[Purpura during Listeria monocytogenes meningoencephalitis].
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Biomedical subjects
Publications and source records attributed to J Pierre.
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The in vitro susceptibilities of 75 clinical isolates of Xanthomonas maltophilia to nalidixic acid, five fluoroquinolones, latamoxef, and doxycycline were determined. Spontaneous mutants were selected, at a frequency of about 10(-5) to 10(-7) from four strains by culturing the strains in the presence of each quinolone. Selection in the presence of nalidixic acid provided mutants that were either resistant only to that compound or that exhibited cross-resistance to all the fluoroquinolones tested. Cross-resistance was always observed for mutants selected on any of the five fluoroquinolones. It was always associated with chloramphenicol resistance and, frequently, with doxycycline resistance. The electrophoretic alterations of the outer membrane proteins of the mutants suggest that different mechanisms may be involved in quinolone resistance in X. maltophilia.
The distribution of GABA-immunoreactive (GABA-I) structures has been studied in the frontal sections of the lumbar spinal cord of the lake frog using PAP-method. GABA-I was revealed as labeled cell bodies, fragments of fibres and small point-like structures assumed to be in most cases synaptic contacts of GABA-I axons. Labeled fragments of fibres and point-like structures were found in gray and white matter of the spinal cord. The GABA-I cell bodies were revealed in the dorsal horn, intermediate zone and ventral part of the gray matter. Labeled cells were found in the cavity of the central canal. The findings are discussed in relation to the modern data on the GABA-ergic control of the spinal cord functions.
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In primary cultures of astrocytes, methylmethane, 2-N-methyl 9-hydroxy-ellepticinium acetate, ditercalinium, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1,3 bis (2-chloroethyl)-1-nitrosourea (BCNU) blocked to various extents the activation of S6 kinase by acidic fibroblast growth factor and insulin [or insulin-like growth factor 1 (IGF1)]. The effects of the most active agent, BCNU, were time and concentration dependent. Pretreatment of cells with 50 microM BCNU for 1 hr completely prevented S6 kinase activation by growth factors for at least 2 days. The S6 kinase activity of unstimulated cells was slightly affected. S6 kinase activation by 12-O-tetradecanoylphorbol 13 acetate was also strongly impaired by treating cells with BCNU whereas activation by 8-bromo-cyclic AMP was slightly reduced. Cyclic AMP-dependent protein kinase and phospholipid and Ca(2+)-dependent protein kinase were unaffected. BCNU had no direct effect on IGF1 binding to cell surface receptors or on the S6 kinase activity of cell cytosols.
Genistein has been shown to inhibit specifically in vitro the epidermal growth factor (EGF)-receptor tyrosine protein kinase activity (Akiyama et al., J Biol Chem 262: 5592-5597, 1987). When the effects of genistein on NIH-3T3 cells were studied, a cytostatic effect was observed at low concentration (less than 40 microM) and a cytotoxic effect at higher concentration (greater than 40 microM). Genistein was able to block the mitogenic effect mediated by EGF on NIH-3T3 cells (IC50 = 12 microM) or by insulin (IC50 = 19 microM). Genistein was also able to block the mitogenic effect mediated by thrombin (IC50 = 20 microM) although the thrombin receptor does not involve a protein tyrosine kinase activity. Genistein at cytostatic concentration (less than 40 microM) did not prevent the induction of c-myc mRNA synthesis caused by the activation of EGF receptor by EGF. Therefore the cytostatic effect of genistein on NIH-3T3 cells did not appear to be mediated by EGF receptor tyrosine kinase inhibition. This hypothesis was also supported by the absence of effect of genistein on the EGF-stimulated phosphorylation of several proteins and particularly of a cytosolic 80 kD protein. The stimulation of S6 kinase activity of cells treated by EGF was prevented by genistein. The stimulation by EGF of in situ S6 phosphorylation was also prevented by genistein. In addition, S6 kinase extracted from cells treated by EGF was inhibited by genistein. These effects occur at similar doses and maximal inhibition of S6 kinase was obtained at about 15 microM.
The effect of dimeric DNA intercalating compounds was assayed on a purified AP endonuclease from Microccoccus luteus using apurinic supercoiled PM2 DNA as a substrate. Binding on apurinic sites was estimated through the competition with the intercalating compound, 9-NH2-ellipticine, which displays great specificity for apurinic sites. An acridine dimer with a spermine linker is at 0.1 microM the best inhibitor of cleavage at the apurinic site induced either by the AP endonuclease or by 9-NH2-ellipticine. Bisintercalating agents are more effective inhibitors of AP endonuclease than monointercalating ones. Most effective inhibitors among dimers have acridine residues.
The presence of an additional penicillin-binding protein (PBP) was demonstrated in methicillin-resistant strains of Staphylococcus epidermidis, S. haemolyticus, S. hominis, and S. simulans. In these four species, the apparent molecular mass of this protein was analogous to that of PBP 2' of methicillin-resistant S. aureus SR 1550-9. It exhibited a low affinity for methicillin, cephalothin, and cefamandole; and its synthesis was methicillin inducible. Peptide mapping of this PBP from the four species yielded identical results that were analogous to those obtained with S. aureus SR 1550-9. These results suggest that this protein is similar to, if not the same as, PBP 2' of S. aureus and that it is involved in methicillin resistance in the four species studied.
A mutant with decreased susceptibility to imipenem (IpR) was selected in vitro from a susceptible clinical isolate of Listeria monocytogenes (IpS). IpR exhibited decreased susceptibility to penicillin G (4 x MIC) and imipenem (16 x MIC) and increased susceptibility to cefotaxime (0.25 x MIC). Electrophoretic profiles of membrane proteins and penicillin-binding proteins (PBPs) were identical in the two strains; each strain had five PBPs with molecular masses of ca. 97, 83.3, 81, 77.1, and 42.6 kilodaltons. A decreased affinity of PBP 3 for penicillin G and imipenem (10-fold) was observed in IpR. In contrast, the affinity of PBP 3 for cefotaxime in IpR was increased twofold and correlated with the decreased MIC of this drug. From these findings and competition experiments with different beta-lactam antibiotics, we conclude that the alteration of PBP 3 is responsible for the decreased susceptibility of IpR to penicillin and imipenem and that PBP 3 might be an essential target of beta-lactam antibiotics in L. monocytogenes.
Analyses of total solubilized proteins and penicillin-binding proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were demonstrated to be accurate methods for the identification of coagulase-negative staphylococci. However, penicillin-binding protein profiles were found to be much clearer for the identification of these organisms to species level than was examination of the total solubilized proteins. By using the former technique, 13 reference strains were found to have species-specific penicillin-binding protein profiles, and 150 of 160 randomly collected clinical isolates were identified as belonging to eight of these species. A group of three clinical strains probably represents the recently described species Staphylococcus lugdunensis; the other seven clinical isolates belonging to five species remained unclassified.
Using the immunohistochemical PAP method GABA-immunopositive cells were revealed in horizontal and transverse sections of lamprey spinal cord. The most numerous intensively stained small oval cells were located in the dorsal part of the spinal cord. The larger cells with 2-3 long nonbranching processes were located at the border of lateral column, the main part of which is composed of GABA-immunonegative cells. Some of the largest, but less intensively stained cells were observed in the lateral part of the spinal cord beyond the cell column and in the ventrolateral corner of transverse sections. The latter are identified as previously described edge cells. Functional identification of the remaining GABA-immunopositive cells is rather difficult. Some of them may be glial elements.
The distribution of serotoninergic neurons (localization of somata, principal fiber tracts and projection zones) was investigated in the brain of the lizard Ophisaurus apodus using a specific antibody directed against serotonin (5-HT). A comparison of the results with those of the literature revealed that in spite of minor variations in the distribution of 5-HT in the different reptiles examined there exist common features which correspond to a general organizational pattern.
Tyrosine phosphorylation plays a crucial role in cell proliferation and cell transformation which suggests that tyrosine kinase-specific inhibitors might be used as anticancer agents. When the cytotoxic effect of the potent tyrosine kinase inhibitor genistein on various cell lines was studied, we observed that 9-hydroxyellipticine-resistant Chinese hamster lung cells (DC-3F/9-OH-E) were markedly more resistant to genistein than the parental cell line (DC-3F). The DC-3F/9-OH-E cells have been shown to have an altered DNA topoisomerase II activity. We therefore examined the effects of genistein on DNA topoisomerase II-related activities of nuclear extracts from DC-3F cells as well as on purified DNA topoisomerase II from calf thymus. Our results show that genistein (a) inhibits the decatenation activity of DNA topoisomerase II and (b) stimulates DNA topoisomerase II-mediated double strand breaks in pBR322 DNA on sites different from those of 4'-(9-acridinylamino)methanesulfon-m-anisidide, etoposide, and 2-methyl-9-hydroxyellipticinium. Structure-activity studies with six chemically related compounds show that only genistein has an effect on the cleavage activity of DNA topoisomerase II in the concentration range studied. Finally, genistein treatment of DC-3F cells results in the occurrence of protein-linked DNA strand breaks as shown by DNA filter elution. Viscometric (lengthening) studies demonstrate that genistein is not a DNA intercalator. Genistein is therefore an interesting compound because it induces cleavable complexes without intercalation. Taken together, our results show that genistein is an inhibitor of both protein tyrosine kinases and mammalian DNA topoisomerase II. This could be accounted for by the sharing of a common structure sequence between the two proteins at the ATP binding site.
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19 critically ill adults with acute mediastinitis after cardiac surgery were treated with granulated sugar, either directly (11 patients) or after failure of continuous irrigation (8 patients). Mediastinal tissue cultures were positive in 18 patients. Packing the mediastinal cavity with granulated sugar every 3 or 4 h resulted in near-complete debridement of the wound and rapid formation of granulation tissue in all patients and sterilisation of the wound after an average of 7.6 days. Dressings were easy and painless to change. 5/19 (26%) patients died before discharge, but none because of wound complications. The rest were discharged on average 54.2 days (range 29-120) after initial debridement of the wound; 11 underwent secondary surgical closure of the wound and in 3 the wound healed by granulation tissue formation alone. No recurrence of sternal infection has occurred after a mean follow-up of 8.2 months (range 3 to 17).