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Biomedical subjects

M Fournier

Publications and source records attributed to M Fournier.

At least 217 records · Page 12Linked to original sources
PubMed1989

Human immunodeficiency virus reverse transcriptase expressed in transformed yeast cells. Biochemical properties and interactions with bovine tRNALys.

Human immunodeficiency virus (HIV) reverse transcriptase has been purified from yeast transformed by an autoreplicating plasmid containing the retroviral DNA polymerase gene. The previously described purification procedure for the yeast-expressed reverse transcriptase [Barr, P.J., Power, M.D., Chun Ting Lee-Ng, Gibson, H. & Luciw, P. (1987) Bio/Technology 5, 486-489] has been substantially modified, leading to an increased yield and a higher degree of purity. Several biochemical properties of the enzyme are described (template specificity, effect of DNA synthesis inhibitors); interestingly, HIV reverse transcriptase is highly resistant to N-ethylmaleimide. A complex between the human retroviral enzyme and the bovine tRNALys was shown, using a direct approach, by glycerol gradient centrifugation, as well as by the protective and specific effect of the tRNALys against enzyme inactivation by thermal denaturation and trypsin digestion. A competitive type of inhibition of HIV reverse transcriptase by tRNALys, but not by tRNAVal, is observed when viral RNA or activated DNA are used as templates.

Animals↗
PubMed1989

Fiber type composition of muscle units in the cat diaphragm.

The fiber type composition of muscle units in the cat diaphragm was examined. As expected, slow-twitch units were composed of type I fibers and fast units were composed of type II fibers. Fast fatigable units were composed of type IIB fibers and fast fatigue resistant units were composed of type IIA fibers. Surprisingly, fast fatigue intermediate units were comprised of both type IIA and IIB fibers.

Adenosine Triphosphatases↗
PubMed1989

Cerebral-activating (EEG) properties of two inverse agonists and of an antagonist at the benzodiazepine receptor in the rat.

In order to assess the effects of inverse benzodiazepine agonists and antagonists on brain function, computerized EEG (CEEG) analysis was performed in rats following the i.p. administration of SR 95195 (7-phenyl-3-methyl-1,2,4 triazolo-[4,3-b]pyridazine) and CGS 8216 (2-phenylpyrazolo-[4,3c]-quinoline-3-[5H]-one) two benzodiazepine receptor inverse agonists (BRIAGs) and of flumazepil (Ro 15-1788), a benzodiazepine receptor antagonist (BRANT). The EEG effects of SR 95195 (3, 10, 30 and 60 mg/kg), CGS 8216 (10 and 30 mg/kg) and flumazepil (3, 10, 30 and 60 mg/kg) were compared to those of the psychostimulant drugs DL-amphetamine (0.1, 0.3 and 1 mg/kg), and caffeine (10 and 30 mg/kg) and those of aniracetam (100 and 300 mg/kg), a nootropic pyrrolidone derivative. The CEEG profiles of SR 95195, CGS 8216 and flumazepil were mainly characterized by a power increase in the 20-32 Hz frequency range and by a power reduction in the 8-16 Hz range. These effects were quite similar to those of the psychostimulants DL-amphetamine and caffeine as well as to those of the nootropic aniracetam. Other psychotropic drugs with CNS-depressant properties, namely diazepam (10 mg/kg p.o.), pentobarbital (30 mg/kg p.o.), chlorpromazine (10 mg/kg i.p.) and imipramine (10 mg/kg i.p.) induced quite different EEG power modifications. These results show that BRIAGs and BRANTs possess a marked intrinsic activity at the central level and suggest that this activity is CNS-activating in nature.

Animals↗
PubMed1989

The response of the pulmonary surfactant-associated alkaline phosphatase following acute cadmium chloride inhalation.

In order to identify sensitive and specific biochemical indicators of pulmonary damages caused by industrial contaminants, male Long-Evans rats were exposed to a cadmium chloride (CdCl2) aerosol (5 mg Cd/m3; MMAD = 1.4 microns; SDg = 1.8) for 1 hr. The rats were sacrificed at 1, 4, 8, and 16 days after treatment. The response of the pulmonary surfactant (SF) system, which prevents alveolar collapse during expiration by lowering the surface tension at the air-liquid interface, was of particular interest. The effect of CdCl2 inhalation on the SF system was monitored by assaying the alkaline phosphatase (AKP) activity and phospholipid (PL) content in an enriched surface active SF fraction purified from bronchoalveolar lavages. The AKP activity of the SF fraction was markedly decreased (99%) on Day 1, indicating an inhibition of AKP by Cd. The PL content remained at control level while the total protein content was significantly increased (199%). On day 4, the high recovery of PL (207%) and AKP activities (639%) may reflect an increased secretion caused by Type II cell hyperplasia. By Day 8 these parameters returned to baseline levels. On Day 16 both the AKP activity and the PL content of the SF fraction were decreased significantly. Concurrently, the activities of the acid phosphatase and the B-N-acetylglucosaminidase followed, but to a lesser extent, the response of the AKP activity on Days 1 and 4. They differed from AKP, however, in that their activities remained significantly elevated on Day 8 and in that they returned to baseline levels on Day 16.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗
PubMed1989

Cytotoxic and neoplastic transforming effects of industrial hexavalent chromium pigments in Syrian hamster embryo cells.

Twenty eight moderately water-soluble to insoluble chromium (VI) compounds, such as zinc and lead chromate, industrial and laboratory synthesized pigments, and the analytical reagents strontium, barium and calcium chromate, were physicochemically characterized and studied for cytotoxicity and morphological transformation in cultured Syrian hamster embryo (SHE) cells. In vivo validation of malignancy of transformed SHE cells was performed. A high physicochemical diversity among the complex chromium pigments was revealed. The solubility of the compounds was greatly increased after incubation in a complete medium and even higher under cell culture conditions. The cytotoxic effects appeared to be due principally to extracellular solubilized chromium because the most solubilized compounds. Zn, Ca and Sr chromates, were equitoxic at about the same Cr concentration treatment and 8-fold more cytotoxic than less soluble compounds such as some Pb chromates and Ba chromate. However, certain physicochemical properties of lead chromate pigments could also influence their cytotoxic activity. All test compounds were, in a dose-dependent manner, efficient in inducing morphological transformation of SHE cells. Many of the Cr pigments, although physicochemically different, were similarly effective in transformation induction. Nevertheless, compounds among Zn and Pb chromates had various transforming potencies. Ba chromate was the least active in inducing transformation. Certain physicochemical properties could mediate the transforming activity but no particular relationship could be established between any one of the physicochemical parameters and the transforming potency. Cloned morphologically-transformed colonies of SHE cells were grown in soft agar medium and showed true neoplastic behaviour by tumour formation in syngeneic animals. These results show that various chromate pigments containing either Zn or Pb, of medium to very low aqueous solubility, induced neoplastic transformation of SHE cells.

Animals↗
PubMed1989

Developmental expression of the P0 glycoprotein and basic protein mRNAs in normal and trembler mutant mice.

Mice affected by the autosomal dominant Trembler mutation exhibit a severe hypomyelinization of the PNS. Previous biochemical studies have shown that the accumulation of the major PNS myelin proteins, P0 and myelin basic protein (MBP), is strongly diminished in Trembler sciatic nerves during postnatal development. We performed Northern blots which showed that the size of mRNA species for P0 and MBP in normal and mutant mice are indistinguishable. Densitometric analysis of Northern blots showed that, in normal mice, the proportion of P0 mRNA increases up to the 12th day, then decreases slowly. At day 40, the proportion is 60% of the maximal value. In the mutant, the proportion of P0 mRNA increases up to the 12th day and then decreases much faster than in the control. At days 12 and 40, the P0 mRNA proportion measured in Trembler sciatic nerves represents only 40% and 7%, respectively, of the proportion measured in control littermates. The MBP mRNA proportion in the normal mice increases up to the 16th day, and then decreases to attain 45% of the maximum level at day 40. In the Trembler mouse, there is a maximum level at day 12, representing 25% of the normal level, but the MBP mRNA is barely detectable at days 8 or 40. Thus, these data seem to indicate that in the Trembler sciatic nerves, the proportions of P0 and MBP mRNAs are too small to allow the synthesis of normal levels of the corresponding proteins.

Actins↗
PubMed1989

Diaphragm motor unit recruitment during ventilatory and nonventilatory behaviors.

The forces generated by the cat diaphragm (DIA) during different ventilatory and nonventilatory behaviors were determined by measuring transdiaphragmatic pressures (Pdi). The Pdi generated during eupnea was only approximately 12% of the maximum Pdi (Pdimax) generated by bilateral phrenic nerve stimulation. When the animals breathed a gas mixture of 10% O2 and 5% CO2, the Pdi increased to approximately 28% of Pdimax. During total airway occlusion, the Pdi generated by the diaphragm increased to approximately 49% of Pdimax. Only during the gag reflex and sneezing did Pdi reach maximal levels. A model for diaphragm motor unit recruitment during these different behaviors was presented based on the proportion of different motor unit types within the diaphragm, the relative tetanic tensions produced by each unit type, and the assumption of an orderly pattern of motor unit recruitment.

Animals↗
PubMed1989

Oxidative capacity and capillary density of diaphragm motor units.

Motor units in the cat diaphragm (DIA) were isolated in situ by microdissection and stimulation of C5 ventral root filaments. Motor units were classified based on their isometric contractile force responses and fatigue indexes (FI). The muscle fibers belonging to individual units (i.e., the muscle unit) were identified using the glycogen-depletion method. Fibers were classified as type I or II based on histochemical staining for myofibrillar adenosine triphosphatase (ATPase) after alkaline preincubation. The rate of succinate dehydrogenase (SDH) activity of each fiber was determined using a microphotometric procedure. The location of capillaries was determined from muscle cross sections stained for ATPase after acid (pH = 4.2) preincubation. The capillarity of muscle unit fibers was determined by counting the number of capillaries surrounding fibers and by calculating the number of capillaries per fiber area. A significant correlation was found between the fatigue resistance of DIA units and the mean SDH activity of muscle unit fibers. A significant correlation was also observed between DIA unit fatigue resistance and both indexes of muscle unit fiber capillarity. The mean SDH activity and mean capillary density of muscle unit fibers were also correlated. We conclude that DIA motor unit fatigue resistance depends, at least in part, on the oxidative capacity and capillary density of muscle unit fibers.

Adenosine Triphosphatases↗
PubMed1989

Epithelial vs. serosal stimulation of tracheal muscle: role of epithelium.

There is evidence implying an active role of airway epithelium in the modulation of bronchomotor tone. To study this phenomenon, we designed an in vitro system allowing pharmacological stimulation of either the inside or outside of the airway lumen. Rat tracheas were excised, cannulated, and their inside and outside perfused independently with Krebs solution. Two hooks were inserted through opposite sides of the tracheal wall, the lower one was attached to a fixed point, while the upper one was connected to a force transducer. Isometric contractions of the tracheal muscle were elicited by carbachol solution perfused in single and cumulative concentrations. In one-half of the preparations the epithelium was mechanically removed. Stimulation of the inside or outside of the trachea produced equal maximal tracheal muscle tension [1.55 +/- 0.14 and 1.2 +/- 0.09 (SE) g in and out, respectively]. The time course of tension development was longer when carbachol was administered inside the trachea: an effect that was abolished when the epithelium was removed. In addition, removal of the epithelium was found 1) to increase the maximal tension irrespective of the route of carbachol perfusion and 2) to increase the sensitivity of the preparation to carbachol stimulation.

Animals↗
PubMed1989

Intraepithelial T-lymphocyte subsets in the airways of normal subjects and of patients with chronic bronchitis.

Lymphocyte infiltration of central airway epithelium was evaluated in 13 normal nonsmoking subjects (Group 1), in 11 smokers without clinical signs of chronic bronchitis (Group 2), and in 34 patients who were smokers with chronic bronchitis and mild airflow limitation (Group 3). Bronchial samples were obtained through fiberoptic bronchoscopy. Murine monoclonal antibodies directed against cell-surface antigens and an immunoperoxidase technique were used on cryostat sections to label in situ the following lymphocyte populations: T-lymphocytes (CD3+), helper/inducer T-cells (CD4+), suppressor/cytotoxic T-cells (CD8+) and B-lymphocytes (leu 12+). Virtually no B-cells were found in central airway epithelium from subjects of any group. Conversely, consistent infiltration of epithelial layers with T-lymphocytes of both subsets was observed in all subjects, with a constant predominance of CD8+ over CD4+ cells. For any T-cell marker, differences between mean scores from Group 1 and Group 2 subjects were not statistically significant. On the other hand, mean lymphocyte numbers of both subsets were found increased in patients from Group 3 compared with subjects from the two other groups: statistically significant differences were observed for CD3+, CD4+, and CD8+ cells (p less than 0.001). Furthermore, lymphocyte scores at two different airway generation were compared in some patients from Groups 2 and 3, and a significant positive correlation was observed. These results suggest that T-lymphocyte infiltration of central airway epithelium (1) may be a naturally occurring phenomenon that is amplified in the airways of smokers with chronic bronchitis, and (2) may represent the counterpart to the intraepithelial population of the intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Cysteine-induced changes of low molecular sulfhydryl/disulfide ratio in rat lymphoid cells.

Changes in total protein and nonprotein sulfhydryl content, cell membrane sulfhydryls and mitogen response were examined after incubation of rat lymphoid cells with L-cysteine. Distribution of 35S L-cysteine within the metabolic pool of low molecular thiols and protein thiols was determined by quantitative analysis of metabolites of the oxidative taurine pathway, glutathione, mixed disulfides and protein-associated radioactivity. Significant, incubation time-dependent increase of [3H] thymidine, [3H] uridine and [14C] leucine incorporation was observed in cysteine-preincubated, PHA-stimulated lymph node cells. Subsequent inhibition of PHA-response of lymphocytes and a marked increase of intracellular content of free (reduced form) cysteine was observed as a result of constant supply of cysteine into cells from the incubation medium. Maintenance of [35S] L-cysteine, transported into thymocytes within 3 hours, mainly in -SH form, was dependent on the constant presence of cysteine in the medium and slightly dependent on its concentration (0.01-10 mM). Cysteine catabolites of the oxidative taurine pathway, i.e. taurine, cysteinesulfinic acid and cysteic acid, as well as glutathione, low molecular mixed disulfides, protein cysteine mixed disulfides and proteinincorporated cysteine increased proportionally to the time of cysteine uptake but not to the increasing amounts of intracellular free cysteine. These results support the hypothesis of changed-SH/SS equilibrium of low molecular thiols due to the presence of high amounts of free cysteine, reflecting cell metabolism and functions.

Animals↗
PubMed1989

Carcinoma of the lung. Evaluation of satellite nodules as a factor influencing prognosis after resection.

Satellite nodules are considered to be predictive of poor prognosis in breast cancer and in melanoma. In lung cancer, there is no information as to their definition, prevalence, or implication as a prognosis factor of survival after resection. Over the past 18 years (1969 to 1987), 84 patients underwent pulmonary resection for primary lung cancer accompanied by satellite nodules. These nodules were defined as well-circumscribed accessory carcinoma foci clearly separated from the main tumor but with identical histologic characteristics. All were smaller than the primary carcinoma and most were located within the same lobe. Survival rates of patients with satellite nodules were compared to those of 1021 patients without satellite nodules who underwent resection during the same time interval. The 1-, 3-, and 5-year survival rates for all patients classified as having no satellite nodules were 78%, 54%, and 44%, respectively, and the median survival for the entire group was 30 months. In patients with satellite nodules, these survival rates were 60.9%, 32.7%, and 21.6%, respectively, with a median survival of 15 months. The deleterious effect of satellite nodules was more significant in patients with stage I disease (p = 0.0008) than in patients with stage II (p = 0.0354) or stage III (p = 0.0145) disease. Survival data obtained by comparison of satellite nodule status and histologic characteristics shows that 5-year survival figures are better for patients with no satellite nodules in both the squamous and the nonsquamous groups. This study demonstrates that satellite nodules associated with lung cancer are indicative of locally advanced and/or premetastatic disease. These patients should be included in the stage group IIIa of the TNM stage grouping classification.

Adult↗
PubMed1988

Po, MBP, histone, and DNA levels in sciatic nerve. Postnatal accumulation studies in normal and trembler mice.

We studied the quantitative changes in proteins (total, Po, MBP, and histones) and DNA from sciatic nerves of normal and Trembler mice during postnatal development. Polyacrylamide gel electrophoresis and immunoblotting procedures allowed an accurate characterization of Po, MBP, and histones, as well as the comparison of their respective amounts from d 2 to d 120 after birth. It was found that 1. The immunoblotting procedure ascertains the presence of Po in the sciatic nerve of Trembler. In the 2-d-old mice, Po is detected in essentially similar amounts in Trembler and normal PNS, whereas its level in adult mutant sciatic nerves is never greater than 20% of the control. The sharp increase in Po levels observed during the third week in the normal nerves is not observed in those of the mutant; 2. MBP species are at most 4% of the control in the 10- to 12-d-old Trembler mice, whereas they were not detectable in adult nerves. The distribution of the different MBP species is the same in both mutant and control mice; 3. In normal mice, Po and MBP accumulate at similar rates, but the 14 kDa MBP accumulates faster than the 18.5 kDa MBP; and 4. Histone and DNA contents decrease 3- to 5-fold in normal nerves, whereas they remain constant, or increase slightly, in the mutant.

Animals↗
PubMed1988

Transient inhibition of mixed lymphocyte reactivity by dieldrin in mice.

Dieldrin, a non-aromatic organochlorinated pesticide, was shown to be a potent modulator of the immune system. We had earlier demonstrated that mice treated with a single sublethal dose of dieldrin showed an impaired antibody response and reduced viral restriction mediated by macrophages. These dieldrin-induced immunosuppressive effects were shown to be dose dependent, when administered by the oral or intraperitoneal (i.p.) route. This study was undertaken to investigate the effect of dieldrin on the T-cell immune response. Lymphoid cells from mice injected i.p. 7 days earlier with 36 mg/kg body weight (0.6 LD50) dieldrin were assessed for their ability to recognize a foreign antigen and to proliferate in a mixed lymphocyte reaction (MLR) at 4, 7, 14 and 24 days post-treatment. We have demonstrated a strong but transient inhibition of MLR at 7 days after pesticide exposure. This effect was reversible and could not be attributed to a direct cell cytotoxicity, nor to the modulation of the T-cell ratio in lymphoid organs. Since the mitogen response was not impaired at this time point, we suggest that T-cell ability to recognize a foreign antigen can be altered by dieldrin, but not the proliferative potential of the cells.

Animals↗
PubMed1988

Abrogation of graft-versus-host reaction by dieldrin in mice.

Sublethal exposure to the organochlorine pesticide, dieldrin, decreased the T-cell immune response in mice. Indeed, a transient inhibition of the mixed lymphocyte reactivity (MLR) was noted at 7 days after intraperitoneal exposure to 0.6 LD50 dieldrin. The present study was undertaken to further investigate the effects of dieldrin on the T-cell immune response, using the graft-versus-host reaction (GVHR) as a model, in order to assess T-cell subset efficiency. Lymphoid cells of A/J mice injected intraperitoneally 7 days earlier with 36 mg/kg body weight dieldrin were transferred into H-2-incompatible F1 hybrids. With this model, known to induce a marked GVHR, we have observed that dieldrin inhibited the potential of parental cells to induce a GVHR in hybrid mice. This effect could not be attributed to a direct cell cytotoxicity, nor to the modulation of major T-cell subsets as shown by thymic and peripheral T-cell subpopulation analysis. Collaboration processes between these cellular subsets seem to represent a potential site for the dieldrin-induced suppression.

Animals↗
PubMed1988

Toxicity of inhaled cadmium chloride: early responses of the antioxidant and surfactant systems in rat lungs.

In order to establish an animal model for assessing early and sensitive biochemical indicators of pulmonary damage, we studied the effects of inhaled CdCl2 (5 mg/m3.h; mass median aerodynamic diameter (MMAD) = 1.4 microns; SDg = 1.8) on the antioxidant defense and pulmonary surfactant systems of rat lungs. Rats were sacrificed 1, 4, 8, and 16 d after inhalation. Pulmonary edema (wet/dry weight) was observed on d 1. The total activities of the enzymes superoxide dismutase (SOD) and glucose-6-phosphate dehydrogenase (G6PD) in the lung homogenates of the treated animals were significantly throughout the 16-d period. Glutathione reductase (GR) was increased on d 4 and after. The general increases of SOD, GR, and the lysosomal enzymes acid phosphatase and beta-N-acetylglucosaminidase could be attributed to changes in the cellularity of the lung tissue. The significant increase in the specific activity of G6PD on d 4 suggested enzyme stimulation. Concurrently, the response of the surfactant system was measured by assaying the alkaline phosphatase (AKP) and the phospholipid content in the homogenates and in the cell-free bronchoalveolar lavage (BAL) fluids. The AKP activity in the homogenates decreased by 30%, while no activity was detected in the BAL on d 1, suggesting an inhibition of AKP by Cd. The secretion of surfactant seemed altered at this early time: phospholipid in the BAL decreased by 44%, although it increased by 61% in the tissue. The high recovery of phospholipid (312%) in the BAL on d 4 and the important changes in the AKP activity in the BAL from d 4 to 16 may reflect alterations in the processing of the surfactant. The effect of Cd on AKP makes this enzyme a potential marker of the metal redistribution in the pulmonary alveolar region, which could be a useful tool in long-term studies.

Acetylglucosaminidase↗