Search PubMed⌕ Search

Biomedical subjects

M Denis

Publications and source records attributed to M Denis.

At least 91 records · Page 5Linked to original sources
PubMed1994

Blockade of leukocyte function-associated antigen (LFA-1) in a murine model of lung inflammation.

We examined the contribution of the leukocyte function-associated antigen (LFA-1) in a murine model of lung inflammation determined by exposure to the thermophilic actinomycete Faeni rectivirgula. The exposure generated a large influx of cells in the bronchoalveolar space and in the lung parenchyma, as seen from enhanced numbers of cells recovered by bronchoalveolar lavage (BAL) and histologic scoring of lung lesions. Repeated intranasal exposure to F. rectivirgula also resulted in a significant increase in lung hydroxyproline levels. Histologic analysis showed that alveolar wall inflammation, interstitial swelling and congestion, epithelial cell destruction, and granulomas with occasional epithelioid cells were observed in the lungs of challenged mice. Mice injected with rat antibodies against LFA-1 concomitantly with an antigen challenge showed no reduction in the number of BAL inflammatory cells, but lung fibrosis was significantly reduced by anti-LFA-1 treatment as assessed by lung hydroxyproline levels; parenchymal inflammation and tissue damage were also significantly reduced as seen from morphometric analysis. Anti-LFA-1 treatment of mice with established hypersensitivity pneumonitis was found to significantly reduce the levels of lung hydroxyproline and tissue damage; the numbers of BAL cells remained unaffected. From these results, we conclude that the fibrosis and tissue-damaging reactions in hypersensitivity pneumonitis, but not the alveolitis, are partly dependent on LFA-1-mediated cellular interactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic↗
PubMed1994

A mouse model of lung injury induced by microbial products: implication of tumor necrosis factor.

Mice of the C57BL/6 strain were injected with bacterial lipopolysaccharide (LPS) followed by formylnorleucyl-leucyl-phenylalanine (FNLP) by the intraperitoneal route; markers of acute lung injury were examined in mice given a fusion protein of soluble human tumor necrosis factor-alpha (TNF-alpha) receptor (p80) linked to the Fc portion of human IgG (TNFR:Fc) or excipient. Challenge with LPS/FNLP elicited an adult respiratory distress syndrome-like pathology characterized by sharp increases in levels of lactate dehydrogenase (LDH) and total proteins in bronchoalveolar lavage as well as in lung myeloperoxidase (MPO) content at 16 and 20 h after challenge. Infusion of 1 mg of TNFR:Fc 2 h before challenge very significantly abrogated the increases in LDH, protein levels, and MPO. Histologic analysis revealed that LPS/FNLP infusion resulted in an intravascular neutrophil agglomerate and perivascular/peribronchial damage; the extent of tissue lesions was significantly reduced, but not abrogated, by TNF-alpha depletion. There were moderate levels of antigenic TNF-alpha in lung homogenates at 16 and 20 h after challenge, not affected by infusion with TNFR:Fc. No bioactive TNF-alpha was detected in lung homogenates of challenged mice given TNFR:Fc. High levels of antigenic interleukin-6 (IL-6) were found in lung homogenates of challenged mice treated with TNFR:Fc or with diluent. Elevated levels of antigenic IL-6 and TNF-alpha were found in sera of challenged mice at 16 and 20 h after injection; TNFR:Fc-treated mice had a higher level of antigenic TNF-alpha than did challenged mice given diluent, but it was not bioactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Interaction between Mycobacterium avium and human immunodeficiency virus type 1 (HIV-1) in bronchoalveolar macrophages of normal and HIV-1-infected subjects.

Bronchoalveolar lavage (BAL) macrophages from patients with symptomatic or asymptomatic HIV-1 infections were obtained, and their ability to restrict in vitro the growth of an AIDS-associated strain of Mycobacterium avium was compared with cells obtained from normal volunteers. BAL macrophage populations from HIV-1-infected subjects (symptomatic or asymptomatic) spontaneously released significant amounts of IL-6, IL-1 beta, and TNF-alpha, whereas BAL macrophages from normal volunteers released very low amounts of these cytokines. Phagocytosis of M. avium was shown to be similar in both HIV-1-infected subjects and in control subjects. BAL macrophages from HIV-1-infected subjects released significantly greater quantities of IL-6, IL-1 beta, and TNF-alpha than did cells from normal volunteers upon M. avium ingestion. Growth of M. avium was similar in BAL macrophages from all three subject groups. Finally, BAL macrophages from normal volunteers were obtained, and these cells were doubly infected with a macrophage tropic isolate of HIV-1 at a low multiplicity of infection and with an AIDS-associated strain of M. avium. There were no significant differences in cytokine release by cells co-infected with M. avium and HIV-1 and cells infected with M. avium alone. The growth of mycobacteria and the viral replication in doubly infected cells were compared with those in cells infected with only one of the pathogens, and it was shown that HIV-1 infection had no significant effect on M. avium growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1994

[Bone mineral density of the femoral neck, a cross-sectional study of normal values in 827 French women aged 36 to 86 years].

The need for determining country-specific reference bone mineral density values has been emphasized. The effects of age and time since menopause on femoral neck bone mineral density in healthy women are still insufficiently documented. The goal of this study was to determine age-specific femoral neck bone mineral density values and postmenopausal bone loss rates in French women. Dual-energy X-ray absorptiometry was used to measure lumbar spine, femoral neck, and Ward's triangle bone mineral densities in 827 women aged 36 to 86 years. Inclusion criteria included a negative history for established or suspected osteoporosis. A cross-sectional, retrospective design was used. Lumbar spine bone mineral densities were similar to reference values reported previously in healthy subjects from other countries. Consequently, we considered that the femoral neck values that we obtained were those of a healthy population. Results were as follows: 1) The annual rate of bone loss at the femur increased within one or two years after menopause (to 1.5% and 2% at the femoral neck and Ward's triangle, respectively), remained high for 12-13 years, then declined (0.8% and 1.2%, respectively). 2) Femoral bone loss was slow before the age of 55 years (0.2% and 0.5% per year) and continued at a faster rate thereafter (1.3% and 1.7% per year). Our study provides normal reference femoral bone mineral density values for French women. Our data confirm that age and time since the menopause have a substantial influence on bone mineral density, not only at the lumbar spine, but also at the femoral neck.

Absorptiometry, Photon↗
PubMed1994

Neutralization of transforming growth factor-beta 1 in a mouse model of immune-induced lung fibrosis.

We examined the contribution of the cytokine transforming growth factor beta 1 (TGF-beta 1) in the inflammatory response and fibrotic reaction in a mouse model of immune-induced lung fibrosis caused by repeated intranasal exposure to heat-killed bacillus Calmette-Guérin (BCG). Mice received 200 micrograms of BCG 3 days/week for 4 weeks, and simultaneous intraperitoneal injections of a monospecific rabbit antiserum against mouse TGF-beta 1 or a preimmune serum (normal rabbit globulin). BCG instillations generated a copious release of antigenic TGF-beta 1 in the lungs at 1, 2, 3 and 4 weeks (up to 15 ng/lungs/mouse). Treatment with anti-TGF-beta 1 antiserum significantly diminished the number of free lung cells recovered by bronchoalveolar lavage (BAL), although the BAL cellular profile was not affected. Moreover, anti-TGF-beta 1 treatment of challenged mice diminished very significantly the total levels of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) in the lungs of animals challenged with BCG. Histological examination and morphometric analysis of Masson's Trichrome-stained sections and measurements of total lung hydroxyproline levels showed a substantial decrease in lung fibrosis and granulomatous response of challenged mice given anti-TGF-beta 1. These data argue for a role for TGF-beta 1 in inducing inflammation and lung fibrosis in response to an immune stimulus.

Animals↗
PubMed1993

IL-10 neutralization augments mouse resistance to systemic Mycobacterium avium infections.

In this contribution, we examined the involvement of the cytokine IL-10 in the progression of experimental murine Mycobacterium avium infections in susceptible BALB/c mice. Addition of anti-IL-10 antibodies in the supernatants of peritoneal macrophages infected with virulent M. avium resulted in a significantly enhanced mycobacteriostatic activity of macrophages. In BALB/c mice infected with the B101 or B102 virulent M. avium strains, examination of the cytokine release profile in splenocytes from infected mice showed that infection was associated with an initial copious release of both IFN-gamma and IL-10. IL-10 production increased as the infection progressed, whereas IFN-gamma levels diminished. Infected mice were given repeated infusions of a rat mAb against mouse IL-10 or rat IgM. Examination of IgM serum levels in anti-IL-10-treated mice (infected or not) showed that depletion of endogenous IL-10 resulted in much decreased IgM levels. Results showed that infusions of large dosages of the monoclonal anti-IL-10 resulted in a very significantly diminished bacterial growth in the spleens. These findings indicate that IL-10 may have a negative impact on resistance to M. avium infections, due, at least in part, to decreased macrophage activity.

Animals↗
PubMed1993

Isolation, characterization and function of the two cytochromes c of the yeast Candida parapsilosis.

Candida parapsilosis is a strictly aerobic yeast which possesses two respiratory chains with a peculiar organisation, different from that of plant mitochondria. Besides the classical electron transport pathway, mitochondria of C. parapsilosis develops an alternative pathway, which does not branch off at the ubiquinone level, but merges at the complex IV level. Two pools of cytochromes c were distinguished by their spectrometric and potentiometric properties: (i) sequential cytochrome c reduction was promoted by two substrates, PMS (Em = 70 mV) and TMPD (Em = 280 mV). TMPD promoted the reduction of a cytochrome c with maxima at 551.9 and 417.3 nm for the alpha and the Soret bands, respectively, whereas cytochrome c reducible by PMS exhibited maxima at 549.7 and 419.9 nm; (ii) two midpoint redox potentials were resolved at 180 mV and 280 mV, respectively. The two cytochromes c were copurified by ion-exchange chromatography on Amberlite; after this step, the two cytochromes c can always be differentiated by TMPD and PMS, these reductants promoting different absorption bands. The two cytochromes c were separated by reverse-phase HPLC; this last purification step resolved two proteins with the same relative molecular mass of 13600 but a different amino-acid composition. Comparison of N-terminal sequences revealed differences between the two proteins. It was hypothesized that one cytochrome c is implicated in the functioning of the main chain and the other in that of the secondary pathway.

Amino Acid Sequence↗
PubMed1993

Retinoic acid modulation of alpha(1-->2) fucosyltransferase activity and sensitivity of tumor cells to LAK-mediated cytotoxicity.

We examined the effects of all-trans retinoic acid (RA) on alpha(1-->2) fucosyltransferase activity and sensitivity to LAK-mediated cytotoxicity in two rat colon carcinoma cell lines differing by their glycosylation state and their tumorigenic potential. RA induced a decrease in alpha(1-->2) fucosyltransferase activity in the more tumorigenic variant PROb. Fucosyltransferase mRNA levels were not affected by RA treatment in PROb cells, suggesting a posttranscriptional control. This inhibition was accompanied by a decreased expression of fucosylated membrane glycoconjugates and by a significant increase in the sensitivity to LAK-mediated cytotoxicity. REGb cells, which exhibited a very low enzymatic activity and very few fucosylated glycoconjugates, were more sensitive to LAK-lysis than PROb cells and were not affected by RA treatment.

Adenocarcinoma↗
PubMed1993

[Phlebitis of the upper limbs on pacemaker electrodes. 4 cases and review of the literature].

We report four cases of deep venous thrombosis of the upper extremity, which occurred in two women and two men (mean age 79 years) in whom a pacemaker electrode had been inserted 4 years on averages previously. In three of these four cases phlebitis developed after immobilization of the limb containing the electrode. Deep venous thrombosis of the upper extremity is rare, but 28% of catheterizations are responsible for phlebitis. One to 3% of patients fitted with a pacemaker have symptomatic phlebitis, but these figures rise to 28-65% when phlebography is systematically performed in subjects wearing a pacemaker. The clinical signs are the same as those of the classical forms, and the diagnosis is made by doppler-ultrasonography and by phlebography which informs on the collateral circulation. Cure is obtained with efficient anticoagulant therapy. These cases prompt us to prescribe a preventive subcutaneous heparin therapy in those pacemaker-fitted subjects whose arm is immobilized. The heparin dosage remains to be determined precisely.

Aged↗
PubMed1993

Cyclosporin A increases the pulmonary eosinophilia induced by inhaled Aspergillus antigen in mice.

We evaluated the effects of anti-inflammatory drugs in a murine model of allergic bronchopulmonary aspergillosis (ABPA). Mice instilled with 100 micrograms of Aspergillus fumigatus antigen (intranasally, 3 days a week for 3 weeks) developed pulmonary lesions, characterized by a perivascular and peribronchial eosinophil infiltration, a bronchoalveolar lavage (BAL) eosinophilia, and elevated levels of total IgE, total IgG1 and A. fumigatus-specific IgG1. Under the same conditions, groups of mice receiving a daily dose of 2 mg/kg dexamethasone showed decreased numbers of eosinophils and total cells in BAL, had less numerous eosinophils in their pulmonary infiltrates, and had lower levels of serum and BAL fluid total IgE, total IgG1 and A. fumigatus-specific IgG1. Conversely, groups of mice pretreated with an immunosuppressive agent, cyclosporin A (CsA) at a dose of 50 mg/kg, three times per week, developed pulmonary lesions with enhanced lung eosinophilic influx and increased total IgE levels, both in serum and in BAL fluid. These findings show that dexamethasone potently prevents the murine immunopathologic response to A. fumigatus. The effect of CsA on this inflammatory response was paradoxical, insofar as it suggests an activation of the T helper 2 subset, which up-regulates eosinophil recruitment and IgE production.

Administration, Inhalation↗
PubMed1993

A study of monokine release and natural killer activity in the bronchoalveolar lavage of subjects with farmer's lung.

We examined the interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) releasability of alveolar macrophages and the natural killer (NK) cell activity in the bronchoalveolar lavage (BAL) cells of 11 patients with Farmer's lung at different stages of the disease. Although there were some variations in the levels of monokine release, macrophages of patients with acute disease secreted significantly higher spontaneous levels of TNF alpha than did a nonfarming control group (p = 0.0002). Conversely, TNF alpha release stimulated by bacterial lipopolysaccharide (LPS) was similar in patients with acute disease when compared with that in normal control subjects. IL-1 was also spontaneously secreted in significantly greater amounts by patients with acute Farmer's lung than by subjects in a control group (p = 0.0001). However, LPS-induced IL-1 release was significantly diminished in BAL macrophages from patients with acute manifestations of the disease when compared with that in control subjects (p = 0.001). Treating hypersensitivity pneumonitis with corticosteroids or by contact avoidance resulted in very significant decrease in spontaneous and LPS-stimulated IL-1 production by BAL macrophages (p = 0.0001 and p = 0.03, respectively), as well as in a decrease in spontaneous TNF alpha release that was also significant (p = 0.01). In addition, BAL cells of patients in the acute phase had a significant NK cell activity (mean +/- SEM of 18.33 +/- 2.65%). Treatment of these patients resulted in an increase in NK cell activity (mean of 40.17 +/- 7.86%), which was significantly different from values of patients with acute disease (p = 0.037).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

Release of interleukin-8, interleukin-6, and colony-stimulating factors by upper airway epithelial cells: implications for cystic fibrosis.

Cystic fibrosis (CF) is characterized by a dramatic neutrophil recruitment and repeated Pseudomonas infections in the lungs. To evaluate cytokine releasibility by airway epithelial cells in the context of CF, we studied primary nasal epithelial cells isolated from the upper airways and continuous epithelial cell lines from normal and CF subjects. Relatively low levels of interleukin (IL)-8, IL-6, and granulocyte/macrophage colony-stimulating factor (GM-CSF) were produced spontaneously by primary epithelial cells (< 50 pg/10(6) cells) and higher levels of colony-stimulating factor-1 (CSF-1) (1 to 2 ng/10(6) cells). Cells were stimulated with substances that are likely to be present in the inflamed lungs of CF patients-namely, the proinflammatory monokines IL-1 and tumor necrosis factor-alpha (TNF alpha) as well as neutrophil elastase and bacterial products from Pseudomonas (mucoid exopolysaccharide [MEP] and rhamnolipids). Both IL-1 and TNF alpha induced a dose-dependent release of IL-6 (5 to 10 ng/10(6) cells) and GM-CSF (2 to 3 ng/10(6) cells) by primary epithelial cells from eight normal volunteers. The TNF alpha/IL-1-stimulated GM-CSF release was blocked by the addition of 1 microM dexamethasone, whereas basal CSF-1 release was unaffected. Neutrophil elastase was a potent inducer of IL-8 and GM-CSF both in primary epithelial cells and in cell lines. Dexamethasone (1 microM) did not inhibit elastase-induced IL-8 release in either normal or CF epithelial cells. Rhamnolipids and MEP were found to stimulate the copious release of IL-8, GM-CSF, and IL-6 from epithelial cells, in a steroid-sensitive fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Mechanical ventilation for Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. Is the prognosis really improved?

The mortality rate among patients with human immunodeficiency virus (HIV) requiring mechanical ventilation (MV) for acute respiratory failure (ARF) secondary to Pneumocystis carinii pneumonia (PCP) is still a matter of discussion. For some authors, it is in the 50 percent range, while for others the prognosis is grim, with virtually no survivors. The aim of this retrospective study conducted between January 1987 and January 1992 was to analyze the outcome of such patients. We studied 33 patients, 29 men and 4 women (38.6 +/- 9.9 years, 21 homosexuals, 8 intravenous drug users, 3 transfusion related, 1 heterosexual) infected by HIV for at least 19.7 +/- 21.6 months. It was the first PCP episode in all but 2 patients and the diagnosis was made by bronchoalveolar lavage (n = 32) or lung biopsy specimen (n = 1). Only three patients were receiving primary prophylaxis for PCP (trimethoprim-sulfamethoxazole [TMP-SMZ], n = 2; pentamidine, n = 1). Pneumocystis carinii pneumonia was the first manifestation of AIDS in nine patients. The duration of symptoms prior to treatment was 19.6 +/- 11.3 days. At the time of hospital admission, laboratory findings were as follows: PaO2 = 40.7 +/- 7.8 mm Hg on room air; serum LDH = 1,172 +/- 792 IU/L; T4 cell count = 60.2 +/- 67/mm3. Mechanical ventilation was always required for ARF, which was never induced by bronchoscopy. The interval between treatment and MV was 8.1 +/- 6.5 days and the duration of MV was 11.4 +/- 9.9 days. The patients were classified into 3 groups on the basis of the duration and type of treatment before MV, as follows: group 1, n = 10: TMP-SMZ (20-100 mg/kg) IV and methylprednisolone (MP) < 5 days before MV; group 2, n = 4: TMP-SMZ > or = 5 days and MP < 5 days; group 3, n = 19: TMP-SMZ and MP > or = 5 days before MV. (The MP dose was as follows: 240 mg/d once a day from day 1 to day 3; 120 mg/d from day 4 to day 6; and 60 mg/d from day 7 to day 9.) Despite MV, TMP-SMZ, and MP, death secondary to PCP-related ARF occurred in 81.9 percent of patients, 20 +/- 4.8 days after the beginning of treatment and 11.4 +/- 9.9 days after the beginning of MV. Six patients survived, five in group 1 and one in group 3.(ABSTRACT TRUNCATED AT 400 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1993

[Acute drug-induced lung diseases with hypoxemia, cytotoxic drugs excluded].

Drug-induced acute lung diseases constitute a chapter of pneumology and intensive care that is now in full mutation. In practice, these diseases are still inadequately indexed and little known, the only exception being those caused by cytotoxic drugs observed in onco-haematology. They create for clinicians difficult diagnostic and therapeutic problems. From the cases reported in the literature, recent review papers and 10 personal cases, the authors ask five successive questions concerning hypoxic pneumopathies: 1) which patients?; 2) which clinical features?; 3) which initial diagnostic discussion?; 4) which are the elements likely to support the drug-induced hypothesis?; 5) which outcome?

Acute Disease↗
PubMed1993

Identification of different target glycoproteins for bovine herpes virus type 1-specific cytotoxic T lymphocytes depending on the method of in vitro stimulation.

Vaccinia virus recombinants expressing the three major bovine herpes virus-1 (BHV-1) glycoproteins gI, gIII and gIV were used to identify the major target antigens for BHV-1-specific CTL isolated from immune cattle. Peripheral blood mononuclear cells (PBMC) expanded in vitro in the presence of interleukin-2 (IL-2) and lysed both gIII- and gIV-infected target cells. Secondary in vitro stimulation of PBMC was also performed in the presence of either fixed BHV-1-infected autologous fibroblasts or ultraviolet (UV)-inactivated virus. Both methods of antigen presentation allowed the proliferation of BHV-1-specific CTL but the target glycoprotein for these CTL differed depending on the method of stimulation. Vaccinia-gIV-infected targets were lysed predominantly when PBMC were stimulated by fixed infected fibroblasts, whilst PBMC stimulated by UV-inactivated virus lysed mostly vaccinia-gIII-infected targets. This observation could be explained by a different processing pathway of BHV-1 antigens in each cell type involved.

Animals↗
PubMed1992

Minocycline-induced cell-mediated hypersensitivity pneumonitis.

OBJECTIVE: To identify the cause of a hypersensitivity pneumonitis and to determine its pathogenesis. DESIGN: Case study. SETTING: Intensive care unit of a referral hospital. PATIENT: A 51-year-old man with chronic bronchitis who developed a hypersensitivity pneumonitis within 1 month after exposure to minocycline, amoxicillin, and erythromycin. INTERVENTION: Sequential bronchoalveolar lavages after reexposure to minocycline and amoxicillin. MEASUREMENTS: Immunologic analysis of the phenotype and function of alveolar lymphocytes. RESULTS: Reexposure to minocycline but not to amoxicillin was followed by an interstitial pneumonitis. Sequential bronchoalveolar lavages showed a transient rise of eosinophils and neutrophils and a persistent alveolar lymphocytosis. Alveolar lymphocytes consisted predominantly of CD8+ but also CD4+ cells. Two CD8+ lymphocyte subsets were identified: CD8+ D44+ cytotoxic T cells that increased rapidly after the drug was resumed and CD8+ CD57+ suppressor T cells that predominated 11 days after the drug's withdrawal. In-vitro assays showed the presence of a lymphocyte-mediated specific cytotoxicity against minocycline-bearing alveolar macrophages. CONCLUSION: These results support the hypothesis of a central role of T lymphocytes in the pathogenesis of drug-related hypersensitivity pneumonitis.

Alveolitis, Extrinsic Allergic↗