Manfred Kiese

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Manfred Kiese (born June 28, 1910 in Stettin , † February 22, 1983 in Munich ) was a German pharmacologist and toxicologist . He has made particular contributions in the field of biochemical pharmacology and toxicology.

Life

He attended the humanistic grammar school in Dramburg and then studied medicine in Hamburg, Frankfurt, Munich and Berlin. At the Berlin Pharmacological Institute he began his scientific career in 1935 with a dissertation prepared by Wolfgang Heubner “Pharmacological investigations on the smooth muscles of the lungs (especially with some ephedrine- like substances)”. From 1937 to 1939 he worked on a Rockefeller Foundation scholarship with Albert Baird Hastings (1895-1987) at the Department of Biological Chemistry at Harvard Medical School in Boston , Massachusetts . Back in Berlin, he completed his habilitation in 1940 with a thesis entitled "The Effects of Carbon Dioxide ". From 1939 he was a member of the NSDAP and the SA . Shortly before the end of the Second World War , the remains of the Berlin institute were relocated to the intact agricultural school in Kappeln an der Schlei , where two institutes of the Christian-Albrechts-Universität zu Kiel had also been relocated, namely the Pharmacological Institute under Behrend Behrens (1895-1969 ) and the Institute for Physiological Chemistry under Hans Netter (1899–1977). The Berlin pharmacology building on Dorotheenstrasse was almost completely destroyed by fire bombs in April 1945. From 1947 to 1950, Kiese was in charge of the laboratory of the Medical Clinic of Kiel University, headed by Helmuth Reinwein (1895–1966), and also took part in pharmacology classes in Kiel. In 1947 he married Edith geb. Schaffler.

In 1950 he followed a call to the chair of pharmacology and toxicology at the Philipps University of Marburg , where he succeeded Hans Gremels (1896-1949). From 1952 to 1953 he was dean of the medical faculty in Marburg. In 1956 he switched to the pharmacology-toxicology chair at the Eberhard Karls University of Tübingen as the successor to Felix Haffner (1886–1953) . At the time, the institute moved to new premises in the Lothar Meyer building northeast of the old institute on Wilhelmstrasse in Tübingen. In 1959 he was chairman of the German Pharmacological Society . After five years in Tübingen, he took over the chair of his subject at the Ludwig Maximilians University in Munich in 1961 as the successor to August Wilhelm Forst (1890–1981) . For the institute which was destroyed in 1944 and only poorly repaired under Forst, he built a new building. In 1980 he retired. His successor was Wolfgang Forth . In 1981, just over a year before his own death, his wife died.

research

Early work

The research at Heubner's Berlin institute was broad. After his dissertation and a few other works on various topics, including another on ephedrine, Kiese concentrated on biochemical pharmacology with special attention to hemoglobin , a focus of Heubner's interests.

With Hastings in Boston, then alone in Berlin, he investigated the physicochemical properties of the enzyme carbonic anhydrase , which was discovered in 1932 and later became important as a target for diuretics , and which catalyzes the reaction of carbon dioxide and water to form carbonic acid and back. The habilitation thesis also belongs here.

The green verdoglobins are among the derivatives of hemoglobin that can also be formed after taking drugs . Kieses group in Berlin suggested calling the verdoglobin produced when hemoglobin came into contact with hydrogen sulfide in the presence of oxygen , verdoglobin S , a nomenclature also used later. The publication shows Kieses' close collaboration with Heubner and two other members of the Berlin Institute who later became known, namely Robert Havemann and Friedrich Jung . Even in the makeshift rooms at the agricultural school in Kappeln, Kiese continued to research verdoglobine. Of his eight essays in the first post-war volume, Volume 204, 1947 from Naunyn-Schmiedeberg's Archive for Experimental Pathology and Pharmacology , five were sent in from Berlin in 1944 and 1945, the other three from Kappeln, stating “Presentation and properties of Verdoglobins” with the indication of origin "From the Pharmacological Institute and the Physiological-Chemical Institute of the University of Kiel in Kappeln an der Schlei".

Methemoglobin formation

In the red blood cells , hemoglobin is constantly divalent Fe 2+ and serving the transport of oxygen to methemoglobin or Hemiglobin by trivalent Fe 3+ incompetent and can transport oxygen, oxidized . Kieses' first hemoglobin study apart from the verdoglobin studies was the reconversion of methemoglobin into hemoglobin. He recognized that several mechanisms are involved, most importantly a flavin-containing enzyme that he called hemiglobin reductase , now mostly called methemoglobin reductase or, because NADH and cytochrome b 5 are cofactors , NADH-dependent cytochrome B 5 reductase .

Apart from this natural methemoglobin formation, many substances convert hemoglobin into methemoglobin and can thereby trigger methemoglobinaemia with cyanosis and other symptoms of intoxication. These include aromatic amines such as the prototype aniline and aromatic nitro compounds such as the prototype nitrobenzene . The amines and nitro compounds are first activated by biotransformation to the corresponding hydroxylamines or nitroso compounds . The subsequent formation of methemoglobin is a complicated cycle. Based on the work of Heubner and Jung, Kiese and his colleagues enlightened him - the Kiese cycle - in 1949 and 1950 in a series of ten publications in Naunyn-Schmiedeberg's archive, all “from the Kiel Medical Clinic”. His student and biographer Peter Eyer (* 1942) calls Kieses' monograph Methemoglobinemia: A Comprehensive Treatise his "most valuable scientific heirloom".

Oxidation and reduction on nitrogen

The formation of methaemoglobin by aromatic amines and nitro compounds led to the question of how they were activated. Heubner had already concluded that the aniline nitrogen on the benzene nucleus could be oxidized directly. Kiese succeeded in proving this with a new method in Tübingen: “A major effect of the uptake of aniline in the organism of warm-blooded animals, namely the formation of hemiglobin, is not an effect of the aniline itself, but of one - or more - of its reaction products. Among the known simple derivatives of aniline, phenylhydroxylamine and nitrosobenzene cause the strongest formation of hemiglobin. The two substances can oxidize a large number of equivalents of hemoglobin to hemiglobin in an enzymic cycle. ... So far, phenylhydroxylamine and nitrosobenzene have not been detected as biological oxidation products of aniline in the organism. We determined nitrosobenzene in the blood of aniline-injected dog and found that nitrosobenzene was present in the blood of dogs after an intravenous injection of aniline. ”As predicted by cycle theory, nitrosobenzene was subsequently reduced back to phenylhydroxylamine (and then further, outside the cycle, to aniline). The enzymes for N-oxidation were located in the endoplasmic reticulum of the liver cells. According to Eyer, Kiese was even more fascinated by the oxidation of nitrogen than the formation of methaemoglobin. Kiese and his student Hartmut Uehleke (* 1924) have summarized them in overview articles. Here, too, Kiese is one of the most important researchers. His Munich institute was internationally known as "the home of the biochemical pharmacology of N-oxidation".

Treatment of prussic acid poisoning

Hydrocyanic acid and its salts, the cyanide , endanger the lives by blocking the respiratory chain belonging to cytochrome c oxidase . One principle of the treatment is the binding of the cyanide ion CN - to other places, for example to the Fe 3+ of methemoglobin. Kieses group found a methaemoglobin producer in Munich that was particularly suitable for this, namely 4-dimethylaminophenol. Today it is considered the best antidote with this principle of action.

student

The following scientists completed their habilitation at Kiese (place and year):

  • Maximilian Frimmer (Tübingen, 1959), later professor for pharmacology and toxicology in the veterinary medicine department at the Justus Liebig University in Giessen ;
  • Hartmut Uehleke (Tübingen, 1962), later Managing Director at the Federal Health Office in Berlin;
  • Hermann Kurz (Munich, 1963), later professor at the Munich Institute;
  • Gerhard Lange (Munich, 1963), later head of the Institute for Toxicology of the Society for Radiation and Environmental Research ;
  • Peter Hlavica (Munich, 1970), later professor at the Munich Institute;
  • Hermann Kampffmeyer (Munich, 1970), later professor at the Munich Institute;
  • Nikolaus Weger (Munich, 1970);
  • Gerhard Renner (Munich, 1971), later professor at the Munich Institute;
  • Hansjörg Teschemacher (Munich, 1971); later professor at the Rudolf Buchheim Institute for Pharmacology at the University of Giessen;
  • Werner Lenk (Munich, 1972), later professor at the Munich Institute;
  • Jörg Remien (Munich, 1974), later professor at the Munich Institute;
  • Peter Eyer (Munich, 1976), later professor at the Munich Institute.

recognition

In 1977 the participants of a conference on biological oxidation of nitrogen dedicated the book to Manfred Kiese about their conference. The editor wrote (from English): “Although hydroxylamines had been suspected as active metabolites of aromatic amines for many years, it was not until 1959 that Professor Kiese demonstrated this reaction in two publications. ... Professor Kiese has worked on numerous questions on cardiac pharmacology and carbonic anhydrase, but his works on the formation and toxicology of N-oxidized compounds are of the greatest importance. ... He was the first to expressly create a research group to clarify the oxidation of nitrogen. "

The magazine Xenobiotica dedicated a commemorative publication to Kiese on his 70th birthday with articles by his students and "others who know him, appreciate his scientific achievements and regard him as friends."

literature

  • Margitta Albinus, Hartmut Osswald: Institute for Pharmacology and Toxicology, Medical Faculty of the Eberhard Karls University of Tübingen. In: Athineos Philippu (Ed.): History and work of the pharmacological, clinical-pharmacological and toxicological institutes in German-speaking countries. Berenkamp-Verlag, Innsbruck 2004, pp. 600–609. ISBN 3-85093-180-3 .
  • Peter Eyer: Manfred Kiese 1910–1983 . In: Munich Medical Weekly . 125, No. 14, 1983, p. 83.
  • Peter Eyer: Walther Straub Institute for Pharmacology and Toxicology, Medical Faculty of the Ludwig Maximilians University in Munich. In: Athineos Philippu (Ed.): History and work of the pharmacological, clinical-pharmacological and toxicological institutes in German-speaking countries. Berenkamp-Verlag, Innsbruck 2004, pp. 518-531. ISBN 3-85093-180-3 .
  • John W. Gorrod: Biological Oxidation of Nitrogen. Proceedings of the 2nd International Symposium on the Biological Oxidation of Nitrogen in Organic Molecules held at the Chelsea College, University of London, United Kingdom, September 19-23, 1977. Elsevier / North-Holland Biomedical Press, Amsterdam 1978.
  • John W. Gorrod, Dennis V. Parke: Editorial. (via Manfred Kiese). In: Xenobiotica 10, 1980, pp. 455-456.
  • Jürgen Lindner and Heinz Lüllmann : Pharmacological institutes and biographies of their directors. Editio-Cantor-Verlag, Aulendorf 1996. ISBN 3-87193-172-1 .
  • Rudolf Morgenstern: Institute for Pharmacology and Toxicology, Medical Faculty (Charité) of the Humboldt University in Berlin. In: Athineos Philippu (Ed.): History and work of the pharmacological, clinical-pharmacological and toxicological institutes in German-speaking countries. Berenkamp-Verlag, Innsbruck 2004, pp. 91–116. ISBN 3-85093-180-3 .
  • Karl Joachim Netter: Pharmacological Institute, Medical Faculty of the Philipps University of Marburg. In: Athineos Philippu (Ed.): History and work of the pharmacological, clinical-pharmacological and toxicological institutes in German-speaking countries. Berenkamp-Verlag, Innsbruck 2004, pp. 490–509. ISBN 3-85093-180-3 .

Web links

Individual evidence

  1. ↑ Manfred Kiese: Pharmacological examinations on the smooth muscles of the lungs (especially with some ephedrine-like substances) . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 178, 1935, pp. 342-366. doi : 10.1007 / BF01861351 .
  2. ↑ Manfred Kiese: Effects of carbon dioxide . In: Biochemical Journal . 305, 1940, pp. 22-56.
  3. ^ Ernst Klee: Das Personenlexikon zum Third Reich , Frankfurt am Main 2007, p. 307
  4. ^ August Wilhelm Forst on the website of the Walther Straub Institute for Pharmacology and Toxicology. Retrieved August 27, 2013.
  5. ↑ Morgenstern 2004, p. 99.
  6. ↑ Manfred Kiese, Reschad Garan, Alfons Krautwald: On the heart effect of ephedrine and some related substances . In: Clinical weekly . 17, No. 28, 1938, pp. 967-971. doi : 10.1007 / BF01770195 .
  7. ^ Klaus Starke: A history of Naunyn-Schmiedeberg's Archives of Pharmacology. In: Naunyn-Schmiedeberg's Archives of Pharmacology 1998; 358: 1-109, here p. 40. PMID 9721010 . doi : 10.1007 / PL00005229
  8. ↑ Manfred Kiese, A. Baird Hastings: The catalytic hydration of carbon dioxide . In: Journal of Biological Chemistry . 132, 1940, pp. 267-280.
  9. ↑ Manfred Kiese: Kinetics of carbonic acid anhydrase. I. . In: Biochemical Journal . 307, pp. 400-413.
  10. ↑ Manfred Kiese: The activation energy of the reaction between carbon dioxide and water . In: Biochemical Journal . 307, pp. 207-214.
  11. ↑ Manfred Kiese, Hedwig Kaeske: Connections of muscle hemoglobin . In: Biochemical Journal . 312, 1942, pp. 121-149.
  12. ↑ W. Schwerd, E. Döllefeld: A new method for the detection of verdoglobin S (sulfhemoglobin) . In: Archives for Toxicology . 22, 1967, pp. 400-403. doi : 10.1007 / BF00577594 .
  13. ↑ Manfred Kiese: Representation and properties of verdoglobins . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 204, 1947, pp. 385-413. doi : 10.1007 / BF00245705 .
  14. ↑ Manfred Kiese: The reduction of hemiglobin . In: Biochemical Journal . 316, 1944, pp. 264-294.
  15. ^ Klaus Starke: A history of Naunyn-Schmiedeberg's Archives of Pharmacology. In: Naunyn-Schmiedeberg's Archives of Pharmacology 1998; 358: 1-109, here p. 58. PMID 9721010 . doi : 10.1007 / PL00005229
  16. ↑ Reinhard Mischke, Peter Eyer: Blood and blood-forming organs. In: Hans Marquardt, Siegfried G. Schäfer, Holger Barth: Toxikologie , pp. 383–405. Wissenschaftliche Verlagsgesellschaft , Stuttgart 2013. ISBN 978-3-8047-2876-9 .
  17. ^ The last of the ten publications: Hartwig Dannenberg, Manfred Kiese: Kinetik der Hämiglobinbildung. X. Reduction of nitrosobenzene in red cells . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 211, 1950, pp. 410-420. doi : 10.1007 / BF00248985 .
  18. ↑ Manfred Kiese: Methemoglobinemia: A Comprehensive Treatise . CRC Press 1974. ISBN 0-87819-0-54-6 .
  19. ↑ Eyer 1983.
  20. ^ Franz Herr, Manfred Kiese: Determination of nitrosobenzene in the blood . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 235, 1959, pp. 351-353. doi : 10.1007 / BF00246016 .
  21. ↑ Manfred Kiese: Oxidation of aniline to nitrosobenzene in dogs . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 235, 1959, pp. 354-359. doi : 10.1007 / BF00246017 .
  22. ↑ Manfred Kiese: The importance of the oxidation of aniline to nitrosobenzene for hemiglobin formation after aniline is absorbed into the organism . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 235, 1959, pp. 360-364. doi : 10.1007 / BF00246018 .
  23. ↑ Jürgen Haan, Manfred Kiese, Annemarie Werner: Reduction of nitrosobenzene to aniline in red blood cells . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 235, 1959, pp. 365-372. doi : 10.1007 / BF00246019 .
  24. ↑ Manfred Kiese, Hartmut Uehleke: The place of the N-oxidation of the aniline in the higher animal . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 242, 1961, pp. 117-129. doi : 10.1007 / BF00258508 .
  25. ↑ Hartmut Uehleke: Biological oxidation and reduction on nitrogen of aromatic amino and nitro derivatives and their consequences for the organism. In: Advances in Pharmaceutical Research 8, 1964, pp. 195-260.
  26. ↑ Manfred Kiese: The biochemical production of ferrihemoglobin-forming derivatives from aromatic amines, and mechanisms of ferrihemoglobin formation. In: Pharmacological Reviews 18, 1966, pp. 1091-1161. Retrieved August 21, 2013.
  27. ↑ John H. Weisburger, Elizabeth K. Weisburger: N-oxidation enzymes. In: BB Brodie, JR Gillette (Ed.): Concepts in Biochemical Pharmacology Part 2. Handbook of Experimental Pharmacology vol. 28/2, pp. 312-333. Springer-Verlag , Berlin 1971. ISBN 3-540-05389-1 .
  28. ↑ JW Gorrod, D. Manson: The metabolism of aromatic amines . In: Xenobiotica . 16, 1986, pp. 933-955. doi : 10.3109 / 00498258609038975 .
  29. ↑ Gorrod and Parke 1980.
  30. ↑ Manfred Kiese, Elli Rauscher, Nikolaus Weger: The role of N, N-dimethylaniline-N-oxide in the formation of hemoglobin following the absorption of N, N-dimethylaniline . In: Naunyn-Schmiedebergs Archive for Pharmacology and Experimental Pathology . 254, 1966, pp. 253-260. doi : 10.1007 / BF00536223 .
  31. ↑ Manfred Kiese, Nikolaus Weger: Formation of ferrihaemoglobin with aminophenols in the human for the treatment of cyanide poisoning . In: European Journal of Pharmacology . 7, 1969, pp. 97-105. doi : 10.1016 / 0014-2999 (69) 90170-8 .
  32. ↑ Doris Christel, Peter Eyer, Michael Hegemann, Manfred Kiese, Wiltrud Lörcher, Nikolaus Weger: Pharmacokinetics of cyanide in poisoning of dogs, and the effect of 4-dimethylaminophenol or thiosulfate . In: Archives of Toxicology . 38, 1977, pp. 177-189. doi : 10.1007 / BF00293652 .
  33. ↑ Kai Kehe, Peter Eyer: Gaseous compounds. In: Hans Marquardt, Siegfried G. Schäfer, Holger Barth: Toxikologie , pp. 855–884. Wissenschaftliche Verlagsgesellschaft, Stuttgart 2013. ISBN 978-3-8047-2876-9 .
  34. ↑ Gorrod 1978 in the foreword of the book.
  35. ↑ Gorrod and Parke 1980.
personal data
SURNAME Kiese, Manfred
BRIEF DESCRIPTION German pharmacologist and toxicologist
DATE OF BIRTH June 28, 1910
PLACE OF BIRTH Szczecin
DATE OF DEATH February 22, 1983
Place of death Munich