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Biomedical subjects

M Denis

Publications and source records attributed to M Denis.

At least 127 records · Page 7Linked to original sources
PubMed1992

[Lymphocytic alveolitis in the early stages of HIV infection: correlation with biological and prognostic factors].

Broncho-alveolar lavage was performed to assess the degree of pulmonary lymphocytic alveolitis in 32 asymptomatic patients who were infected with the Human Immunodeficiency Virus (VIH). The patients were stages II and III of the CDC classification and the aim of the study was to determine the frequency, nature and prognostic role of the findings. 62.5% of the subjects (20/32) presented with a lymphocytic alveolitis which consisted predominantly of CD8 lymphocyte (64.3 +/- 3.5%), in the absence of an opportunistic infection or broncho-pulmonary tumours. Two sub-populations of alveolar CD8 were shown at comparable levels, a) sub-population CD8+D44+ (22.1 +/- 5%), in whom we showed the possession of cytotoxic activity in particular specific for VIH; b) sub-population CD8+CD57+ (19.6 +/- 3%) which we have shown to be capable in vitro of inhibiting the effector phase of cytotoxic activity of CD8+D44+ alveolar cells specific for VIH. In this group of 32 patients the occurrence of an alveolitis was not correlated with the usual prognostic factors of infection by VIH measured simultaneously with broncho-alveolar lavage (the level of CD4+ blood lymphocytes, and the beta 2-plasma microglobulins and the presence of p24 antigenaemia). In addition the level of CD4 lymphocytes supperior to 400/mm3 and of beta 2-microglobulins less then 3 mg/l whether a lymphocytic alveolitis was there or not confirmed the relatively poorly developed state of the VIH infection in these asymptomatic patients. Also the occurrence of a lymphocytic alveolitis did not seem to be linked to progression of the disease in the group of patients studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Acute respiratory insufficiency caused by hyperinfestation with strongyloides. BALF diagnosis and favourable outcome].

Hyperinfestation with Strongyloides is a severe complication in immunodepressed patients. It may present with various clinical signs, notably acute respiratory failure. Diagnosis may be difficult, particularly when the strongyloidiasis is associated with septicaemia caused by Gram-negative organisms. We report a new case of hyperinfestation with Strongyloides in a patient treated for periarteritis nodosa. This case was remarkable on two scores: the diagnosis problem raised by the presence of intrapulmonary haemorrhages, and the favourable outcome of an acute and initially severe respiratory failure which had required assisted ventilation. The role played in the patient's cure by the doses of thiabendazole given and the duration of their administration is discussed.

Acute Disease↗
PubMed1992

[Epidemiology of micro-organisms responsible for community-acquired pneumonia].

Pneumonias occupy a prominent situation among lower respiratory tract infections where they are remarkable for their potential mortality and for our relative knowledge of the responsible micro-organisms. Analysis and synthesis of each series published must answer several questions, such as: what are the lung diseases considered? which investigations have been performed? which criteria of imputability have been used? in which patients has the study been carried out? in which place, which period and which structure? In spite of methodological lacunae and of the inhomogeneous answers to the questions asked, there is some concordance between the series found in the literature. Thus, more than 90% of community-acquired pneumonias with microbiological identification are caused by Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella pneumophila, Chlamydia psittaci (or pneumoniae), or Influenza A virus.

Adolescent↗
PubMed1992

Technetium-99m-DTPA aerosol and gallium-67 scanning in pulmonary complications of human immunodeficiency virus infection.

We retrospectively compared the results of 67Ga chest scans and 99mTc-DTPA aerosol clearance measurements with those of fiberoptic bronchoscopy in 88 patients infected with the human immunodeficiency virus. Of 100 investigations, a pulmonary infection was diagnosed in 39, mainly Pneumocystis carinii pneumonia and a noninfectious disorder was found in 42, mainly Kaposi's sarcoma and lymphocytic alveolitis. Gallium scans and DTPA clearance were abnormal respectively in 74% and 92% of infectious complications, and in 12% and 60% of noninfectious disorders. In 10 cases, DTPA clearance was accelerated, while chest x-ray, arterial blood gases and even gallium scanning were normal. A value of DTPA clearance greater than 4.5%.min-1 was both sensitive and specific for the diagnosis of Pneumocystis carinii pneumonia. The gallium scan was always normal in bronchopulmonary Kaposi's sarcoma. We conclude that in symptomatic patients: (1) DTPA clearance measurements are useful for detecting lung disease when chest x-ray and/or PaO2 are normal and (2) a gallium scan is indicated to distinguish progressive Kaposi's sarcoma from a superimposed second process when radiological abnormalities of pulmonary Kaposi's sarcoma are present.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Pleurisy in HIV infected patients].

Thirty-seven records of pleural effusion of known cause which occurred in HIV-seropositive patients hospitalized at the Tenon hospital, Paris, between 1985 and 1990 were analyzed retrospectively and divided into two groups: group 1 (n = 21) made up of kaposian effusions, and group 2 (n = 16) of infectious effusions serving as control. Numerous features distinguished group 1 from group 2 pleural effusions: In group 1 the effusion occurred in patients with cutaneous Kaposi sarcoma in 20/21 cases (P less than 0.001), developed slowly (more than 10 days) in 20/21 patients (P less than 0.001), was associated with a specific fever in only 4/21 cases (P less than 0.001), was bilateral in 20/21 cases (P less than 0.001), was regularly associated with bilateral parenchymatous opacities (P less than 0.001) and was haemorrhagic in 18/21 patients (P less than 0.001). Thus, simple semeiological features are sufficient to predict the cause of pleural effusion occurring in HIV-seropositive patients and to guide the diagnostic approach.

Adult↗
PubMed1991

Purification and characterization of the oxidase from the marine bacterium Pseudomonas nautica 617.

The aerobic respiratory system of the hydrocarbonoclastic marine bacterium Pseudomonas nautica 617 ends with a single terminal oxidase. It is a heme-containing membranous protein which has been demonstrated only to reduce molecular oxygen to hydrogen peroxide [Denis, M., Arnaud S. & Malatesta, F. (1989) FEBS Lett. 247, 475-479]. The purification of this oxidase was achieved in a single step through by DEAE-Trisacryl chromatography. SDS/PAGE showed the presence of four subunits. The pI was found to be 4.45 and a Mr of 130,000 was determined by gel filtration. The amino acid composition of the purified terminal oxidase has been determined. About 52% of the residues are hydrophobic, strengthening the membranous nature of this bacterial oxidase. Room temperature optical spectra are typical of heme b with a 560-nm band for the reduced form in the alpha range. The prosthetic group is made of two hemes b, one high-spin (S = 5/2, gl = 5.9, g parallel approximately 2.0), the other low-spin (S = 1/2, gz = 2.94, gy = 2.27). No other metal centre was detected by EPR. The two hemes remained unresolved in optical spectra, even at low temperature, and throughout redox titration. They behaved potentiometrically like a one-electron, single redox couple, with Em = 87 +/- 10 mV at pH 7.2 and 293 K. The purified oxidase did not oxidize ferrocytochrome c, but displayed quinol oxidase activity both with the native quinone (2419 nmol O2.min-1.mg protein-1 and commercially available coenzyme (101.74 nmol O2.min-1.mg protein-1). Exposure of the reduced enzyme to CO induced the collapse of alpha and beta bands as occurred during reoxidation. In contrast, NaCN and NaN3 fully inhibited the oxidase activity. Results are discussed with respect to other purified quinol oxidases.

Amino Acids↗
PubMed1991

Expression of alkaline phosphatase in murine lymphoma cells.

Alkaline phosphatase (ALP) was secreted and expressed at the cell surface of the lymphoma A/63-2 cell line but not on another clone A/63-1 deriving from a single thymoma (A/63) induced by a wild-type Abelson-Moloney viral complex. The enzyme was heat-sensitive and strongly inhibited by L-p-bromotetramisole and L-homoarginine but not by L-phenylalanine. All these data indicated that this enzyme was most likely identical to the L/B/K ALP isoenzyme. Southern blot analysis showed that neither amplification nor polymorphism were responsible for the high expression of the ALP gene observed in A/63-2 cells. On the opposite, the mRNA transcripts of ALP were only detected in A/63-2 cells indicating that a modulation of the ALP gene transcription occurred which could be due to the insertion of the v-abl gene within or near the 5'-flanking region of the ALP promotor in A/63-2 cells. Butyrate strongly increased both the secretion and the expression of the enzyme on A/63-2 cell surface. This induction was strongly inhibited by cordycepin, an RNA biosynthesis inhibitor, and at a lesser degree by cycloheximide, a translation inhibitor suggesting that butyrate induction occurs both at the transcriptional and the translational level.

Alkaline Phosphatase↗
PubMed1991

In vivo modulation of atypical mycobacterial infection: adjuvant therapy increases resistance to Mycobacterium avium by enhancing macrophage effector functions.

Susceptible BALB/c mice were infected iv with a strain of Mycobacterium avium and infused with different biological response modifiers (BRM) in a gel delivery system so as to modify the progression of the infection in a beneficial fashion. Infusion of IL-2 or IL-4 in hydrophobic gels led to no significant enhancement of resistance. Infusion of muramyl dipeptide in hypromellose led to a significant enhancement of resistance against the M. avium, as seen by a significant reduction of colony-forming units (CFU) in the spleens of infected mice. Similarly, infusion of interleukin-1 beta in hypromellose in infected mice led to a significant reduction in CFU counts in the organs of mice. The mechanism(s) responsible for this enhanced resistance was studied further. It was found that infected mice developed profound immunosuppression, as judged by mitogenic and antigenic stimulation. Mice infused with MDP/hypromellose developed a similar immuno-suppression, suggesting that this adjuvant immunotherapy did not act by stimulating a T-cell response or by abrogating a putative suppressive phenomenon. Macrophages from mice infused with MDP alone were no more bacteriostatic for a virulent M. avium than control cells. However, macrophages from infected mice infused with MDP/hypromellose were more bacteriostatic for M. avium than cells from mice infected with M. avium and infused with the hydrophobic gel only. Overall, these results suggest that adjuvant immunotherapy is beneficial in M. avium infections.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1991

Growth of Mycobacterium avium in human monocytes: identification of cytokines which reduce and enhance intracellular microbial growth.

Human monocytes were isolated by standard procedures and their ability to harbor growth of two virulent strains of Mycobacterium avium, TMC724 and TMC7479, was assessed in the absence or presence of cytokines. Both strains of mycobacteria, especially the M. avium TMC7479, grew progressively in untreated human monocytes. Inclusion of certain macrophage-activating cytokines, such as interferon-gamma in the presence of indomethacin or 1.25(OH2)-vitamin D3 (calcitriol) led to significant reductions in bacterial growth at 7 days post-infection. Conversely, treatment of human monocytes with interleukin-(IL) 1, macrophage-colony stimulating factor or IL 3 led to an increased permissiveness of these cells for M. avium. Moreover, these cytokines were shown to increase dramatically extracellular M. avium growth in vitro in tissue culture medium. Further, inclusion of antibodies against IL 1 beta and IL 6 in untreated infected monocytes monolayers led to a reduced growth of M. avium, suggesting that infected monocytes produce factors which enhance their susceptibility to M. avium. Overall, my findings suggest that cytokines may play a bidirectional role in atypical mycobacterial infections, by either increasing or decreasing resistance of the monocyte.

Calcitriol↗
PubMed1991

Modulation of Mycobacterium avium growth in murine macrophages: reversal of unresponsiveness to interferon-gamma by indomethacin or interleukin-4.

The ability of soluble factors to modulate the growth of a virulent strain of Mycobacterium avium in murine peritoneal macrophages was studied. The virulent strain, TMC 702, grew progressively in the organs of susceptible BALB/C mice. In addition, this strain of M. avium grew progressively in untreated peritoneal macrophages. Treatment of macrophage monolayers with interferon-gamma (IFN-gamma) did not change significantly the intracellular growth of M. avium. Addition of indomethacin to IFN-gamma-treated macrophage monolayers rendered them significantly more bacteriostatic than macrophages treated with interferon alone, suggesting a role for prostaglandins in inducing unresponsiveness to IFN-gamma in infected cells. Additionally, treatment with tumour necrosis factor-alpha led to a modest increase in bacteriostasis, as compared to untreated monolayers. Further experiments with recombinant interleukins showed that interleukin-4 (IL-4), on its own, could increase bacteriostatic activity against M. avium in a reproducible fashion. Experiments with interleukin combinations showed that IFN-gamma and IL-4 treatment of macrophages rendered these cells almost fully bacteriostatic against M. avium, inclusion of scavengers of reactive oxygen species did not modify the beneficial effect of IFN-gamma and IL-4. Overall, our results suggest an important role for interleukins in modulating the interaction between virulent mycobacteria and murine macrophages.

Animals↗
PubMed1991

Tumor necrosis factor and granulocyte macrophage-colony stimulating factor stimulate human macrophages to restrict growth of virulent Mycobacterium avium and to kill avirulent M. avium: killing effector mechanism depends on the generation of reactive nitrogen intermediates.

An avirulent and a virulent strain of Mycobacterium avium were selected on the basis of their growth patterns in human monocyte-derived macrophages. The virulent 7497 M. avium grew progressively in untreated macrophages, whereas the avirulent LR/149 M. avium was killed to a moderate extent by untreated human macrophages (50% of the original infectious inoculum killed 7 days after infection). We set out to investigate the possibility of modulating these growth patterns by cytokine treatment. Application of tumor necrosis factor (TNF) (100 U/ml) led to macrophages restricting significantly the growth of virulent M. avium 7497 (tenfold decrease at 7 days). TNF was also effective at modulating positively the interaction between avirulent LR/149 M. avium and macrophages inasmuch as TNF-treated cells killed 99% of infecting mycobacteria at 7 days. Granulocyte macrophage-colony stimulating factor (GM-CSF) (100-10,000 U/ml) treatment led to macrophages being as mycobacteriostatic for virulent 7497 M. avium as TNF-alpha-treated cells (i.e., tenfold reduction in growth). Treatment of macrophages with both GM-CSF and TNF-alpha was shown to have additive effects on bacteriostatic activity on M. avium. The mechanism of killing of avirulent M. avium by TNF-alpha was shown to be dependent on the generation of reactive nitrogen intermediates, as seen by inhibition of effector mechanisms by NG-monomethyl-arginine and arginase. Moreover, there was a correlation between NO2- generation and mycobactericidal activity of macrophages. Addition of superoxide dismutase reversed the killing of avirulent M. avium by untreated or TNF-treated macrophages. This abrogation was also apparent in chronic granulomatous disease (CGD) macrophages, which were inefficient at generating reactive oxygen intermediates. Moreover, macrophages from CGD patients killed avirulent M. avium as efficiently as cells from normal individuals. We conclude from these results that 1) GM-CSF and TNF-alpha, alone or in combination, increase effector functions of macrophages against virulent and avirulent strains of M. avium; 2) reactive nitrogen intermediates seem to be involved in this effector mechanism; and 3) superoxide dismutase protected M. avium against macrophage effector function, seemingly by protecting the bacteria against endogenous superoxide anion. The implications of these findings for host resistance to atypical mycobacteria are discussed.

Arginase↗
PubMed1991

Colony-stimulating factors increase resistance to atypical mycobacteria in resistant mice, whereas they decrease resistance in susceptible strains of mice.

Inbred strains of mice, notably the susceptible C57BL/6 and the resistant A/J strains of mice, were infected with a strain of Mycobacterium evium. The infection in the visceral organs of mice was then studied, and the effect of colony-stimulating factors, i.e., interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and macrophage colony-stimulating factor (CSF-1) on the infectious process was evaluated. Infusion of GM-CSF, CSF-1, and IL-3 led to a significant, albeit rather modest, increase in the mycobacterial resistance of A/J mice, as seen by a decrease in the number of colony-forming units (CFU) in the organs. Conversely, these CSFs dramatically increased the susceptibility of C57BL/6 mice, as seen by increased bacterial numbers in the spleens and livers. In vitro studies demonstrated that resident peritoneal macrophages from susceptible mice were more permissive than cells from resistant mice for mycobacterial growth. Application of CSFs on peritoneal macrophage monolayers led to an increased growth in both A/J and C57BL/6 monolayers for IL-3 and CSF-1 and a small microbiostatic effect for GM-CSF. Cytokine treatment did not, however, change the resistance/susceptibility phenotype of isolated macrophages. Our results indicate that CSFs may exert beneficial or detrimental effects on resistance to mycobacteria depending on the host genetic make up.

Animals↗
PubMed1991

Involvement of cytokines in determining resistance and acquired immunity in murine tuberculosis.

Herein we demonstrate that continuous infusion of either TNF-alpha or IFN-gamma (10(4) U/day) via osmotic micropumps leads to an increased resistance of mice infected with a lethal dose (10(7)) of M. tuberculosis H37Rv, associated with a decreased microbial growth in all target organs. This result was reinforced by the finding that infusion of antibodies against TNF-alpha or IFN-gamma greatly enhanced susceptibility of naive mice to tuberculosis. In a final set of experiments, using neutralizing antibodies, we show that IFN-gamma, not TNF-alpha is involved in determining acquired resistance against murine tuberculosis, as seen by the fact that acquired immunity is resistant to anti-TNF-alpha antibodies, yet sensitive to anti-IFN-gamma antibodies. This suggests a role for both IFN-gamma and TNF-alpha in determining innate resistance whereas IFN-gamma may be the mediator of the anamnestic response.

Animals↗
PubMed1991

Down-regulation of murine lymphocyte responsiveness to mitogens after treatment with antigens of Entamoeba histolytica.

Injection of mice with pathogenic Entamoeba histolytica (strain HM1-IMSS) antigens resulted in a decreased capacity of splenocytes to respond to mitogen-induced blastogenesis following a challenge with concanavalin A (Con A), phytohemagglutinin (PHA), and lipopolysaccharide (LPS), whereas no inhibition was observed in mice that had previously been injected with equivalent amounts of non-pathogenic E. histolytica-like Laredo antigens. Depletion of adherent cells in the splenocyte preparation indicated that these cells were not a major contributor to the observed immunosuppression. Quantification of splenic T-lymphocyte subsets demonstrated a significant decrease in Thy-1+ and Lyt-1+ cells, but Lyt-2+ cells were not affected. Splenocytes treated with pathogenic amoebic antigens in vitro affected the capacity of these cells to respond optimally to Con A- and LPS-induced blastogenesis but not to that induced by PHA. These findings demonstrate that amoebic antigens affect lymphocyte function and may be important co-factors in the immunoregulation and pathogenesis of amoebiasis.

Animals↗
PubMed1991

Interferon-gamma-treated murine macrophages inhibit growth of tubercle bacilli via the generation of reactive nitrogen intermediates.

Murine peritoneal macrophages were isolated and their ability to restrict growth of a virulent Mycobacterium tuberculosis in response to IFN-gamma was assessed in various conditions. Doses of IFN-gamma ranging from 10 to 100 U stimulated high levels of antimycobacterial activity, as seen by inhibition of growth. Addition of catalase, superoxide dismutase, and other scavengers of reactive oxygen species before infection failed to abrogate this restriction of growth, suggestive of a lack of involvement of reactive oxygen species in this phenomenon. Addition of arginase before infection inhibited the bacteriostatic ability of IFN-gamma-pulsed macrophages as did addition of NG-monomethyl L-arginine, an inhibitor of the synthesis of inorganic nitrogen oxide. In both cases, this inhibition was reversed by adding excess L-arginine in the medium. Moreover, nitrite production in macrophages was correlated with their ability to restrict tubercle bacilli growth. These results imply that nitric oxide or another inorganic nitrogen oxide is an important effector molecule in restricting growth of M. tuberculosis in IFN-gamma-pulsed murine macrophages.

Animals↗
PubMed1991

Identification of cytokines which enhance (CSF-1, IL-3) or restrict (IFN-gamma) growth of intramacrophage Listeria monocytogenes.

Murine peritoneal macrophages were isolated by adherence and their listericidal activity assessed in the presence or absence of selected cytokines. Untreated macrophages were not highly listericidal, showing moderate killing in the first 2 h after infection, and allowed progressive microbial growth thereafter (up to 9 h). Pre-treatment of cells with 10 to 100 U/ml of IFN-gamma allowed macrophages to develop sustained listericidal activity for the 9-h observation period, with a 2-log reduction of Listeria CFU per monolayer. Pulsing of cells with TNF-alpha alone did not result in enhanced microbicidal activity but TNF-alpha potentiated IFN-gamma-induced listericidal activity, resulting in high levels of killing when both cytokines were present. Conversely, macrophages pre-treated with interleukin-3 (IL-3) or colony-stimulating factor-1 (CSF-1) were found to be much more permissive for Listeria growth. Neither IL-3 nor CSF-1 abrogated IFN-gamma-induced listericidal activity. Moreover, neither IL-3 nor CSF-1 had any effect on the ability of macrophages to develop a respiratory burst following Listeria infection, as judged by H2O2 release following in vitro infection. Overall, these results suggest that different cytokines may have opposing effects on intracellular microbial growth, and that the balance of cytokine production in vivo may determine the resistance or susceptibility of the infected host.

Animals↗