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S Valisena

Publications and source records attributed to S Valisena.

24 records · Page 2Linked to original sources

Antitumor activity of new anthraquinone derivatives.

Seven new 9,10-anthracenedione derivatives bearing positively-charged side chains at different positions of the condensed ring system have been investigated in their interaction with DNA and their biological effects, including antitumor activity in the P 388 mouse miniscreen. The drug's affinity for DNA was found to be related to the efficacy of inhibition of cell growth and nucleic acid synthesis for a number of cell lines. Moreover, alkaline elution experiments showed a close relationship between mutagenic potential and cytotoxicity. With the exception of one, all compounds behaved like intercalating agents, as shown by the unwinding of supercoiled plasmid DNA. DNA appeared, therefore, to be the more important target for drug action. The marginal in vivo activity shown by two substances in this series suggests a number of possible structural modifications which may increase their therapeutic efficacy.

Animals↗

Laboratory and wild-type Klebsiella pneumoniae strains carrying mannose-inhibitable adhesins and receptors for coliphages T3 and T7 are more pathogenic for mice than are strains without such receptors.

We have shown previously that Klebsiella pneumoniae receptors for coliphages T3 and T7 also mediate mannose-inhibitable adherence to human epithelial cells and protect bacteria from phagocytosis and intracellular killing by human polymorphonuclear cells. In this paper we analyze the possible role of such mannose-inhibitable adhesins and T3-T7 receptors (MIAT) in K. pneumoniae intraperitoneal pathogenicity for mice. We showed that intraperitoneal pathogenicity for mice of four different Klebsiella strains (one laboratory and three wild-type) that carry the MIAT was approximately 60-fold higher than that of four derivative strains that lost such receptors by spontaneous mutation. The MIAT could be repressed by Klebsiella phage AP3 lysogenic conversion. Two laboratory and two wild-type strains converted by phage AP3 were also approximately 60-fold less pathogenic for mice than parental strains and showed a pathogenicity level equal to that of the MIAT-negative mutants. Studies of protection in mice with anti-whole cell antisera showed that passive immunization against MIAT-positive cells was more protective than immunization against MIAT-negative cells. Studies of protection in mice by both active and passive immunization with lipopolysaccharide and purified outer membrane proteins have shown that the proteins are the most protective outer membrane components. Since it has been shown previously that the Klebsiella receptors for T3-T7 have a proteic component and that an outer membrane protein is missing in the strains resistant to T3-T7 (C. Pruzzo et al., in R. C. Berkely (ed.), Microbial Adhesion to Surfaces, 1980); the latter finding further supports the role of MIAT in the pathogenicity of Klebsiella for mice.

Adhesiveness↗

Biochemical and physical properties of the endo-beta-N-acetylglucosaminidases from Staphylococcus aureus, Staphylococcus simulans, and Staphylococcus saprophyticus.

Biochemical and physical properties of the pure bacteriolytic enzymes excreted by three different Staphylococcus species (S. aureus, S. simulans, and S. saprophyticus) were investigated. Although the three enzymes have previously been shown to share the same specificity of action (endo-beta-N-acetylglucosaminidase activity), their biochemical features clearly indicated that they were three different enzymes, confirming what had previously been suggested by the different lytic-activity patterns displayed by each species and the different procedures needed to achieve purification of each enzyme. Very different values resulted from molecular weight determination: 80,000 for the S. aureus enzyme, 45,000 for the S. simulans enzyme and 31,000 for the S. saprophyticus enzyme. Other important differences were observed in their kinetics of activity on Micrococcus luteus purified cell walls; their stability; their bacteriolytic spectrum against heat-killed cells of various microorganisms; and their response to physical and chemical factors, such as temperature, pH, ionic strength, divalent cations, chelating agents, thiol compounds, and glucose derivatives.

Acetylglucosaminidase↗

Production of inhibitors of lytic activity in the Micrococcaceae.

Eight Staphylococcus xylosus strains lacking lytic activity (LA) were found to excrete agar-diffusible factors inhibiting the LA of LA-positive strains of the same species. The same eight strains, when tested against LA-positive indicator strains from other species of Micrococcaceae, caused marked LA inhibition only of strains of S, saprophyticus and S. cohnii, both species closely related to S. xylosus. Micrococci and planococci, unlike staphylococci, do not normally show LA, yet Micrococcus lylae and M. sedentarius strains produced inhibitors effective against the LA of almost all the indicator strains, and planococci inhibited the LA of a few indicator strains. Micrococcus luteus strains caused LA inhibition of homologous indicators only, i.e. exceptional M. luteus strains exhibiting LA. Thus, a specific and a non-specific type of LA inhibition can be distinguished, and it is suggested that the apparent lack of LA might, in some instances, be explained by the simultaneous production of a specific inhibitor.

Bacteriolysis↗

Purification and characterization of three separate bacteriolytic enzymes excreted by Staphylococcus aureus, Staphylococcus simulans, and Staphylococcus saprophyticus.

As a further development of previous investigations showing that different staphylococcal species display different bacteriolytic activity patterns (lyogroups), the bacteriolytic enzymes excreted by three different Staphylococcus species, Staphylococcus aureus (lyogroup I), S. simulans (lyogroup II), and S. saprophyticus (lyogroup IV); have been purified and characterized. A representative strain from each species was grown in a preselected medium made of fully dialyzable products. Culture supernatants were collected in the appropriate growth phase. Two different affinity adsorbents were used for enzyme purification. One was obtained by coupling lysozyme-digested pure peptidoglycan from Micrococcus luteus to cyanogen bromide-activated Sepharose 4B. The second affinity adsorbent used was chitin. The S. aureus bacteriolytic enzyme bound to the solubilized peptidoglycan but not to chitin, whereas the opposite was true for the S. simulans enzyme. The bacteriolytic enzyme from S. saprophyticus did not bind to either the Sepharose 4B-peptidoglycan resin or to chitin, and its purification was achieved by two ion-exchange chromatography steps combined with gel filtration. All three enzymes were purified to apparent homogeneity. Their subsequent characterization indicated that all acted as endo-beta-N-acetylglucosaminidases. However, the three glucosaminidases differed significantly in their kinetics of activity and bacteriolytic spectrum against heat-killed cells of a variety of microorganisms. Very different values also resulted from molecular weight determinations: 80,000 for the S. aureus enzyme, 45,000 for the S. simulans enzyme, and 31,000 for the S. saprophyticus enzyme. Other important differences were observed in their stability, optimal pH and ionic strength for their activity, and their responses to temperature and divalent cations. These results confirmed the previous proposal that different staphylococcal species excrete different lytic enzymes.

Acetylglucosaminidase↗

Stimulation of spreading of trypsinized human fibroblasts by lysozymes from Staphylococcus aureus, hen egg white, and human urine.

The effect of lysozyme from three different sources--Staphylococcus aureus, hen egg white, and human urine--on adhesion to substrate and spreading of trypsinized human fibroblasts was studied. Several fibroblast strains were tested under various conditions. It was found that the different cell strains did not show the same capability of spreading and stably attaching to substrates when resuspended in media not containing serum. Some strains did not spread, whereas others spread even in the absence of serum. Cell spreading in these strains did not occur when the cells were pregrown for 5 weeks in media supplemented with 1% fetal bovine serum. Lysozyme from S. aureus allowed stable adhesion to substrate and spreading of all the fibroblast strains unable to elongate in nonsupplemented minimal essential medium. This enzyme accelerated and augmented spreading of the strains capable of elongating in the absence of serum. S. aureus lysozyme also allowed spreading and stable adhesion to substrates of all these strains when they were pregrown for 5 weeks in the presence of 1% fetal bovine serum. Furthermore, hen egg white lysozyme and the lysozyme purified from human urine were both capable of stimulating anchorage to substrate and spreading of trypsinized fibroblasts although their effect was less pronounced than that of the S. aureus lysozyme. Some tentative hypotheses for the mechanism of cell spreading in the presence of lysozyme are made. The possibility that lysozymes, virtually ubiquitous enzymes, may play a specific role in nature in the regulation of cell differentiation and tissue development is finally raised and discussed in light of several previous observations and findings.

Animals↗