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Biomedical subjects

F Michel

Publications and source records attributed to F Michel.

At least 109 records · Page 6Linked to original sources
PubMed1997

Supplementation with wine phenolic compounds increases the antioxidant capacity of plasma and vitamin E of low-density lipoprotein without changing the lipoprotein Cu(2+)-oxidizability: possible explanation by phenolic location.

OBJECTIVES: To evaluate the effect of the red wine phenolic compound (RWPC) dietary supplementation without alcohol interference on: (1) some of the biochemical characteristics of LDL, (2) the oxidative susceptibility of LDL and (3) the antioxidant capacity of total plasma (Pl-AOC). In order to account for discrepancies between the three series of data, the in vitro stability of the association of phenolic compounds and LDL was tested. DESIGN: An intervention study with 20 volunteers. Each served as his own control. Cu(2+)-oxidizability of LDL and Pl-AOC were tested on blood samples before and after dietary supplementation. Cu(2+)-oxidizability of LDL was also tested by co-incubation in the presence of RWPC or phenolic acids with or without extensive dialysis. SETTING: The Laboratory of Lipid Biochemistry and Biology, School of Medicine, and the Laboratory of Metabolic Diseases, Lapeyronie Hospital, University of Montpellier, France. SUBJECTS: Healthy males, nonsmokers and moderate drinkers, submitted to a dietary regimen deprived of vitamin E and C for a period of 10 d before supplementation. They also abstained from alcohol, wine, fruit juices, coffee, tea and cola beverages during this period. INTERVENTION: Six 0.33 g capsules/d (namely two capsules at each meal) of a preparation of red wine phenolic compounds in a dry powder form were given to the volunteers over a period of two weeks. Blood samples were drawn in fasting conditions at day 0 and day 14 of the supplementation period. RESULTS: Supplementation led to: (1) in LDL, a significant increase in vitamin E content (n = 20, P = 0.01) or vitamin E/total fatty acid bis-allylic carbon number ratio (n = 20, P = 0.006) without modification in the other biochemical characteristics or Cu(2+)-oxidizability; (2) in plasma, a significant increase in the antioxidant capacity (n = 11, P = 0.01). In vitro studies showed that RWPC or sinapic, caffeic or ferulic acids incubated in the presence of LDL increased the protection of the lipoparticle against oxidation (caffeic > sinapic > ferulic). This effect, however, was totally lost after extensive dialysis. CONCLUSIONS: The enhancing effect of the RWPC supplementation on Pl-AOC may be due to a phenolic-compound action both in the aqueous phase of plasma and at the surface of lipoprotein particles. Surface location possibly explains the enhancing-sparing effect of supplementation on LDL vitamin E and the absence of effect on dialysed-LDL oxidizability.

Adult↗
PubMed1997

[The contribution of imagery in the early diagnosis of Fournier's gangrene].

Scrotal ultrasonography, completed by MRI, allowed the early diagnosis of a case of Fournier's gangrene, before the appearance of subcutaneous crepitation allowing rapid treatment adapted to the extent of necrosis. Ultrasonography is recommended in the assessment of inflammatory disease of the scrotum and/or perineum. MRI is able to refine the ultrasonographic data, and define the extent of gangrene as well as its starting point.

Adult↗
PubMed1997

[Oxidative stress and chronic renal insufficiency: what can be a prophylactic approach?].

Cardiovascular diseases represent the first cause of mortality in chronic renal failure patients treated by hemodialysis. Alterations in lipid metabolism and oxidative stress are recognized as vascular risk factors. Their corrections could be of interest for atherosclerosis prevention. In order to evaluate interest of an therapeutic intervention, we have analyzed oxidative metabolism in hemodialysis patients by determining the production of oxygen reactive species (ROS), the level of defense mechanisms, and the balance between nitric oxide (NO) and ROS, responsible for anti- or proxidant effects of NO. During dialysis sessions performed with cellulosic membrane (Cuprophan) an increase in hydroperoxide production by platelets was noted (12 HETE) (5.62 +/- 0.94 pg); similarly, superoxide anion (O2(0)-) production by monocytes (fluorescence index: 115 +/- 24) and by polynuclear cells (fluorescence index: 115 +/- 24) was enhanced. On the other hand, anti-oxidant defenses were significantly reduced with a decrease in RBC SOC activity (0.92 +/- 0.06 U/mg Hg) and in RBC vitamin E (0.7 +/- 0.07 mg/l) concentration. We have demonstrated a profound alteration in the L-arginine/NO pathway consequently to an accumulation of NO synthases inhibitors or activators. The necessity to reduce the production of ROS during dialysis sessions justifies the use of more biocompatible membranes, such as modified cellulosic or synthetic membranes, decreasing leucocyte activation. In addition, NO synthetase inhibitors can be preferentially eliminated by convection. Finally, a supplementation with an exogenous anti-oxidant, such as oral vitamin E (500 mg/day for 6 months) normalizes RBC vitamin E levels and concomitantly allows a decrease in MDA concentrations In conclusion, oxidative metabolism alterations observed in hemodialysis are multifactorial: preventive measures include the use of a more biocompatible material, the reequilibrium of the NO/ROS balance, and supplementation with exogenous anti-oxidants.

Antioxidants↗
PubMed1996

Mutation of tyrosines 492/493 in the kinase domain of ZAP-70 affects multiple T-cell receptor signaling pathways.

The protein-tyrosine kinase ZAP-70 is implicated, together with the Src kinase p56(lck), in controlling the early steps of the T-cell antigen receptor (TCR) signaling cascade. To help elucidate further the mechanism by which ZAP-70 regulates these initial events, we used a dominant-negative mutant approach. We overexpressed in the Jurkat T-cell line ZAP-70 mutated on Tyr-492 and Tyr-493 in the putative regulatory loop of its kinase domain. This mutant inhibited TCR-induced activation of nuclear factor of activated T cells by interfering with both intracellular calcium increase and Ras-regulated activation of extracellular signal-regulated kinases. Moreover, TCR-induced phosphorylation of pp36-38, thought to play a role upstream of these pathways, was found to be reduced. In contrast, overexpression of wild-type ZAP-70 induced constitutive activation of nuclear factor of activated T cells. The ZAP-70 mutant studied here could be phosphorylated on tyrosine when associated to the TCR zeta chain and was able to bind p56(lck). This result demonstrates that Tyr-492 and Tyr-493 are not responsible for the Src homology domain 2-mediated association of p56(lck) with ZAP-70. Our data are most consistent with a model in which recruitment to the TCR allows ZAP-70 autophosphorylation and binding to p56(lck), which in turn phosphorylates Tyr-492 and/or Tyr-493 with consequent up-regulation of the ZAP-70 kinase activity. ZAP-70 will then be able to effectively control phosphorylation of its substrates and lead to gene activation.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Induction of T cell adhesion by antigen stimulation and modulation by the coreceptor CD4.

T cell adhesion induced after physiological stimulation by antigen was investigated using murine T cell hybridomas specific for a tetanus toxin peptide. By employing a novel assay, the T cell hybridomas were shown to strongly adhere to peptide-pulsed APC in a dose-dependent fashion. Adhesion peaked at 30-60 min and declined thereafter. This assay allowed us to study the relationship between T cell adhesion and later activation responses using tetanus toxin peptide and alanine monosubstituted analogs. We show that the degree of peptide-induced T cell adhesion correlated with the magnitude of late functional responses. CD4, LFA-1 (CD11a/CD18), and CD28 were critical in the adhesion response. The enhancing role of CD4 was further demonstrated by reduced levels of T cell adhesion and late responses of CD4- T cell hybridomas. Reexpression of CD4 reversed these defects. Our data suggest a link between antigen-induced T cell adhesion and late responses and also suggest that signals mediated by TCR and CD4 coengagement may induce a greater activation and/or recruitment of molecules involved in T cell adhesion.

Animals↗
PubMed1996

p95vav associates with tyrosine-phosphorylated SLP-76 in antigen-stimulated T cells.

p95vav, the product of the vav protooncogene, has been implicated in the T cell receptor (TCR)-mediated signaling cascade p95vav is phosphorylated on tyrosine residues after TCR stimulation by anti-TCR/CD3 antibodies and possesses a number of landmark features of signaling molecules such as a putative guanine nucleotide exchange factor domain, a pleckstrin homology domain, and an Sre homology (SH) 2 and two SH3 domains, which provide the capacity to form multimeric signaling complexes. However, the precise role of p95vav in TCR signaling remains unclear. In this work we show that physiological stimulation of T cell hybridomas with antigen presented by major histocompatibility complex class II molecules leads to a strong tyrosine phosphorylation of p95vav and its association with tyrosine-phosphorylated SLP-76. SLP-76 is a newly described SH2-containing protein that has been previously found to bind to the adapter molecule Grb2. Moreover, we provide evidence that p95vav-SI P-76 association is SH2-mediated by demonstrating that this interaction can be inhibited by a phosphopeptide containing a putative p95vav-SH2-binding motif (pYESP) present in SLP-76. Furthermore, in vitro experiments show that after antigen stimulation, phosphorylated p95vav-SLP-76 can bind to Grb2 in a complex that contains pp36/38 and pp116 proteins. Our data provide a clue to explain recent independent observations that overexpression of p95vav or SLP-76 enhances TCR-mediated gene activation.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Two different readers in the same brain after a posterior callosal lesion.

Two different types of reading, one in each hemifield, were exhibited by a patient with a lesion of the posterior half of the corpus callosum. The patient read normally when words and non-words were presented to his right visual field. However, with left visual field presentations, the patient could not read non-words and vocalized real words very slowly, especially abstract words, inflected verbs and function words. He often replaced concrete words by semantic associates. Such an abnormal reading pattern is similar to that known as deep dyslexia. This unilateral deficit reveals the competence of the right hemisphere to initiate some semantic processing and its inability to manage phonological coding. The hypothesis that deep dyslexia is due to right hemisphere reading is reinforced by the present case.

Adult↗
PubMed1996

Determination of trunk motion patterns associated with permanent or transient stenosis of the lumbar spine.

Dynamometric devices used to assess back function are becoming increasingly used in research as well as in clinical practice. These devices provide values for a variety of movement variables such as torque, displacement, and velocity, but they also enable the study of movement patterns. The purpose of this study was to determine the movement patterns of patients presenting with specific spinal pathologies. Thirteen patients with spinal stenosis and 14 patients with degenerative changes and a borderline spinal canal diameter, as well as a control group of 30 symptom-free subjects, were studied. An isoinertial trunk-testing dynamometric device was used. Sagittal velocity and position were measured against a resistance set to 50% of the subject's maximum isometric torque. A phase plane analysis (velocity against position) was performed for each subject. An ensemble averaging technique was used to average the repetitions of every subject and a normalization technique was employed to draw an average graph for each group. This graph showed distinct patterns of movement for the three groups. The differences appeared mostly during the extension phase of movement, as confirmed by statistical analysis. The spinal stenosis group showed lower velocities than the controls during the entire extension phase (P < 0.05), while the borderline spinal canal group demonstrated a significant decrease in velocity at the end of the extension phase (P < 0.01). These findings can be related to the increase in disk bulge and decrease in the diameter of the spinal canal during extension. This study shows the relation between some spinal pathologies and movement patterns. This type of functional assessment may be a valuable tool for assessing the relation between anatomical lesions and function and for determining the responsibility of findings such as bulging disk and/or facet syndrome in causing a patient's complaints.

Adult↗
PubMed1996

Manual performance and laterality in twins of known chorion type.

Manual performance, direction, and degree of laterality were tested in monozygotic (MZ) twins (8-12 years old) of known chorion type and dizygotic (DZ) twins. Three manual tasks rarely employed in twin studies were used; dot-filling, tapping, and peg-moving tasks. No chorion effect was observed: the monochorionic and dichorionic MZs differed neither for frequency of discordant pairs nor for handedness, laterality measurements, and manual performance. The pooled MZs and DZs were then compared in a classic twin design. The within-pair resemblance was not higher in MZs than in DZs for variables measuring level of manual performance. For laterality scores intraclass correlations were close to zero in MZ and DZ twin groups.

Child↗
PubMed1996

Function of a pseudoknot in the suppression of an alternative splicing event in a group I intron.

Like most mitochondrial group I introns with a free-standing open reading frame (ORF) located downstream of their catalytic core, the Sd.cob, 1 intron in the gene coding for the cytochrome b of Saccharomyces douglasii mitochondria possesses a putative proximal 3' splice site. However, incubation of Sd.cob, 1 preRNA transcripts under optimal in vitro splicing conditions essentially results in splicing at the authentic, distal 3' splice junction. The mechanism by which the proximal splicing event is suppressed in vitro involves formation of a tertiary interaction which is only found in the Sd.cob, 1 intron. Core nucleotides located in loop L5 block proximal splicing by forming Watson-Crick base pairs with the nucleotide sequence of the proximal 3' splice site. This tertiary base pairing, also important for the folding of the intron into an active conformation, may be regarded as equivalent to the L9/P5, GNRA-loop/helix interaction found in more than one-third of known group I introns.

Alternative Splicing↗
PubMed1996

New loop-loop tertiary interactions in self-splicing introns of subgroup IC and ID: a complete 3D model of the Tetrahymena thermophila ribozyme.

BACKGROUND: Group I introns self-splice via two consecutive trans-esterification reactions in the presence of guanosine cofactor and magnesium ions. Comparative sequence analysis has established that a catalytic core of about 120 nucleotides is conserved in all known group I introns. This core is generally not sufficient for activity, however, and most self-splicing group I introns require non-conserved peripheral elements to stabilize the complete three-dimensional (3D) structure. The physico-chemical properties of group I introns make them excellent systems for unraveling the structural basis of the RNA-RNA interactions responsible for promoting the self-assembly of complex RNAs. RESULTS: We present phylogenetic and experimental evidence for the existence of three additional tertiary base pairings between hairpin loops within peripheral components of subgroup IC1 and ID introns. Each of these new long range interactions, called P13, P14 and P16, involves a terminal loop located in domain 2. Although domains 2 of IC and ID introns share very strong sequence similarity, their terminal loops interact with domains 5 and 9 (subgroup IC1) and domain 6 (subgroup ID). Based on these tertiary contacts, comparative sequence analysis, and published experimental results such as Fe(II)-EDTA protection patterns, we propose 3D models for two entire group I introns, the subgroup IC1 intron in the large ribosomal precursor RNA of Tetrahymena thermophila and the SdCob.1 subgroup ID intron found in the cytochrome b gene of Saccharomyces douglasii. CONCLUSIONS: Three-dimensional models of group I introns belonging to four different subgroups are now available. They all emphasize the modular and hierarchical organization of the architecture of group I introns and the widespread use of base-pairings between terminal hairpin loops for stabilizing the folded and active structures of large and complex RNA molecules.

Animals↗
PubMed1995

Frequent use of the same tertiary motif by self-folding RNAs.

We have identified an 11 nucleotide RNA motif, [CCUAAG...UAUGG], that is extraordinarily abundant in group I and group II self-splicing introns at sites known, or suspected from co-variation analysis, to interact with hairpin terminal loops with a GNRA consensus sequence. Base substitution experiments using a ribozyme-substrate system derived from a group I intron reveal that this motif interacts preferentially with GAAA terminal loops and binds them with remarkable affinity, compared with other known combinations of GNRA loops and matched targets. A copy of the [CCUAAG...UAUGG] motif which is present in domain I of many group II introns is shown to interact with the GAAA terminal loop that caps domain V. This is the first interaction to be identified between these two domains, whose mutual recognition is known to be necessary and sufficient for group II ribozymic activity. We conclude that interaction of [CCUAAG...UAUGG] with GAAA loops is one of the most common solutions used by nature to solve the problem of compacting and bringing together RNA structural domains.

Base Sequence↗
PubMed1995

Red blood cell vitamin E concentrations in fetuses are related to but lower than those in mothers during gestation. A possible association with maternal lipoprotein (a) plasma levels.

OBJECTIVE: The purpose was to establish which blood characteristic of vitamin E status were highly correlated between mothers and fetuses during gestation. STUDY DESIGN: Twenty-four pregnant women were selected because of suspicion of toxoplasmosis or other disease and malformation or intrauterine growth delay justifying cord blood puncture. After maternal and fetal blood was collected, analyses of plasma and red blood cell vitamin E contents were performed together with analyses of standard lipid parameters and lipoprotein (a) in maternal plasma and fatty acid compositions of maternal and fetal red blood cells. RESULTS: The maternal population was characterized by a plasma lipid-normalized vitamin E mean content higher (3.5 mmol/mol lipids) than usually found in nonpregnant adults. There was no relationship between plasma and red blood cell vitamin E contents. This was also true for fetuses. When the vitamin E status of mothers was compared with that of fetuses, we found no correlation in plasma vitamin E in the whole population and in the high lipoprotein (a) (> 300 mg/L) and low lipoprotein (a) (< 300 mg/L) groups. In contrast, statistically significant correlations appeared between maternal and fetal red blood cell contents and red blood cell relative charges in vitamin E in the whole population, whereas still higher correlations occurred in the high lipoprotein (a) group (r = 0.94 for the red blood cell content). Improved correlations were also found in the high lipoprotein (a) group for the interrelationship between vitamin E and plasma lipid contents (cholesterol and triglycerides), whereas improvement was noted in the low lipoprotein (a) group by positive correlation between age and vitamin E red blood cell content or red blood cell relative charge. CONCLUSION: Determination of red blood cell vitamin E and plasma lipoprotein (a) in mothers could be useful in antenatal blood analysis in cases of risk of prematurity at birth, to prevent peroxidative membrane damage in neonates, and > 85% of the mothers in the current population would benefit from vitamin E supplementation from the viewpoint of the fetal red blood cell vitamin E requirement in spite of the rather high maternal lipid-normalized vitamin E plasma content.

Adult↗
PubMed1995

Effects of insulin therapy upon plasma lipid fatty acids and platelet aggregation in NIDDM with secondary failure to oral antidiabetic agents.

The effects of intensive insulin therapy on metabolic control, fatty acid metabolism and platelet function were studied in 18 non-obese non-insulin-dependent diabetics (NIDDs) with secondary failure to oral antidiabetic drugs (OAD). Patients were randomly allocated either to continue maximal OAD (Group I, n = 9) or to receive a multiple injection regimen of insulin therapy (Group II, n = 9) for a 6-month period. At baseline both groups were identical for clinical and biological parameters. At study day 180, fasting blood glucose (P < 0.01) and mean capillary blood glucose (P < 0.05) were reduced in group II but the difference between HbA1 percentages remained non-significant. At study day 60, in total plasma lipids, oleic acid was lower (P < 0.05), linoleic acid (P < 0.05) and the sum of polunsaturated fatty acids (PUFA) (P < 0.05) were higher in group II than I. In triglycerides, palmitic acid was lower in group II at study days 60 (P < 0.01) and 180 (P < 0.05), whereas gamma-linolenic acid was decreased (P < 0.05) at study day 180 only. A similar change was noted in cholesterol esters for gamma-linolenic acid at study day 60 (P < 0.05). No difference was noted between both groups for platelet agregation, insulin sensitivity and clinical parameters despite a significant increase in body weight in group II at study day 180. Positive correlations were obtained between the content of different lipid fractions in some PUFA and the glucose clearance. We conclude that optimized insulin therapy in NIDDs with secondary failure to OAD leads to a transient improvement in glucidic and lipidic metabolism but has no significant effect upon platelet aggregation and insulin sensitivity.

Adenosine Diphosphate↗