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G Till

Publications and source records attributed to G Till.

18 recordsLinked to original sources

Secondary metabolites by chemical screening. 8. Decarestrictines, a new family of inhibitors of cholesterol biosynthesis from Penicillium. I. Strain description, fermentation, isolation and properties.

A family of new 10-membered lactones was detected by chemical screening. Taxonomic studies and fermentation conditions of the producing organisms, which belong to the species Penicillium simplicissimum and Penicillium corylophilum, are presented. The isolation as well as physico-chemical data of the new compounds named decarestrictines A to D are reported. In vitro testing using the HEP-G2 cell assay showed the decarestrictines to be inhibitors of cholesterol biosynthesis, which could be confirmed in vivo. In addition to the decarestrictines from P. corylophilum epoxyagroclavine-I (1) was isolated.

Animals

Activation of complement by radiographic contrast media: generation of chemotactic and anaphylatoxin activities.

Iodinated radiographic contrast media such as methylglucamine diatrizoate and sodium ioglycamate activate serum complement in vitro. This was shown by a dose-, time-, and temperature-dependent decrease of total hemolytic complement activity in normal human serum, consumption of C4 and C6 activity, conversion of C3 to C3b, and generation of C5-derived chemotactic and smooth muscle contracting activity. Complement activation was achieved even in sera depleted of immunoglobulin and properdin, which may indicate that contrast media induce complement activation by mechanisms different from the classical or alternative pathway.

Anaphylatoxins

Chemotactic activity of lectins in vitro.

The effects of concanavalin A (Con A) and leucoagglutinin (LA) on the locomotor response of phagocytes have been studied in vitro. At concentrations of 1 to 4 microgram/mol, Con A and LA induced maximal chemokinesis and chemotaxis of monocytes, macrophages and, to a lesser degree, also of neutrophils. The lectin-induced locomotion was accompanied by membrane alterations and metabolic changes, as shown by an increase of the 3H-uridine uptake and a rise of the hexose monophosphate shunt activity. The chemotactic activity of Con A was inhibited by alpha-methyl mannoside (50 mM) or by pretreatment of the cells with trypsin. These data indicate that lectins such as Con A induce chemotaxis by a specific binding to receptors of the cell membrane. It is suggested that bivalent ligand binding is required as a signal to elicit chemotactic locomotion.

Agglutinins

Enhancement of the PGE1 response of macrophages by concanavalin A and colchicine.

The effect of concanavalin A (Con A) and colchicine on the prostaglandin E1 (PGE1)-mediated cyclic AMP generation in rat peritoneal macrophages have been studied. Although Con A and colchicine by themselves did not affect cyclic AMP levels, they greatly enhanced cyclic AMP production induced by PGE1. There was not only augmentation of cyclic AMP levels at maximally active concentrations of PGE1, but also an increased sensitivity to low (inactive) concentrations of PGE1. Except for lentil lectin, none of the other lectins affected PGE1 sensitivity whereas lumicolchicine was as effective as colchicine. In addition, both Con A and colchicine raised the sensitivity to isoproterenol and choleraenterotoxin. Although details of the mechanisms by which Con A or colchicine influenced the membrane-bound adenyl cyclase and PGE1 receptors remain unclear, these observations suggest that certain alterations of the cell membrane may render macrophages more susceptible to the regulating effects of prostaglandins.

Adenylyl Cyclases

Release of cyclic AMP from macrophages by stimulation with prostaglandins.

The effect of various prostaglandins (PG)on the generation of cyclic AMP in rat peritoneal macrophages has been studied in vitro. PGE1 produced a rapid intracellular accumulation of cyclic AMP which was followed by its release into the extracellular space. More cyclic AMP was released with prostaglandins of the E-type than with A- and F-types. It is suggested that release of cyclic AMP from macrophages may participate in the modulation of leukocyte function.

Animals

Two distinct chemotactic factor inactivators in human serum.

The chemotactic factor inactivator (CFI) has been isolated from whole human serum by a combination of techniques including salt precipitation, anionic exchange, and gel filtration chromatography. Two inactivators have been obtained, a beta-globulin with a sedimentation velocity of approximately 7S and an alpha-globulin with a sedimentation velocity of approximately 4S. The former has a specificity for inactivation of the chemotactic activity associated with the C3 fragments, whereas the C5 chemotactic fragment is specifically inactivated by the alpha-globulin CFI. CFI in crude fractions of human serum is heat labile, time and temperature dependent for its activity, and pH dependent, expressing optimal activity at a pH range of 7.2 to 7.4.

Alpha-Globulins