Search PubMed⌕ Search

Biomedical subjects

A Nowotny

Publications and source records attributed to A Nowotny.

82 records · Page 5Linked to original sources

Endotoxic glycolipid from a heptoseless mutant of Salmonella minnesota.

The endotoxin of a heptoseless mutant of Salmonella minnesota R595 was extracted with phenol-water. Most of this material was found distributed in the insoluble fraction of the extract. The results showed that the R595 endotoxin behaved as a lipid rather than as a lipopolysaccharide (LPS). The preparation, although it does not contain O-specific polysaccharides, does contain 2-keto-3-deoxyoctonic acid (KDO), hexosamine, and several other unidentified compounds. Therefore, the term "glycolipid" is used in this paper instead of lipopolysaccharide. The crude glycolipid fraction, which was soluble in a mixture of chloroform-methanol (8:2), was purified by a procedure including fractionation with organic solvents and by different-column chromatographic methods. Although a chromatographic fraction of the glycolipid showed homogeneity in most systems investigated, the presence of contaminants could not be excluded. Chemical analysis of the glycolipids showed the absence of hexoses and heptoses. Constituents which were found were hexosamine, KDO, fatty acids, and phosphorus, which showed a relatively simple chemical composition. Partial acidic hydrolysis of the glycolipid yielded hexosamine-phosphates, as described in "Lipid A" fractions of smooth LPS preparations. Thin-layer chromatography of the partially hydrolyzed glycolipid showed a pattern similar to "Lipid A" fractions of other strains. The biological activity of the glycolipid was at the same level as that of other gram-negative endotoxins. Pyrogenicity, Shwartzman reactivity, and chick embryo ld(50) values were as high or higher than those of purified Serratia marcescens endotoxin preparations, but mouse ld(50) measurements gave significantly lower results.

Amino Acids↗

Review of the molecular requirements of endotoxic actions.

Old and new data are compiled to confirm earlier claims and to substantiate new concepts regarding the structural requirements of endotoxic reactions. The major points can be summarized as follows. (1) Recent results obtained by the use of synthetic analogues of lipid A structures proved unequivocally that the lipid moiety of the endotoxin is the carrier of toxic properties. Incomplete or attenuated structures are inactive in some or all toxic reactions, depending on the extent of deviations from the structure of the native product. (2) On the other hand, some beneficial reactions can be initiated not only by the complete structures but by their structural remains, which are no longer toxic. (3) Some of the split products in the lipid-free and polysaccharide-rich preparations can induce beneficial reactions. (4) Gram-negative bacteria can produce endotoxin-unrelated and beneficial compounds. Conventional endotoxin preparations are heterogeneous and often contain some of these unrelated substances. (5) Elucidation of the exact structural requirements of endotoxic reactions has just begun. It appears to be safe to predict that individual reactions will require highly specific structures or physicochemical properties. The potential rewards of such research might be quite significant by facilitating our understanding of the molecular events of the beneficial effects of endotoxins and by directing the search for preparations with therapeutic applications.

Animals↗