Dipeptide processing activates recombinant human prochymase

Human chymase (h-chymase) is a serine protease that efficiently converts angiotensin I to II. Its structure and homology to other serine proteases suggest that it is synthesized as a zymogen, and is processed to the active form by cleavage of a 19-residue signal peptide and of a dipeptide pro-segment. To evaluate maturational processing of this enzyme, the proteins encoded by three h-chymase cDNA constructs (wild-type, lacking the pro- or lacking the prepro-segment) were characterized after expression in COS-1 cells. These recombinant proteins were not catalytically active. Purification and NH2-terminal sequence analysis of the protein expressed from the wild-type construct revealed processing to the proenzyme. Prochymase activation was achieved by incubation with a B-cell lymphoma homogenate, which apparently contains a heterologous processing enzyme sensitive to thiol protease inhibitors. NH2-terminal sequence analysis of the activated h-chymase revealed cleavage of the pro-segment, and its biochemical characteristics were identical to those of native h-chymase purified from the myocardium. These findings indicate that processing of the dipeptide pro-segment is necessary and sufficient for activation of human chymase. Such processing is probably also required for the activation of related serine proteases, e.g., cathepsin G, which have homologous dipeptide pro-segments

Molecular characterization of autonomic and neuropeptide receptors

© 1994 by Marcel Dekker, Inc. All Rights Reserved. For many years, it was believed that the control of airway function was dependent on the balance between the cholinergic (parasympathetic) and adrenergic (sympathetic) nervous systems. The cholinergic system is considered excitatory because it plays a role in maintaining airway tone and in mediating acute bronchospastic responses (Casale, 1993). The effect of acetylcholine to produce narrowing of the airways is blocked by atropine, indicating that this effect is mediated by muscarinic acetylcholine receptors (Colebatch and Halmagyi, 1963; Olsen et al., 1965). In contrast, the adrenergic system in the lung is considered inhibitory because stimulation of β-adrenergic receptors produces relaxation of bronchial smooth muscle. The beta-blockade theory of the pathogenesis of asthma from Szentivanyi (1968) proposed that asthma was related to an imbalance in the autonomic control of airway diameter due to a decrease in β-adrenergic sensitivity in bronchial smooth muscle, mucus glands, and mucosal blood vessels

A Review of Fuzzy Sets in Decision Sciences: Achievements, Limitations and Perspectives

International audienceWe try to provide a tentative assessment of the role of fuzzy sets in decision analysis. We discuss membership functions, aggregation operations, linguistic variables, fuzzy intervals and valued preference relations. The importance of the notion of bipolarity and the potential of qualitative evaluation methods are also pointed out. We take a critical standpoint on the state of the art, in order to highlight the actual achievements and try to better assess what is often considered debatable by decision scientists observing the fuzzy decision analysis literature