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Ohne Zusammenfassung     

A broadly cross-protective monoclonal antibody binding to Escherichia coli and Salmonella lipopolysaccharides

During the last decade, episodes of sepsis have increased and Escherichia coli has remained the most frequent clinical isolate. Lipopolysaccharides (LPS; endotoxin) are the major toxic and antigenic components of gram-negative bacteria and qualify as targets for therapeutic interventions. Molecules that neutralize the toxic effects of LPS are actively investigated. In this paper, we describe a murine monoclonal antibody (MAb; WN1 222-5), broadly cross-reactive and cross-protective for smooth (S)-form and rough (R)-form LPS. As shown in enzyme-linked immunosorbent assay and the passive hemolysis assay, WN1 222-5 binds to the five known E. coli core chemotypes, to Salmonella core, and to S-form LPS having these core structures. In immunoblots, it is shown to react with both the nonsubstituted core LPS and with LPS carrying O-side chains, indicating the exposure of the epitope in both S-form and R-form LPS. This MAb of the immunoglobulin G2a class is not lipid A reactive but binds to E. coli J5, an RcP+ mutant which carries an inner core structure common to many members of the family Enterobacteriaceae. Phosphate groups present in the inner core contribute to the epitope but are not essential for the binding of WN1 222-5 to complete core LPS. Cross-reactivity for clinical bacterial isolates is broad. WN1 222-5 binds to all E. coli clinical isolates tested so far (79 blood isolates, 80 urinary isolates, and 21 fecal isolates) and to some Citrobacter, Enterobacter, and Klebsiella isolates. This pattern of reactivity indicates that its binding epitope is widespread among members of the Enterobacteriaceae. WN1 222-5 exhibits biologically relevant activities. In vitro, it inhibits the Limulus amoebocyte lysate assay activity of S-form and R-form LPS in a dose-dependent manner and it neutralizes the LPS-induced release of clinically relevant monokines (interleukin 6 and tumor necrosis factor). In vivo, WN1 222-5 blocks endotoxin-induced pyrogenicity in rabbits and lethality in galactosamine-sensitized mice. The discovery of WN1 222-5 settles the long-lasting controversy over the existence of anti-core LPS MAbs with both cross-reactive and cross-protective activity, opening new possibilities for the immunotherapy of sepsis caused by gram-negative bacteria.     

Managing information technology in the nineties

Business, not technology leaders should manage the change of Information Technology (IT) from a self-contained business support unit of the sixties to a distributed strategic business function of the nineties. Top management should recognize that a good business plan can only be developed and executed through the partnership between the business unit managers and the managers of the financial, the personnel, and the IT resource units. The technical problems associated with the management of IT may again be the easier part of the total management challenge.     

Symbolic parametrization of curves

If algebraic varieties like curves or surfaces are to be manipulated by computers, it is essential to be able to represent these geometric objects in an appropriate way. For some applications an implicit representation by algebraic equations is desirable, whereas for others an explicit or parametric representation is more suitable. Therefore, transformation algorithms from one representation to the other are of utmost importance.We investigate the transformation of an implicit representation of a plane algebraic curve into a parametric representation. Various methods for computing a rational parametrization, if one exists, are described. As a new idea we introduce the concept of working with classes of conjugate (singular or simple) points on curves. All the necessary operations, like determining the multiplicity and the character of the singular points or passing a linear system of curves through these points, can be applied to such classes of conjugate points. Using this idea one can parametrize a curve if one knows only one simple point on it. We do not propose any new method for finding such a simple point. By classical methods a rational point on a rational curve can be computed, if such a point exists. Otherwise, one can express the coordinates of such a point in an algebraic extension of degree 2 over the ground field.