Specific inhibition of human leukocyte elastase by substituted alpha-pyrones

Several a-pyrones have been synthesized and investigated for their in vitro inhibitory activity using a-chymotrypsin (a-CT), porcine pancreatic elastase (PPE) and human leukocyte elastase (HLE). 4-Hydroxy-6-undecyl-2H-pyran-2-one 4, 4-Hydroxy-6-[(1-butyl)heptyl]-2H-pyran-2-one 5 and 4-Methoxy-6-[(1-butyl) heptyl]-2H-pyran-2-one 6 were found to be specific inhibitors of HLE. These compounds constitute a promising new class of HLE inhibitors.     

Proteolytic inactivation of human leukocyte elastase

Summary Human leukocyte elastase can be proteolytically inactivated by bovine pancreatic trypsin. Neither porcine pancreatic elastase nor bovine pancreatic chymotrypsin causes inactivation of leukocyte elastase, nor are trypsin, pancreatic elastase, or chymotrypsin themselves susceptible to proteolysis. The trypsin-catalyzed inactivation of leukocyte elastase can be slowed by inhibition of trypsin with benzamidine or by occupation of elastase's active site with elastatinal.     

Proteolytic inactivation of human leukocyte elastase

Human leukocyte elastase can be proteolytically inactivated by bovine pancreatic trypsin. Neither porcine pancreatic elastase nor bovine pancreatic chymotrypsin causes inactivation of leukocyte elastase, nor are trypsin, pancreatic elastase, or chymotrypsin themselves susceptible to proteolysis. The trypsin-catalyzed inactivation of leukocyte elastase can be slowed by inhibition of trypsin with benzamidine or by occupation of elastase's active site with elastatinal.     

Inhibition of human pancreatic elastase II activity on human aortic elastin by human alpha 2-macroglobulin

Human alpha 2-macroglobulin-human pancreatic elastase II binding were investigated using a homologous substrate, human aortic elastin, in order to test the enzymatic activity. We demonstrated that two moles of alpha 2-M are required to inhibit one mole of HPEII when the enzyme is added to a mixture of elastin and alpha 2-M. In addition, when the elastase-alpha 2-M complex is prepared under some circumstances, it exhibits an elastinolytic activity.     

Specific inhibition of formation of acid-fastness in mycobacteria by 3,3'-di-O-methylellagic acid.

3,3'-Di-O-methylellagic acid obtained from Euphorbia adenochlora selectively inhibited the formation of acid-fastness in mycobacteria without retardation of their growth. Gross reductions in contents of wax D, cord factor and free mycolic acids were found in the nonacid-fast bacilli compared with the normal ones.     

Specific inhibition of mast cell disruption in vitro

Résumé Les «mast cells» péritonéales de Rats hypersensibles à la -globuline humaine, subissent une «dégranulation» in vitro en présence de l'antigène. Cette «dégranulation» est inhibée par les antisérums spécifiques. Les sérums de Rats hypersensibles ont la propriété de sensibiliser au même antigène les «mast cells» de Rats normaux.     

Mechanism of elastolysis by pancreatic elastase

Résumé Nous présentons une étude du mécanisme de l'élastolyse par une élastase partiellement purifiée du pancréas. La méthode utilisée consiste dans le dosage spectrophotométrique de l'«azoelastine» dissoute. Cette protéine n'est que très lentement hydrolysée par la trypsine et chymotrypsine cristallisées. L'élastase possède une activité protéasique considérable. L'enzyme est très rapidement adsorbée sur l'élastine. Après une incubation à pH 4,5 avec l'enzyme adsorbée, le temps de latence de l'élastolyse disparaît et la rapidité de la réaction devient proportionnelle à la concentration en élastase.     

Magnesium enhances human pancreatic elastase digestion of 125I-labeled elastin

The effect of some divalent cations, especially Mg++, on elastinolysis by porcine or human pancreatic elastase has been determined using 125Iodine-labeled elastin as substrate. Elastin degradation was significantly increased in the presence of 10(-3) M Mg++. If elastin was pre-incubated with 0.5 (w/v) Triton, there was a further increase in elastinolysis to 2.6 times the original rate.     

Specific inhibition of a calcium dependent activation of brain cyclic AMP phosphodiesterase activity by vinblastine

Summary Vinblastine selectively inhibits the activation of brain cyclic AMP phosphodiesterase activity by Ca⁺⁺-protein activator (50% inhibition by 2×10^–5 M). This inhibitory effect was reversed by excessive amounts of the activator, whereas large quantities of Ca⁺⁺ caused only a slight suppression of the vinblastine effect. This result of vinblastine suggests a new site of its action and also suggests the possible role of protein activator, phosphodiesterase proteins or cyclic nucleotides in the previously known effects of vinblastine in vivo and in vitro.Our thanks to Drs A. R. Rhoads, C. B. Klee and R. A. Fergusson for analyzing PA preparations by gel electrophoresis and gel electrofocusing, and to Drs A. A. Suran and D. Soifer for their valuable critiques to this work. This work was partly supported by Biochemical Research Support Grant No. 5SO7RRO5361 to K.W. and Graduate Training Grant No. 5TO2GMO500002 to W.L.W. from NIH.     

Magnesium enhances human pancreatic elastase digestion of125I-labeled elastin

Summary The effect of some divalent cations, especially Mg⁺⁺, on elastinolysis by porcine or human pancreatic elastase has been determined using¹²⁵Iodine-labeled elastin as substrate. Elastin degradation was significantly increased in the presence of 10^–3 M Mg⁺⁺. If elastin was pre-incubated with 0.5 (w/v) Triton, there was a further increase in elastinolysis to 2.6 times the original rate.     

Specific inhibition of a calcium dependent activation of brain cyclic AMP phosphodiesterase activity by vinblastine.

Vinblastine selectively inhibits the activation of brain cyclic AMP phosphodiesterase activity by Ca++-protein activator (50% inhibition by 2 x 10(-5) M). This inhibitory effect was reversed by excessive amounts of the activator, whereas large quantities of Ca++ caused only a slight suppression of the vinblastine effect. This result of vinblastine suggests a new site of its action and also suggests the possible role of protein activator, phosphodiesterase proteins or cyclic nucleotides in the previously known effects of vinblastine in vivo and in vitro.     

Collagen breakdown by gingival collagenase and elastase

Summary The granule fraction of human polymorphonuclear leucocytes (PMNs), the concentrated product of gingival washing from 2 human volunteers and the culture fluid of samples of human gingiva were incubated with neutral salt soluble collagen from rat skin and the patterns of collagen degradation were studied by SDS polyacrylamide gel electrophoresis. Collagenase from human gingiva cleaved the collagen molecules in a fashion similar to that of the PMN granule fraction. Collagen was also attacked by elastase from human PMNs and, to a lesser extent, by elastase from the gingival washings.Supported by a grant of Swiss National Fund for Scientific Research No. 3.604.0.75.Acknowledgments. We thank Prof. M. Baggiolini, Wander S.A., Bern for his helpful advice. We are very grateful to Mrs I. Condacci and Miss E. Andersen for their skillful technical assistance.     

Effect of lead acetate of human leukocyte chromosomes in vitro

Zusammenfassung Experimente mit menschlichen Leukocytenkulturen lassen vermuten, dass die Wirkung von Bleiacetat von der Kulturmethode abhängig ist. In 72-h-Kulturen wurde eine Erhöhung von achromatischen Läsionen, Chromatidbrüchen und Isochromatidbrüchen induziert, nicht jedoch in 48-h-Kulturen. Chemisch- und strahleninduzierte Aberrationshäufigkeiten wurden durch Bleiacetat nicht beeinflusst.     

Action of antituberculosis drugs on human leukocyte chromosomes in vitro

Zusammenfassung Die AntituberkulosemittelPara-aminosalizylsäure (PAS), Ethambutol (EMB) und Capreomycin (CM) zeigen keine chromosomenbrechende Aktivität an menschlichen Leukozytenchromosomen in vitro.

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We thank Mrs.R. Pieper for her careful technical assistance.     

Mitotic inhibition induced in human kidney cells by methylglyoxal and kethoxal

Zusammenfassung Synchronisierte menschliche Nieren-T-Zellen zeigen eine Mitoseverzögerung, wenn sie in der G₁-, S- oder G₂-Phase des Zyklus Methylglyoxal oder Kethoxal ausgesetzt werden. Die Mitoseverzögerung wird durch 5mM Cysteamin eliminiert.