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Biomedical subjects

M Bernier

Publications and source records attributed to M Bernier.

At least 73 records · Page 4Linked to original sources
PubMed1994

Glucagon-like peptide-1(7-36) amide (GLP-1) enhances insulin-stimulated glucose metabolism in 3T3-L1 adipocytes: one of several potential extrapancreatic sites of GLP-1 action.

We investigated the effects of glucagon-like peptide-1(7-36) amide, GLP-1, on glucose metabolism in 3T3-L1 adipocytes and we used polymerase chain reaction to search for the presence of GLP-1 receptors in various rat tissues. GLP-1 at 1 nM significantly increased insulin-mediated 2-deoxyglucose uptake by 40% while having no effect on basal uptake. In conjunction with the elevated uptake, the insulin-dependent incorporation of 14C-glucose into fatty acids was also increased. Moreover, neither glycogen synthesis nor insulin binding to its receptor were affected by GLP-1. In addition to the presence of GLP-1 receptor in pancreas we found messenger RNA for this receptor in brain, kidney, heart, fat, skeletal muscle, liver, and intestine. This study indicates that GLP-1, in addition to its well known effect of stimulating insulin secretion, may improve insulin responsiveness by promoting fatty acid synthesis in adipose cells and possibly modulating insulin signaling in other insulin sensitive tissues.

3T3 Cells↗
PubMed1993

Mercury inhibition at the donor side of photosystem II is reversed by chloride.

Mercury is an environmental contaminant that strongly inhibits photosynthetic electron transport, photosystem II being the most sensitive target. We investigated in greater detail the effect of mercury using photosystem II submembrane fractions of higher plants. Oxygen evolution was strongly inhibited and variable chlorophyll fluorescence was severely quenched by mercury. Chloride, an inorganic cofactor known to be essential for the optimal function of photosystem II, significantly reversed the inhibitory effect of mercury. However, calcium, another essential cofactor, showed no reversal capacity. It is concluded that on the donor side of PSII, mercury exerts its action by perturbing chloride binding and/or function. Considering the exceptional affinity of mercury for sulfhydryl groups of proteins, the results suggest the implication of cystein residue(s) in maintaining structural and functional integrity of photosystem II.

Chlorides↗
PubMed1993

Regulation of the C/EBP-related gene gadd153 by glucose deprivation.

gadd153 encodes a CCAAT/enhancer-binding protein (C/EBP)-related protein that lacks a functional DNA-binding domain. Since the gadd153 protein is capable of heterodimerizing with other C/EBPs, gadd153 may function as a negative regulator of these transcription factors. Here we examined the role of glucose in regulating gadd153 expression. We found that glucose deprivation markedly induces gadd153 mRNA levels in both HeLa and 3T3-L1 cells and that addition of D-(+)-glucose resulted in a rapid decrease of gadd153 mRNA. Similar induction and reversal of gadd153 expression were observed at the protein level. Because C/EBP alpha appears to play an important role in regulating genes involved in adipogenesis and energy metabolism, we examined gadd153 expression during the differentiation of 3T3-L1 preadipocytes and as a function of glucose utilization in differentiated adipocytes. Using a standard differentiation protocol that consisted of hormonal stimulation for 2 days followed by medium changes every 2 days thereafter, we observed that both C/EBP alpha and gadd153 mRNAs were elevated. However, C/EBP alpha induction occurred on day 3, while gadd153 expression was not seen until day 4, when the cells were fully differentiated. Frequent addition of fresh medium to the cells during the differentiation process, as well as supplementation of medium with glucose, reduced gadd153 expression without preventing C/EBP alpha expression or interfering with cellular differentiation. Thus, gadd153 expression is not essential for the process of adipocyte differentiation but is significantly influenced by the availability of glucose to the cell.

3T3 Cells↗
PubMed1993

Characteristics of pro-T ALL subgroups: comparison with late T-ALL. The Groupe d'Etude Immunologique des Leucémies.

A group of 30 acute lymphoblastic leukemias (ALL) with the early pro-T phenotype CD7+/cCD3+/CD1-/CD3-/CD4-/CD8-were identified among 103 newly diagnosed ALL with T-lineage markers (T-ALL). Pro T-ALL was more often observed in adults, and showed a lower incidence of hyperleukocytosis than more mature T-ALL. Mediastinal masses and polar acid phosphatase positivity in blast cells were however observed with the same frequency in pro T-ALL and late T-ALL, and rearrangements of both T-cell receptor (TCR) beta and gamma genes were observed in half the pro T-ALL cases tested. The expression of CD34, DR, and myeloid (My) markers was significantly more frequent in pro T-ALL than in late T-ALL, and these three features were strongly linked. TCR gene rearrangements were two to three times more frequent in CD34- and My-pro T-ALL. However, both CD34+ and My+ pro T-ALL showed an incidence of mediastinal masses and polar acid phosphatase positivity similar to this observed in CD34- and My- cases. This supports the assumption that both types of ALL indeed are engaged in the T-lineage, and confirms intracytoplasmic cCD3 as the earliest marker for this lineage. Moreover, CD34 appears to persist up to an early stage of T-cell maturation, where the cells retain myeloid potentiality. Loss of CD34 correlates with TCR-beta gene rearrangement and definitive commitment to the T lineage. Event-free survival analysis suggested a poorer outcome for pro T-ALL in adult patients.

Adolescent↗
PubMed1992

Antibiotic susceptibility profiles of 941 gram-negative bacteria isolated from septicemic patients throughout Canada. The Canadian Study Group.

The choice of antimicrobial therapy for the treatment of bacteremia is often empirical and based on the knowledge of antibiotic susceptibility profiles of the most common bacteria causing such infections. It therefore is crucial to survey the susceptibility of bacteria causing sepsis. This study examines the susceptibility profiles of 941 gram-negative bacteria, isolated from septic patients in 10 Canadian hospitals, to 28 antimicrobial agents. Among the isolates, 30 different species were represented; Escherichia coli dominated, representing 52.5% of isolates. More than 50% of all bacteria were resistant to ampicillin. Only 67% of the E. coli isolates were susceptible to ampicillin, while 30% of all strains were resistant to ticarcillin. Of the cephalosporins, ceftazidime and cefoperazone/sulbactam were the agents to which isolates were the most susceptible (90%). Only 51% of the E. coli strains were susceptible to cephalothin, while 91% were still susceptible to cefazolin. A total of 93% and 98% of the strains were susceptible to aztreonam and imipenem, respectively. Aminoglycosides were highly active against most isolates, in general in the following order: netilmicin greater than tobramycin greater than gentamicin greater than amikacin. Tobramycin was the most active against Pseudomonas aeruginosa. Nearly all isolates were susceptible to the quinolones. Tolerance (MBC/MIC ratio, greater than or equal to 32) was rarely observed. This survey of the susceptibility of gram-negative bacteria causing sepsis provides valuable information for implementing the chemotherapy for gram-negative septicemia and demonstrates that several older and newer agents, alone or in combination, can be used as adequate initial therapy for gram-negative sepsis in Canada.

Anti-Bacterial Agents↗
PubMed1992

Mental health, constraints, and organization of work as interactive variables. A study of word processing secretaries.

The effect of a work constraint is specific to the type of work organization. This article deals with the effects of different types of work organization on the mental health of secretaries. The advantage of choosing secretarial work as a research subject lies in the fact that we can identify three distinct types of work organization: (1) a secretary working directly for someone (the "paired" secretary-boss), (2) the "pool," geared toward keyboard input with no specific pairing of secretaries and authors, and (3) the departmental "team," a hybrid of the two preceding types, characterized by the presence of several secretaries, each one assigned to several authors. A study was conducted on the health problems reported by secretaries in the Québec civil service. Data available from a Santé Québec study, carried out at the same time, allowed us to constitute a general population reference group of secretaries and other working women. The findings indicate that secretaries in the general population are no more at risk than are other similar working women, but that secretaries in the provincial civil service are at risk. Regression analysis shows that the same traditional constraints do not affect secretaries in the same way regardless of whether they are members of pair, pool, or team organizations. This suggests that the context of work organization is an interactive or a "specifying variable" of the effect of work constraints on the secretaries' mental health.

Adaptation, Psychological↗
PubMed1992

[Bone marrow autograft in malignant hemopathies. The Team of the Sterile Unit].

Only in the last decade have autologous grafts begun to be studied extensively. Their most attractive feature is the avoidance of GVHD. However, GVHD has antitumoral effect on residual leukemic cells called "graft versus leukemia" effect and better understanding of this phenomenon explains the higher relapse rate after autologous bone marrow transplantation. New approaches such as cyclosporin--induced GVHD and IL-2 administration after autograft bring great expectations in this field. Colony stimulating factors and harvesting of peripheral stem cells help to reduce the duration of neutropenia. Finally, various techniques for marrow purging and hematopoietic cell isolation should make it possible to eliminate minimal residual disease. Recent results of autologous bone marrow transplantation in various malignancies are discussed.

Bone Marrow Transplantation↗
PubMed1991

Pharmacological studies of arrhythmias induced by rose bengal photoactivation.

Singlet oxygen and superoxide production by rose bengal photoactivation leads to rapid electrophysiological changes and arrhythmias. To investigate which intermediate is causative and to probe possible mechanisms, hearts (n = at least 6/group) were perfused aerobically for 10 min without rose bengal followed by 5 min with rose bengal before illumination for 20 min. In controls, all or most hearts exhibited ventricular premature beats, ventricular tachycardia, and complete atrioventricular block. Most antioxidants tested had no protective effect; histidine, however, significantly delayed the onset of electrocardiographic (ECG) changes. In further studies, two antiarrhythmic agents (quinidine and verapamil) had no little protective effect, whereas R56865 significantly delayed the onset of ECG changes and reduced the incidence of arrhythmias. However, spectrophotometric and laser pulse radiolysis studies showed that this apparent protective effect might have resulted from an interaction between R56865 and the rose bengal molecule, leading to a reduction in singlet oxygen production. In conclusion, the electrophysiological changes induced by rose bengal photoactivation are likely to be due to singlet oxygen; antiarrhythmic drugs appear to be unable to protect against the injury unless there is some interaction with the photoactivation process.

Animals↗
PubMed1991

Blood coagulation abnormalities during adoptive immunotherapy with interleukin-2 (r-Met Hu IL-2 [ala 125]).

Immunotherapy with Interleukin-2 (IL-2) and LAK cells has shown antitumoral activity in metastatic cancer patients. So far, thrombocytopenia is the major side effect reported in hemostasis. We have studied coagulation parameters in 6 patients treated with r-Met Hu IL-2 [ala-125]. In each case, we have observed a significant fall in prothrombin time, fibrinogen, protein C, anti-thrombin III, plasminogen, alpha 2-antiplasmin and all of the clotting factors except factor VIII. There was a significant increase in the activated thromboplastin time. No significant modifications of the D-Dimer test, fibrin-fibrinogen degradation products (FDP) and thrombin time were observed. Our data suggest that r-Met Hu IL-2 [ala-125] could interfere with the hepatic synthesis of the clotting factors and their inhibitors.

Blood Coagulation↗
PubMed1990

Singlet oxygen and myocardial injury: ultrastructural, cytochemical and electrocardiographic consequences of photoactivation of rose bengal.

Photoactivation of rose bengal leads to the generation of reactive oxygen intermediates (predominantly singlet oxygen with some superoxide anion) which are potentially injurious to biological systems. Isolated rat hearts were perfused aerobically at 37 degrees C with bicarbonate buffer for 10 min without rose bengal and for 10 min with rose bengal (500 nM). During the last 5 min of perfusion with rose bengal, hearts were globally illuminated (5500 lux) with light (530 to 590 nm) and electrocardiographic changes were detected within 2.7 +/- 0.3 s (approximately 15 beats) of the onset of illumination. All hearts developed ventricular premature beats, ventricular tachycardia and complete atrioventricular block after 20.2 +/- 6.6, 68.0 +/- 29.7 and 184.3 +/- 20.9 s, respectively. Photoactivation by rose bengal also resulted in severe ultrastructural damage including intracellular clarifications, swelling of mitochondria with disruption and clumping of cristae and the development of contraction band necrosis. Extensive degranulation of mast cells was also observed. These changes were most evident in myocytes adjacent to large epicardial blood vessels. Cytochemical studies demonstrated that there was a loss of the calcium which is normally localized at the inner sarcolemmal surface, and the appearance of intramitochondrial calcium precipitates. In control hearts (no illumination and/or no rose bengal), arrhythmias did not develop and tissue morphology and calcium distribution remained normal. In additional studies, rose bengal-perfused hearts were illuminated regionally for 10 min over an area (approximately 6 mm2) of the left ventricle. Extensive tissue injury and calcium overload developed in the area of maximum illumination.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Reperfusion-induced arrhythmias are not prevented by ibuprofen in isolated rat heart.

Free radicals have been implicated in the genesis of reperfusion-induced arrhythmias and the cyclooxygenase pathway has been suggested as a potential source. We have therefore assessed whether a cyclooxygenase inhibitor, ibuprofen, is able to reduce reperfusion-induced injury in the isolated perfused rat heart. A duration of 10 min of regional ischemia, which resulted in a high (83%) incidence of ventricular fibrillation, was selected and hearts (n = 12/group) were perfused with ibuprofen (2, 20, or 30 mg/L) throughout the experiment. Ibuprofen did not affect heart rate, although it did produce a dose-dependent increase in coronary flow. However, at all doses studied, ibuprofen had no effect upon the time to onset, incidence, or duration of arrhythmias. In subsequent studies with 30 min of regional ischemia, ibuprofen (30 mg/L) again caused vasodilatation but without effect upon heart rate or severity of arrhythmias. In conclusion, we were unable to obtain evidence in support of the concept that cyclooxygenase activity or cyclooxygenase-derived free radicals are involved in the genesis of ischemia- and reperfusion-induced arrhythmias.

Animals↗
PubMed1990

Photoactivation of porphyrins: studies of reactive oxygen intermediates and arrhythmogenesis in the aerobic rat heart.

STUDY OBJECTIVE: In situ production of reactive oxygen intermediates (singlet oxygen and superoxide) during the photoactivation of rose bengal can induce arrhythmias in the aerobically perfused rat heart. The present study was undertaken (1) to assess whether these effects occur with other photosensitizers; (2) to identify the injurious intermediates; (3) to probe the site of action of these phenomena. DESIGN - The study involved the use of meso-tetra-(4-sulphonatophenyl)-porphine (TPPS), a porphyrin which, in contrast to rose bengal, promotes the production of singlet oxygen alone when illuminated. After 10 min of TPPS free perfusion, rat hearts (n = 6 per group) were perfused aerobically with TPPS (1, 5, 10 or 50 mumol.litre-1) for 25 min; during the last 20 min, the hearts were illuminated (3600 lux). In additional studies, TPPS (50 mumol.litre-1) was washed out before illumination. EXPERIMENTAL MATERIAL: Hearts from 30 male Wistar rats, weighing 220-280 g, were excised and perfused retrogradely. MEASUREMENTS AND MAIN RESULTS: Cardiac function was unaffected with TPPS alone. Upon illumination, electrocardiographic changes (increase in QT interval and/or T wave changes) and arrhythmias developed in a dose dependent manner. At the highest dose, electrocardiographic changes occurred within 7.0(SEM 0.4) s; all hearts exhibited ventricular premature beats and complete atrioventricular block; 67% developed ventricular tachycardia and 17% ventricular fibrillation. During illumination, hearts also exhibited a dose and time dependent decrease in coronary flow. In additional studies, despite the absence of TPPS in the perfusate, all hearts exhibited complete atrioventricular block, 67% developed ventricular premature beats and 33% ventricular tachycardia; none exhibited ventricular fibrillation. CONCLUSIONS: The results suggest that singlet oxygen, as opposed to superoxide, is responsible for the injury which occurs at tissue surfaces to which photosensitizer is bound.

Animals↗
PubMed1990

R56865, a potent new antiarrhythmic agent, effective during ischemia and reperfusion in the rat heart.

The antiarrhythmic effects of R56865 were characterized both in vivo and in vitro. Four groups (n = 12 per group) of anesthetized rats, subjected to 5- or 30-min coronary artery ligation and reperfusion, were studied: saline, dimethyl sulfoxide (DMSO) carrier, and R56865 (0.5 or 2 mg/kg) were administered as an intravenous (i.v.) bolus before ligation. After 5 min of ischemia, the incidences of reperfusion-induced ventricular tachycardia (VT) and fibrillation (VF), which were high in the saline (100 and 75%, respectively) and DMSO (100 and 82%, respectively) control groups, were abolished with both doses of R56865. With 30 min of ischemia, R56865 (2 mg/kg) significantly reduced the incidences of ischemia-induced VT and VF (from 100 and greater than 50% to 25 and 8%, respectively). For in vitro studies, five groups (n = 12 per group) of isolated rat hearts subjected to 10- or 30-min coronary ligation and reperfusion were studied: unmodified buffer and buffer containing DMSO or R56865 (10(-7), 10(-8), 10(-9) M). After 10 min of ischemia, R56865 (10(-7) M) decreased reperfusion-induced VT and VF (from 100 and 75% in buffer controls to 42 and 8%, respectively) when administered throughout the experiment. With 30 min of ischemia, R5685 (10(-7) M) reduced the incidences of ischemia-induced VT and VF (from 75 and 67% in the buffer controls to 25 and 25%, respectively). Although reperfusion after 30 min of ischemia did not induce VF in any of the groups studied, VT and other arrhythmias did occur and their incidences were reduced significantly by R56865. To investigate whether calcium overload might mediate the effects of R56865, hearts were perfused aerobically with a high-calcium/low-sodium medium. VT and VF occurred in 80% of control hearts; R56865 (10(-7) M) did not prevent these arrhythmias. In conclusion, R56865 exerts a potent effect against ischemia- and reperfusion-induced arrhythmias through a mechanism which appears to operate during ischemia.

Analysis of Variance↗
PubMed1990

Exacerbation of reperfusion arrhythmias by sudden oxidant stress.

A burst of free oxygen radical production has been demonstrated during the early moments of reperfusion, coincident with the onset of reperfusion arrhythmias, which can be attenuated by antioxidants. We have investigated whether a sudden burst of oxidant stress, superimposed on that occurring during reperfusion, can exacerbate reperfusion arrhythmias. Rat hearts (n = 12/group) were subjected to 12 minutes of aerobic perfusion; during the last 2 minutes, rose bengal (1 mumol/l) was added to the perfusion fluid. Then, regional ischemia was induced, and rose bengal-free perfusion was restored. After 5 minutes of ischemia, reperfusion was initiated for 5 minutes, and during the first 30 seconds of reperfusion, hearts were uniformly illuminated (8,500 lux) with green light (530-590 nm). The photoactivation of rose bengal trapped in the tissue, producing singlet oxygen and superoxide, resulted in an exacerbation of reperfusion arrhythmias. Thus, 92% of hearts developed ventricular premature beats, 83% ventricular tachycardia, and 33% ventricular fibrillation. In contrast, hearts with regional ischemia and reperfusion in the absence of rose bengal and/or illumination did not develop ventricular fibrillation; only one heart exhibited ventricular tachycardia, and the incidence of ventricular premature beats was lower (42-50%). Furthermore, the burst of oxidant stress shortened the time to onset of ventricular premature beats from 21.7 +/- 5.6 to 9.9 +/- 2.1 seconds. Additional studies revealed that rose bengal photoactivation without reperfusion was less arrhythmogenic compared with the combination of reperfusion plus photoactivation. These results demonstrate that a sudden burst of oxidant stress during the early moments of reperfusion can exacerbate the vulnerability to reperfusion arrhythmias.

Animals↗
PubMed1990

The influence of N-acetylcysteine on cardiac function and rhythm disorders during ischemia and reperfusion.

To assess the ability of N-acetylcysteine to reduce the vulnerability of the heart to arrhythmias and improve its mechanical function during ischemia and reperfusion, groups of Langendorff-perfused rat hearts (15 per group) were subjected to 20 minutes of aerobic perfusion, 10 minutes of regional ischemia and 10 minutes of reperfusion. The hearts were perfused with N-acetylcysteine throughout the study. The incidences of ventricular premature beats and ventricular tachycardia induced by ischemia fell from 93% and 67%, in the N-acetylcysteine-free control group, to 40% and 27% with 8 microM N-acetylcysteine, to 33% and 27% with 80 microM N-acetylcysteine, and to 40% and 13% with 2000 microM N-acetylcysteine. The incidence of ventricular fibrillation induced by reperfusion was reduced from 93% to 60%, 67% and 47%, respectively. N-acetylcysteine had no significant effect upon the coronary flow and heart rate. When the ischemic period was prolonged to 30 minutes, N-acetylcysteine (8 microM) was shown to delay the time of onset of arrhythmias during ischemia and reperfusion. Thus, the incidences of ventricular premature beats and ventricular tachycardia were greatest after 15 minutes of ischemia in controls but were maximal after 18 minutes in hearts treated with N-acetylcysteine. N-acetylcysteine (8 microM) also improved the recovery of mechanical function after ischemia both in Langendorff preparations and in working preparations. In the working heart the post-ischemic recovery of aortic flow, coronary flow, cardiac output and aortic developed pressure after ischemia was improved from their control values of 30 +/- 5%, 82 +/- 2%, 43 +/- 2% and 63 +/- 4% to 59 +/- 7%, 98 +/- 5%, 71 +/- 3% and 80 +/- 6% respectively. Our results support the concept that agents which can alter redox state may exert protective effects against myocardial injury during both ischemia and reperfusion.

Acetylcysteine↗
PubMed1989

A preliminary pharmacokinetic study of 111In-labeled 260F9 anti-(breast cancer) antibody in patients.

The pharmacokinetics of 111In-labeled 260F9, a murine monoclonal antibody directed against a breast-cancer-associated antigen, was determined in seven patients with advanced breast cancer. Six patients were administered 1 mg antibody containing 1 mCi 111In. The seventh patient was administered 20 mg unlabeled antibody followed by 1 mg 111In-labeled antibody all via a peripheral vein. Immunoprecipitation, HPLC and SDS-PAGE gels demonstrated the stability of radiolabel on the antibody. The serum clearance of the radiolabel closely fits (r2 greater than 0.95) a two-compartment model for the first six patients. The apparent volume of distribution of the radiolabel approximated to the plasma volume (31) and its mean residence time was 23.7 h. The radiolabel had an average t 1/2 beta of 22.9 +/- 12.21 h at the 1-mg dose. At the 20-mg dose one-compartment elimination kinetics were observed with the radiolabel and antibody showing similar mean residence times (36-41 h) and a t 1/2 beta of 26-28 h. Whole-body imaging showed that the blood-pool: liver ratio of radioactivity increased fourfold (at 48 h postinfusion) at the higher dose and the percentage of the injected dose of radioactivity in the liver decreased from 25% to 8% (24 h postinfusion). In one patient 7-14 times more radioactivity was localized in a breast tumor than in fat (normal breast). Over the first 25 h an average (cumulative) 7.5% of the total dose was excreted in urine. A study of 260F9 in CDF-1 mice demonstrated that the radiolabel remained associated with the antibody in serum. The antibody, however, cleared 60-fold slower in mice than in patients and showed an increased mean residence time of 191 h. The disparity in the pharmacokinetics of the antibody seen in the mouse and in the clinic, points to the different behavior shown by murine monoclonal antibodies in humans. This points to the need for preliminary studies of antibodies in patients for preclinical evaluations of their effectiveness as drug-targeting agents.

Adult↗