Search PubMed⌕ Search

Biomedical subjects

R Favier

Publications and source records attributed to R Favier.

At least 73 records · Page 4Linked to original sources

A novel genetic thrombocytopenia (Paris-Trousseau) associated with platelet inclusions, dysmegakaryopoiesis and chromosome deletion AT 11q23.

We report a novel case of hereditary thrombocytopenia. A chronic thrombocytopenia was noted in a woman with mild hemorrhagic complications as well as in her very young son. A platelet fraction contained giant granules stained in red on blood smears. The number of bone marrow megakaryocytes was increased with many micromegakaryocytes. Since the platelet life span was normal, these results indicated an ineffective platelet production. A constitutional cytogenetic abnormality was detected in the two patients: a deletion of the long arm of chromosome 11. The association of these abnormalities constitute a new disorder: this never described cytological entity is a valuable model for exploring the role of some genes involved in the regulation of thrombopoiesis.

Adult↗

Glucose and free fatty acid utilization during prolonged exercise in prepubertal boys in relation to catecholamine responses.

Ten prepubertal boys performed 60-min cycle exercise at about 60% of their maximal oxygen uptake as previously measured. To measure packed cell volume, plasma glucose, free fatty acids (FFA), glycerol and catecholamines, blood samples were drawn at rest using a heparinized catheter and at the 15th, 30th and 60th min of the exercise and after 30 min of recovery. At rest, the blood glucose concentrations were at the lowest values for normal. Exercise induced a small decrease of blood glucose which was combined with an abrupt increase of the noradrenaline concentration during the first 15 min. The FFA and glycerol concentrations increased throughout the exercise linearly with that of adrenaline. Compared to adults, the FFA uptake expressed per minute and per litre of oxygen uptake was greater in children. These results suggested that it is difficult for children to maintain a constant blood glucose concentration and that prolonged exercise provided a real stimulus to hypoglycaemia. An immediate and large increase in noradrenaline concentration during exercise and a greater utilization of FFA was probably used by children to prevent hypoglycaemia.

Blood Glucose↗

Effects of torbafylline on muscle atrophy: prevention and recovery.

The effects of torbafylline on the prevention of and the recovery from 5 weeks of hindlimb suspension induced atrophy were analyzed in rat soleus and extensor digitorum longus muscles. Muscle alterations were investigated by determining a suite of electrophysiological, histochemical, and muscle ultrastructural characteristics. Administration of torbafylline during the suspension period was ineffective in preventing any of the observed muscle atrophic changes. Application of torbafylline during the recovery period resulted in a faster recovery of some soleus muscle structural and functional properties. Mitochondrial volume densities and capillary to fiber ratios returned towards baseline values earlier in the recovery process with torbafylline. Furthermore, the drug significantly improved soleus muscle fatigue resistance 4 weeks after cessation of hindlimb suspension.

Animals↗

Rapid aequorin loading into platelets in the presence of DMSO--characteristics of the responses (changes in light transmission and in calcium) to various agonists.

We have looked at different parameters which could modify platelet behaviour during and after aequorin loading in the presence of DMSO. There is a decreased platelet reactivity in response to ADP, PAF and A-23,187 which appears to be mainly due to the exposure to EGTA during washing and loading and the 1 ml volume of the test suspension. All the studied agonists (including PMA) which elicit aggregation are able to induce an intracellular Ca2+ change detected with the aequorin probe. By contrast, epinephrine alone induces neither aggregation nor Ca2+ rise, but potentiates the responses to ADP. Different consecutive phases in Ca2+ changes after stimulation with ADP, PMA and A-23,187 can be evidenced. In the presence of external Ca2+, the second component of the Ca2+ change evoked with ADP is dependent on aggregation and the subsequent TXA2 synthesis. When the external medium is Ca2+ depleted, the two Ca2+ peaks induced by ADP disappear whereas a Ca2+ rise persists (endogenous mobilization) with the other agonists, being independent of TXA2 and ADP release. Ca2+ mobilization parallels activation with A-23,187 but not with low concentrations of thrombin.

Aequorin↗

Whole body and muscle respiratory capacity with dobutamine and hindlimb suspension.

The effects of repeated injections of dobutamine, a synthetic catecholamine, were studied in control and tail-suspended rats to determine whether this drug could improve the metabolic response to unweighting. Dobutamine prevented the decrease in maximal oxygen uptake (VO2max) induced by hindlimb suspension. Furthermore, VO2max was 12% greater in dobutamine-treated animals than in saline-treated control animals. Soleus muscle weight and mean fiber cross-sectional area were decreased by 60 and 75%, respectively, in saline- and dobutamine-treated suspended rats. Total capillary length was unaffected by unweighting and increased 21% in all animals receiving dobutamine. The drug prevented the increase in total mitochondrial volume density (+30%) induced by unweighting but did not change total mitochondrial volume. Our results suggest that 1) dobutamine is useful to prevent the decrease of total aerobic capacity during hindlimb suspension, 2) dobutamine increases VO2max in control rats, and 3) total capillary length in soleus muscle is increased by the drug in all groups, although no beneficial effects on mitochondria can be detected.

Animals↗

Aequorin-detected calcium changes in stimulated thrombasthenic platelets. Aggregation-dependent calcium movement in response to ADP.

Calcium changes in normal and thrombasthenic platelets were recorded using the PICA-apparatus. Aequorin was loaded in the presence of DMSO, EGTA and PGE1. Platelets of three patients with type I thrombasthenia stimulated with A-23, 187, thrombin, PMA in the presence 1 mM Ca++ and 1 mM Mg++ were able to normally raise their calcium concentrations. The maximal values could be found below the normal range with collagen, ADP and PAF-acether. Calcium mobilization from internal stores in response to thrombin was normal. There were two calcium peaks in normal platelets stimulated with ADP. The second one was suppressed by omitting fibrinogen, stirring, or by adding aspirin, and was absent in thrombasthenic platelets. Thus the GP IIb-IIIa complex is not a prerequisite for calcium fluxes but is involved, when weak agonists such ADP are used, through an aggregation-dependent reinforcement of platelet activation.

Adenosine Diphosphate↗

Attenuated mutants of the intracellular bacterium Listeria monocytogenes obtained by single amino acid substitutions in listeriolysin O.

Listeriolysin O (LLO), a major virulence factor of the intracellular bacterium Listeria monocytogenes, shares with other known 'thiol-activated toxins' a conserved undecapeptide, ECTGLAWEWWR, located in the C-terminal region of the protein and containing the unique cysteine of the molecule. Single amino acid substitutions were created in this region to study the role of cysteine and tryptophan residues in the lytic activity of LLO as well as in the virulence of the bacterium. Transformation of a transposon-induced non-haemolytic mutant with plasmids carrying the mutated genes allowed allele exchange and transfer of mutations on to the chromosome by in vivo recombination. The mutant strains secreted a full-length 59 kilodalton LLO. A decrease of 25% in the haemolytic activity in culture supernatants was observed in the case of mutation Cys-484 to Ala and of 80% for mutation Cys-484 to Ser. Mutations Trp-491 and Trp-492 to Ala decreased activity by, respectively, 95% and 99.9%. LLOs produced by the mutants, as the wild type, were active at low pH, inhibited by cholesterol, and able to bind to cell membranes. A close relationship was found between virulence of mutants in the mouse model and haemolytic activity in their culture supernatants. These results demonstrate that the thiol group of Cys-484 is not essential for either haemolytic activity in vitro or virulence in vivo. In contrast, Trp-492 appears to be required for both haemolytic activity and virulence. The finding that the nearly non-haemolytic mutant Trp-492-Ala persisted in the spleen for several days after inoculation indicates that mutagenesis of a virulence determinant can attenuate virulence and provides a novel approach to the development of live vaccine strains.

Alleles↗

Calcium rise in human platelets elicited by anti-CD9 and -CD41 murine monoclonal antibodies.

Three murine monoclonal antibodies (anti-CD9: ALB6, anti-CD41: VI-PL3 and PL2-49/GPIIb - final concentration: 7.5 micrograms/mL) are shown to elicit after a lag time aggregation of washed platelets and a calcium signal (as detected by light emitted by loaded aequorin), which is only partially inhibited by aspirin. By comparison the rise induced by thrombin is greater and almost instantaneous. In the presence of EGTA a calcium mobilization from internal stores can be detected with thrombin and with ALB6, but neither with PL2-49 nor with VI-PL3, whereas platelets still change their shape and release ATP. It is tempting to speculate that although all the antibodies induce a calcium change, they activate platelets by different pathways: calcium may be not primarily involved in the activation induced by the anti-CD41 antibodies.

Adenosine Triphosphate↗

PL2-49, a monoclonal antibody against glycoprotein IIb which is a platelet activator.

PL2-49 is a murine monoclonal IgG1 antibody obtained after immunization of Balb/c mice with EDTA washed platelets. Binding could be detected on Zwa(+) as well as Zwa(-) platelets, but not on type I Glanzmann's thrombasthenia platelets using an ELISA screening test. Immunoprecipitation studies showed that PL2-49 bound to glycoprotein IIb when the glycoprotein IIb/IIIa complex dissociation was performed after the monoclonal antibody binding. Experiments with a human alloantibody against Zwa antigen were run in parallel to control the complex dissociation. Ascitic fluid, as well as the purified antibody, induced activation and aggregation of washed platelets and ATP release. PL2-49-induced aggregation did not require exogenous fibrinogen and was inhibited, partially, in the presence of aspirin, apyrase, isosorbide dinitrate. Raising intra-platelet cyclic AMP with a stable PGI2 analogue, iloprost, and/or a phosphodiesterase inhibitor, RA 233, suppressed the responses to PL2-49. F(ab')2 fragments did not induce aggregation of normal platelets but inhibited the response to the whole immunoglobulin. Finally PL2-49 was shown to induce aequorin-detected elevations in intraplatelet Ca++ levels. Thus PL2-49 seems to differ from monoclonal antibodies so far described, since it binds to glycoprotein IIb in a complex-dependent manner at least under our experimental conditions for immunoprecipitation studies, and it induces platelet Ca++ mobilization and platelet aggregation after a lag-time. These reactions depend both on Fab and Fc domains of the antibody and require neither complement nor exogenous fibrinogen.

Animals↗

Effects of treadmill running and swimming on plasma and brain vasopressin levels in rats.

The influence of treadmill or swimming exercise on resting values of plasma and brain arginine vasopressin (AVP), and plasma sodium, potassium, osmolality and proteins was studied after 5 weeks of training using female Wistar rats. The duration of daily training sessions was progressively increased to reach 6 h/day for swim training (S) and 3 h/day for treadmill running (T). Compared to their untrained controls, treadmill and swim training were respectively associated with: a significant lower body weight; a decreased plasma AVP (36.4% for T and 47.4% for S) and hypothalamic AVP (20% for T and 16% for S); a higher hypophyseal AVP (145% for T and 36.3 for S); a decreased plasma osmolality (6.7% for T and 6.1% for S), sodium (1.2% for both) and potassium (15% for T and 22.4% for S); and no change in protein concentration. For T, rectal temperature increased (38.5 +/- 0.20 to 39.7 +/- 0.5) and for S rectal temperature decreased from 38.6 +/- 0.12 to 37.74 +/- 0.10). The differences observed in AVP contents of the pineal and Harderian glands (enhanced only in the treadmill groups) could be explained by the supposed role of these glands in thermoregulation. Two conclusions could be drawn from this study: there are no parallel changes in the hypothalamo-hypophyseal system (where AVP plays its endocrine role) and the brain (where AVP is a neurotransmitter); plasma changes could be explained by an extracellular fluid expansion with Na and K loss leading to a decrease in AVP secretion.

Animals↗

Attenuation by propranolol of exercise training effects in spontaneously hypertensive rats.

The effects of propranolol (10 mg/kg) on systolic blood pressure (SBP), resting and exercising heart rates (HR), and body weight (BW) were examined in 11-week swim-trained spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. In both species, SBP was significantly reduced by either propranolol or training, but the reduction was greater with propranolol than with training. However, when propranolol was administered to rats during training, their independent beneficial effects on SBP were annulled. HR was modified slightly by propranolol and training, but they both decreased BW. The mechanism of propranolol action on BW is not clear. Maximum oxygen uptake (VO2 Max), relative heart weight (RHW), and absolute heart weight (AHW) were measured after 11 weeks of training. In both SHR and WKY rats, VO2 Max was elevated by exercise training; moreover, VO2 Max was greatest among those receiving propranolol while training. However, the combined effects of propranolol and training produced a significant reduction of AHW in SHR. The RHW was increased by training, but it was decreased by propranolol. SHR rats were more sensitive to the effects of training and propranolol than WKY rats. In humans, several observations have been reported on the attenuation of certain exercise-induced cardiovascular and metabolic changes by beta-adrenergic blocking agents. Our results obtained with rats confirm some of those observations. It would seem that the hypertensive strain of rats could serve as a model for the study of attenuation mechanisms by beta-adrenergic blockers.

Animals↗

Swim training in genetically hypertensive rats of the Lyon strain: effects on plasma lipids and lipoproteins.

We studied the effects of training by forced swimming on plasma lipid and lipoprotein concentrations in the Lyon genetically hypertensive rats (LH), its normotensive (LN) and low blood pressure (LL) controls. Training was carried out 5 days a week for 5 weeks. The duration of daily training sessions was increased 15 min per day, from 2 to 6 h/day. Following training low density lipoprotein-cholesterol (LDL-C) was significantly lower (P less than 0.01) in LL, and the very low density lipoprotein (VLDL-C) was also lower in LN (P less than 0.01) and LH (P less than 0.05) rats compared with their sedentary controls. High density lipoprotein-cholesterol (HDL-C) was not significantly increased after training in all strains. Compared with controls, plasma total cholesterol, plasma triglycerides and phospholipids were not modified by training. The reduction of LDL-C, VLDL-C as well as the increase of the HDL-C:VLDL-C ratio suggest a beneficial effect of training on atherosclerosis and perhaps coronary heart disease risk.

Animals↗

Effect of swim training on systolic blood pressure, vasopressin and total neurophysins in the Lyon hypertensive rat.

This study reports the effects of 5 weeks of swim training on systolic blood pressure, body weight, plasma and brain vasopressin and total neurophysins in the Lyon genetically hypertensive (LH) rat and in their normotensive (LN) and low blood pressure (LL) controls. Swimming was unable to influence any studied parameters. These results shed doubt on the efficiency of this model of training on the evolution of hypertension in the LH rats.

Animals↗

Free dopamine in dog plasma: lack of relationship with sympathoadrenal activity.

To investigate the relationship between dopamine (DA) released into the bloodstream and sympathoadrenal activity, levels of free DA, norepinephrine (NE), and epinephrine (E) in plasma were recorded in four dogs subjected to three tests: treadmill exercise at two work levels [55 and 75% maximal O2 uptake; 15 min], normobaric hypoxia (12% O2; 1 h), combined exercise and hypoxia. Normoxic exercise induced slight nonsignificant decreases in the arterial partial pressure of O2 (PaO2), increases in NE [median values and ranges during submaximal work vs. rest: 1086 (457-1,637) vs. 360 (221-646) pg/ml; P less than 0.01] and E [277 (151-461) vs. 166 (95-257) pg/ml; P less than 0.05], but it failed to alter the DA level. Hypoxia elicited large decreases in PaO2 [hypoxia vs. normoxia: 42.8 (40.3-50.0) vs. 97.6 (83.2-117.6) Torr; P less than 0.01], increases in DA [230 (105-352) vs. 150 (85-229) pg/ml; P less than 0.01] and NE [383 (219-1,165) vs. 358 (210-784) pg/ml; P less than 0.05], but it failed to alter the E level. Combined exercise and hypoxia further increased NE levels but did not alter the DA response to hypoxia alone. The data indicate that free DA in plasma may vary independently of the sympathoadrenal activity.

Adrenal Medulla↗

[Effect of physical training by swimming on the arterial pressure, plasma and hypothalamo-post-hypophyseal vasopressin in genetically hypertensive rats of the Lyon strain].

The effect of a 5-week swimming training on systolic blood pressure (PAS) and vasopressin (AVP) and Neurophysins (NpT) concentration in the blood and content in the pituitary and the hypothalamus was studied in Lyon genetically hypertensive rats [LH] and in their controls: the normotensive [LN] and low blood pressure [LL] rats belonging to the 28th generation. Nine female rats of each group were trained 5 days a week for 5 weeks, starting with 2 h a day, with a 15 min increase every day, up to 6 h a day. The PAS was measured using an indirect plethysmographic technique one time a week during the whole training session. At the end of the training, the rats were decapitated. AVP and NpT were measured in blood, pituitary and hypothalamus, by radioimmunoassay (RIA). Hematocrit as well as plasma Na+, K+, protein and osmotic content were also measured. Results show that the training did not affect any of the studied parameters: mainly, there was no decrease in PAS or plasma AVP level in the hypertensive rats compared to the normotensive ones. The only difference was a lower AVP content in the pituitary of LH rats compared to LN (p less than 0.01), which is difficult to interpret. Our results shed doubt on the efficiency of a swimming training on the evolution of hypertension in the Lyon rat model.

Animals↗