Literaturzitate - Wissenschaftliche Arbeit Internist Innsbruck

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LiteraturZitate & Wissenschaftliche Arbeit

Selection of Publications

1)      R. Fischer und F. Schmalzl: Über die Hemmbarkeit der Esteraseaktivität in Blutmonozyten durch Natriumfluorid. Klin. Wschr., 42, 751 (1964)

2)      F. Schmalzl und H. Braunsteiner: Zur Herkunft der Monozyten. Wien. Zschr. Inn. Med. 48, 409 (1967)

3)      F. Schmalzl and H. Braunsteiner: On the origin of monocytes. Acta haemat.39, 177 (1968)

4)      F. Schmalzl und H. Braunsteiner: Cytochemische Darstellung von Esteraseaktivitäten in Blut- und Knochenmarkzellen. Klin. Wschr. 46, 642 (1968)

5)      F. Schmalzl, C. Huber and H. Braunsteiner: Demonstration of proliferating monocytic precursors by the combination of cytochemical and autoradiographic methods. Klin.Wschr. 47, 887 (1969)

6)      F. Schmalzl and H. Braunsteiner: Remarks to the review of L.-D. Leder:” On the term ‘reticulosis’ and ‘reticulum cell sarcoma’ with regard to the modern concept of the monocyte-macrophage system. The contribution of cytochemical tests to the study of the origin of blood monocytes. Klin.Wschr. 57, 589 (1979)

7)      G. Konwalinka, P. Glaser, R. Odavic, E. Bogusch, F. Schmalzl and H. Braunsteiner: A new approach to the cytological and cytochemical evaluation of human bone marrow CFUc in agar cultures. Exp. Hematol. 8, 434 ( 1980)

8)      F. Schmalzl und H. Braunsteiner: Zytochemische Untersuchungen zur Entwicklung der großen mononukleären Zellen des Hautfensters. Acta haemat. 38, 281 (1967)

9)      F. Schmalzl, H. Huber, H. Asamer, K. Abbrederis and H. Braunsteiner: Cytochemical and immunohistological investigations on the source and the functional changes of mononuclear cells in skin window exudates. Blood 34, 129 (1969)

10)   F. Schmalzl and H. Braunsteiner: The cytochemistry of monocytes and macrophages. Ser.Haemat. III/2, 93 (1970)

11)   H. Braunsteiner and F. Schmalzl: (Review) Cytochemistry of monocytes and macrophages. In: Mononuclear Phagocytes, Ed. R.van Furth, Oxford, Blackwell, 1970

12)   F. Schmalzl, C. Steger e H. Braunsteiner: Ricerche citochimiche a carico degli elementi corpuscolati del materiale purulento. Minerva med. 62,325 (1971)

13)   F. Schmalzl, K. Abbrederis und H. Braunsteiner: Der Einfluß lokaler Glukokortikoidapplikation auf die Umwandlung von Monozyten in Makrophagen. Zytochemische Untersuchungen an Rebuck’schen Hautfensterexsudaten. Int.Z.klin.Pharmakol.Therapie Toxikol. 5, 206 (1972)

14)   F. Schmalzl, R. Günther und K. Abbrederis: Untersuchungen zur zellulären Exsudation bei Kranken mit primär chronischer Polyarthritis im Hautfensterversuch nach Rebuck. Z.Rheumatol. 33,413 (1974)

15)   F. Schmalzl, C.J. Wiedermann und H. Braunsteiner: Quantitativ-cytochemische Untersuchungen der saure-Phophatase-Aktivität in Hautfenstermakrophagen. Acta med. Austriaca 9,29 (1982)

16)   F. Schmalzl und H. Braunsteiner: Zur Zytochemie der Monozytenleukämie. Klin.Wschr. 46, 1185 (1968)

17)   F. Schmalzl, K. Abbrederis und H. Braunsteiner: Über das Verhalten leukämischer Monozyten bei der lokalen Entzündung. Untersuchungen mit der Rebuck’schen Hautfenstertechnik. Klin.Wschr. 46,962 (1968)

18)   F. Schmalzl, D. Pastner, K. Abbrederis and H. Braunsteiner: In vitro cultivation of leukemic monocytes. Acta haemat. 41, 225 (1969)

19)   F. Schmalzl: Die Monozytenleukämie – zytochemische, immunologische und invitro-Untersuchungen. In: Chemo – und Immunotherapie der Leukosen und malignen Lymphome (Internationale Arbeitstagung, Wien 1969) Bohmann Verlag, Wien 1969

20)   F. Schmalzl: Unreifzellige Monozytenleukämie. Blut 22, 157 (1971)

21)   D. Huhn, F. Schmalzl und K. Demmler: Monozytenleukämie. Licht – und elektronen-mikroskopische Morphologie und Zytochemie. Dtsch.med.Wschr. 96, 1594 (1971)

22)   F. Schmalzl, D. Huhn, H. Asamer, K. Abbrederis and H. Braunsteiner: Atypical (monomyelocytic) myelogenous leukemia. Cytochemical, electron microscopic, and bochemical investigations. Acta haemat. 48, 72 (1972)

23)   K. Abbrederis, F. Schmalzl und H. Braunsteiner: Subakute und chronische monozytäre Leukämien. Med. Klin. 74, 1803 (1979)

24)   F. Schmalzl and K. Abbrederis: Prognostic value of the cytologic classification of monocytic leukemias. In: Therapy of acute leukemias. Ed. F. Mandelli; Lombardo, Roma 1979, p. 108

25)   H. Asamer, F. Schmalzl und H. Braunsteiner: Der immunzytologische Lysozymnachweis in menschlichen Blutzellen. Acta haemat. 41, 49 (1968)

26)   H. Asamer, F. Schmalzl and H. Braunsteiner: Immunocytological demonstration of lysozyme (muramidase) in human leukemic cells. Brit. J. Haemat. 20, 571 (1971)

27)   H. Asamer, F. Schmalzl und H. Braunsteiner: Die diagnostische und prognostische Bedeutung der Muramidase - (Lysozym-) Bestimmung in Leukozytenlysaten, Serum und Harn von Leukämiepatienten. Klin. Wschr. 49, 587 (1971)

28)   H. Asamer, F. Schmalzl and H. Braunsteiner: Immunocytologic and biochemical demonstration of lysozyme in leukemic cells. In: Lysozyme. Ed. E. F. Ossermann, Acad.press, New York, 1974

29)   F. Schmalzl, H. Asamer and H. Braunsteiner: Immunological demonstration and quantitative determination of intracellular lysozyme in various types of leukemia. In: Therapy of acute leukemia. Eds. F. Mandelli, S. Amadori, G. Mariani; Minerva med., Roma, 1975, p. 755

30)   K. Abbrederis, F. Schmalzl und H. Braunsteiner: Zur Differentialdiagnose akuter Leukämien mittels zytochemischer Methoden. Schweiz.Med.Wschr. 99, 1425 (1969)

31)   F. Schmalzl, B. Lederer and H. Braunsteiner: Atypical myeloblastic leukemia with differentiation into „paraneutrophils“. Blut 20, 337 (1970)

32)   D. Huhn, F. Schmalzl und U. Krug: Unreifzellige myeloische Leukämie: Zytochemie, Elektronenmikroskopie und Zytogenetik. Blut 23, 189 (1971)

33)   F. Schmalzl and H. Braunsteiner: The application of cytochemical methods to the study of acute leukemia. Acta haemat. 45, 209 (1971)

34)   G. Michlmayer, H. Huber, H. Asamer, Ch. Huber, F. Schmalzl und H. Braunsteiner: Erfahrungen in der Behandlung unreifzelliger Leukämien mit Cytosin-Arabinosid und Daunorubidomycin. Wien. Klein. Wschr. 83, 452 ( 1971)

35)   D. Huhn, W. Kaboth und F. Schmalzl: Di Guglielmo-Syndrom. Klinische, zytochemische, elektronenmikroskopische Befunde. Dtsch. med. Wschr. 98, 355 (1973)

36)   D. Huhn und F. Schmalzl: Licht- und elektronenmikroskopische Cytochemie der unreifzelligen Leukämien. Klin. Wschr. 50, 423 (1972)

37)   F. Schmalzl, D. Huhn, K. Abbrederis, and H. Braunsteiner: Acute lymphocytic leukemia. Cytochemistry and ultratrsucture. Blut 29, 87 (1974)

38)   K. Rameis, R. Kurz, F. Schmalzl, B. Lederer und H. Berger: Unterschiedlicher Ausreifungsgrad leukämischer Blasten bei einer tumorösen Form einer akuten kindlichen Myelose. Pädiatrie und Pädologie 10, 32 (1975)

39)   F. Schmalzl, D. Huhn, H. Asamer, and H. Braunsteiner: Hairy cell leukemia (‘leukemic reticuloendotheliosis’, reticulosarcoma, and monocytic leukemia – Cytochemical and ultratstructural investigations. Acta haemat. 53, 257 (1975)

40)   F. Schmalzl, G. Keiser, E. Kresbach, H. Fritz, H. Asamer und H. Braunsteiner: Plasmozytom, Alkylantien und akute myelogene Leukämien. Dtsch. med. Wschr. 100, 1961 (1975)

41)   K. Abbrederis, G. Michlmayr, F. Schmalzl, Ch. Huber und H. Braunsteiner: Prolymphzytäre Leukämie. Dtsch. med. Wschr. 104, 11 (1979)

42)   G. Lingg, F. Schmalzl, J. Breton-Gorius, A. Tabilio, D. Geissler, M. Schweiger, W. Kirchmayr: Megakaryoblastic – Mickromegakarycytic Crisis in chronic myeloid leukemia.

Blut 51, 275 (1985)

43)   G. Gastl, H. Rumpold, D. Kraft, C. Gattringer, G. Schuler, R. Margreiter, F. Schmalzl, Ch. Huber: Abnormal expansions of Granular Lymphocytes: Reactive Lymphocytosis or Chronic Leukemia? Case Report and Literature Review. Blut 52, 73 (1986)

44)   F. Schmalzl, M. Lechleitner: Biphenotypic maturation of myeloid cells in myelodysplastic syndromes and Leukemias. Brit. J. Haematol. 62, 400 (1986)   

45)   R. Kurz, J. Glatzl und F. Schmalzl: Congenitale Agranulocytose. I. Fallbericht und Verlaufsstudie. Pädiatrie und Pädolologie 6, 75 (1971)

46)   F. Schmalzl, R. Kurz und J. Glatzl: Congenitale Agranulozytose.              II. Cytochemische und experimentelle Untersuchungen mit der Rebuck’schen Hautfenstertechnik. Pädiat. Pädol. 6, 84 (1971)

47)   F. Schmalzl, D. Huhn, H. Asamer, R. Rindler und H. Braunsteiner: Cytochemistry and ultratsructure of pathologic granulation in myelogenous leukemia. Blut 27, 243 (1973)

48)   F. Schmalzl, S. Platzer, G. Weiser und H. Frötscher: Zytochemische Untersuchungen an Blut – und Knochenmarkszellen von Alkoholikern. In: Probleme der Erythropoese, Granulopoese und des malignen Melanoms; Berlin – Heidelberg – New York, Springer 1978 (Hämatologie und Bluttransfusion, Bd. 21), S. 38

49)   K. Abbrederis und F. Schmalzl: Zytochemische Kriterien zur Differentialdiagnose myeloischer Reaktionen und leukämischer Erkrankungen. In: Probleme der Erythropoese, Granulopoese und des malignen Melanoms; Berlin – Heidelberg – New York, Springer 1978 (Hämatologie und Bluttransfusion, Bd. 21), S. 389

50)   H.E. Schaefer, F. Schmalzl und R. Fischer: Stammen eosinophile und neutrophile Granulozyten von einer gemeinsamen promyelozytären Vorstufe ab? Untersuchungen an der normalen, Peroxydase – defekten und leukämischen Granulopoese. Verh. Dtsch. Ges. Path. 62, 343 (1978)

51)   F. Schmalzl und K. Abbrederis: Zytochemische Befunde an den Knochenmarkzellen bei makrozytären Anämien. Acta med. Austriaca 6 Suppl., 382 (1979)

52)   A. Shibata, J. M. Bennett, G. L. Castoldi, D. Catovsky, G. Flandrin, E. S. Jaffe, I Katayama, K. Nanba, F. Schmalzl, L. T. Yam (Fort the international committee for standardization in haematology): Recommended methods for cytological procedures in haematology. Clin. lab. Haemat. 7, 55 (1985)

53)   R. Rindler, F. Schmalzl, H. Hörtnagl and H. Braunsteiner: Naphthol-AS-D-chloroacetate esterase in granule extracts from human neutrophil granulocytes. Blut 23, 223 (1971)

54)   R. Rindler, H. Hörtnagl, F. Schmalzl and H. Braunsteiner: Hydrolysis of chymotrypsin sub-strate and naphthol-AS-D-chloroacetate by human leukocyte granules. Blut 26, 239 (1973)

55)   R. Rindler-Ludwig, F. Schmalzl and H. Braunsteiner: Esterase in human neutrophil granulocytes: Evidence of their protease nature. Brit. J. Haemat. 27, 57 (1974)

56)   R. Rindler, F. Schmalzl und H. Braunsteiner: Isolierung und Charakterisierung der chymotrypsinähnlichen Protease aus neutrophilen Granulozyten des Menschen. Schweiz. Med. Wschr. 104, 132 (1974)

57)   G. Konwalinka, Ch. Peschel, F. Schmalzl, G. Michlmayr, L. Peer, H. Huber und H. Braunsteiner: Knochenmarkskulturen             bei aplastischen Anämien und Präleukämien. Acta med. Austriaca 6, 219 ( 1980)

58)   G. Konwalinka, D. Geissler, Ch. Peschel, B. Tomaschek, F. Schmalzl, H. Huber, R. Odavic, and H. Braunsteiner: A micro agar culture system for cloning human erythrpoietic progenitors in vitro. Exp. Hematol. 10, 71 (1982)

59)   G. Konwalinka, Ch.Peschel, F. Schmalzl, H. E. Schaefer, D. Geissler, G. Schuler, H. Huber, B.Tomaschek, R. Odavic, H. Braunsteiner: CFUgm assay, cytochemical and electron microscopic studies in agar in patients with preleukemic syndromes and aplastic anemia. Intern. J. Cell Cloning 3, 367 (1985)

60)   D. Geissler, H. Zwierzina, Ch. Pechlaner, F. Schmalzl, G. Konwalinka and H. Braunsteiner:  

Abnormal megakaryopoiesis in patients with myelodysplastic syndromes: Analysis of cellulat and humoral defects. Brit. J. Haematol. 73, 29 (1989)

61)   F. Schmalzl und Ch. J. Wiedermann: Zur Technik quantitativer enzymzytochemischer Untersuchungen an polymorphkernigen Neutrophilen des Menschen. Acta histochem., Suppl. XXVIII, 157 (1983)

62)   F. Schmalzl und Ch. J. Wiedermann: Zur Bedeutung quantitativ-enzymzytochemischer Untersuchungen für die hämatologische Zytologie. Wien. klin. Wschr. 95, 158 (1983)

63)   Ch. J. Wiedermann, F. Schmalzl and H. Braunsteiner: Investigation on granulocytopoietic kinetics by microphotometric evaluation of primary granule naphthol-AS-D-chloroacetate esterase activity. Blut 47, 271 (1983)

64)   H. Braunsteiner, F. Schmalzl und R. Rindler-Ludwig: Die Funktion der neutrophilen Granulozyten und der Monozyten im Rahmen der zellulären Abwehr. Haematologica 8, 341 (1974)

65)   P. Spath, F. Schmalzl, L. E. Spitler, L. Petz, N. Cooper und H. H. Fudenberg: Abwehrdefekte beim multiplen Myelom. In: Probleme der Erythropoese, Granulozytopoese und des malignen Melanoms; Berlin-Heidelberg-New York, Springer 1978 (Hämatologie mund Bluttransfusion, Bd. 21), S. 441

66)   Ch. Huber, U. Fink, W. Leibold, F. Schmalzl, P. A. Peterson, L. Klareskog and H. Braunsteiner: The role of adherent HLA-DR+ mononuclear cells in autologous and allogeneic MLR.                J. Immunol. 127, 726 (1981)

67)   M. Zirm, D. Stunzner, F. Schmalzl, B. Stiassny und J. Möse: Die herpetische Uveitis. Makrophagenstimulation im Tierexperiment. Ber. Dtsch. Ophthalmol. Ges. 78, 329 (1981)

68)   G. Gastl, F. Schmalzl, D. Huhn, C. Gattringer and Ch. Huber: Large granular lymphocytes: Morphological and functional properties. I. Results in normals. Blut 46, 297 (1983)

69)   W. Vogel, R. Margreiter, F. Schmalzl, G. Judmaier: Preliminary results with finde needle aspiration biopsy in liver grafts. Transplantation proceedings 16, 1240 (1985)

70)   E. Leiter, R. Pfister, D. Lutz, G. Michlmayr, H. Gadner, C. Gattringer, F. Schmalzl, H. Braunsteiner, Ch. Huber: Surface glycoproteins (S-GP) on normal and malignant human leukocytes. Blut 50, 157 (1985)

71)   M. Lechleitner, C. Gattringer, G. Gastl, T. Radaskiewicz. W. Pfaller F. Schmalzl, H. Huber: Macrophage infiltration in Non-Hodgkin’s lymphoma. A quantitative in situ study. Immunobiol. 171, 381 (1986)

72)   H. Zwierzina, F. Schmalzl and H. Braunsteiner: Interleukin-3: In vitro effects and future clinical relevance. Acta medica Austriaca 1, 24 (1991)

73)   H. Zwierzina, M. Herold, S. Schoellenberger and F. Schmalzl: Soluble interleukin-2 receptor expression in patients with myelodysplastic syndromes induced by GM-CSF and interleukin-3. Blood (letter) 78, 2795 (1991)

74)   H. Zwierzina, M. Herold, S. Schoellenberger, D. Geissler and F. Schmalzl: Detection of soluble IL-2 receptor in the serum of patients with myelodysplastic syndromes: Induction under therapy with CM-CSF. Brit. J. Haematol. 79, 438 (1991)

75)   F. Schmalzl, M. Ciresa und H. Braunsteiner: Zur Zytochemie der Drüsenfieberzellen. Acta haemat. 39, 257 (1968)

76)   Ch. Huber, H. Huber, F. Schmalzl, B. Lederer, D. Bütterich und H. Braunsteiner: DNS – Synthese in Blut-Lymphozyten beim malignen Lymphogranulom Acta haemat. 444, 222 (1970)

77)   Ch. Huber, H. Huber, F. Schmalzl and H. Braunsteiner: Decreased proliferative activity of erythroblasts in granulocytic stem cell leukemia. Nature 229, 113 (1971)

78)   F. Kunz, R. Constantini, E Semenitz, G. Mikuz, F. Schmalzl and F. Holzknecht: The production of disseminated intravascular coagulation (DIC) by spaced injections of endotoxin in non pregnant normolipaemic rats.   Thrombosis research 12, 119 (1977)

79)   F. Schmalzl: Lymphomatoide Granulomatose. Dtsch. Med. Wschr. 105, 1702 ( 1980)

80)   F. Schmalzl: Etoposid in der Behandlung monozytärer Leukämien. In: Etoposid (VP-213) in der Therapie maligner Erkrankungen. Hsg: J. Schwarzmeier, E Deutsch, K. Karrer, Springer, Wien – New York (1984)

81)   F. Schmalzl, G. Konwalinka, G. Michlmayr, K. Abbrederis, and H. Braunsteiner: Detection of cytochemical and morphological anomalies in „Preleukemia“. Acta haemat. 59, 1 (1978)

82)   F. Schmalzl and M. Lechleitner: Disappearence of a sideroblastic cell clone during the chronic phase of a preleukemic myelodysplastic syndrome. Brit. J. Haematol. 64, 410 (1986)

83)   H. Zwierzina, N. Sepp, E Ringler and F. Schmalzl: Delayed maturation of skin window macrophages in myelodysplastic syndromes. Leukemia Research 13, 433 (1989)

84)   N. Sepp, H. Zwierzina, J. Smolle, F. Schmalzl, P. Fritsch and G. Schuler: Epidermal Langerhans cells in myelodysplastic syndromes are abnormal. J. Invest. Dermatil. 96, 932 (1990)

85)   H. Zwierzina, G. Mufti and F. Schmalzl: Therapy of myelodysplastic syndromes; advances and perspectives. Leukemia 5, 166 (1991)

Books
  1. “Probleme der Erythropoese, Granulozytopoese und des malignen Melanoms”, Herausgeber: G. W. Löhr, H. Arnold, R. Engelhardt, W. Möbius und G. Mähr, F. Schmalzl und Ch. Sauter, , Springer, Berlin-Heidelberg-New York, 1978, 457 Seiten
  2. “Preleukemia”, Eds. F. Schmalzl and K. P. Hellriegel, Springer, Berlin-Heidelberg-New York, 1979,       194 pages
  3. “Disorders of the Monocyte Macrophage System”, Eds. F. Schmalzl, D. Huhn and H. E. Schaefer, Springer, Berlin-Heidelberg-New York, 1981, (256 pages)
  4. “Myelodysplastic Syndromes”, Eds. F. Schmalzl and G. J. Mufti, Springer, Berlin-Heidelberg-New York, 1992, 336 pages.
Wissenschaftliche Arbeit

Topics of interest in my scientific work.

Tit. a. o. Univ. Prof. Dr. Franz Schmalzl

The following presentation of my major scientific interests is based on a selection of 85 papers out of approximately 140 published – abstracts are not reported or counted.

I)                    Origin and development of monocytes.

The still controversial origin of blood monocytes was approached by adapting a double staining cytochemical technique (see 1/1964) for the selective staining of blood monocytes in blood smears (1/1964,3/1968) due to the NaF-sensitivity of their high esterase activity. The same technique allowed the identification of mature and immature monocytes (promonocytes) in human bone marrow (2/1967, 3/1968) and their clear distinction from promyelocytes (4/1968) which, in some publications were thought by other author to be the direct precursors of bood monocytes. Combining this cytochemical technique with H3-thymidine autoradiography the proliferation of the monocytic series including promonocytes was proved in human bone marrow (5/1969). Based on this procedure G. Meuret described in a very specific and reliable way the proliferative activity of promonocytes and monocytes (Exp.Hemat. 2, 238 (1974)). In 6/1979 this concept of monocytopoiesis had to be defended against L.-D. Leder (Literature see 6) repeating the concept of mature promyelocytes as the physiologic precursors of monocytes. In vitro cultures of human bone marrow stem cells on agar allowed the clearcut distinction between pure monocytic and pure neutrophil granulocytic-promyelocytic or mixed clusters and colonies (7/1980).     

Review article: H. Braunsteiner and F. Schmalzl : Cytochemistry of monocytes and macrophages. In: Mononuclear phagocytes. Ed. R. van Furth, Oxford, Blackwell, (1970), p. 62 – 81.

II)                  Macrophages

The also controversial issue of the origin of macrophages was addressed investigating their development from monocytes in skin window exudates (Rebuck) (8/1967,9/1969). The transformation of monocytes into macrophages and into polynucleated giant cells could be followed at nearly hourly intervalls allowing to check the sequential changes of the enzymatic equipment and especially the increase of lysosomal enzymes (9,10/1969, 11/1970). Very large and extremely acid phosphatase positive polynucleated macrophages were identified in pus and represent the final stage of macrophage maturation in putride exudates (12/1971). The inhibition of lysosomal maturation of macrophages by local application of glucocorticoids and aminophylline on skin windows could easily be followed by visual evaluation of acid phosphatase staining (13/1971) as well as relying on the cytophotometric evaluation of the acid phosphatase staining product (15/1982). Defects in the enzymatic maturation of macrophages could be seen in patients suffering from rheumatoid arthritis (14/1974) and in myelodysplastic syndromes (83/1989) (see chapter XII). Concerning the transformation of leukemic monocytes into macrophages see next topic.

III)                Monocytic leukemia and their variants.

The cytochemical characterization of blood monocytes and their precursors resulted very useful for the unequivocal characterization of monocytic leukemia ( 16/1968,19/1969). The functional capacities of leukemic monocytes in terms of immigration into inflammatory exudates as well as macrophage development were studied in skin window exudates (17/1968). Additional experiments using liquid in vitro cultivation disclosed the unique feature of leukemic monocytes to transform into macrophages in contrast to other acute leukemia cells of myeloid or lymphatic origin, confirming thus the findings of the skin windows exudates (18/1969). Electron microscopic investigations together with D. Huhn elaborated on the ultratsructural distinction of monocytic leukemias in contrast to other types of acute myeloid and lymphoid leukemias (21/1971). “Acute immature monocytic” leukemia was first described addressing morphologic, cytochemical, electron microscopic, as well as functional aspects of these peculiar leukemic cell populations (20/1971). Since 1976 the FAB group also realized an immature variant of monocytic leukemia - FAB 5 a - in their official classification. Cases of acute myeloid leukemia characterized by chimeric leukemic cell populations exhibiting simultaneously monocytic and promyelocytic features were extensively studied by means of morphologic and ultrastructural as well as functional investigations and by determination of intracellular as well as secreted lysozyme (22/1972). Similar chimeric forms of AML have been confirmed since 1982. Further publications were concerned with the characterization of chronic myelomonocytic leukemias (23/1979) and the prognosis of different types of monocytic leukemias (24/1979).

The engagement in the pathology of the monocyte-macrophage system resulted in the publication of: “Disorders of the Monocyte Macrophage System”, Eds. F. Schmalzl, D. Huhn and H. E. Schaefer, Springer, Berlin-Heidelberg-New York, 1981, (256 pages)

IV)               Lysozyme (muramidase) in normal and leukemic monocytes.

Together with H. Asamer the presence of lysozyme (muramidase) was studied in blood cells by means of immunocytology (25/1968). Consequently, the lysozyme content of leukemic cell was studied both by immunocytogy as well as by quantitative immunologic techniques in lysates of leukemic cells and in serum and urine of patients suffering from different types of leukemia (26,27/1971, 28/1974, 29/1975 ).

V)                 Classification of leukemic cell populations in cases of acute and chronic leukemias.

Due to intense diagnostic activity in my lab from 1965 to 1987 I overlooked a great number of leukemias, both from the department of internal medicine in Innsbruck as well as from foreign haematological departments and from large international studies. Besides leukemic disorders an enormous number of smears from myelodysplastic syndromes and a large collection of general haematologic disorders were accumulated.                                                                                                     In each case examination of morphology in panoptic stained smears was always combined with a varying series of cytochemical stainings, thus providing an extensive information on the enzymatic equipment of the studied cell populations. Generally immunologic and immunocytologic tests and demonstration of lysozyme as well as electron microscopy and cytogenetic analyses as well as cytogenetic studies in selected cases were also available. In addition to the publications presented in chapter III about the leukemias of the monocytic series typical cases of acute myeloid leukemia (AML) as well as their variants were also described (30/1969, 32, 33/1971, 35/1973, 36/1972). Special attention deserve first descriptions of atypical AML presenting maturation of the leukemic blasts into “paraneutrophils” (31/1971) and of chimeric myelocytic-monocytic leukemia (22/1972, 44/1986) and of atypical tumorous paediatric AML (38/1975) and extensively studied megakaryoblastic-micromegakaryocytic crisis in chronic myeloid leukemia (42/1985). Further extensive studies on acute undifferentiated leukemia (36/1972), acute lymphoblastic leukemia (37/1974), hairy cell leukemia (39/1975), prolymphocytic leukemia (41/1979), and LGL-leukemia (43/1986) were also published. Publications on therapy related or secondary AML (40/1975) and about experiences with new therapies in AML (34/1971) conclude this field of scientific interest.

VI)                The application of cytochemical techniques to the routine examination of blood and bone marrow smears

allows a very sensitive evaluation of maturation disorders in the myeloid cells. In many cases the cytochemical findings were controlled by means of electron microscopy and functional tests. The following topics were examined:
Acute and chronic leukemias: see chapter V.
Congenital agranulocytosis : (45, 46/1971)
Pathologic granulation of neutrophil granulocytes : (47/1973)
Toxic effects of alcohol on the myeloid haematopoiesis : (48/1978)
Diagnostic approach to the distinction of leukemic and reactive neutrophilia: (49/1978)
Development of eosinophil granulocytes studied in normal, leukemic and peroxydase deficient human bone marrow : (50/1979)
Human bone marrow cells in macrocytic anaemias : (51/1979)
Recommended cytochemical methods – WHO international committee for standardization in haematology (Chairman: A. Shibata) : (52/1985)                                                                                                     Prekeukemia and Myelodysplastic Syndromes: See chapter XII

VII)                 Cytochemically detectable naphthol-AS-D-chloroacetate esterase – activity in human neutrophil granulocytes. Biochemical characterization of their protease nature and investigations on their subcellular localization.

These investigations were performed in cooperation with the biochemist Dr. R. Rindler-Ludwig, who joined my working group in 1970 with the purpose to identify the chemical nature of the strong cytochemically detetctable activity capable to split naphthol-AS-chloroacetate esters in human neutrophils granulocytes (53/1971). The neutral protease nature of this enzymatic activity was demonstrated and their suspected subcellular localization to primary granules was confirmed by centrifugation techniques (54/1973, 55,56/1974).

 

VIII)                 Haematopoietic stem cell cultures on agar.

G. Konwalinka in our clinic developed haematopoietic stem cell culture systems on agar for CFUs of different maturation capacity which permitted to easily study the morphological and cytochemical development of the cells growing in colonies and clusters (7/1980, 58/1982). Adaptation for cloning megakyopoietic progenitors was also achieved (60/1989). Important alterations of growth and cytological development were reported for normal, preleukemic, and myelodysplastic syndromes presenting higher counts of blasts as well as for aplastic anemia (57/1980, 59/1985, 60/1989). (See chapter XII)

 IX)                 Quantitative approach  to evaluate the cytochemical reaction products in intact cells spread on glass slides or cover glasses using a cytophotometric device.

Using a scanning microscope photometer SMP 05 (Zeiss) the technical requirements for the quantitative evaluation of cytochemical reaction products in cells spread in smears of blood, bone marrow, or inflammatory exudates had to be elaborated (61, 62/1983). These methods were also used to evaluate the changes of acid phosphatase activity observed in developing skin window macrophages exposed to methyl-prednisolone and aminophylline (15/1982). Evaluating quantitatively the activity of naphthol-AS-D-chloroacetate esterase in polymorphonuclear neutrophils as well as in neutrophil granulocytic precursors in bone marrow smears, informations were derived about the number of mitoses occurring between promyelocytes and polymorphonuclears in normal humans as well as in inflammatory disorders (63/1983).

 

X)                 Papers on various aspects of immunology and inflammation.

In the context of the engagement concerning the origin and the maturation of macrophages (see chapter II) studies on the cellular defense system (64/1974, 67/1981, 68/1983) were also published, as well as a paper on the inflammatory cells in human liver transplantats obtained by fine needle biopsies (69/1985) and about the infiltration of Non Hodgkin-lymphomas with macrophages (71/1986). In the same context papers on HLA-DR+-mononuclear cells and their role in MLR (66/1981) and on large granular lymphocytes (68/1983) should be mentioned, as well as on surface glycoproteins on leukocytes (70/1985) . Disturbed defense mechanisms in multiple myeloma (65/1978) have also been studied. H. Zwierzina was joined in studies on interleukin-3 (72/1991) and on soluble Interleukin-2 receptor (73,74/1991).

 

XI)                 Publications on single aspects of haematology and related disorders.

In a paper on infectious mononucleosis the difference between big mononuclear cells in the peripheral blood of this disease and blood monocytes was elaborated (75/1968). In cooperation with Ch. Huber the H3-thymidine incorporation in lymphocytes in malignant lymphogranuloma ( 76/1970) as well the proliferative activity of erythroblasts in granulocytic stem cell leukemia were investigated (77/1971). The experimental induction of disseminated intravascular coagulation in rats was studied together with F. Kunz (78/1977). A peculiar case of lymphomatoid granulomatosis with primary affection of striated muscles induced an extensive study of this kind of diseases (79/1980). The special interest on the therapy of monocytic leukemias determined a publication about etoposid activity in acute leukemia (80/1984).

 

XII)                 Preleukemia and myelodysplastic syndromes.

Anomalies of the granules of polymorphonuclear neutrophils in humans suffering from myeloid leukemic disorders were detected by cytochemical techniques and confirmed by electron microscopic examinations (47/1973). However, similar granulation defects were also disclosed in etiologically unclear disorders affecting myeloid haematopoiesis without an increase in blasts in the peripheral blood or in the bone marrow but terminating in a considerable proportion of cases ( up to 40 per cent) after a varying number of years into an acute myeloid leukemic disorder (81/1978). Years later the FAB-group included this kind of disorders into the newly created “myelodysplastic syndromes” (MDS), combining them with bone marrow disorders presenting markedly increased numbers of blasts in the peripheral blood or in the bone marrow, (here up to 30 % ) or with myelomonocytic leukemia (CMML). In the last years WHO expert panels progressively corrected the concept of MDS, defining CMML as a single entity not belonging any more to MDS, and separated cases with excessive accumulation of blasts (20 – 30 %) from MDS. Continuing cytochemical examinations revealed biphenotyic maturation of cells also in MDS, not only in AML (44/1986), and showed, that also from a cytological point of view, MDS is a clonal disease with possible loss of pathologic clones (82/1986).   Extensive studies revealed that the cytochemical alterations observed in blood and bone marrow cells were also detectable in myeloid cells maturing on agar cultures (57/1980, 59 /1985,60/1989). Further studies disclosed in MDS-patients a defect in the capacity of monocytes to develope into mature macrophages (83/1989), in the development of Langerhans cells (84/1990), as well as disturbed immunologic regulations concerning the metabolism of soluble interleukin-2 receptor (73, 74/1991) . Therapeutic studies on MDS were conducted in our group (85/1991) as well, but mainly within the activities of the Leukemia Study Group of the EORTC.   

The work in this field resulted in the publication of two books, which contain more specific informations: “Preleukemia”, Eds. F. Schmalzl and K. P. Hellriegel, Springer, Berlin-Heidelberg-New York, 1979, 194 pages and         “Myelodysplastic Syndromes”, Eds. F. Schmalzl and G. J. Mufti, Springer, Berlin-Heidelberg-New York, 1992, 336 pages.

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