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Biomedical subjects

M Fournier

Publications and source records attributed to M Fournier.

At least 37 records · Page 2Linked to original sources

Contrasting changes of sensitivity by lymphocytes and neutrophils to mercury in developing grey seals.

Mercury is the principal metal contaminant in the St Lawrence Estuary. It impairs humoral, cellular and non-specific immune responses in many species. Since the immune system of juvenile seals is immature, it should react differently to the effects of contamination compared to that of mature animals. Phagocytosis and lymphoblastic transformation responses have been evaluated in the peripheral blood leukocytes of eight juvenile grey seals at different intervals of time over 11 weeks. Dose-response curves of 10(-9)-10(-3)M of methylmercury chloride have also been performed in vitro for evaluation of these two immune functions. The immune response of grey seals differs during their development. The phagocytosis response increased from the 2nd to 5th week post-weaning and then reached a plateau. As for the lymphoblastic transformation response, it was stable from the 2nd to the 3rd week post-weaning, increased significantly at week 4 post-weaning and then reached a plateau. These data suggest that these animals should be particularly vulnerable to infections, diseases and parasites before the 5th week post-weaning. Furthermore, mercury decreased the immune response, and age of seals had an effect on cell sensitivity to mercury. Concentrations of 10(-5)M of methylmercury chloride decreased phagocytosis and lymphoblastic transformation responses. Phagocytosis is more affected by MeHgCl contamination before this immune function reaches complete development which occurs at week 5 post-weaning. On the other hand, lymphoblastic transformation is more affected by this contaminant after its complete development which occurs at week 4 post-weaning.

Age Factors↗

Effects of exposure of Mya arenaria and Mactromeris polynyma to contaminated marine sediments on phagocytic activity of hemocytes.

Two species of bivalves, Mya arenaria and Mactromeris polynima, were exposed to contaminated marine sediments from Baie des Anglais, Quebec, for a period of 10 and 12 weeks, respectively, in order to determine if there was an effect on the phagocytic activity of hemocytes from each species. These sediments contain elevated levels of both PAHs and PCBs. Uncontaminated beach sand was used as control sediments. After a period of 4 weeks, each species of bivalves were sampled and hemocyte phagocytic activity was monitored by flow cytometry. While phagocytosis by hemocytes from M. polytiyma was significantly suppressed, those from M. arenaria were not different from beach sand-exposed controls. At the end of the exposure period, the phagocytic activity of hemocytes from both species was suppressed. Physiological parameters such as mantle proteins or malondialdehyde levels, total protein and total glycogen levels in the digestive gland were not affected by exposure to contaminated sediments. Moreover, the suppression of phagocytosis was well correlated with the transfer of contaminants from the sediments to the bivalves and their subsequent bioaccumulation, as demonstrated by the PCB body burden. These results support the use of bivalves as good sentinel species to survey sediment contamination and the usefulness of hemocyte phagocytic activity as a sensitive biomarker of exposure to organic contaminants.

Animals↗

Location of protons in anhydrous Keggin heteropolyacids H(3)PMo(12)O(40) and H(3)PW(12)O(40) by (1)H[(31)P]/(31)P[(1)H] REDOR NMR and DFT quantum chemical calculations.

HeteroPolyAcids (HPA's) are a class of solid acids that have broad applications in many fields of science and technology, including catalysis and chemical engineering. The proton locations within the thermally stable and commonly known Keggin unit, which is the primary structure building unit/block, has remained undetermined in anhydrous HPAs, despite numerous theoretical and experimental efforts. However, Rotational Echo DOuble Resonance (REDOR) NMR and Density Functional Theory (DFT) quantum chemical calculations offer a new opportunity to determine the exact locations of protons within the Keggin unit. The crucial experimental evidence is provided for the basic and very extensively studied acidic form of H(8-n)X(n+)M(12)O(40), X = Si, P and M = Mo, W, belonging to the Keggin structure. While showing that the acidic protons are located in the bridging oxygen positions (R(P-H) = 520 +/- 20 pm) in H(3)PMo(12)O(40) and in the terminal oxygen positions (R(P-H) = 570 +/- 20 pm) in H(3)PW(12)O(40), REDOR measurements also provide for the first time the structural basis to consistently rank the acid strength for the important class of Keggin solid catalysts.

Journal Article↗

Phagocytic response of terrestrial and aquatic invertebrates following in vitro exposure to trace elements.

The potential of the trace elements Ag, As, Cd, Hg, Mo, Ni, Pb, Se, and Zn to inhibit the phagocytosis response of extruded coelomocytes of different worm species was tested. We used flow cytometry to evaluate the sensitivity of cell viability and phagocytic potential for Eisenia fetida, Lumbricus terrestris, Aporrectodea turgida, and Tubifex tubifex. Extruded cells were exposed 18 h in vitro to concentrations ranging from 10(-9) to 10(-4) M. Mercury was the most potent immunotoxic element, with 50% inhibition of phagocytosis occurring at concentrations between 10(-7) and 10(-6) M. Cadmium, Cu, Ni, and Zn also showed significant immunosuppressive effects with concentrations inducing 50% inhibition ranging from 10(-5) to 10(-4) M. Species-specific sensitivity varied by about a factor of 10, with no species showing a systematically higher or lower in vitro sensitivity across the range of trace elements tested.

Animals↗

Phagocytic activity of marine and freshwater bivalves: in vitro exposure of hemocytes to metals (Ag, Cd, Hg and Zn).

We measured non-specific immune function of various bivalves from marine (Cyrtodaria siliqua, Mactromeris polynyma, Mesosdesma arctatum, Mya arenaria, Mya truncata, Mytilus edulis, Serripes groenlandicus, Siliqua costata) and freshwater environments (Dreissena polymorpha and Elliptio complanata). We used flow cytometry to quantify the phagocytosis of fluorescent microspheres by hemocytes exposed in vitro to increasing levels of various metal compounds (AgNO(3), CdCl(2), CH(3)HgCl, HgCl(2) and ZnCl(2)). In some species, low doses of mercury (organic and inorganic) and Zn suggest a hormesis-like stimulation of phagocytic activity. At higher levels of exposure, all metals tested induced a significant dose-related inhibition of hemocyte phagocytosis. The species-specific sensitivity of the assay was determined by comparing the in vitro exposure using the metal concentration inducing a 50% suppression (EC(50)) of the phagocytic activity. Different species expressed different levels of sensitivity. Our results show the variability of the toxic response of different species within a group of similar organisms. It also highlights the need to consider species-species differences in ecotoxicological risk assessment.

Animals↗

HIV-1 integrase and RNase H activities as therapeutic targets.

The retroviruses are a large, diverse family of enveloped RNA viruses defined by their structure, composition and replicative properties. The hallmark of the family is its replicative strategy, essential steps of which include reverse transcription of the viral RNA and the subsequent integration of this DNA into the genome of the cell. These steps are performed by two viral-encoded enzymes, reverse transcriptase (RT), which possesses DNA polymerase and ribonuclease H (RNase H) activities, and integrase (IN). These enzymes are excellent targets for retroviral therapy since they are essential for viral replication. Numerous substances capable of inhibiting the DNA polymerase activity of HIV-1 RT are available, while few specific inhibitors of RNase H activity have been described. IN is absolutely necessary for stable and productive infection of cells. Some IN inhibitors have been recently reported and are available demonstrating the potential of IN as an antiviral target. This paper is an overview of the inhibitors of RNase H and IN and describes the most promising inhibitors.

Anti-HIV Agents↗

Severe axonal polyneuropathy after a FK506 overdosage in a lung transplant recipient.

FK506-induced polyneuropathies are rarely encountered. We report a case of axonal sensorimotor polyneuropathy in a lung transplant recipient that occurred during a FK506 overdosage. Onset was acute in the form of severe areflexic tetraparesis and resolution was observed after reduction of dosage. Because of increasing use of FK506 in solid organ transplantation, caution should be paid with FK506 dosage monitoring in cases of peripheral nervous system symptoms.

Dose-Response Relationship, Drug↗

[Chronic obstructive pulmonary disease and bronchial colonization/infection].

BACTERIAL FLORA IN THE SUBGLOTTAL AIRWAYS: In healthy non-smoking subjects, the subglottal airways are sterile. Inversely, bacteria are often isolated from the sublottal airways in patients with obstructive or non-obstructive chronic bronchitis, both during and between acute exacerbations. The significance of this bacterial colonization/infection, its natural history, and its impact on the course of chronic lung disease is poorly understood. BETWEEN EXACERBATIONS: 30 to 40% of all patients with chronic obstructive pulmonary disease in a stable situation without recent antibiotic therapy harbor potential pathogens in their intra-thoracic airways. The prevalence of Gram-negative bacilli increases in the more severe forms. This estimation is possibly biased due to the involuntary inclusion of patients with bronchial dilatation, since bronchectasia involves a high prevalence of bronchial colonization/infection. DURING EXACERBATIONS: The prevalence of bronchial colonization/infection by potential pathogens is to the order of 30-50%, irrespective of the bacteria isolated from endobronchial samples made during or between exacerbations. About half of the exacerbations would not be related to bacterial infection, but to viral infection. The other identified causes of exacerbations are: occupational or accidental exposure, co-morbidity (chronic sinus infection, chronic pharyngeal discharge, left ventricular failure, non-specific bronchial hyperreactivity). INFLAMMATION: Inflammation of the bronchial mucosa is a constant feature of chronic obstructive pulmonary disease. The biological and histocytological features are distinctive from those observed in asthma. Polynuclear activation appears to play an important role in polynuclear infiltration of the mucosa, amplified during bacterial colonization.

Aged↗

Influence of preservation solution on early graft failure in clinical lung transplantation.

The aim of this study was to assess the influence of preservation solution type and extra- or intracellular composition on the occurrence of early graft dysfunction after clinical lung transplantation. For 170 patients who underwent a single (n = 124) or bilateral (n = 46) lung transplantation in two centers in Paris between 1988 and 1999, the preservation technique applied to the donor lung was single-flush perfusion of the pulmonary artery with one of several solutions of intracellular (Euro-Collins, n = 61; University of Wisconsin, n = 24) or extracellular composition (Cambridge, n = 64; Celsior, n = 21). The early postoperative outcome of these patients was reviewed. Reimplantation edema occurred in 48% of all patients, and the overall 1-mo survival rate was 84%. No significant difference in the incidence of edema, duration of mechanical ventilation, and 1-mo survival rate was observed between the four groups or between intra- and extracellular groups. After adjustment for graft ischemic time by means of multivariate analysis, the use of extracellular preservation fluid was associated with a lower incidence of reimplantation edema without effect on 1-mo mortality. Graft ischemic time was associated with both edema occurrence and 1-mo survival rate (p = 0.02 and p = 0.01, respectively). We conclude that extracellular-type solutions are associated with better lung preservation than intracellular-type solutions in clinical transplantation.

Female↗

Preventive effect of inhaled nitric oxide and pentoxifylline on ischemia/reperfusion injury after lung transplantation.

BACKGROUND: The preventive effect of inhaled nitric oxide (NO) and pentoxifylline (PTX) administered during reperfusion has been demonstrated on experimental models of lung ischemia/reperfusion (I/R) injury but this strategy is not validated in clinical lung transplantation. The aim of this study was to assess retrospectively the protective effect of inhaled NO and PTX after lung transplantation. METHODS: Twenty-three consecutive patients who received inhaled NO (10 ppm) and PTX (NO-PTX group) at the time of reperfusion were compared retrospectively with (1) 23 consecutive patients transplanted just before the use of NO-PTX (control group 23); (2) 95 patients representing all the patients of the series who did not receive NO-PTX (control group 95), with respect to I/R injury related complications. In particular, the incidence of pulmonary reimplantation edema and early hemodynamic failure, the PaO2/FIO2 ratio as well as the duration of mechanical ventilation and the 2-month mortality rates were compared. RESULTS: Reimplantation edema was observed in 6/23 patients (26%) in the NO-PTX group vs. 13/23 patients (56%) in the control group 23 (P=0.035) and 48/95 patients (50%) in the control group 95 (P=0.035). The worst PaO2/FIO2 ratio during the first three postoperative days was 240-102 mmHg in the NO-PTX group vs. 162+/-88 mmHg (P=0.01) and 176+/-107 mmHg (P=0.01) in the control group 23 and the control group 95, respectively. The duration of mechanical ventilation was 2.1+/-2.4 days in the NO-PTX group vs. 7+/-9 days in the control group 23 (P=0.02) and 6+/-7 days in the control group 95 (P=0.01). The 2-month mortality rate was 4.3% in the NO-PTX group vs. 26% (P=0.04) and 21% (P=0.07) in the control group 23 and the control group 95, respectively. CONCLUSIONS: The marked decrease in the incidence of allograft dysfunction compared with two historical control groups suggests that PTX and inhaled NO given before and throughout reperfusion are protective against I/R injury in the setting of clinical transplantation.

Administration, Inhalation↗

Effects of in vivo exposure of Mya arenaria to organic and inorganic mercury on phagocytic activity of hemocytes.

Marine bivalves are aquatic invertebrate organisms which can be used as bioindicators in environmental monitoring. In vivo effects of mercuric chloride (HgCl(2)) and methylmercury (CH(3)HgCl) on phagocytic function of Mya arenaria hemocytes were evaluated in this study. Clams were exposed to single metal in water for up to 28 days at concentrations ranging from 10(-9) to 10(-5) M. Phagocytic activity of hemocytes was determined by uptake of fluorescent microspheres and flow cytometry. All clams exposed to 10(-5) M HgCl(2) died by day 7 of exposure. The viability of hemocytes was decreased only in clams exposed to 10(-6) M HgCl(2) for 28 days. A significant decrease in phagocytic activity of hemocytes was observed in clams exposed to 10(-6) M of HgCl(2) for 28 days. A similar pattern was observed with CH(3)HgCl, but at an earlier time. Chemical analysis performed on the tissues of the animals clearly show a greater uptake of the organic form of mercury by clams. Furthermore, a clear correlation was established between body burden of mercury and effects on phagocytic activity of hemocytes. Overall, the results of this study show that both speciations of mercury inhibited phagocytic function of Mya arenaria hemocytes following in vivo exposures.

Animals↗

Phagocytic response of macrophages from the pronephros of American plaice (Hipoglossoides platessoides) exposed to contaminated sediments from Baie des Anglais, Quebec.

Sediments of Baie des Anglais on the St. Lawrence estuary have a history of environmental contamination, but little information exists regarding their toxicity. The purpose of the present study was to determine the effects of contaminated Baie des Anglais sediments on American plaice (Hippoglossoides platessoides) immune function. Three sites in Baie des Anglais were selected which vary in proximity to local industries and in their sediment contaminant load. Sites 1 and 2 (within the bay) are the closest to shore and most heavily contaminated while sediments at Site 3, which is outside the bay, are the least contaminated. In the first experiment, American plaice were placed in cages at each site for three weeks and immune function was assessed by measuring the phagocytic activity of pronephric macrophages. At the time of sampling, plaice displayed pronephros cell immune response disturbances indicating that Site 1 and 2 were most toxic and Site 3 the least toxic. The results obtained for phagocytosis revealed that contaminants present in the sediments are bioavailable to fish, which came in contact with them and significantly affected their immune system. In the second experiment, sediments from the most toxic site, Site 1, were collected for a laboratory controlled experiment in which plaice were exposed for up to 3 months to these contaminated marine sediments, while the control group was exposed to relatively uncontaminated beach sand. At the end of the exposure period, plaice were transferred from contaminated sediment to beach sand and sampled one month later in order to determine if immune function had returned to control levels. The total number of macrophages decreased following three months of exposure, while the active macrophages had already decreased after the first month of exposure. Following the rehabilitation period a significant trend toward normal response was noted. Sediments from Baie des Anglais contain primarily less highly chlorinated PCBs and lower concentrations of the intermediate and highly chlorinated PCBs. The total concentration of PCBs (sum of 20 congeners) in the contaminated sediments was 1500 ng/g while in the beach sand, the levels were 13.6 ng/g dry weight. Only the low chlorinated PCB congeners were efficiently transferred from the sediments to the plaice liver. Together, these results suggest that the effect of chemical exposure on the phagocytosis of plaice macrophages may be reversible if the fish are returned to a non-contaminated habitat.

Adaptation, Physiological↗

A prospective survey of nutritional support practices in intensive care unit patients: what is prescribed? What is delivered?

OBJECTIVES: To assess the amount of nutrients delivered, prescribed, and required for critically ill patients and to identify the reasons for discrepancies between prescriptions and requirements and between prescriptions and actual delivery of nutrition. DESIGN: Prospective cohort study. SETTING: Twelve-bed medical intensive care unit in a university-affiliated general hospital. PATIENTS: Fifty-one consecutive patients, receiving nutritional support either enterally or intravenously for > or = 2 days. We followed patients for the first 14 days of nutritional delivery. MEASUREMENTS AND MAIN RESULTS: The amount of calories prescribed and the amount actually delivered were recorded daily and compared with the theoretical energy requirements. A combined regimen of enteral and parenteral nutrition was administered on 58% of the 484 nutrition days analyzed, and 63.5% of total caloric intake was delivered enterally. Seventy-eight percent of the mean caloric amount required was prescribed, and 71% was effectively delivered. The amount of calories actually delivered compared with the amount prescribed was significantly lower in enteral than in parenteral administration (86.8% vs. 112.4%, p < .001). Discrepancies between prescription and delivery of enterally administered nutrients were attributable to interruptions caused by digestive intolerance (27.7%, mean daily wasted volume 641 mL), airway management (30.8%, wasted volume 745 mL), and diagnostic procedures (26.6%, wasted volume 567 mL). Factors significantly associated with a low prescription rate of nutritional support were the administration of vasoactive drugs, central venous catheterization, and the need for extrarenal replacement. CONCLUSIONS: An inadequate delivery of enteral nutrition and a low rate of nutrition prescription resulted in low caloric intake in our intensive care unit patients. A large volume of enterally administered nutrients was wasted because of inadequate timing in stopping and restarting enteral feeding. The inverse correlation between the prescription rate of nutrition and the intensity of care required suggests that physicians need to pay more attention to providing appropriate nutritional support for the most severely ill patients.

Adult↗

Functional interactions of human immunodeficiency virus type 1 integrase with human and yeast HSP60.

Integration of human immunodeficiency virus type 1 (HIV-1) proviral DNA in the nuclear genome is catalyzed by the retroviral integrase (IN). In addition to IN, viral and cellular proteins associated in the high-molecular-weight preintegration complex have been suggested to be involved in this process. In an attempt to define host factors interacting with IN, we used an in vitro system to identify cellular proteins in interaction with HIV-1 IN. The yeast Saccharomyces cerevisiae was chosen since (i) its complete sequence has been established and the primary structure of all the putative proteins from this eucaryote has been deduced, (ii) there is a significant degree of homology between human and yeast proteins, and (iii) we have previously shown that the expression of HIV-1 IN in yeast induces a lethal phenotype. Strong evidences suggest that this lethality is linked to IN activity in infected human cells where integration requires the cleavage of genomic DNA. Using IN-affinity chromatography we identified four yeast proteins interacting with HIV-1 IN, including the yeast chaperonin yHSP60, which is the counterpart of human hHSP60. Yeast lethality induced by HIV-1 IN was abolished when a mutated HSP60 was coexpressed, therefore suggesting that both proteins interact in vivo. Besides interacting with HIV-1 IN, the hHSP60 was able to stimulate the in vitro processing and joining activities of IN and protected this enzyme from thermal denaturation. In addition, the functional human HSP60-HSP10 complex in the presence of ATP was able to recognize the HIV-1 IN as a substrate.

Amino Acid Sequence↗

Prognosis of patients with advanced idiopathic pulmonary fibrosis requiring mechanical ventilation for acute respiratory failure.

STUDY OBJECTIVE: To evaluate the beneficial effect of mechanical ventilation (MV) in patients with idiopathic pulmonary fibrosis (IPF) who develop acute respiratory failure (ARF), with special emphasis on prognosis. DESIGN: Retrospective study. SETTING: Ten-bed respiratory ICU that is a part of a respiratory department actively involved in lung transplantation (LTx). PATIENTS: From 1991 to 1999, 23 patients (mean age, 52.9 years; range, 21 to 82 years) with IPF required MV for ARF. At admission to the ICU, 16 patients were potential candidates for LTx, with 5 patients already on the waiting list. MEASUREMENTS AND RESULTS: Survival and gas exchange under MV were assessed. The precipitating cause of ARF was also analyzed. With the exception of 1 patient who successfully received a single-lung transplant 6 h after initiation of MV, all the remaining 22 patients died while receiving MV (median survival, 3 days; range, 1 h to 60 days). The duration of MV correlated positively with baseline vital capacity (percent predicted) (R = 0.54; p = 0.01) and baseline total lung capacity (percent predicted) (R = 0.71; p < 0.001), and correlated negatively with baseline PaCO(2) (R = - 0.47; p = 0.03) and the duration of evolution of IPF (R = -0.50; p = 0.01). Duration of MV did not correlate with the duration of immunosuppressive therapy (R = - 0.24; p = 0.27) or duration of oxygen therapy (R = - 0.32; p = 0.14) prior to admission. The precipitating cause of ARF was most often not identified. CONCLUSIONS: Our data support the general belief that MV does not benefit IPF patients presenting with ARF. Initiation of MV in IPF patients is thus questionable and should, in our opinion, be restricted to patients in whom LTx can be performed within a few days after initiation of MV.

Acute Disease↗