Biomedical subjects

M Fournier

Publications and source records attributed to M Fournier.

At least 73 records · Page 4Linked to original sources

PubMed1999

Toxicological characterization of sediments from Baie des Anglais on the St. Lawrence Estuary.

The sediments of Baie des Anglais on the St. Lawrence Estuary have a history of environmental contamination, but no information exists relating to their toxicity. The purpose of the present study was to characterize three sites in and near Baie des Anglais, in terms of sediment toxicity and contaminants. Sites 1 and 2 within the Baie des Anglais are relatively close to local industry and municipal sewage discharge points, while Site 3 is outside the bay. Three microscale bioassays, Microtox, echinoderm fertilization and Toxi-ChromoPad, showed that sediments from Site 1 were the most toxic, followed by Site 2. Site 3 was non-toxic. While the solid phase Microtox test did indicate that Site 1 was most toxic, the absolute response was weak. Liver cytochrome P450 1A1 mRNA in American plaice (Hippoglossoides platessoides), captured at Site 1 in the bay was significantly induced compared to the P450 system of plaice captured at Sites 2 and 3. Hepatic metallothionein mRNA levels were not significantly different between plaice captured at all three sites. Sediment chemical analyses revealed a gradient in polycyclic aromatic hydrocarbons, polychlorinated biphenyls and dibenzofurans (PCDF) with the highest levels recorded at Site 1, about 10-fold less at Site 2 and 100-fold less at Site 3. Amongst the organochlorines the PCDF group were deemed the most important due to their prevalence and known toxicity. Heavy metal concentrations were low and representative of background levels for the St. Lawrence Estuary.

Animals↗

PubMed1999

Pulmonary hypertension following hepatopulmonary syndrome in a patient with cirrhosis.

We report the case of a patient with liver cirrhosis who successively developed hepatopulmonary syndrome and portopulmonary hypertension. Initially, the patient presented with severe dyspnea and hypoxemia at rest. Technetium-99 macroaggregated albumin lung perfusion scan demonstrated right-to-left shunt, and hemodynamic study revealed a hyperdynamic state with low pulmonary vascular resistance, thus confirming the diagnosis of hepatopulmonary syndrome. More than 2 years after the onset of pulmonary symptoms, a marked improvement in dyspnea and gas exchange was observed. Lung perfusion scan did not disclose any right-to-left shunt and right-sided heart catheterization showed evidence of severe pulmonary hypertension. We conclude that hepatopulmonary syndrome and portopulmonary hypertension are not mutually exclusive. We hypothesize that, by reversing the phenomenon of intrapulmonary vasodilatation, the development of portopulmonary hypertension interfered with each of the potential causes of hypoxemia in hepatopulmonary syndrome (ventilation-perfusion inequalities, intrapulmonary shunting, oxygen diffusion limitation) and, as a result, led to a correction of hypoxemia.

Hepatopulmonary Syndrome↗

PubMed1999

Blockade of cannabinoid receptors by SR141716 selectively increases Fos expression in rat mesocorticolimbic areas via reduced dopamine D2 function.

The present study investigated, in rats, whether blockade of cannabinoid CB1 receptors may alter Fos protein expression in a manner comparable to that observed with antipsychotic drugs. Intraperitoneal administration of the selective CB1 receptor antagonist, SR141716, dose-dependently (1.0, 3.0 and 10 mg/kg) increased Fos-like immunoreactivity in mesocorticolimbic areas (prefrontal cortex, ventrolateral septum, shell of the nucleus accumbens and dorsomedial caudate-putamen), while motor-related structures such as the core of the nucleus accumbens and the dorsolateral caudate-putamen were unaffected. In the ventrolateral septum, taken as a representative structure, the Fos-inducing effect of SR141716 (10 mg/kg) was maximal 2 h after injection and returned to near control levels by 4 h. Within the prefrontal cortex, SR141716 increased the number of Fos-positive cells predominantly in the infralimbic and prelimbic cortices, presumptive pyramidal cells being the major cell types in which Fos was induced. The D1-like receptor antagonist, SCH23390 (0.1 mg/kg), did not prevent the Fos-inducing effect of SR141716 in any brain region examined (prefrontal cortex, nucleus accumbens, ventrolateral septum and dorsomedial caudate-putamen), although SCH23390 significantly reduced Fos expression induced by cocaine (20 mg/kg) in all these regions. By contrast, the dopamine D2-like agonist, quinpirole (0.25 mg/ kg), counteracted SR141716-induced Fos-like immunoreactivity in the ventrolateral septum, the nucleus accumbens and the dorsomedial caudate-putamen, while no antagonism was observed in the prefrontal cortex. Microdialysis experiments in awake rats indicated that SR141716, at doses which increased Fos expression (3 and 10 mg/kg), did not alter dopamine release in the shell of the nucleus accumbens. Finally, SR141716 increased the levels of neurotensin-like immunoreactivity in the nucleus accumbens, but not in the caudate-putamen. Collectively, the present results show that blockade of cannabinoid receptors increases Fos- and neurotensin-like immunoreactivity with characteristics comparable to those reported for atypical neuroleptic drugs.

Animals↗

PubMed1999

Optimism and adaptation to multiple sclerosis: what does optimism mean?

The aim of the present study was to determine the meaning of optimism by explicating the dimensions underlying the notion and their links to adjusting to MS. Seventy-three patients responded to optimism questionnaires (i.e., the LOT, Generalized Self-Efficacy Scale) and outcome questionnaires. In confirmatory factor analyses, the underlying dimensions of optimism were specified. Explanatory structural equation modeling was used to examine the relation of the dimensions of optimism to coping (CISS), depression (BDI), and impaired mobility range (SIP). Optimism was found to consist of three dimensions, namely, outcome expectancies, efficacy expectancies, and unrealistic thinking. Outcome and efficacy expectancies explained depression via emotion-oriented coping but did not explain impaired mobility range either directly or indirectly. Unrealistic thinking directly explained impaired mobility range. The present study can be seen as a first step in explicating the role of optimism in the management of chronic disease.

Adaptation, Psychological↗

PubMed1999

Blockade of neurotensin receptors suppresses the dopamine D1/D2 synergism on immediate early gene expression in the rat brain.

A remarkable feature of dopamine functioning is that the concomitant activation of D1-like and D2-like receptors acts to intensify the expression of various dopamine-dependent effects, in particular the expression of the immediate-early genes, c-fos and zif268. Using non-peptide neurotensin receptor antagonists, including SR48692, we have determined that blockade of neurotensin receptors reduced the cooperative responses of direct acting D2-like (quinpirole) and partial D1-like (SKF38393) dopamine agonists on the expression of Fos-like antigens and zif268 mRNA. Pretreatment with SR48692 (3 and 10 mg/kg) reduced the number of Fos-like immunoreactive cells produced by the combined administration of SKF38393 (20 mg/kg) and quinpirole (1 mg/kg) in the caudate-putamen, nucleus accumbens, globus pallidus and ventral pallidum. High-affinity neurotensin receptors are likely to be involved in these D1-like/D2-like cooperative responses, as compounds structurally related to SR48692, SR48527 (3 mg/kg) and its (-)antipode, SR49711 (3 mg/kg), exerted a stereospecific antagonism in all selected brain regions. Pretreatment with SR48692 (10 mg/kg) also diminished Fos induction by the indirect dopamine agonist, cocaine (25 mg/kg), particularly at the rostral level of the caudate-putamen. In situ hybridization experiments in the caudate-putamen indicated that SR48692 (10 mg/kg) markedly reduced zif268 mRNA labelling produced by SKF38393 plus quinpirole in cells not expressing enkephalin mRNA, but was unable to affect the concomitant decrease of zif268 mRNA labelling in enkephalin-positive cells. Taken together, the results of the present study indicate that neurotensin is a key element for the occurrence of cooperative responses of D2-like and partial D1-like agonists on immediate-early gene expression.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1999

Alterations in diaphragm contractility after nandrolone administration: an analysis of potential mechanisms.

The aim of this study was to evaluate the potential mechanisms underlying the improved contractility of the diaphragm (Dia) in adult intact male hamsters after nandrolone (Nan) administration, given subcutaneously over 4 wk via a controlled-release capsule (initial dose: 4.5 mg. kg-1. day-1; with weight gain, final dose: 2.7 mg. kg-1. day-1). Control (Ctl) animals received blank capsules. Isometric contractile properties of the Dia were determined in vitro after 4 wk. The maximum velocity of unloaded shortening (Vo) was determined in vitro by means of the slack test. Dia fibers were classified histochemically on the basis of myofibrillar ATPase staining and fiber cross-sectional area (CSA), and the relative interstitial space was quantitated. Ca2+-activated myosin ATPase activity was determined by quantitative histochemistry in individual diaphragm fibers. Myosin heavy chain (MHC) isoforms were identified electrophoretically, and their proportions were determined by using scanning densitometry. Peak twitch and tetanic forces, as well as Vo, were significantly greater in Nan animals compared with Ctl. The proportion of type IIa Dia fibers was significantly increased in Nan animals. Nan increased the CSA of all fiber types (26-47%), whereas the relative interstitial space decreased. The relative contribution of fiber types to total costal Dia area was preserved between the groups. Proportions of MHC isoforms were similar between the groups. There was a tendency for increased expression of MHC2B with Nan. Ca2+-activated myosin ATPase activity was increased 35-39% in all fiber types in Nan animals. We conclude that, after Nan administration, the increase in Dia specific force results from the relatively greater Dia CSA occupied by hypertrophied muscle fibers, whereas the increased ATPase activity promotes a higher rate of cross-bridge turnover and thus increased Vo. We speculate that Nan in supraphysiological doses have the potential to offset or ameliorate conditions associated with enhanced proteolysis and disordered protein turnover.

Anabolic Agents↗

PubMed1999

Influence of uranium(VI) speciation for the evaluation of in vitro uranium cytotoxicity on LLC-PK1 cells.

Very few data are available concerning the in vitro toxicity of uranium. In this work, we have determined the experimental chemical conditions permitting the observation of uranium(VI) cytotoxicity on LLC-PK1 cells. Uranium solutions made either by dissolving uranyl acetate or nitrate crystals, or by complexing uranium with bicarbonate, phosphate or citrate ligands, were prepared and tested. Experiments demonstrated that only uranium solutions containing citrate and bicarbonate ligands concentrations tenfold higher than the metal, were soluble in the cell culture medium. Cytotoxicity studies of all these uranium compounds were performed on LLC-PK1 cells and compared using LDH release, neutral red uptake and MTT assays. Dose dependent cytotoxicity curves were only obtained with uranium-bicarbonate medium. This study has revealed a toxicity of uranium-bicarbonate complexes for 24 h expositions and for concentrations ranging from 7 x 10(-4)-10(-3) M, under these conditions, the CI50 (cytotoxicity index) was evaluated between 8.5 and 9 x 10(-4) M. In contrast, we noticed a lack of cytotoxicity response for uranium(VI)-citrate complexes. Electron transmission microscopy studies revealed, when LLC-PK1 cells were exposed to the uranium-bicarbonate system, that uranium penetrated and precipitated within the cytoplasmic compartment. Morphological studies conducted with citrate complexes did not show any cellular intake of uranium.

Animals↗

PubMed1999

Effect of weight loss on muscle fiber type, fiber size, capillarity, and succinate dehydrogenase activity in humans.

To examine the effects of weight loss on muscle oxidative properties, nine obese subjects (body mass index, 34 +/- 1.5) had muscle biopsies before and after weight loss and weight stabilization. Weight loss ranged from 13-32 kg and represented 20.8 +/- 2.1% of initial weight. After weight loss, there was no change in the proportions of oxidative (type I and type IIa) fibers and also no change in mean fiber cross-sectional area, whereas there was a small, but significant, decrease in the relative interstitial space (P < 0.05). However, weight loss resulted in a 32 +/- 6% (mean +/- SEM) increase in capillary/fiber ratio and a 54% increase in capillary density (P < 0.05). In addition, there was a 41 +/- 13% increase in succinate dehydrogenase (SDH) activity (P < 0.05). This increase in muscle capillarization and SDH activity was seen in all fiber types, even the relatively lower oxidative type IIx fibers. There was a strong correlation between the change in capillary/fiber ratio and the change in SDH activity (r = 0.82; P < 0.02). Thus, weight loss resulted in no change in muscle fiber type or cross-sectional area, but produced increases in capillary/fiber ratio, capillary density, and SDH activity, suggesting an increase in muscle oxidative capacity.

Adult↗

PubMed1999

Immediate and long-term results of bronchial artery embolization for life-threatening hemoptysis.

STUDY OBJECTIVES: Bronchial artery embolization (BAE) has been established as an effective technique in the emergency treatment of life-threatening hemoptysis, but few data concerning long-term results and complications of the procedure are available. The aim of this study was to analyze retrospectively the experience of BAE in our center with particular emphasis on medium-term and long-term results and on morbidity. SETTING: University hospital. PATIENTS: Fifty-six patients underwent bronchial arteriography from 1986 to 1996 in our center for the management of life-threatening hemoptysis. Of them, BAE was performed in 46 patients. Their mean age was 51 years (range, 19 to 89 years). The most frequent etiologies of hemoptysis were active or inactive tuberculosis, bronchiectasis, or idiopathic hemoptysis. RESULTS: BAE resulted in an immediate cessation of hemoptysis in 43 of the initial 56 patients (77%). During the first month after BAE, four patients who died from causes other than hemoptysis or who were referred to surgery were excluded from follow-up and in the 39 remaining patients, a complete cessation of hemoptysis was observed in 32 patients. A remission was noted in 28 of the 29 patients followed up between 30 and 90 days after BAE. Long-term control of bleeding was achieved in 25 of the initial 56 patients (45%) followed up beyond 3 months after BAE (median follow-up of 13 months; range, 3 to 76 months). Overall, complications of BAE consisted of two episodes of mediastinal hematoma and three episodes of neurologic damage, two of which improved without permanent sequelae. CONCLUSION: We conclude that BAE may result in long-term as well as immediate control of life-threatening hemoptysis but that complications are not unusual.

Adult↗

PubMed1999

[Asbestosis].

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Asbestos↗

PubMed1999

Effect of chlorpyrifos on immune function in rats.

A commercial formulation of chlorpyrifos was evaluated for effects on selected immune system functions in male Fisher 344 rats. Chlorpyrifos in an olive oil vehicle was administered by oral gavage twice weekly for 28 d at a dose of 5.0 mg/kg for each treatment. Body weight and organ/body weight ratios were unaffected by the chlorpyrifos. In contrast, chlorpyrifos impaired T-lymphocyte blastogenesis induced by concanavalin A (P = 0.03) and phytohemagglutinin (P = 0.023), but did not alter B-lymphocyte blastogenesis induced by lipopolysaccharide/dextran (P = 0.082. Humoral immunity (anti-sheep red blood cell), a T-lymphocyte macrophage-dependent response, was also reduced (P = 0.019) when the antibody response was expressed/10(6) spleen cells, although the response expressed/spleen was unaffected (P = 0.32), reflecting increased lymphocyte production. The total splenic lymphocyte counts in the chlorpyrifos-treated rats increased by 91% (P < 0.0001), therefore reducing the antibody response when expressed/10(6) spleen cells. Chlorpyrifos had no effect on macrophage phagocytosis (P = 0.27), but increased the relative percentage expression of CD5+ (P = 0.028) and CD8+ (P = 0.003). The presence of normal antibody and phagocytic responses in association with reduced T-lymphocyte blastogenesis and enhanced expression of specific cell surface antigens indicated that chlorpyrifos induced immune alterations associated with lymphocyte subpopulations.

Animals↗

PubMed1998

Effects of in vitro exposure of beluga whale leukocytes to selected organochlorines.

The effects of in vitro exposure to different organochlorines were evaluated on immune functions of beluga whale peripheral blood leukocytes and splenocytes. The effects of different concentrations of four different congeners of PCBs (138, 153, 180, and 169) as well as two DDT metabolites (p,p'-DDT and p,p'-DDE) were evaluated on phagocytosis and cell proliferation. The effects of dioxins and mixtures of organochlorines were also evaluated on cell proliferation. The different compounds tested had no marked effect on phagocytosis. PCB 138 and p,p'-DDT, but not PCB 153, PCB 180, PCB 169, and p,p'-DDE, reduced significantly the proliferative response of beluga splenocytes cultured either with or without phytohemagglutinin A (PHA). Proliferation of beluga splenocytes was not markedly affected by exposure to 5 ppm of PCB 138, 153, 180, and 169 separately. Exposure to a mixture of congeners 138, 153, and 180 (5 ppm each) significantly reduced splenocytes proliferation, but not the mixture of congeners 138, 153, 180, and 169 (5 ppm each). TCDD did not affect cell proliferation in our study. The reduced proliferation of beluga cells exposed in vitro to mixtures of organochlorines at concentrations in the range of those observed in tissues of St. Lawrence belugas might provide a basis to support the hypothesis that contaminants induce immunosuppression in these animals.

Animals↗

PubMed1998

Structural constraints in the HIV-1 reverse transcriptase-primer/template complex for the initiation of DNA synthesis from primer tRNALys3.

The topography and functional implications of the complex formed in vitro between human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and its primer tRNALys3 were studied in this work. On the basis of previous results showing the high affinity both of the native primer, tRNALys3, as well as that of mismatched short oligonucleotide primers for HIV-1 RT, we synthesized chimeric primers containing tRNALys3 linked to U and T residues of different lengths. We found that the affinity of the oligonucleotide primers for HIV-1 RT is dramatically increased when linked to primer tRNA. Our results also show that in the tRNA.RT complex, before annealing tRNALys3 to the retroviral RNA genome, the 3'-terminal nucleotide of tRNALys3 is positioned at a distance of one nucleotide unit away from the template in the active polymerization site of the enzyme.

Binding Sites↗

PubMed1998

Lack of suppressive effects of mixtures containing low levels of methylmercury (MeHg), polychlorinated dibenzo-p-dioxins (PCDDS), polychlorinated dibenzofurans (PCDFS), and aroclor biphenyls (PCBS) on mixed lymphocyte reaction, phagocytic, and natural killer cell activities of rat leukocytes in vitro.

Rat splenocyte mixed leukocyte reaction (MLR), splenic natural killer (NK) cell activity, and phagocytic activities of splenic, peritoneal, and peripheral blood leukocytes (PBLs) were evaluated in vitro to determine the immunotoxicity of mixtures containing low levels of methylmercury (MeHg), polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and Aroclor polychlorinated biphenyls (PCBs). The mixtures were based on the concentrations of the chemicals in fish flesh. Leukocytes from male Fischer rats were exposed to MeHg (0.1-2 microg/ml), PCDD/PCDF mixtures (1-15 pg/ml) of three PCDDs (2,3,7,8-tetrachlorodibenzo-p-dioxin, 1,2,3,7,8-pentachlorodibenzo-p-dioxin, and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin) and two PCDFs (2,3,7,8-tetrachlorodibenzofuran and 1,2,3,7,8-pentachlorodibenzofuran), three Aroclor PCB (Aroclor 1242, 1254, and 1260) mixtures (0.01-0.5 microg/ml), or combinations of MeHg/PCB/PCDD/PCDF mixtures for 24 or 72 h before immunological assays. Phagocytosis and NK cell cytotoxicity were evaluated with a flow cytometer, and MLR of Fischer rat responder splenocytes cultured with mitomycin C-treated Long-Evans splenocytes by [3H]thymidine uptake. Exposure to MeHg (2 microg/ml) alone or with PCB/ PCDD/PCDF resulted in significant cytolethality in rat splenocytes, peritoneal leukocytes, and PBLs at 24 h exposure. Treatment with Aroclor PCB mixtures, PCDD/PCDF mixtures, 0.1 microg MeHg/ml (noncytolethal), or PCB/PCDD/PCDF mixtures with 0.1 microg MeHg/ml caused no suppression of splenocyte MLR response, splenic NK cell-mediated lysis of Yac-l cells, or phagocytosis of fluorescent beads by splenic, peritoneal, and peripheral blood phagocytic cells. The results indicate that in vitro exposure of rat leukocytes to low levels of MeHg, Aroclor PCB mixtures, PCDD/PCDF mixtures, or MeHg/PCB/PCDD/PCDF mixtures had no suppressive effects on the immune functions assayed, and thus produced no additive immunotoxicity. However, in order to predict the potential risk of these chemical mixtures to the human immune system, in vivo animal studies with blood (tissue) levels compatible with the levels of MeHg, PCBs, and PCDDs/PCDFs in exposed human populations should be evaluated.

Animals↗

PubMed1998

Increased apoptosis, changes in intracellular Ca2+, and functional alterations in lymphocytes and macrophages after in vitro exposure to static magnetic field.

Electromagnetic-related alteration of cellular functions is well documented for extremely low-frequency low-energy pulsing electromagnetic fields (ELF-EMF). In this study we examined the in vitro effects of static magnetic fields (SMF) on the cellular immune parameters of the C57BI/6 murine macrophages, spleen lymphocytes, and thymic cells. The cells were exposed in vitro for 24 h at 37 degrees C, 5% CO2, to 250-1500 G SMF. Exposure to the SMF resulted in the decreased phagocytic uptake of fluorescent latex microspheres, which was accompanied by an increased intracellular Ca2+ level in macrophages. Exposure to SMF decreased mitogenic responses in lymphocytes, as determined by incorporation of [3H]thymidine into the cells. This was associated with the increased Ca2+ influx in concanavalin A-stimulated lymphocytes. Furthermore, exposure to SMF produced markedly increased apoptosis of thymic cells, as determined by flow cytometry. Overall, in vitro exposure of immunocompetent cells to 250-1500 G SMF altered several functional parameters of C57BI/6 murine macrophages, thymocytes, and spleen lymphocytes.

Animals↗

PubMed1998

Effect of pentachlorophenol on immune function.

The organochlorine compound, pentachlorophenol, was evaluated for effects on immune system function in male Fisher 344 rats. Pentachlorophenol was prepared in an olive oil vehicle and was administered by oral gavage twice weekly for 28 days at a dose of 2.0 mg/kg per treatment. Exposure to pentachlorophenol increased body weight gains (P=0.024) during the treatment period. Liver (P=0.034) and kidney (P=0.012) body weight ratios were also increased. Pentachlorophenol exposure enhanced T-lymphocyte blastogenesis induced by concanavalin A (Con A)(P=0.0001) and phytohemagglutinin (PHA)(P=0.048) evaluated using stimulation indices. Corresponding B-lymphocyte blastogenesis induced by lipopolysaccharide/dextran (LPS/dex)(P=0.0034) was also enhanced by pentachlorophenol exposure. Pentachlorophenol suppressed the antibody response against sheep red blood cells (SRBCs) by 39% when the response was expressed per viable spleen cell (P=0.006). This suppression was not evident when the response was expressed per spleen (P=0.22), suggesting that a compensatory mechanism or extramedullary splenic hemopoiesis was occurring minimizing the overall impact on humoral immunity. The enhanced B- and T-lymphocyte blastogenesis may also reflect compensatory or hemopoietic activity. Pentachlorophenol exposure had no effect on peritoneal macrophage phagocytosis (P=0.31) or lymphocyte cell surface antigen expression. The observed alterations in lymphocyte blastogenesis and humoral immunity subsequent to pentachlorophenol exposure do not appear to be associated with phagocytosis or lymphocyte cell surface antigen expression.

Animals↗

PubMed1998

p66/p51 and p51/p51 recombinant forms of reverse transcriptase from human immunodeficiency virus type 1--interactions with primer tRNA(Lys3), initiation of cDNA synthesis, and effect of inhibitors.

Human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) initiates reverse transcription from tRNA(Lys3). HIV-1 RT is a heterodimer consisting of two polypeptides, p66 and p51. In this work, the possible role of each subunit of RT in the interaction with its natural primer tRNA(Lys3) was studied. Two recombinant forms of HIV-1 RT, heterodimer p66/p51 and homodimer p51/p51, were used. Previously we have expressed and purified recombinant RT p51/p51 which possesses DNA polymerase activity [El Dirani-Diab, R., Andreola, M. L., Nevinsky, G., Tharaud, D., Barr, P. J., Litvak, S. & Tarrago-Litvak, L. (1992) FEBS Lett. 301, 23-28]. Here we show that HIV-1 RT p51/p51 displays certain properties very similar to the p66/p51 recombinant enzyme. The homodimer was able to anneal tRNA(Lys3) to the primer-binding site of the HIV-1 RNA template leading to a functional complex capable of synthesizing cDNA. Further, the p51/p51 enzyme behaved like RT p66/p51 concerning the strong inhibition produced by a non-nucleoside RT inhibitor. These data show that for RT p51/p51, one of the subunits of the homodimer adopts a conformation similar to the catalytic subunit (p66) present in the heterodimeric form. Part of this work was devoted to the study of the complex between the recombinant forms of HIV-1 RT and its primer tRNA. Each enzymatic form was cross-linked to tRNA(Lys3) in the presence of a platinum derivative, giving different ribonucleoprotein complexes of molecular masses higher than 100 kDa, suggesting that primer tRNA may interact with both subunits in the heterodimeric enzyme. After RNase A treatment of the complex RT p66/p51 x tRNA, the label was mainly found to migrate with the p66 subunit, although some cross-linking was also found associated to the p51 subunit. These results show that the p66 and p51 subunits of RT interact with tRNA(Lys3). Moreover, cross-linking of tRNA(Lys3) with HIV-1 RT p66/p51 in the presence of a DNA template containing the primer-binding-site sequence yielded an enzymatically active complex.

Base Sequence↗

PubMed1998

Phagocytic and metabolic activities of macrophages from mummichog naturally exposed to pulp mill effluents in the Miramichi River.

Chemicals present in bleached kraft pulp mill effluents (BKMES) can modulate the immune response of fish. This work was conducted to determine if mummichogs living downstream from a bleached kraft pulp mill (BKM) had an impaired immune response. Head kidney phagocytes from males and females were tested for their phagocytic and metabolic activities. Mummichogs were captured 4 km (S2) and 39 km (S1) downstream from a BKM in the Miramichi estuary (New Brunswick, Canada) and at two sites located upstream (S3) and 20 km downstream (S4) in a reference estuary, the Bouctouche. Both male and female mummichogs captured at S2 in the Miramichi estuary had a lower phagocytic activity, whereas only females from the same site had a decreased oxidative burst response, indicating a difference between sexes in the susceptibility to pollutants present in the Miramichi. Therefore, the results indicate that mummichogs exposed to BKMES have an impaired immune response and that females are more sensitive than males to the chemicals present in BKMES.

Animals↗