Magnetic and magnetotransport properties of erbium silicide epitaxial films.
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Biomedical subjects
Publications and source records attributed to J Pierre.
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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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Epidemiologic studies of nosocomial bacterial pneumonia in patients requiring mechanical ventilation have been limited because of the poor reliability of diagnosis procedures in this setting. To determine prognostic and descriptive factors of ventilator-associated (V-A) pneumonia, we prospectively studied 567 patients who had been receiving mechanical ventilation for more than 3 days in our unit. Fiberoptic bronchoscopy using a protected specimen brush (PSB) was performed on each patient suspected of having pneumonia because of the presence of a new pulmonary infiltrate and purulent tracheal secretions. The diagnosis of V-A pneumonia was retained only if PSB specimens yielded greater than 10(3) cfu/ml of at least one microorganism, unless this result was established to be a false positive result on follow-up. V-A pneumonia developed in 49 patients for a total of 52 episodes (9%). The actuarial risk of V-A pneumonia was 6.5% at 10 days, 19% at 20 days, and 28% at 30 days of ventilation. Patients with pneumonia were significantly older (65 versus 57 yr of age, p less than 0.01) and more frequently had severe underlying illnesses (24 versus 10%, p less than 0.01) than did patients without pneumonia. A total of 84 microorganisms (51 gram-negative and 33 gram-positive) were isolated in significant concentrations from PSB specimens. Pseudomonas aeruginosa and Staphylococcus aureus were involved in 31 and 33% of these pneumonias, respectively. Forty percent of all specimens yielded a polymicrobial flora with more than one potential pathogen.(ABSTRACT TRUNCATED AT 250 WORDS)
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The optic tecta of 55 Rutilus rutilus were examined at intervals varying from 2 days to 4 years after unilateral retinal ablation. Qualitative ultrastructural examination of the retinal target lamina of the optic tectum (stratum fibrosum et griseum superficiale, SFGS) revealed that an initial period of degeneration and glial reaction, each of which could take one of a variety of forms and which lasted for 1-3 months after ablation, was followed by the temporary formation of heterologous synapses which persisted for a further 1-12 months. This in turn was followed by the degeneration of these synapses during the second year after ablation. Quantitative analysis at the level of the light microscope revealed a shrinkage of the SFGS throughout the level of the light microscope revealed a shrinkage of the SFGS throughout the first 14 postoperative months with no further reduction taking place thereafter. Analysis at the ultrastructural level revealed that this shrinkage was due to the disappearance, and not to the reduction in size, of pre- and postsynaptic profiles accompanied by glial reaction. No signs of collateral sprouting were seen throughout the survival period. Thus, partial deafferentation of the SFGS leads in the long run to a marked impoverishment of its neuronal network, without any apparent compensation.
Sacroiliac joint (SIJ) involvement has been reported in up to 9.7 percent of patients with skeletal tuberculosis. Lack of awareness of this now uncommon form of infection often leads to diagnostic delay and increased morbidity. Eleven consecutive cases of SIJ tuberculosis are reported; clinical and radiologic features, diagnosis, treatment, and outcome are discussed. Buttock pain was the presenting complaint in all patients. However, radicular pain in the lower back (seven patients) or lower limb (10 patients) was common and in one patient precipitated an unnecessary surgical intervention. SIJ tuberculosis is frequently an isolated phenomenon. Therefore, direct sampling of the SIJ is necessary to establish the diagnosis. The recently described technique of closed needle biopsy of the SIJ was employed in all 11 patients and established the diagnosis in nine of the 11.
To determine the usefulness of samples obtained by bronchoscopy using a protected specimen brush and evaluated by quantitative culture techniques in establishing the diagnosis of nosocomial pneumonia in patients requiring mechanical ventilation, we prospectively studied 147 ventilated patients suspected of having nosocomial pneumonia because of the presence of a new pulmonary infiltrate and purulent tracheal secretions. Positive cultures of protected brush specimens (greater than 10(3) cfu/ml) were found in only 45 patients (31%). Subsequent follow-up confirmed the diagnosis of pneumonia in 34 of 45 patients, and in only 4 of 45 patients was a positive culture firmly established to be a false positive result. No patient with less than 10(3) cfu/ml was subsequently shown to have had pneumonia, and the diagnosis was definitely excluded in 72 of 102 patients by the absence of pneumonia at autopsy or recovery without antibiotic therapy. In contrast, when 16 clinical variables were evaluated by stepwise logistic regression analysis, no combination could be identified that was useful in distinguishing patients with bacterial pneumonia. Furthermore, when the actual costs of evaluation and therapy of our patients were compared with the projected costs entailed in treating all patients suspected of having pneumonia with antibiotics, evaluation using the protected specimen brush and quantitative cultures was less expensive after only 6 days of treatment. These results suggest that the appearance of pulmonary infiltrates and purulent tracheal secretions does not result from bacterial pneumonia in a majority of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Regeneration of the different components of the optic tract of Rutilus takes place at a variable rate and follows a relatively precise pattern. The first optic centres to be reinnervated belong to the lateral thalamo-pretectal group (5 weeks at 14 degrees C after section of the optic nerve), followed by the anterior optic tectum and lateral geniculate nucleus (8 weeks after section), the central regions of the tectum, the suprachiasmatic nucleus and the nucleus of the basal optic root (10-15 weeks after section), and finally the medial thalamo-pretectal nuclei and the caudal regions of the optic tectum (16-25 weeks after section).
Forty-seven nosocomial cases of legionellosis due to Legionella pneumophila serogroup 1 were diagnosed in one major outbreak from November 1982 to March 1983 in a 960-bed teaching hospital. Contaminated water was considered to be a possible source of infection because, during that period, monthly samples were found to be positive with averages of 10(4) CFU/l. After chlorination of hot water associated with flushing of outlets, nearly all samples taken in the next two years were found to be negative. A case-control study was performed to examine potential risk factors. Three groups of controls were randomly selected among eligible patients. In a multivariate analysis, only three clinical factors were found to be associated with legionellosis patients: malignant illness (relative risk, RR = 3.5), presence of an ultimately fatal disease (RR = 2.6), and exposure to corticosteroids prior to admission (RR = 7.9). Investigations of in-hospital exposures suggest that during this nosocomial outbreak diagnostic or therapeutic respiratory procedures had not increased the risk of illness. Although the epidemiological association between water contamination and disease remains unclear, the eradication of L. pneumophila from the identified supply seems to have been effective in preventing disease in this hospital.
The relationship between capsular polysaccharide types 5 and 8 and resistance of Staphylococcus aureus to oxacillin was studied with a collection of 406 clinical isolates from six French hospitals. Of 175 type 5 isolates, 84 (48%) were resistant to oxacillin. In contrast, only 8 of 160 type 8 isolates (5%) and 5 of 71 nontypeable isolates (7%) were resistant to oxacillin. Therefore, capsular typing of clinical isolates of S. aureus may facilitate the choice of first-line antibiotic therapy.