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Biomedical subjects

M Fournier

Publications and source records attributed to M Fournier.

At least 163 records · Page 9Linked to original sources
PubMed1994

O6-methylguanine-DNA adducts in rat lymphocytes after in vivo exposure to N-nitrosodimethylamine (NDMA).

A non-invasive approach in immunopathological risk assessment was applied for analysis of the in vivo formation of DNA adducts. DNA methylation was studied in peripheral blood lymphocytes (PBLs) collected from Sprague-Dawley rats exposed to a single dose (75 mg/kg b.w.) of N-nitrosodimethylamine (NDMA). Three different techniques were applied for characterization and quantification of DNA adducts: (i) colloidal gold ultraimmunocytochemical localization of O6-methylguanosine (O6-meG)-DNA adducts, using affinity-purified, polyclonal antibody directed against O6-meG, (ii) quantitative assay using enzyme-linked immunosorbent assay (ELISA), amplified by the avidin-biotin (AB) system, and (iii) high-performance liquid chromatography (HPLC). The O6-meG-immunoreactive sites in PBLs seem to be concentrated in the nucleus. However, significant immunolabelling was also noted in the cytoplasm of the in vivo NDMA-exposed PBLs. Control preparations showed no specific gold immunolabelling. The O6-meG-DNA adduct formation in PBLs and hepatocytes, at 2-24 h following the exposure to NDMA, was analogous for both types of cells. The data showed high correlation for the ELISA and HPLC analytical methods. The data suggest an efficient O6-metG-DNA repair mechanism in lymphocytes, possibly analogous to the enzymatic repair of DNA adducts in liver cells.

Animals↗
PubMed1994

SR 48692, a non-peptide neurotensin receptor antagonist differentially affects neurotensin-induced behaviour and changes in dopaminergic transmission.

Unilateral microinjection of neurotensin in the ventral tegmental area of the rat (2.5 micrograms/0.5 microliter) produced behavioural excitation illustrated by contralateral circling. Given orally, SR 48692, a selective and potent non-peptide neurotensin receptor antagonist, significantly reduced these rotations with a triphasic dose-effect relationship. Inhibition occurred at 0.12 mg/kg; further increases in dose up to 2.5 mg/kg produced no significant antagonism, then at doses > or = 5 mg/kg, a second phase of antagonism was observed. Bilateral injection of neurotensin (0.5 microgram each side) into the nucleus accumbens antagonized the increase in locomotor activity following intraperitoneal injection of amphetamine. Given orally, SR 48692 reduced dose-dependently (0.1-1 mg/kg) these intra-accumbens neurotensin effects. Using high pressure liquid chromatography with electrochemical detection, we showed that microgram amounts of neurotensin injected into the ventral tegmental area increased dihydroxyphenylacetate/dopamine ratios in the nucleus accumbens. Using in vivo voltammetry techniques, we found that the injection of nanogram and picogram amounts of neurotensin in the ventral tegmental area stimulated dopamine efflux in the nucleus accumbens. None of these biochemical changes were affected by SR 48692 (0.1-10 mg/kg). These results indicate complex interactions between neurotensin and the mesolimbic dopamine system. More particularly, the differential ability of SR 48692 to affect neurotensin-evoked behavioural versus biochemical changes supports the concept of neurotensin receptor heterogeneity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Priming of HIV replication by tRNA(Lys3): role of reverse transcriptase.

The fundamental role played by reverse transcriptase in the replication of retroviruses has stimulated the study of the mechanism of action of this enzyme. The reverse transcriptase of the type 1 human immunodeficiency virus forms a stable complex with its cognate transfer RNA replication primer (tRNA(Lys3)). Here, we outline the role of this enzyme in the selection of its primer tRNA, the annealing of primer tRNA to the complementary region of the retroviral genome, and the first attempts to use the reverse-transcriptase-tRNA complex as a new target for antiviral agents.

Base Sequence↗
PubMed1994

Modulation of exercise-induced immunosuppression by dietary polyunsaturated fatty acids in mice.

The possible interaction between intense exercise, known to suppress the immune response, and nutritive factors, such as polyunsaturated fatty acids (PUFA), was examined in inbred female C57Bl/6 mice. The animals received for 8 wk either a natural ingredient diet or a diet supplemented with 10 g/100 g linseed oil containing over 50% of 18:3 (n-3) alpha-linoleic acid. Other groups received PUFA containing only traces of 18:3 (n-3) fatty acid; beef tallow, containing mostly 18:1 (n-9) saturated fat, safflower oil, an 18:2 (n-6) PUFA, and fish oil, containing longer chain (n-3) PUFA. Each dietary group was divided into two subgroups: sedentary diet controls and exercised animals. Exercise consisted of continuous swimming at high intensity until exhaustion. It was shown in three separate experiments that (1) the primary humoral response to sheep red blood cells, determined by the plaque-forming cell (PFC) assay, was affected by PUFA diet in sedentary animals in the order beef tallow > control diet > safflower oil > fish oil > linseed oil, and (2) the PFC response was suppressed by the exhaustive exercise, as compared to sedentary controls, except for animals fed 18:3 (n-3) linseed oil, where the normal response was noted. Phagocytosis of fluorescent microspheres by peritoneal macrophages, determined by flow cytometry, was significantly lower in exercised animals receiving the linseed oil diet, whereas other diets either increased or did not significantly change the macrophage phagocytic activity, compared to the sedentary diet controls. Spleen lymphocyte subsets were unchanged in exercised animals except for a marked shift from the lymphoid peak toward the erythroid peak. Generally, our data showed a marked immunomodulatory effect of 18-3 (n-3) alpha-linoleic acid on the exhaustive exercise-related immunosuppression, as compared to the effects of other selected PUFA.

Animals↗
PubMed1994

Immunocytochemical evidence for a nuclear and a cytoplasmic O6-methylguanine repair mechanism in cultured rat hepatocytes.

The localization of DNA and RNA adducts was studied at the ultrastructural level using antibodies directed against O6-metG and the protein A-gold technique. Primary rat hepatocyte cultures were exposed for 2-24 h to 5 mM N-nitrosodimethylamine (NDMA) or 0.1 mM N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In both cases, the O6-metG immunoreactive sites were concentrated in the nucleus and in the rough endoplasmic reticulum (RER) rich cytoplasmic regions. The highest gold labeling density measured was observed at 2 h of NDMA or MNNG treatment. However, after a 24-h exposure, very little labeling was observed in both the nuclear and the cytoplasmic compartments. The rate of disappearance of immunoreactive sites was faster in the cytoplasm than in the nucleus, Untreated control preparations showed no specific immunogold labeling. Furthermore, when cells were exposed first to NDMA and MNNG for a few hours and then to culture medium containing no genotoxin, and subsequently were reexposed to NDMA or MNNG for a few hours, very little labeling of both the nuclear and cytoplasmic compartments was observed. Control preparations without a second genotoxin exposure showed a normal labeling pattern. Control preparations without genotoxin showed no gold labeling. Our results provide evidence for the existence of a cytoplasmic O6-metG repair mechanism that behaves like its nuclear counterpart.

Animals↗
PubMed1994

Evaluation and use of the white blood cell differential provided by the Coulter STKS in a children's hospital.

The Coulter STKS was evaluated in a children's hospital, in order to (a) compare the WBC differential given by the instrument to a 400 cell visual differential (reference method); (b) evaluate the sensitivity and specificity of the alarm system, and (c) provide data concerning the use and interpretation of results in children. 653 blood samples were collected. The Coulter STKS results were studied in 523 patients having no morphological abnormalities in the blood smears, separated into subgroups according to the presence of STKS alarms and according to age. The results were found accurate both in STKS negative and STKS positive patients (i.e., those with alarms: 'Blasts', Imm Gran 2, Variant Lymph, NRBC, review slide). Negative STKS results had the same accuracy in all age groups, except in neonates where slide review must be systematically performed. The instrument exhibited a good sensitivity of the suspect flags studied (91.4%), with a lower specificity (72%) reflecting the number of false positive results found in our group, probably due to the cytological features particular to children. However, it was shown that the numerical results given by the Coulter STKS in positive patients could be taken into account, provided that a scan of the blood smear was negative for morphological WBC abnormalities.

Adolescent↗
PubMed1994

Experimental allergic bronchopulmonary aspergillosis in the mouse: immunological and histological features.

C57BL/6 mice treated with intranasal instillation of 100 micrograms of Aspergillus antigen three times a week developed a pulmonary eosinophilia, observed in the bronchoalveolar lavage (BAL) and on histopathological examination. At week 3, the instillation of Aspergillus antigen provoked a 10-fold increase in the BAL cell number and eosinophils were the predominant inflammatory cells (66.4%). Histopathological findings showed focal alveolar lesions with peribronchial and perivascular infiltration of lymphoid cells, numerous eosinophils, epithelioid cells, and granulomas with giant cells. Increases in total IgE and IgG1 levels in BAL fluid (33-fold and 14-fold) and serum (67-fold and 8-fold) were observed also (P < 0.05). IgG1 specific to Aspergillus fumigatus (Af) was detected only in the antigen-treated mice. At 12 weeks, there was a persistent but less intense eosinophilia both in BAL and on histopathological examination accompanied by steadily elevated total IgE and total IgG1 and a higher level of specific IgG1-Af in BAL fluids and sera. No bronchocentric granulomatosis, mucoid impaction nor bronchiectasis could be observed. Data from the study described here showed that in mice repeated exposure to Aspergillus antigen leads to a strong inflammatory pulmonary response, characterized by remarkable pulmonary eosinophilia and elevations of total IgE, total IgG1 and specific IgG1-Af in both BAL and serum, which are the hallmarks of human allergic bronchopulmonary aspergillosis also. However, this inflammation did not induce the chronic histological features of the human disease.

Animals↗
PubMed1994

Long-term viral enhancement of lung response to Saccharopolyspora rectivirgula.

The current study was done to look at the long-term enhancing effect of a single viral infection on repeated Saccharopolyspora rectivirgula (SR) antigenic challenges in mice and at inflammatory cytokines in this enhancement. Four groups of C57BI/6 mice were studied: Group 1 received intranasal instillations of saline, 3 days per week; Group 2, intranasal instillations of saline plus one intranasal instillation of 80 hemagglutination units (HAU) of Sendai virus after 3 wk of saline; Group 3, instillations of SR, 3 days per week; and Group 4, instillations of SR, 3 days per week, plus one instillation of Sendai virus after 3 wk of SR. Bronchoalveolar lavages (BAL) were performed 15 and 30 wk after the virus inoculation in the appropriate groups. Each time, a two- to threefold increase in BAL cell counts was obtained from virus-infected animals challenged with SR compared with animals that received the SR alone. Animals infected with virus only showed values similar to those of control animals. A higher percentage of large foamy multinucleated cells were found in the BAL from the SR+Sendai group than the SR alone group (7.92 +/- 0.730% compared with 1.8 +/- 0.296%). These cells were not seen in the other groups. BAL levels of TNF-alpha and IL-1 alpha at 15 wk were much higher in SR+Sendai-treated (1,439 +/- 268 and 96 +/- 9 pg/ml, respectively) than SR alone-treated animals (361 +/- 100 and 23 +/- 4 pg/ml). BAL fluid of control animals and Sendai alone animals contained 64 +/- 24 and 65 +/- 15 pg/ml of TNF-alpha, but no IL-1 alpha was detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Functional results of single-lung transplantation for chronic obstructive lung disease.

The feasibility and immediate tolerance of single-lung transplantation were recently demonstrated in patients with severe obstructive lung disease. Since initial reports, hundreds of procedures have been performed worldwide in such patients, but views regarding the results are still controversial. Since few data concerning medium-term functional results are available, we report here our series of 20 patients with chronic obstructive pulmonary disease who received a single-lung transplant. A group of 16 patients who survived for 6 mo or more form the basis of this report. Current 1- and 2-yr actuarial survival are 75 and 70%, respectively, with 4 perioperative deaths and 2 deaths at 9 and 15 mo after transplantation. Before transplantation the patients were severely obstructive, with a FEV1 of 17 +/- 6% of predicted, a PaO2 of 51 +/- 10 mm Hg, a PaCO2 of 49 +/- 11 mm Hg, and a 6 min walk test of 99 +/- 84 m. A significant functional improvement was observed postoperatively, the patients' FEV1 at 3 mo reached 53 +/- 13%, PaO2 81 +/- 3 mm Hg, and PaCO2 39 +/- 3 mm Hg. The distance covered during 6 min was 587 +/- 147 m at 6 mo. Throughout postoperative follow-up, lung function remained stable in some patients but decreased in others after several mo, this decline related to the occurrence of bronchiolitis obliterans, except in two patients who had airway complications. Impairment in lung function led to retransplantation in four patients, with good clinical results in three patients, one patient dying postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1994

Tracheal malacoplakia.

Malacoplakia is a rare granulomatous disease well described in the urinary tract but which rarely involves the lung. We report for the first time, to our knowledge, tracheal localization of this unusual disorder. The larynx and probably kidneys were also involved. Differential diagnosis, physiopathology, and treatments are discussed.

Adult↗
PubMed1994

Persistence of porcine reproductive and respiratory syndrome virus infection in a swine operation.

A herd of Quebec seedstock pigs experienced in early 1992 a typical outbreak of porcine reproductive and respiratory syndrome (PRRS) associated with lesions of interstitial, proliferative and necrotizing pneumonia in weaned piglets. The nature of the infection was confirmed by serology using indirect immunofluorescence (IIF) and virus isolation in primary cultures of porcine alveolar macrophages (PAM). Farm production recovered after eight weeks of losses. In order to evaluate the persistence of infection in the herd, five SPF-piglets were introduced in two different sections of the PRRS-affected barn four months after the disappearance of clinical symptoms, and two others were placed in a neighboring building with apparently healthy farrow-to-finnish pigs. Clinical signs, body temperature, humoral immune response, virological and histopathological findings were recorded over a 42-day period. Clinical signs were evident in all of the sentinels and prolonged fever (> or = 40 degrees C) was recorded one day post-exposure (PE). Antibody titers to PRRS virus could be detected by IIF on PAM seven days PE, and reached 1:1024 by day 21 PE. Three of the sentinels developed significant virus neutralizing antibody titers (> 1:8 to < or = 1:128) by day 35 PE. In all cases, the virus could be isolated from the serum between day 7 and 42 PE. Thus, the virus and specific antibodies coexisted for several weeks. Lesions of interstitial pneumonia was demonstrated in few animals. In experimental inoculation studies, the viral strain isolated from the sentinel pigs produced severe reproductive disorders in two sows inoculated at 95 days of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Mechanisms of bronchial hyperreactivity. Role of the epithelium].

Bronchial epithelial cells are present all along the airways. They play a role of barrier and protect the airways against inhaled pollutants. However it is known to day that they could play an active role, through synthesis and release of mediators which modulate the airway muscles, the epithelium permeability and the vascular tone. Shedding of the epithelium is a constant feature of the asthmatic airways as can be observed directly on the bronchial biopsies and indirectly through and increased number of epithelial cells in the bronchoalveolar lavage fluid. The epithelial shedding is well correlated to the bronchial hyperreactivity. In vitro, bronchial epithelial cells release higher quantities of 15 HETE, endothelin and PGE2 in asthmatics than in normal control subjects. They express HLA-DR and ICAM-1 in higher quantities in asthmatic patients. Bronchial epithelial cells might play an important role in inflammatory lesions which are observed in asthmatic patients. They could be a good target for new therapeutic approaches in asthma.

Animals↗
PubMed1994

[Evaluation of Abbott CD 3500 in severe leukopenia].

Leucopenia patient follow-up remains, in terms of laboratory turnaround, a heavy workload due to the leucoconcentrations necessary for evaluating leucocytic formulas. We tested the CD 3500 with the objective of defining its' analytical performances and routine practice. 101 leucopenia samples (< 2.10(9)/l) procured from the onco-hematology department (adults and children) were studied during a 1 month period. The leucocytic formula obtained after leuconcentrations was our reference. The alarm sensitivity, as a whole, was of 97% for a 15.5% specificity. The correlation coefficients (Cell-Dyn/microscope) for polynuclears, lymphocytes and monocytes were respectively 0.889, 0.925 and 0.926. The correlation coefficients observed in both following subgroups: < or = 0.5.10(9)/l and > 0.5.10(9)/l were superposable. In 95% of the cases, the numeric value difference between the two methods attained a maximum of 21% for all neutrophils and lymphocytes and 13% for the monocytes. There was an excellent concordance between both methods for eosinophilia and basophils with confidence intervals of +/-8.8% and +/-2.2%. In practice, we feel that the use of a CD 3500 in post chemotherapy leucopenia, is perfectly adaptable and appreciated for leucocytic formulas, as well as a good exit for aplasia.

Autoanalysis↗
PubMed1993

Use of mouse hepatocytes for the flow cytometric determination of DNA levels of nuclei extracted from fresh tissue of hybrid larch (Larix x eurolepis Henry).

A rapid and reliable method is presented to release intact nuclei from small amounts (100 mg) of fresh plant tissue. Further, an accurate and readily accessible new standard is proposed. Both techniques have potential application for many plant systems. The system chosen as a standard (inbred mouse strain Balb/C or B6/AF1 hepatocyte nuclei) contains both diploid and polyploid cells. This system was applied in the flow cytometric determination of absolute nuclear DNA values of female gametophytes and in vitro propagated shoots of hybrid larch (Larix x eurolepis Henry). The amount of DNA in 2C nuclei of in vitro grown larch is 32.48 +/- 4.04 or 31.97 +/- 6.14 pg/nucleus, respectively, when calculated using the mouse hepatocyte 4C or 8C nuclear peak as a reference standard. The amount of DNA in female gametophyte nuclei is 17.47 +/- 1.33 pg DNA/nucleus when these haploid larch nuclei were analyzed with trout red blood cell nuclei as the standard. When hepatocyte 4C nuclei were used as a standard, the absolute value of DNA per haploid larch nucleus was estimated as 16.8 +/- 0.53 pg. Plant tissue with as little as 4-6 pg DNA/nucleus up to as much as 35 pg DNA/nucleus can be tested using mouse hepatocytes as a standard while retaining an optimal sample/standard ratio.

Animals↗
PubMed1993

Cytometric profiles of bone marrow and spleen lymphoid cells after mercury exposure in mice.

The potential immunotoxic effects of mercury chloride on murine bone marrow (bm) cell subpopulations, including analysis of maturation patterns for B-cells, were evaluated by flow cytometric analysis. CD-1 outbred mice were exposed for 28 days to relatively low doses of 25-100 ppm HgCl2 in drinking water and the mercury-related functional cellular changes were validated in a macrophage phagocytosis assay. Lymphocyte subsets from the bone marrow population were stained with PNA lectin and a panel of monoclonal antibodies against cell surface antigens. The incidence of subset-specific staining was also monitored in spleens and thymuses. A dose-effect correlation was noted for the mercury-related activation of macrophage phagocytosis. Subchronic exposure to mercuric chloride resulted in a transient (7-14 day) decrease of the lymphoid/total bm cell ratio and affected the incidence of splenic T-cell subsets, however, without a clear dose-response correlation. The B-cell population in spleen and maturation patterns of B-cells in bm appeared to be unaffected by the mercury exposure. Overall, cytometric analysis of lymphoid cell subsets in murine bone marrow revealed transient and subset-non-specific cell fluctuations after subchronic exposure to inorganic mercury.

Animals↗