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Biomedical subjects

M Bernard

Publications and source records attributed to M Bernard.

At least 73 records · Page 4Linked to original sources
PubMed1999

Receptor-independent activators of heterotrimeric G-protein signaling pathways.

Heterotrimeric G-protein signaling systems are activated via cell surface receptors possessing the seven-membrane span motif. Several observations suggest the existence of other modes of stimulus input to heterotrimeric G-proteins. As part of an overall effort to identify such proteins we developed a functional screen based upon the pheromone response pathway in Saccharomyces cerevisiae. We identified two mammalian proteins, AGS2 and AGS3 (activators of G-protein signaling), that activated the pheromone response pathway at the level of heterotrimeric G-proteins in the absence of a typical receptor. beta-galactosidase reporter assays in yeast strains expressing different Galpha subunits (Gpa1, G(s)alpha, G(i)alpha(2(Gpa1(1-41))), G(i)alpha(3(Gpa1(1-41))), Galpha(16(Gpa1(1-41)))) indicated that AGS proteins selectively activated G-protein heterotrimers. AGS3 was only active in the G(i)alpha(2) and G(i)alpha(3) genetic backgrounds, whereas AGS2 was active in each of the genetic backgrounds except Gpa1. In protein interaction studies, AGS2 selectively associated with Gbetagamma, whereas AGS3 bound Galpha and exhibited a preference for GalphaGDP versus GalphaGTPgammaS. Subsequent studies indicated that the mechanisms of G-protein activation by AGS2 and AGS3 were distinct from that of a typical G-protein-coupled receptor. AGS proteins provide unexpected mechanisms for input to heterotrimeric G-protein signaling pathways. AGS2 and AGS3 may also serve as novel binding partners for Galpha and Gbetagamma that allow the subunits to subserve functions that do not require initial heterotrimer formation.

Amino Acid Sequence↗
PubMed1999

Metabolic and functional effects of low-potassium cardioplegic solutions for long-term heart preservation.

Cardioplegic solutions used to arrest the heart during open heart surgery and cardiac transplantation are based on potassium as a cardioplegic agent in a concentration range of 15-35 mM. However, high to moderate K+ concentrations increase Ca2+ influx and impair endothelial function. We have therefore evaluated the possible advantage of a lower potassium concentration in a new cardioplegic solution (named CRMBM solution) designed for long-term heart preservation. Nine isolated perfused rat hearts were submitted to 8 h of hypothermic ischemia after cardioplegic arrest, followed by 60 min of reflow at 37 degrees C. Two cardioplegic solutions were compared: (1) the CRMBM solution with 10 mM potassium (K-10 group), and (2) the CRMBM solution with 4 mM potassium (K-4 group). The quality of heart preservation was assessed by a metabolic study using P-31 magnetic resonance spectroscopy (energy metabolism and intracellular pH) combined to a functional evaluation and a measure of cellular integrity (biochemical assays in effluents and tissues). Decreasing the potassium concentration to 4 mM improved heart preservation, as shown by a higher functional post-ischemic recovery represented by the rate pressure product and a better preservation of cellular integrity. The evolutions of intracellular pH and high energy phosphate levels during ischemia and reflow were similar in both groups.

Animals↗
PubMed1999

Cardiac troponin I cutoff values to predict postoperative cardiac complications after circulatory arrest and profound hypothermia.

OBJECTIVE: Cardiac failure and myocardial infarction are complications of thoracic aorta, thoracoabdominal aorta, or aortic arch surgery, especially when surgery is performed using profound hypothermia and circulatory arrest (PHCA). Moreover, the diagnosis of non-Q-wave postoperative myocardial infarction (PMI) is challenging because there is no gold standard. The aims of this study were to determine values for cardiac troponin I (cTnl) in patients undergoing aortic arch or thoracoabdominal aortic surgery with PHCA who were free of cardiac complications in the postoperative period, and to test the validity of cutoff values of cTnl to predict postoperative cardiac complications in such patients. DESIGN: Prospective, nonrandomized study. SETTING: Single university hospital; Departments of Anesthesiology, Biochemistry and Vascular Surgery. PARTICIPANTS: Fifty-two consecutive patients were studied over a 2-year period. None was excluded, even patients who underwent emergency surgery. INTERVENTIONS: Patients undergoing aortic arch or thoracoabdominal aortic surgery with PHCA were studied. Thirty patients undergoing coronary artery bypass grafting (CABG) in the same period constituted a control group. MEASUREMENTS AND MAIN RESULTS: The cTnl concentrations were determined using an immunoenzymofluorometric assay on a Stratus analyzer (Dade, Massy, France) on blood samples obtained at recovery and on day 1 (D1) and D2. Seventeen patients developed a cardiac complication, which was lethal in 10 patients. In patients without cardiac complication, the peak level for cTnl was observed on D1. Cutoff values of cTnl were identical in both the CABG control group (11 .6 microg/mL) and the sternotomy group (12.2 microg/mL), but were significantly greater (20.5 microg/mL) in patients with a thoracotomy approach. Sensitivity and specificity of these cutoff values were high in both groups (control group, sensitivity = 100%, specificity = 100%; sternotomy group, sensitivity = 78%, specificity = 100%; thoracotomy group, sensitivity = 100%, specificity = 94%). CONCLUSION: In patients who underwent surgery using PHCA for aortic arch or descending aorta repair, myocardial damage related to cardiac arrest, vents or fibrillation explains the increased cutoff value (12.2 microg/mL). This value is similar to patients undergoing CABG surgery through a sternotomy approach with cardioplegia administration. In contrast, and probably related to the absence of cardioplegia, patients undergoing surgery through a left thoracotomy approach had a greater cutoff value (20.5 microg/mL). Values of cTnl greater than these respective cutoff values were closely related to cardiac complications during the postoperative period.

Adult↗
PubMed1999

Optimized cardiac graft preservation: a comparative experimental study using P-31 magnetic resonance spectroscopy and biochemical analyses.

BACKGROUND: The University of Wisconsin (UW), St. Thomas (ST) and Broussais (B) solutions were compared to the CRMBM solution, that we developed for long term heart preservation. METHODS: Isolated isovolumic rat hearts were arrested with each cardioplegic solution (n = 5) to 8 hearts in each group), submitted to 12 hours of cold storage (4 degrees C) in the same solution and then reperfused for 60 minutes at 37 degrees C. Function was measured during control and reflow. High energy phosphates and intracellular pH were monitored by P-31 magnetic resonance spectroscopy. Analyses were performed by biochemical assays and HPLC in coronary effluents (CK, Pi, lactate, purines) and in freeze-clamped hearts (amino acids, nucleotides, CK, LDH) at the end of reperfusion. RESULTS: Functional recovery was significantly improved with the new cardioplegic solution (50+/-12% recovery for the rate pressure product at the end of reflow vs 8+/-3% with UW, 0% with B and with ST). This result was correlated with the best metabolic and cellular protection as assessed in particular by higher PCr levels during reflow (30+/-3% vs 10+/-3% with UW, 8+/-4% with B, and 7+/-1% with ST) as well as reduced creatine kinase leakage during reflow (110+/-15 IU/60 minute vs 270 +/- 57 IU/60 minute with UW, 323+/-36 IU/60 minute with Broussais solution and 237+/-18 IU/60 minute with ST). CONCLUSION: This new solution is more effective in prolonged myocardial protection than the three most widely used solutions.

Acid-Base Equilibrium↗
PubMed1999

Procedure to protect confidentiality of familial data in community genetics and genomic research.

The collection of familial data is an essential step for community genetics programs or genetic research. Ethical issues concerning privacy and confidentiality present a major challenge in such programs. In order to keep familial data confidential, we have developed a family-based numerical coding procedure which allows the use of confidential data and the determination of familial relationships without risk of disclosure. This procedure is composed of two parts: the physical separation of identifying information and individual data; and the use of a code containing all the information required to build family trees. This procedure has been used in Eastern Quebec since 1995, mainly for screening, genetic counseling, research on familial dyslipidemias, public health intervention, and research projects on the genetics of complex traits, such as arterial hypertension and coronary artery disease.

Abstracting and Indexing↗
PubMed1999

Long-term follow-up of allogeneic bone marrow transplantation in patients with poor prognosis non-Hodgkin's lymphoma.

Relapsed or very aggressive high-grade NHL and refractory low-grade NHL have a poor clinical outcome. Autologous BMT may be used but is of limited efficacy in these cases. Allogeneic BMT offers the advantage of tumour-free bone marrow and a possible GVL effect. Between 1987 and 1996, 13 patients (median age 31 years) suffering from lymphoid malignancies underwent allo-BMT. Four patients had low-grade NHL, three intermediate-grade and six high-grade NHL. Three patients were grafted with evolutive disease, four were in partial remission after several courses of chemotherapy, two were in CR2 and four were in CR1 after initial therapy. The mean number of prior treatments was 2.7 (1-6). Median time from diagnosis to BMT was 25 months (4-90). The conditioning regimen consisted of cyclophosphamide (120 mg/kg/day for all, plus VP16 in one case) and total body irradiation. Five out of the seven patients who were not in CR at the time of transplantation entered CR after BMT. Eight patients developed acute GVHD grade > or = II and four had chronic GVHD. Nine patients are alive, eight in CR with a median follow-up of 49.8 months post BMT (2-125). Overall survival is 67.3% and the median time for EFS is 102 months. Two patients with low-grade NHL relapsed 61 and 102 months post BMT and were treated with DLI. One patient with a stage IV SLL had a partial remission and one with multiple cutaneous localisation of FL entered CR after grade IV acute GVHD. Allo-BMT is a highly effective treatment for advanced poor prognosis lymphoid malignancies with acceptable toxicity. Moreover, DLI can be effective in relapsing patients.

Adult↗
PubMed1999

Radiation induced effects on cephalosporins: an ESR study.

PURPOSE: This paper reports experimental data on the ESR identification of four irradiated cephalosporins (cefpodoxime, cefsulodin, cefixime and ceftizoxime). MATERIALS AND METHODS: Equations to describe the ESR curves versus the dose and storage time were developed using mathematical procedures. RESULTS: Limits of detection (LOD) and limits of quantification (LOQ), estimated on the basis of the S/N ratios are 1.0+/-0.5 kGy and 2.5+/-0.5 kGy respectively. The yield of free radicals are in the range 4.6 10(19) - 2.2 10(20) radicals mol(-1) (G values from 0.1 to 0.4). Besides a very unstable situation (cefsulodin), the time limit of detection of free radicals after storage ranges from about 1 year to over 2 years. These time intervals are comparable with the shelf-life of the antibiotics and to the time limits found for 10 other cephalosporins described previously. Apart from qualitative detection, ESR spectrometry can be used for dose estimation. Exponential loss of ESR signal (first-order reaction) correlates well with the data. CONCLUSION: Given the sensitivity of ESR spectrometry, this experimental technique is promising for identification of irradiated cephalosporins.

Cefixime↗
PubMed1999

Comparison of lenograstim vs filgrastim administration following chemotherapy for peripheral blood stem cell (PBSC) collection: a retrospective study of 126 patients.

Mobilization techniques for peripheral blood stem cell (PBSC) collection include the administration of chemotherapy followed by hematopoietic growth factors or growth factors alone. Two forms of recombinant human granulocyte colony-stimulating factor (rhG-CSF) are available for PBSC mobilization: lenograstim and filgrastim which are the glycosylated and non-glycosylated forms respectively. In order to determine the influence of the two forms of G-CSF following chemotherapy on PBSC collection, we conducted a retrospective study in 126 patients with various hematological malignancies: 65 and 61 for the lenograstim and filgrastim groups respectively. No significant differences between the two groups were observed in terms of sex, age and diagnosis. Prior therapies and PBSC mobilization regimen were also equivalent. No significant difference was observed between the groups for the median CD34+ cells harvested. The number of leukapheresis necessary to obtain a minimal number of 3 x 10(6) CD34+ cells/kg was equivalent for the two groups. The proportion of patients affected by a failure in PBSC collection was similar in the two groups. Our data suggest that lenograstim and filgrastim are equivalent for PBSC mobilization after chemotherapy.

Adolescent↗
PubMed1999

Remediating the effects of sarcopenia in the elderly client's plan of care.

Because home care nurses are in close contact with frail elders, it is important that they recognize sarcopenia and understand options available to remediate the dangerous consequences of this condition. This article describes an overview of human aging and muscle mass loss, the effects of regular exercise on muscle mass, muscle strength, and functional capacity, and implications for creating interdisciplinary plans of care that impact outcomes.

Activities of Daily Living↗
PubMed1999

Hepatitis C virus infection risk factors in patients admitted in hospital emergency departments in Picardy. Value of oriented screening based on recommendations of the 'Direction Générale de la Santé'.

OBJECTIVE AND DESIGN: Oriented hepatitis C virus (HCV) screening on the basis of transfusion, previous or current parenteral drug addiction, invasive procedures, and in family members of patients with hepatitis C, was recommended in France by the 'Direction Générale de la Santé' (DGS). The aim of this study was to estimate the frequency of these risk factors in patients admitted in hospital emergency departments in Picardy. METHODS: Between 1 June and 31 July 1996, physicians of the emergency units of seven hospitals in Picardy were asked to question admitted patients about risk factors mentioned in the DGS recommendations, and to suggest a screening test when at least one of these risk factors was present. RESULTS: Among 1648 patients, 68.7% had at least one of these risk factors. Screening was accepted by 723 patients, 58.7% of those with at least one risk factor, and more than 70% of those with history of transfusion and/or drug addiction. It was immediately performed in 451, and 2.4% had anti-HCV antibodies. The prevalence of anti-HCV antibodies was 1.5% in patients without history of transfusion or drug addiction and 7.9% in those with at least one of these two risk factors. CONCLUSION: Oriented screening based on transfusion or drug addiction history seems to have better efficiency than the screening policy recommended by the DGS. Poor reliability of answers about medical history was observed probably because of stress related to emergency circumstances. A screening test proposed to patients with these major risk factors by their usual physician would be probably more efficient.

Aged↗
PubMed1999

Dietary fish oil promotes positive inotropy of ouabain in the rat heart.

We tested the hypothesis that a fish oil (FO) diet promotes positive inotropy of ouabain without increased toxicity. For 2 mo, two groups of adult male rats were fed 1) a regular food diet supplemented with dietary long-chain polyunsaturated fatty acid from FO or 2) a regular food diet (control). The responsiveness to ouabain was evaluated for the two groups in Langendorff-perfused hearts, by (31)P nuclear magnetic resonance spectroscopy, and on purified membrane-bound Na-K-ATPase. The maximum positive inotropy achieved with ouabain was nearly two times higher in the FO than in the control group and was not associated with significant changes in energetics. Alteration of function and energetic metabolism and inhibition of Na-K-ATPase in response to 3 x 10(-4) M ouabain were delayed in the FO group. This study demonstrates that dietary FO, by a cardiac membrane incorporation of n-3 polyunsaturated fatty acid, promotes positive inotropy of ouabain without toxicity and changes in cardiac metabolism.

Animals↗
PubMed1999

Serotonin N-acetyltransferase mRNA levels in photoreceptor-enriched chicken retinal cell cultures: elevation by cyclic AMP.

Serotonin N-acetyltransferase (AA-NAT; arylalkylamine N-acetyltransferase; EC 2.3.1.87) is a key regulatory enzyme in the biosynthesis of melatonin. Previous studies have shown that the activity of this enzyme in the chicken retina is regulated by a cyclic AMP-dependent mechanism. In the present report, we investigated whether cyclic AMP can regulate the levels of AA-NAT mRNA in photoreceptor-enriched chick retinal cell cultures. AA-NAT mRNA levels were elevated by acute treatment with cyclic AMP protagonists, including forskolin; this response was blocked by H-89, a selective inhibitor of cyclic AMP-dependent protein kinase. Forskolin did not alter the rate of disappearance of AA-NAT mRNA in actinomycin D-treated cells, suggesting that cyclic AMP enhances transcription of the AA-NAT gene. Forskolin-induced elevation of AA-NAT mRNA levels was enhanced by cycloheximide, which decreased the degradation of the transcript in cells treated with actinomycin D. These studies indicate that the abundance of AA-NAT mRNA is regulated in part through a cyclic AMP-dependent mechanism.

Animals↗
PubMed1998

Structural analysis of the chicken hydroxyindole-O-methyltransferase gene.

Hydroxyindole-O-methyltransferase (HIOMT) catalyzes the final step of melatonin synthesis, a neurohormone involved in photoperiodism and produced specifically in the pineal gland and in the retina. In the chicken, HIOMT gene transcription appears to be controlled by a circadian oscillator located in the pineal gland. We have characterized the chicken HIOMT gene over 17 kb, including 2.9 kb of 5'-flanking sequence. The major transcript (1.6 kb) is composed of eight exons distributed over 7.5 kb of genomic DNA. A ninth alternative exon was identified 6 kb downstream of exon 8. It was found in minor transcripts in the pineal gland and in the retina. Sequence similarity between exons 8 and 9 suggests their origin by exon duplication. Due to early stop codons, inclusion of exon 9 truncates the open reading frame by up to 33%. A restriction fragment length polymorphism was detected for a BglII site in intron 8. Fluorescence hybridization localized the HIOMT gene on chicken chromosome 1q22. The 5'-flanking region contains GATTAA and TAATCC sequences that may be related to tissue-specific expression. An ATTTAAAT sequence at position -29 would play the role of a TATA box, as evidenced by electrophoretic mobility shift assay. Information obtained in this study open the way to further studies aimed at analyzing the circadian rhythm of transcription at promoter level.

Acetylserotonin O-Methyltransferase↗
PubMed1998

Cloning of STK13, a third human protein kinase related to Drosophila aurora and budding yeast Ipl1 that maps on chromosome 19q13.3-ter.

This report describes the identification of a cDNA encoding STK13, a third human protein kinase related to the Drosophila Aurora and the budding yeast Ipl1 kinases. After screening of a human placental cDNA library with a Xenopus laevis cDNA encoding the pEg2 protein kinase and 5' RACE on testis mRNA, a full-length cDNA was isolated. The chromosomal localization of STK13 on 19q13.3-ter between the markers D19S210 and D19S218 was established by a combination of somatic cell and radiation hybrid panel PCR screening. The localization of STK13 on human chromosome 19 was confirmed by fluorescence in situ hybridization (FISH) using a genomic clone containing STK13 as a probe.

Amino Acid Sequence↗