1955).

    PubMed  CAS  Google Scholar 

  87. Humphrey, J. H.: Biochemical aspects of reactions in hypersensitive responses. In: H. S.Lawrence with 25 contributing authors. Cellular and humoral aspects of the hypersensitive states, p. 1–9. A Hoeber-Harper Book 1961.

  88. — andR. Jaques: The release of histamine and 5-hydroxytryptamin (serotonin) from platelets by antigen-antibody reactions (in vitro). J. Physiol. (Lond.)128, 9–27 (1955).

    CAS  Google Scholar 

  89. Ingeaham, J. S.: Specific, complement-dependent hemolysis of sheep erythrocytes by antiserum to Azo hapten groups, p. 268–275. Chicago (Ill.): Univ. Chicago Press 1952.

    Google Scholar 

  90. Jaccard, G.: Experimentell erzeugte Tuberkulincytolyse und Tuberkulinhautempfindlichkeit. Schweiz. med. Wschr.87, 1558–1559 (1957).

    PubMed  CAS  Google Scholar 

  91. Johnson, W. M., andW. Salem: A case of granulopenia following Amidopyrine, with recurrences. J. Amer. Med. Ass.103, 1299 (1934); zit. beiKracke u.Roberts, Ann. intern. Med.8, 146 (1934).

    Google Scholar 

  92. Kabat, E. A., and M.Mayer: Springfield (Ill.): Thomas 1961.

  93. Karush, F.: The interaction of purified antibody with optical isomeric haptens. J. Amer. chem. Soc.78, 5519–5526 (1956).

    CAS  Google Scholar 

  94. Katz, G., andS. Cohen: Experimental evidence for Histamine release in allergy. J. Amer. med. Ass.117, 1782–1783 (1941).

    CAS  Google Scholar 

  95. Kern, R. A.: Anaphylactic drug reactions. J. Amer. med. Ass.179, 19–22 (1962).

    CAS  Google Scholar 

  96. Kiely, J. M., andJ. M. Stickney: Agranulocytosis caused by phenylbutazone and 4-amino-antipyrine. Proc. Mayo Clin.28, 341–345 (1953).

    PubMed  CAS  Google Scholar 

  97. Killmann, S. A.: On the occurrence of leukocyte agglutinins. Acta med. scand.163, 449–465 (1959).

    Article  PubMed  CAS  Google Scholar 

  98. —: Leukocyte agglutinins. Blut4, 8–10 (1960).

    Google Scholar 

  99. Kissmeyer-Nielsen, F.: Demonstration of a thrombocytopenic and a leukopenic factor in the blood of patients with thrombocytopenia and leukopenia. Acta haemat. (Basel)9, 337–345 (1953).

    CAS  Google Scholar 

  100. Klein, P., u.P. Burkholder: Ein Verfahren zur fluoreszenzoptischen Darstellung der Komplementbindung und seine Anwendung zur histochemischen, immunologischen Untersuchung der experimentellen Nierenanaphylaxie. Dtsch. med. Wschr.84, 2001–2004 (1959).

    PubMed  CAS  Google Scholar 

  101. Köhler, H.: Blut und blutbildende Organe, B. Knochenmark (einschl. Leukose). In:P. Cohrs, R. Jaffe u.H. Meessen: Pathologie der Laboratoriumstiere, S. 235–311. Berlin-Göttingen-Heidelberg: Springer 1958.

    Google Scholar 

  102. Kopelowitz, J. C.: Agranulocytic angina. Missouri Med.26, 315–370 (1929); zit. in: J. Amer. med. Ass.93, 490 (1929).

    Google Scholar 

  103. Kracke, E. R.: Experimental production of agranulocytosis. Amer. J. clin. Path.2, 11–30 (1932).

    Google Scholar 

  104. —: Experimental agranulocytosis. Arch. intern. Med.49, 709–710 (1932).

    Google Scholar 

  105. —: Relation of drug therapy to neutropenic states. J. Amer. med. Ass.111, 1255–1259 (1938).

    Google Scholar 

  106. — andP. P. Parker: The etiology of granulopenia. J. Lab. clin. Med.19, 799–818 (1934).

    CAS  Google Scholar 

  107. —: The relationship of drug-therapy to agranulocytosis. J. Amer. med. Ass.12, 960–966 (1935).

    Google Scholar 

  108. Krauel, G.: Beitrag zur experimentellen Agranulocytose. Klin. Wschr.16, 1245–1246 (1937).

    Google Scholar 

  109. Krohs, W., u. O.Hensel: Pyrazolone und Dioxopyrazolidine. Arzneimittelforsch. 11. Beiheft (1961).

  110. Landsteiner, K.: The specificity of serological reactions. Cambridge: Harvard University Press 1947.

    Google Scholar 

  111. — andJ. Jakobs: Studies on the sensitization of animals with simple chemical compounds. J. exp. Med.64, 625–639 (1936).

    CAS  PubMed  Google Scholar 

  112. — andJ. van der Scheer: zit. bei H. N.Eisen in: Cellular and humoral aspects of the hypersensitivity states. Hoeber-Harper, 1961. J. exp. Med.63, 325 (1936).

    CAS  PubMed  Google Scholar 

  113. Larson, R. K.: The mechanism of quinidine purpura. Blood8, 16–25 (1953).

    PubMed  CAS  Google Scholar 

  114. Levine, B. L., andZ. Ovary: Studies on the Mechanism of the formation of the penicillin antigen. J. exp. Med.114, 875–964 (1961).

    PubMed  CAS  Google Scholar 

  115. Lindström, G. A.: An experimental study of myelotoxic sera. Therapeutic attempts in myeloid leukaemia. Acta med. scand. Suppl.22, 1–169 (1927).

    Google Scholar 

  116. van Loghem jr.,J. J. M. van der Hart, W. Hijmans, andH. R. E. Schutt: The incidence and significance of complete and incomplete white cell antibodies with special reference to the use of the Coombs Consumption test. Vox sang. (Basel)3, 203–223 (1958).

    Google Scholar 

  117. Lowry, H. O., H. T. Graham, P. B. Harris, M. K. Priebat, A. R. Marks, andR. U. Bregmann: The chemical measurement of histamine in blood plasma and cells. J. Pharmacol. exp. Ther.112, 116–126 (1954).

    PubMed  CAS  Google Scholar 

  118. Madison, P. W., andT. L. Squier: The etiology of primary granulocytopenia (agranulocytic angina). J. Amer. med. Ass.102, 755–759 (1934).

    Google Scholar 

  119. Magis, C., St. Thierfelder, M. Saint-Paul etJ. Dausset: Etude sérologique d'une agranulocytose allergique a l'aminopyrine. Nouv. Rev. franÇ. Hemat.2, 602–608 (1962).

    CAS  Google Scholar 

  120. Marriott, H. J. L., andH. R. Peters: Blood discrasias secondary to gold. Ann. inter. Med.32, 864–877 (1950).

    CAS  Google Scholar 

  121. Matsuno, M.: Über den Einflu\ des Antikaninchenleukocytenserums auf die Phagocytose. Tohoku J. exp. Med.19, 168–195 (1932); zit. beiPinch, Cajano, andRoss: J. Lab. clin. Med.46, 871–878 (1955).

    Google Scholar 

  122. McCarthy, F. P., andR. Wilson: The blood dyscrasias following the Arsphenamines. J. Amer. med. Ass.99, 1557–1563 (1932).

    Google Scholar 

  123. McCord, C. P.: The present status of benzene (Benzol) poisoning. J. Amer. med. Ass.93, 280–283 (1929).

    Google Scholar 

  124. Middleton, E., W. B. Sherman, W. Fleming, andP. P. van Arsdel: Some biochemical caracteristics of allergy histamine release from leukocytes of ragweed-sensitive subjects. J. Allergy31, 448–454 (1960).

    CAS  Google Scholar 

  125. Miescher, P.: Leucopénies et agranulocytoses d'origine immunologique. Sang26, 71–75 (1955).

    PubMed  CAS  Google Scholar 

  126. — u.A. Miescher: Die Sedormid Anaphylaxie. Schweiz. med. Wschr.82, 1279–1283 (1952).

    PubMed  CAS  Google Scholar 

  127. — u.K. H. Vorlaender: Immunopathologie in Klinik und Forschung. Stuttgart: Thieme 1961.

    Google Scholar 

  128. Milgrom, F., M. Palester, G. Wozniczko, andZ. Dudziak: Complement binding leukocyte antibodies. Vox sang. (Basel)2, 263–267 (1957).

    Article  CAS  Google Scholar 

  129. Miller, D. K.: Histological changes in the bone marrow of the dog following Amidopyrin administration. Science80, 320 (1934).

    CAS  PubMed  Google Scholar 

  130. — andC. P. Rhoads: The effect of diet on the susceptibility of the canine hematopoietic function to damage by amidoparin. J. exp. Med.66, 367–382 (1937).

    CAS  PubMed  Google Scholar 

  131. Moeschlin, S.: Immunoleucopénies et immunoagranulocytoses. Rév. Hemat.8, 249–262 (1953).

    PubMed  CAS  Google Scholar 

  132. —: Bestimmung von Leukocyten-Agglutininen. Med. Klin.49, 1978 (1954).

    Google Scholar 

  133. —: Immunological granulocytopenia and agranulocytosis. Sang26, 32–51 (1955).

    PubMed  CAS  Google Scholar 

  134. —: Agranulocytose und Antikörper. InR. Jürgens u.J. Waldenström: Nebenwirkungen von Arzneimitteln auf Blut und Knochenmark, S. 175 bis 190. Stuttgart: Schattauer 1957.

    Google Scholar 

  135. —,H. Meyer, L. G. Israels, andE. Tarr-Gloor: Experimental agranulocytosis. Its production through leukocyte agglutination by antileukocytic serum. Acta haemat. (Basel)11, 73–94 (1954).

    CAS  Google Scholar 

  136. — u.R. Moreno: Pyramidon-Agranulozytose mit Agglutination arteigener und artfremder Leukozyten. Klin. Wschr.32, 799–802 (1954).

    PubMed  CAS  Google Scholar 

  137. —,W. Siegenthaler, C. Gassee, andA. Haessig: Immunpancytopenia associated with incomplete cold haemagglutinins in a case of primary atypical pneumonia. Blood9, 214–226 (1954).

    PubMed  CAS  Google Scholar 

  138. — u.K. Wagner: Leukozytenagglutinine als Ursache von Agranulozytosen (Pyramidon usw.). Schweiz. med. Wschr.82, 1104–1106 (1952).

    PubMed  CAS  Google Scholar 

  139. — —: Agranulocytosis due to the occurrence of leukocyte agglutinins (Pyramidon and cold agglutinins). Acta haemat. (Basel)8, 29–41 (1952).

    CAS  Google Scholar 

  140. Moulinier, J.: Technique de la réaction de consommation d'antiglobuline. Rev. franÇ. étud. clin. biol.2, 355–364 (1956).

    Google Scholar 

  141. Müller, W.: Zur Pathogenese der Arzneimittelagranulozytose. Acta haemat. (Basel)12, 304–321 (1954).

    Article  Google Scholar 

  142. —: Immunhämatologische Untersuchungen bei Leukopenien und Agranulocytosen. Klin. Wschr.34, 1057–1067 (1956).

    PubMed  Google Scholar 

  143. — u.J. Weinreich: Die klinische Bedeutung des Nachweises von Leukocyten-Agglutininen. Fol. haemat. (Frankfurt) (N. F.)4, 313–323 (1960).

    Google Scholar 

  144. Noah, J. W., andA. Brand: Release of histamine in the blood of ragweedsensitive individuals. J. Allergy25, 210–214 (1954).

    PubMed  CAS  Google Scholar 

  145. Oliva, G., eD. Furbetta: Attivita leucoltitica del siero di sangue nell agranulocitosi. Boll. Soc. ital. Biol. sper.19, 234–235 (1944).

    Google Scholar 

  146. Payne, R.: Leukocyte agglutinins inhuman sera. Arch. intern. Med.99, 587–606 (1957).

    CAS  Google Scholar 

  147. Pearl, A.: Experimenteller Beitrag zur Pathogenese der allergischen medikamentösen Agranulozytose und Thrombopenie. Blut4, 86–97 (1958).

    PubMed  CAS  Google Scholar 

  148. Pepper, O. H. P.: The history of agranulocytic angina. J. Amer. med. Ass.97, 1100–1101 (1931).

    Google Scholar 

  149. Petrides, P., u.F. E. Schmengler: Über die Bedeutung der allergischen Schädigung für Klinik und Pathologie haematologischer Erkrankungen. Z. ges. exp. Med.117, 279–311 (1951).

    Google Scholar 

  150. Plum, P.: Agranulocytose und Amidopyrin, experimentell beleuchtet. Verh. dtsch. Ges. inn. Med.47, 208–213 (1935).

    Google Scholar 

  151. —: Clinical and experimental investigation in agranulocytosis. London: H. K. Lewis & Co., Ltd. 1937.

    Google Scholar 

  152. Rawls, W. B.: The effect of amidopyrin upon the red, white and polymorphonuclear blood cells of a series of 110 patients. Amer. J. med. Sci.192, 175–179 (1936).

    Google Scholar 

  153. Reye, E.: 3 Fälle von Agranulocytose. Klin. Wschr.5, 1059 (1926).

    Google Scholar 

  154. —: Zur Frage der Agranulocytose. Med. Klin.25, 257–259 (1929).

    Google Scholar 

  155. Roberts, S. R., andR. R. Kracke: Agranulocytosis. J. Amer. med. Ass.95, 780–786 (1930).

    Google Scholar 

  156. Rohr, K.: Blut- und Knochenmarksmorphologie der Agranulocytosen. Fol. haemat. (Frankfurt) (N.F.)55, 305–367 (1936).

    Google Scholar 

  157. —: Agranulocytosen und blutbildende Organe einschl. des lymph. und retikulohistiozytären Systems. InR. Jürgens u.J. Waldenström: Nebenwirkungen von Arzneimitteln auf Blut und Knochenmark, S. 114–128. Stuttgart: Schattauer 1957.

    Google Scholar 

  158. Rosak, M., u.C. Steffen: Erfahrungen mit dem Antihumanglobulinkonsumptionstest bei Granulocytopenien und aleukämischen Leukosen. Proc. 8th Congr. Europ. Soc. Haematol., Vienna 1961, I: 198. Basel: Karger 1962.

    Google Scholar 

  159. Ross, A., andJ. H. Lepow: Studies on immune cellular injury. J. exp. Med.112, 1085–1120 (1960).

    PubMed  CAS  Google Scholar 

  160. Saathoff, J., u.H. Küsel: Leukocytenagglutination bei Pyramidon Agranulocytose, Lupus erythematodes und einem chronischen Rheumatismus. Dtsch. Arch. klin. Med.201, 229–241 (1954).

    PubMed  CAS  Google Scholar 

  161. Sacchetti, S., andE. Salvidio: The biological activities of bone marrow granulopoesis in experimental leucopenia. Acta haemat. (Basel)17, 210 bis 222 (1957).

    Article  CAS  Google Scholar 

  162. Salvin, S. B., andR. F. Smith: The specificity of allergic reactions. III. Contact hypersensitivity. J. exp. Med.112, 158–193 (1960).

    Google Scholar 

  163. — —: The specificity of allergic reactions Contact hypersensitivity. J. exp. Med.114, 185–194 (1961).

    PubMed  CAS  Google Scholar 

  164. Scheiffarth, F., W. Frenger u.Th. Schrikker: Haemozytologische Untersuchungen bei arzneimittelallergischen Reaktionen. Fol. haemat. (Frankfurt) (N.F.)1, 208–218 (1957).

    CAS  Google Scholar 

  165. Schermbr, S.: Blut und blutbildende Organe, A. Blut. InP. Cohrs, R. Jaffe, andH. Meessen: Pathologie der Laboratoriumstiere, S. 176–235. Berlin-Göttingen-Heidelberg: Springer 1958.

    Google Scholar 

  166. Schmid, W., u.S. Moeschlin: Physikalisch chemische und serologische Untersuchungen von Antileukozytenserum. ärztl. Forsch.8, 229–232 (1954).

    Google Scholar 

  167. Schulten, H.: Über Agranulocytose. Münch. med. Wschr.99, 1280–1283 (1957).

    PubMed  CAS  Google Scholar 

  168. Schultz, W.: Akute Erkrankungen des myeloischen Systems. Verh. dtsch. Ges. inn. Med.47, 179–192 (1935).

    Google Scholar 

  169. —: Über eigenartige Halserkrankungen. Dtsch. med. Wschr.48, 1495–1496 (1922).

    Google Scholar 

  170. — u.L. Jakobowitz: Die Agranulocytose. Med. Klin.21, 1642–1645 (1925).

    Google Scholar 

  171. Schuppli, R.: Untersuchungen über die allergische Leukopenie. Kongre\-bericht des 1. Int. Kongr. Allergie 1951 in Zürich, S. 744–748. Basel: Karger 1952.

    Google Scholar 

  172. Seemann, H.: Amidopyrin as etiologgic factor in agranulocytosis. Ugeskr. Laeg.96, 241 (1934); zit. in J. Amer. med. Ass.102, 1822 (1934).

    Google Scholar 

  173. Seideneaden, W.: Künstliche organische Farbstoffe und ihre Anwendungen, S. 151. Stuttgart: Enke 1955.

    Google Scholar 

  174. Shulman, N. R.: Mechanism of blood cell damage by adsorption of antigenantibody complexes. InP. Grabar, andP. A. Miescher: Immunpathology, III Intern. Symp., La Jolla, 1963, S. 338–352. Basel-Stuttgart: Schwabe 1963.

    Google Scholar 

  175. —: A mechanism of cell destruction. Ann. intern. Med.60, 506–531 (1964).

    PubMed  CAS  Google Scholar 

  176. Silverstein, A. M., andP. G. H. Gell: Delayed hypersensitivity to haptenprotein conjugates. J. exp. Med.115, 1053–1064 (1962).

    PubMed  CAS  Google Scholar 

  177. Squier, T. L., andH. J. Lee: Lysis in vitro of sensitized leukocytes by ragweed antigen. J. Allergy18, 156–163 (1947).

    PubMed  CAS  Google Scholar 

  178. — andF. W. Madison: Primary granulocytopenia due to hypersensitivity to amidopyrin. J. Allergy6, 9–16 (1935).

    Google Scholar 

  179. Steffen, C.: Eigenschaften und Wirkungen isolierter inkompletter Thrombozyten- und Leukozytenauto-antikörper, S. 97–106. Proc. 7th Int. Congr. Int. Soc. Haemat. Rome 1958. New York: Grüne and Stratton 1959.

    Google Scholar 

  180. —: Immungranulocytopenien. InL. Heilmeyer u.A. Hittmaier: Handbuch der gesamten Haematologie, S. 258–273. München-Berlin: Urban & Schwarzenberg 1963.

    Google Scholar 

  181. Stenn, F.: The etiologic relationship of Amidopyrine to agranulocytosis. J. Lab. clin. Med.20, 1150–1152 (1935).

    CAS  Google Scholar 

  182. Straessle, R., u.P. Miescheb: Experimentelle Studien über den Mechanismus der Leukozytenschädigung durch Antigen-Antikörper-Reaktionen. Schweiz. med. Wschr.86, 1461–1464 (1956).

    PubMed  Google Scholar 

  183. Strauss, B. S., andCh. A. Stetson: Studies on the effect of certain macromolecular substances on the respiratory activity of the leukocytes of peripheral blood. J. exp. Med.112, 653–669 (1960).

    CAS  PubMed  Google Scholar 

  184. Thierfeldeb, S., C. Magis, M. Saint-Paul etJ. Dausset: Die Pyramidon-Agranulocytose. Dtsch. med. Wschr.89, 506–512 (1964).

    Google Scholar 

  185. Tullis, J. L.: Prevalence, nature and identification of leukocyte antibodies. New Engl. J. Med.258, 569–578 (1958).

    Article  PubMed  CAS  Google Scholar 

  186. Tullis, J. L., D. M. Surgenob, Ph. Baudanza, andD. F. H. Wallach: Comparative studies on leukocyte and platelets-agglutinins. Proc. 7th Int. Congr. Soc. Haematol. Rome 1958, pp. 88–106. New York: Grune and Stratton 1959.

    Google Scholar 

  187. Voss, J., A. Gathof, H. Martin u.W. Spielmann: Über einen Fall von Pyramidon-Agranulozytose mit ungewöhnlich langer Latenzzeit nach der medikamentösen Belastung. Klin. Wschr.34, 814–817 (1956).

    PubMed  Google Scholar 

  188. de Vries, S. I.: Erfahrungen über medikamentöse Agranulocytosen. InR. Jürgens u.J. Waldenström: Nebenwirkungen von Arzneimitteln auf Blut und Knochenmark, S. 191–196. Stuttgart: Schattauer 1957.

    Google Scholar 

  189. Waalkes, Z. P., andH. Coburn: The role of platelets and the release of serotonin and histamine during anaphylaxis in rabbit. J. Allergy30, 394–407 (1950).

    Google Scholar 

  190. Waksman, B. H.: Studies of cellular lysis in tuberculin sensitivity. I. Int. Allergie Kongress, Zürich 1951. Kongre\bericht S. 178–179. Basel: Karger 1952.

    Google Scholar 

  191. —: Specific white cells lysis produced by combination of rabbit antiserum to purified protein (ovalbumin, bovine gammaglobulin) with homologous antigen. The role of non-precipitating antibody. J. Immunol.70, 331–344 (1953).

    PubMed  CAS  Google Scholar 

  192. Waksman, B.: Tissue damagae in the „delayed“ (cellular) type of hypersensitivity. Mechanism of cell and tissue damage produced by immune reactions, pp. 146–160. IInd Int. Symp. on Immunopathology, Brook Logde, 1961. Basel-Stuttgart: Schwabe 1962.

    Google Scholar 

  193. Walfobd, R. L.: Leukocyte antigens and antibodies. New York: Grune and Stratton 1960.

    Google Scholar 

  194. Wasastjerna, C.: Leukocyt-agglutiner i serum vid leukopeni. Nord. Med.55, 462–465 (1956).

    PubMed  CAS  Google Scholar 

  195. de Weck, A. L., andH. N. Eisen: Some immunochemical properties of penicillenic acid. J. exp. Med.112, 1227–1247 (1960).

    Google Scholar 

  196. Weigle, W.O., Ch. G. andF. Y. Cochrane: Anaphylactic properties of soluble antigen. Antibody complexes in the guinea pig and rabbit. J. Immunol.85, 469–477 (1960).

    PubMed  CAS  Google Scholar 

  197. — andF. J. Dixon: Die biologischen Eigenschaften von Antigen-Antikörper-Komplexen und ihre pathogene Bedeutung. InP. Miescher u.K. H. Vorlaender: Immunopathologie in Klinik und Forschung. Stuttgart: Thieme 1961.

    Google Scholar 

  198. Weisberger, A. S., R. A. Guyton, R. W. Henle, andJ. P. Storaasli: The role of the lungs in the removal of transfused lymphocytes. Blood6, 916–925 (1951).

    PubMed  CAS  Google Scholar 

  199. Wintrobe, M. M., andG. E. Cartwright: Blood disorders caused by drug sensitivity. Arch. intern. Med.98, 559–566 (1956).

    CAS  Google Scholar 

  200. Zinber, I. S., L. Katzenstein, andL. E. Wice: Neutropenia following the administration of Amidopyrin. Report of a case. J. Amer. med. Ass.102, 2098–2099 (1934).

    Google Scholar 

  201. Zon, L., E. T. Ceder, andC. W. Crigler: The presence of Histamine on the platelets of the rabbit. Publ. Hlth Rep. (Wash.)54, 1978–1986 (1939).

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medizinische Universitätsklinik Tübingen, Deutschland

    W. Hartl

Authors
  1. W. Hartl
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Meinem Lehrer, Herrn Professor Dr. H. E.Bock, in Verehrung und Dankbarkeit gewidmet.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hartl, W. Tierexperimentelle Untersuchungen zur medikamentös-allergischen Agranulocytose Schultz. Z. Gesamte Exp. Med. 142, 297–333 (1967). https://doi.org/10.1007/BF02044811

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02044811

Search

Navigation