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Biomedical subjects

M Denis

Publications and source records attributed to M Denis.

At least 217 records · Page 12Linked to original sources

Human immunodeficiency virus-related lymphocytic alveolitis.

We observed 276 HIV-infected patients to determine the frequency, degree, and clinical presentation of the lymphocytic alveolitis in different stages of HIV disease, and also to identify the lymphocyte subsets involved. In 154 patients with proved lung infections or tumors (group A), bronchoalveolar lavage fluid showed lymphocytosis in 78 percent of cases. In 122 subjects (31 AIDS and 91 HIV-infected non-AIDS patients) without evidence of lung tumor or infection (group B), lymphocytic alveolitis was seen in 72 percent of cases. In 61 of 88 (69 percent) group B lymphocytic patients, we observed respiratory symptoms or diffuse interstitial opacities; however, we also observed such alveolitis in 27 of 46 (59 percent) group B patients free of respiratory symptoms and abnormality of chest x-ray film. This alveolitis was seen not only in AIDS or ARC patients but also at earlier stages of HIV infection. T-lymphocyte analysis showed a large majority (40 to 93 percent) of CD8 positive lymphocytes in the 37 patients tested. A dual fluorescence analysis revealed, in 18 subjects, that those cells were phenotypically cytotoxic (CD8 + D44 +). These findings suggest that, regardless of HIV-infection stages and of opportunistic lung infections, a CD8-positive T-lymphocyte alveolitis may be present in HIV-infected patients and could be responsible for cough, dyspnea, interstitial pneumonitis, and abnormalities of pulmonary function tests.

Acquired Immunodeficiency Syndrome↗

Pleiotropic effects of the Bcg gene: III. Respiratory burst in Bcg-congenic macrophages.

Macrophage respiratory burst, as assessed by H2O2 and O2- production, and HMS and chemiluminescence activity was investigated in a variety of conditions in macrophages from Bcg-congenic mice. Measurement of HMS and chemiluminescence in splenic macrophages challenged in vitro with BCG showed that the Bcgr cells were more stimulated by the challenge than their Bcgs counterparts. H2O2 production was measured in Bcgr and Bcgs splenic macrophages. PMA-triggering and LK-triggering were shown to stimulate a similar degree of H2O2 production Bcgr and Bcgs macrophages. In contrast, in vitro phagocytosis of BCG was shown to trigger superior production of H2O2 and O2- in the Bcgr splenic macrophages as compared to their Bcgs congenics. Finally, following the in vivo infection with BCG Montreal, Bcgr splenic macrophages were superior producers of H2O2 (both spontaneous and PMA-triggered) in the early phase of infection.

Animals↗

[Comparative study of a combination of amoxicillin and clavulanic acid and a combination of ticarcillin and clavulanic acid on 249 enterobacteria].

A comparison between the MIC of amoxicillin (AMX) and ticarcillin (TIC) in the presence of clavulanic acid (Augmentin: AUG and Claventin: CLV) was made on 168 strains of Escherichia coli resistant to amoxicillin (MIC greater than 16 mg/l) and yet sensitive to ceftriaxone (MIC less than or equal to 4 mg/l) and 81 strains of Klebsiella pneumoniae sensitive to Ceftriaxone. All those strains have been isolated between 1986-87 in Bellevue Hospital in Saint-Etienne. On 168 Escherichia coli, 142 have a MIC greater than 128 mg/l of TIC. Those 142 Escherichia coli are sensitive or of an intermediary sensitivity to Cephalothin (MIC less than or equal to 32 mg/l) in 57% cases. Those 142 strains are sensitive to AUG (MIC less than or equal to 4 mg/l) in 13.4% cases, intermediary sensitive to AUG (4 less than MIC less than or equal to 16) in 30.3% cases, sensitive to CLV (CMI less than or equal to 16 mg/l) in 23.3% cases and intermediary sensitive to Claventin (16 less than MIC less than or equal to 64) in 47.2% cases. The 26 Escherichia coli of MIC less than or equal to 64 mg/l of TIC and resistant to Cephalothin (MIC greater than 32 mg/l) have MIC less than or equal to 4 mg/l of AUG In 3.8% cases and MIC less than or equal to 16 mg/l of Claventin in 79.6% cases. The 81 Klebsiella pneumoniae

Amoxicillin↗

[Lung diseases during therapeutic aplasia: diagnostic and therapeutic strategy].

Lung diseases that occur in patients with drug-induced bone marrow aplasia are part of a wider group of lung diseases in immunocompromised patients. Their most common causes are infections due to Gram-negative bacilli, staphylococci or Aspergillus spp. and intra-alveolar haemorrhages. Their diagnostic approach is often limited by disorders of coagulation, risks of infection by bronchial or pulmonary seeding during endoscopy and the lethal risk of mechanical ventilation after bronchoalveolar lavage in patients with respiratory failure. The therapeutic approach is frequently empirical due to the fact that antibiotic therapy cannot be delayed, even for a few hours, and to the aforementioned diagnostic problems. In practice, the diagnostic and therapeutic approaches usually result from a rational compromise depending on whether the lung disease has occurred at the onset or at the end of an episode of bone marrow aplasia.

Humans↗

Evidence for a cytotoxic T-lymphocyte alveolitis in human immunodeficiency virus-infected patients.

A T8 lymphocyte alveolitis occurs in HIV-positive patients, even in the absence of any lung infections or tumors. Using the monoclonal antibody (MAb) D44, the CD8+ T cells can be further subdivided into two functional subsets of cytotoxic T lymphocytes (CTL; CD8+, D44+) and suppressor T cells (CD8+, D44-). A dual fluorescence analysis of alveolar and peripheral lymphocytes has been used in HIV-positive patients without lung infections or tumors to reveal a dramatic increase in alveolar T8 lymphocytes (83%), compared to peripheral values (52%), which was mainly composed (89%) of CD8+ D44+ CTLs. Functional studies confirmed the cytolytic activity of these phenotypically defined alveolar CTLs on autologous alveolar macrophages used as target cells, excluding a natural killer-like activity. An immuno-enzyme analysis concomitantly revealed the co-expression of the p18 HIV antigen and the CD4 molecule on the autologous alveolar macrophages. These data suggest that CTL alveolitis occurs during HIV infection and is directed against HIV-infected alveolar macrophages which are presumably the targets of the locally recruited lung CTLs.

Acquired Immunodeficiency Syndrome↗

Modification of flow-force relationships by external ATP in yeast mitochondria.

The purpose of this work is to measure protonmotive force and cytochrome reduction level under different respiratory steady states in isolated yeast mitochondria. The rate of respiration was varied by using three sets of conditions: (a) different external phosphate concentrations with a fixed concentration of ADP (ATP synthesis) and (b) different concentrations of carbonylcyanide m-chlorophenylhydrazone in the presence of oligomycin and carboxyatractylate (uncoupling) either in the absence or (c) in the presence of external ATP. ADP plus phosphate stimulates respiration more than uncoupler at the same protonmotive force value. However, the relationships between respiratory rate and protonmotive force were similar when stimulation was induced either by ADP + Pi or by carbonylcyanide m-chlorophenylhydrazone in the presence of ATP. At the same respiratory rate, cytochrome a + a3 is more reduced by uncoupler than by ADP + Pi additions. However, the relationships between respiratory rate and reduction level of cytochrome-c oxidase are similar both under ATP synthesis and with uncoupling conditions in the presence of external ATP. Control of respiration exerted by cytochrome-c oxidase, and support the view the condition mentioned above. This control was low when the respiratory rate was varied by the ATP synthesis rate; it increased as a function of the respiratory rate with uncoupler in the absence of ATP. ATP decreased this control under uncoupling conditions. These results suggest a regulatory effect of external ATP on cytochrome-c oxidase, and support the view that the relationships between respiratory rate and protonmotive force, on the one hand, and respiratory rate and the reduction level of cytochrome-c oxidase, on the other, depend respectively on the kinetic regulations of the system.

Adenosine Triphosphate↗

The molybdate-stabilized nonactivated glucocorticoid receptor contains a dimer of Mr 90,000 non-hormone-binding protein.

A glucocorticoid receptor-associated Mr approximately 90,000 non-hormone-binding protein was purified and characterized. The molybdate-stabilized nonactivated rat liver glucocorticoid-receptor complex (Mr approximately 300,000) was immunoadsorbed on cyanogen bromide-activated Sepharose 4B to which a monoclonal IgG 2a antibody directed against the activated rat glucocorticoid receptor (Mr approximately 94,000) had been coupled. Following removal of molybdate and thermal activation of the receptor immobilized on the immunoaffinity matrix, an Mr approximately 90,000 non-hormone-binding protein was specifically eluted. This protein was further purified to homogeneity using high performance ion exchange chromatography and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, sucrose gradient ultra-centrifugation, and high performance size-exclusion chromatography. Hydrodynamic characterization under nondenaturing conditions revealed that the purified glucocorticoid receptor-associated protein represents a molecular species with a sedimentation coefficient of 6.1 S, a Stokes radius of 6.9 nm, and a calculated Mr approximately 184,000. These results, combined with analysis on denaturing electrophoresis indicate that, under certain conditions, the Mr approximately 94,000 steroid-binding protein is associated with a dimer of Mr approximately 90,000 non-hormone-binding protein.

Animals↗

In situ behavior of the pyrimidine pathway enzymes in Saccharomyces cerevisiae. 2. Reaction mechanism of aspartate transcarbamylase dissociated from carbamylphosphate synthetase by genetic alteration.

The reaction mechanism of Saccharomyces cerevisiae aspartate transcarbamylase was studied in permeabilized cells of a mutant in which this enzyme is not associated to carbamylphosphate synthetase. The results obtained indicate an ordered mechanism in which carbamylphosphate binds first, followed by aspartate, with dissociation of the products in the order phosphate then carbamylaspartate. Interestingly, this clear-cut mechanism differs from the more complex behavior shown by aspartate transcarbamylase when this enzyme is associated to carbamylphosphate synthetase in wild-type S. cerevisiae (B. Penverne and G. Hervé, Arch. Biochem. Biophys. (1983) 225, 562-575). This difference indicates that the association of the two enzymes within the multienzymatic complex alters the apparent kinetic properties of aspartate transcarbamylase. Such an enzyme-enzyme interaction might be related to the channeling of carbamylphosphate from one catalytic site to the other one.

Aspartate Carbamoyltransferase↗

Modulation of fibroblast proliferation by sulfidopeptide leukotrienes: effect of indomethacin.

Because infiltration of mononuclear cells and fibroblast proliferation are associated in chronic inflammatory lesions, we tested the hypothesis that leukotrienes (LT), a product of activated mononuclear cells, may modulate fibroblast growth. Proliferation of cultured human skin fibroblasts was estimated by [3H]thymidine incorporation and cell count at increasing concentrations (0.1 nM to 0.1 microM) of LTC4 or LTD4. LTC4 and LTD4 stimulated cell growth in a dose-dependent manner only in the presence of 50 microM indomethacin. Under similar conditions, LTE4 but not LTB4 (0.1 microM) was active. Both asynchronous, growing cells and synchronous, quiescent cells were sensitive to LT when prostaglandin (PG) synthesis was suppressed by indomethacin. Other blockers of cyclooxygenase such as ibuprofen and aspirin exhibited identical permissive activity, and the effect of indomethacin was totally abolished by addition of PGE2. LTC4 modified neither [3H]arachidonic acid release from prelabeled fibroblasts nor PGE2 production by fibroblasts. These results demonstrate that the sulfidopeptide LT stimulate fibroblast proliferation only when the endogenous synthesis of PG is blocked, but they do not enhance the synthesis of PG in their target cells showing no evidence for a negative feed-back loop. Nevertheless, it seems likely that the initiation and development of the fibrotic process in the different tissues depends in part on the local balance between PG and LT productions.

Adult↗

[Activity of ticarcillin combined with different concentrations of clavulanic acid on 137 Gram-negative bacilli resistant to ticarcillin].

The MIC of ticarcillin exclusively or joined with 3 concentrations of clavulanic acid: (2, 4 and 8 mg/l) was determined by agar dilution in relation to 137 bacilli resistant to ticarcillin (MIC greater than or equal to 256 mg/l) detected between 1985 and 1986 in the Bellevue Hospital in Saint-Etienne. We could study 26 Escherichia coli, 30 Klebsiella, 28 Enterobacter, 36 Serratia and 17 Pseudomonas aeruginosa. The concentration of 2 mg/l of clavulanic acid allows to lower the MIC of ticarcillin over the very large majority of strains of Escherichia coli and Klebsiella resistant to ticarcillin. In those conditions, ticarcillin becomes more active than piperacillin over those species. The concentration of 4 and 8 mg/l of clavulanic acid doesn't bring any real advantage to those bacilli. Moreover the concentrations of 2, 4 and 8 mg/l slightly change the MIC of ticarcillin on the strains of Serratia, Enterobacter and Pseudomonas aeruginosa.

Clavulanic Acids↗

[Isolated pulmonary lymphoma in a patient with acquired immunodeficiency syndrome].

We report the case of a male patient with AIDS who had been hospitalized for various opportunistic infections, from which he recovered, and was readmitted on account of a round opacity in the lower lobe of his right lung. There was no evidence of extrapulmonary pathology. Transtracheal aspiration, alveolar lavage and transbronchial biopsy failed to identify the lesion. Lung biopsy after thoracotomy resulted in a diagnosis of malignant lymphoma type B with anti-IgA and anti-kappa antibodies. Despite chemotherapy the patient died within one month, the lymphoma having spread to both lungs.

Acquired Immunodeficiency Syndrome↗

Interaction of rat liver glucocorticoid receptor with lectins: is the glucocorticoid receptor a glycoprotein?

Although glucocorticoid receptors have been extensively studied in a variety of tissues, the precise nature of the receptor protein still remains unknown. To further characterize this protein we assessed the effects of various lectins on [3H]dexamethasone binding to prepurified preparations of rat liver glucocorticoid receptor. Among the lectins tested only Ulex europeus and Lens culinaris induced a concentration-related decrease in [3H]dexamethasone binding. Following Ulex europeus or Lens culinaris exposure Scatchard analysis showed that these lectins led to a 3-fold reduction in receptor affinity without influencing the concentration of binding sites. These results provide new experimental evidence that rat liver glucocorticoid receptor would possess alpha-L-fucosyl and alpha-D-mannopyranoside residues in close proximity to the glucocorticoid receptor binding domain.

Animals↗

Structure and function of cytochrome-c oxidase.

Recent works on the structure and the function of cytochrome-c oxidase are reviewed. The subunit composition of the mitochondrial enzyme depends on the species and is comprised of between 5 and 13 subunits. It is reduced to 1 to 3 subunits in prokaryotes. The complete amino acid composition has been derived from protein sequencing. Gene sequences are partially known in several eukaryote species. Metal centers are only located in subunits I and II. The mitochondrial cytochrome-c oxidase is Y-shaped; the arms of the Y cross the inner membrane, the stalk protrudes into the intermembrane space. The bacterial enzyme has a simpler, elongated shape. A number of data have been accumulated on the subunit topology and on their location within the protein. All available spectrometric techniques have been used to investigate the environment of the metal centers as well as their interactions. From the literature, attention must be paid to what may be considered or not as an active form. The steady improvement of the instrumentation has yielded evidence for different kinds of heterogeneities which could reflect the in vivo situation. The 'pulsed' and 'resting' conformers have been well characterized. The 'oxygenated' form has been identified as a peroxide derivative of the fully oxidized cytochrome-c oxidase. The mammalian enzyme has been isolated in fully active monomeric form which does not preclude the initially suggested dimeric behavior in situ. The role of the lipids is still largely investigated, mainly through reconstitution experiments. Kinetic studies of electron transfer between cytochrome c and cytochrome-c oxidase lead to a single catalytic site model to account for the multiphasic kinetics. Results related to the low temperature investigation of the intermediate steps in the reaction between oxygen and cytochrome-c oxidase received a sound confirmation by the resolution of compound A at room temperature. It is also pointed out that the so-called mixed valence state might not be a transient state in the catalytic reduction of oxygen. The functioning of cytochrome-c oxidase as a proton pump has been supported by a number of experimental results. Subunit III would be involved in this process. The redox link to the proton pump has been suggested to be at the Fea-CuA site. The molecular mechanism responsible for the proton pumping is still unknown.

Amino Acids↗

Control of the Bcg gene of early resistance in mice to infections with BCG substrains and atypical mycobacteria.

The effect of the Bcg gene on the early host response to intravenous infection with a variety of BCG substrains and some atypical mycobacteria was investigated. The numbers of live bacilli of BCG Pasteur and BCG Tice recovered from the spleens of Bcgs mice (C57BL/6, B10.A and BALB/c) at 3 weeks following infection exceeded the bacterial dose injected, whereas the number of CFU recovered from the spleens of Bcgr mice (A/J, DBA/2 and C3H/HeN) did not exceed the number of CFU injected, thus following the pattern observed in Bcgr mice and Bcgs infected with BCG Montreal. BCG Russia failed to multiply in both test groups; however, the number of CFU recovered in Bcgr mice was significantly lower than in Bcgs mice. On the other hand, the presence of live bacilli in the spleens of either Bcgr or Bcgs mice injected with BCG Japan was undetectable in most cases. Involvement of the Bcg gene in the early resistance to infection with BCG Pasteur, BCG Russia, Mycobacterium kansasii and M. intracellulare was documented by the significant differences in the kinetics of infections in mice of the C.D2 (BALB/c-Bcgr) and BALB/c (Bcgs) congenic lines. In BCG Russia, M. intracellulare and M. fortuitum infections, the phenotypic expression of the Bcg gene resulted in a more rapid elimination of the bacteria in the spleens of Bcgr when compared with Bcgs mice. On the other hand, the hepatic granuloma formation correlated with bacterial load except when C.D2 mice were infected with a small dose of BCG Pasteur or M. kansasii where extensive granulomatous hepatitis developed although no bacterial multiplication occurred in the spleen. It is suggested that granuloma formation could depend of the properties of the mycobacteria as well as the genetic background of the host without implicating the bacterial burden.

Animals↗