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J Féger

Publications and source records attributed to J Féger.

At least 37 records · Page 2Linked to original sources
PubMed1996

Five isoenzymes of protein kinase C are expressed in normal and STZ-diabetic rat hepatocytes: effect of phorbol 12-myristate 13-acetate.

Using isoenzyme-specific antisera, five Protein Kinase Cs (PKCs) were detected in cytosol and membrane hepatocytes from normal rats: PKC alpha (80 kDa), PKC beta II (40, 50, 55, 85 kDa), PKC delta (74, 76 kDa), PKC epsilon (95 kDa), PKC zeta (65, 70 kDa). STZ-diabetes induced a lower expression of the five PKCs, a higher localization in the cytosol, a preferential expression of PKC delta as the 76 kDa phosphorylated species and a decreased kinase activity towards Histone III-S. A 1 microM phorbol 12-myristate 13-acetate (PMA) incubation induced similar translocation to the membrane of PKCs alpha, native 85 kDa beta II and epsilon. The 74 kDa PKC delta was switched to the 76 kDa species, the normal form in STZ-diabetic cells. The truncated PKC beta II and PKC epsilon were unchanged.

Amino Acid Sequence↗
PubMed1996

Effect of polymeric nanoparticle administration on the clearance activity of the mononuclear phagocyte system in mice.

We investigated the consequences of acute and subacute administration of mice with polyisobutylcyanoacrylate (PIBCA), polyisohexylcyanoacrylate (PIHCA), poly(D,L-lactic) acid (PLA), and polystyrene (PS) nanoparticles on the mononuclear phagocyte system phagocytic function. This was done by measuring the clearance rate of colloidal carbon. Single administration of PIBCA and PIHCA (but not PLA and PS) nanoparticles reduced carbon clearance in both a time- and dose-dependent fashion. Since clearance of preopsonized carbon was normal, it was assumed that PIBCA and PIHCA nanoparticles deplete opsonins specific for carbon recognition. A decrease in plasma fibronectin levels resulting from nanoparticle administration suggested its implication in their removal from blood. However, fibronectin does not seem to be responsible for PIBCA and PIHCA blockade. Phagocytic function was preserved after repeated treatment with nanoparticles, probably as a result of increased Kupffer cell phagocytic activity and the contribution of spleen macrophages. Neither toxicity nor effects due to nanoparticle hepatic accumulation were observed.

Animals↗
PubMed1996

Alleviation of experimental hemiparkinsonism by high-frequency stimulation of the subthalamic nucleus in primates: a comparison with L-Dopa treatment.

Experimental studies in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys have shown that akinesia and rigidity are linked to a hyperactivity of glutamatergic subthalamic nucleus neurons and that the lesion of this nucleus can ameliorate parkinsonian motor signs. In our study, high-frequency stimulation applied at the subthalamic level was performed on two Macaca mulatta monkeys rendered hemiparkinsonian by unilateral infusion of MPTP. Its effects on rigidity and bradykinesia have been quantified. The results exhibit an important alleviation of both symptoms during the application of subthalamic stimulation comparable to that obtained during L-Dopa treatment, but without the appearance of abnormal movements such hemiballism or dyskinesia. Our data show that subthalamic stimulation has a beneficial effect on experimental parkinsonian rigidity and bradykinesia and suggests a new therapy approach for the treatment of Parkinson's disease by using subthalamic high-frequency stimulation instead of L-Dopa treatment.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1996

Increased subthalamic neuronal activity after nigral dopaminergic lesion independent of disinhibition via the globus pallidus.

Electrophysiological records of unit activity were used to compare the effects of excitotoxic pallidal lesions and 6-hydroxydopamine-induced damage to the midbrain dopaminergic neurons on the discharge rates and patterns of the subthalamic neurons. Removal of the pallidal input induced a slight, but statistically significant, increase (19.5%) in the discharge rate and no change in the firing pattern when compared to control animals. The rats with a dopaminergic lesion showed greater increase (105.7%) while the firing pattern activity of the subthalamic neurons became more irregular, with burst. These results indicate that the increased activity of the subthalamic neurons following a midbrain dopaminergic lesion cannot be due solely to inhibition-disinhibition involving the striato-pallido-subthalamic pathway and induced by the striatal dopaminergic depletion.

Animals↗
PubMed1996

Kinetic analysis of epidermal growth factor endocytosis in rat hepatocytes. Effects of diabetes.

In the present study we followed the different steps of epidermal growth factor receptor (EGF-R) endocytosis in freshly isolated rat hepatocytes. Hepatocytes exhibit two classes of surface EGF receptors consisting of approximately 5,000 high-affinity sites (Kd = 15 pM) and 166,000 low-affinity sites (Kd = 670 pM). Binding of labeled EGF to hepatocytes permeabilized by digitonin shows that 75% of the total EGF-R are localized at the cell surface. At 37 degrees C, hepatocytes continuously internalized and degraded EGF in spite of a down-regulation of cell surface receptors. The internalization rate constants measured as a function of a range 125I-EGF concentrations (0.01 - 5 nM) involving various degrees of EGF-R occupancy show superimposable curves. This indicates that the specific internalization rate of EGF-R complex is independent of receptor occupancy. Streptozotocin-induced diabetes reduces the number of low-affinity EGF-R to 50,000 and produces a complete loss of high-affinity sites. The dynamics of 125I-EGF endocytosis show that diabetic hepatocytes fail to down-regulate the surface EGF-R efficiently although the constant rate of internalization is not modified. Decreased down-regulation of EGF-R together with enhanced EGF endocytosis suggest a greater efficiency in EGF-R recycling in diabetic rat hepatocytes.

Animals↗
PubMed1995

Differential expression of five protein kinase C isoenzymes in FAO and HepG2 hepatoma cell lines compared with normal rat hepatocytes.

We analyzed the expression of five protein kinase C (PKC) isoforms in cytosolic and membrane fractions from normal rat hepatocytes compared with those of two tumorigenic cell lines FAO and HepG2. Western blots with PKC-specific isoenzymes polyclonal antibodies provide evidences for the presence of the five isoforms alpha, beta II, delta, epsilon and zeta in normal rat hepatocytes. In hepatoma cells, we show differences in the level of expression, the molecular sizes and the responses to Phorbol 12-myristate 13-acetate (PMA).

Amino Acid Sequence↗
PubMed1995

Electrophysiological study of the excitatory parafascicular projection to the subthalamic nucleus and evidence for ipsi- and contralateral controls.

The activity of subthalamic neurons was recorded extracellularly in anaesthetized rats after stimulation, inhibition or lesioning of the parafascicular nucleus. Electrical stimulation of the parafascicular nucleus evoked a complex response with two excitatory phases. The first response was correlated with a monosynaptically-driven excitation via a parafascicular input to the subthalamic nucleus. Since the second phase was observed even when the early excitation was not recorded and was eliminated by lesion of the globus pallidus, we suggest that it is not generated by a mechanism intrinsic to the subthalamic nucleus and is due to a disinhibitory effect originating from the globus pallidus. Microinjection of carbachol into the parafascicular nucleus enhanced by 119% the discharge rate of the neurons in the ipsilateral subthalamic nucleus and that of muscimol decreased the discharge rate by 91%. Opposite changes, a decrease of the discharge rate of 49% after microinjection of carbachol and an increase of 47% after muscimol, occurred in the contralateral subthalamic nucleus. In contrast to the above results, the unilateral excitotoxic lesion of the parafascicular nucleus, performed one week before recording, decreased the discharge rate by 69% of the ipsilateral subthalamic nucleus neurons and by 34% that of the contralateral neurons. We suggest that the parafascicular input to the subthalamic nucleus is an excitatory pathway which can tonically drive the neuronal activity in this structure. The opposite changes recorded in the ipsi- and contralateral subthalamic nucleus during unilateral microinjection of excitatory or inhibitory drugs in the parafascicular nucleus emphasize the importance of this thalamic structure in the bilateral regulation of basal ganglia activity via the subthalamic nucleus.

Animals↗
PubMed1994

The projections from the parafascicular thalamic nucleus to the subthalamic nucleus and the striatum arise from separate neuronal populations: a comparison with the corticostriatal and corticosubthalamic efferents in a retrograde fluorescent double-labelling study.

The parafascicular thalamic nucleus projects to the subthalamic nucleus and the striatum. Double-retrograde fluorescent tracing was used to determine whether these projections arise from the same neurons via axon collaterals. True Blue was injected into the subthalamic nucleus and Nuclear Yellow was injected into the striatum of each rat and the parafascicular thalamic nucleus was examined under the fluorescence light-microscope. Individual parafascicular neurons were not double-labelled with the tracers. The True Blue- and Nuclear Yellow-labelled neurons wee located in different parts of the parafascicular nucleus ipsilateral to the injections. In the rostral part of the parafascicular nucleus, True Blue-labelled neurons were located ventral to the fasciculus retroflexus, and in the caudal part of the nucleus. True Blue-labelled neurons were located close to the medial and lateral borders of fasciculus retroflexus. Nuclear Yellow-labelled neurons were found mainly to encircle the fasciculus retroflexus in the rostral part of the parafascicular nucleus and in the dorsolateral sector of the caudal part of the parafascicular nucleus. Double-labelled neurons were, however, found in the cortex. The proportion of neurons projecting to both the subthalamic nucleus and the striatum accounted for 38% of the total number of cortiscosubthalamic neurons in the prefrontal cortex, 15.5% in the cingulate cortex and 9% in the sensorimotor cortex. The present finding of an individualization between the parafascicular efferents to the subthalamic nucleus and the striatum emphasize the importance of this projection and provides further evidence of the associative functions attributable to the subthalamic nucleus.

Animals↗
PubMed1994

Cell receptors: definition, mechanisms and regulation of receptor-mediated endocytosis.

Receptors allow the cells to recognize specific ligands and to receive extracellular messages. They can be classified into five families: 1) receptors for lipidic or lipophilic ligands; 2) the seven transmembrane receptors which mediate their messages by transduction through the activation of G-proteins, effectors and second messengers to amplify the response; 3) receptors which present an enzymatic activity on their transmembrane domains; 4) channel-receptors, transmembrane oligomeric molecules which let ions flow into the cell and 5) receptors which role is to internalize ligands, whatever their various functions. In parallel a concept of membrane plasticity was developed: vesicles are constantly formed from the plasma membrane, addressing complexes of ligand-receptors to specific intracellular compartments. This receptor-mediated endocytosis of ligand plays a critical role in regulating the number of a given receptor at the plasma membrane and in the cellular uptake of nutrients, growth factors and hormones. Many pathways exist for these transports but little is known about the signals which select the ligands or the receptors and direct them to their appropriate intracellular destination.

Amino Acid Sequence↗
PubMed1993

Reversal of rigidity and improvement in motor performance by subthalamic high-frequency stimulation in MPTP-treated monkeys.

In Parkinson's disease the loss of dopaminergic neurons in the substantia nigra is associated with global disorganization of basal ganglia activity and, in particular, with increased activity of the excitatory glutamatergic neurons of the subthalamic nucleus. Recent experimental studies have shown that parkinsonian symptoms can be alleviated by selective lesioning of the subthalamic nucleus in monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We measured the effect of high-frequency stimulation of the subthalamic nucleus in two unilaterally MPTP-treated monkeys in order to determine whether it was possible to obtain reversible, gradual and controllable functional impairment of this structure. Clinical, mechanographic and electromyographic results demonstrate that this technique can alleviate parkinsonian rigidity and bradykinesia without causing dyskinesia or hemiballismus. This study supports the hypothesis that the subthalamic nucleus and its excitatory projections have an important role in the mechanisms sustaining the expression of parkinsonian motor changes, and suggests that high-frequency stimulation of the subthalamic nucleus could be included in treatment for parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Evidence that the parafascicular projection to the subthalamic nucleus is glutamatergic.

The parafascicular nucleus projection to the subthalamic neurones has an excitatory synaptic effect. We have examined the possible glutamatergic mediation of this pathway. The initial excitatory response elicited by electrical stimulation of the parafascicular neurones was inhibited by a microinjection of excitatory amino acid receptor antagonists into the subthalamic nucleus. The antagonists were the broad spectrum kynurenic acid, the NMDA selective antagonist d-AP-5 and the AMPA antagonist CNQX. Their effects were dose-dependent and reversible. The results suggest that the excitatory effect of the parafascicular neurones is mediated by AMPA and NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1992

Effect of monensin and diabetes on asialoglycoprotein degradation in rat hepatocytes.

We have studied the effects of two modulations--streptozotocin-induced diabetes in vivo, and the presence of the carboxylic proton ionophore monensin in vitro--on the degradation of 3H-asialoorosomucoid ligand in isolated rat hepatocytes. The ligand was internalized by means of a synchronous wave procedure. Diabetes was associated with a marked decrease in the amount of total degraded radioactive ligand compared to that in normal cells (3.6% and 37.3% of internalized ligand respectively, at 60 min), together with increased secretion of degradation products into the incubation medium (87% and 46.3% of the total degraded ligand was secreted by diabetic and normal cells, respectively). Monensin induced similar effects in normal cells, but had no apparent effect in diabetic cells.

Animals↗
PubMed1992

Evaluation of the hepatotoxicological effects of a drug in an in vivo/in vitro model.

Both in vivo and in vitro models have certain disadvantages for the study of the chronic hepatotoxicity of drugs. The aim of this work was to evaluate a new approach based on an in vivo/in vitro model. After chronic in vivo treatment of rats with Vincamine and Vindeburnol (an eburnamenine derivative which exhibits hepatotoxic properties in man) liver cells were isolated, and functional and metabolic disorders (metabolic utilization of fructose and protein biosynthesis) were studied to determine injury. The results showed no modification of blood parameters, but a direct relationship between the dose of Vindeburnol administered in vivo and the metabolic disorders observed in vitro, evidencing the high sensitivity and reliability of this model.

Animals↗
PubMed1991

Opioid delta agonists and endogenous enkephalins induce different emotional reactivity than mu agonists after injection in the rat ventral tegmental area.

The possible role of opioid receptor heterogeneity in the biphasic changes in locomotion (activation and inhibition) induced by non-selective opiates such as morphine, has been investigated by measuring the behaviour of rats exposed to different environments after injection into the ventral tegmental area, of selective mu (DAGO) or delta (DTLET, DSTBULET, BUBU) opioid agonists and of kelatorphan, a complete inhibitor of enkephalin metabolism. delta agonists or kelatorphan-induced hyperactivity in a familiar (actimeter), unfamiliar (four-hole box) and a fear inducing (open-field) environment. These effects were suppressed by naloxone and delta selective antagonists (ICI 174, 864 2 mg/kg SC, naltrindole 7 nmol in the ventral tegmental area). Moreover, the delta agonists and endogenous enkephalins protected by kelatorphan did not affect the emotional state of rats measured in an elevated plus maze. Infused into the ventral tegmental area, DAGO also enhanced locomotion in the actimeter but in contrast to delta agonists and kelatorphan, the mu agonist decreased activity in the open-field and the four-hole box. The hypoactivity observed in these tests could be related to an enhanced emotionality produced by mu receptor stimulation, as shown by the significant decrease in the number of visits and time spent in open arms of the elevated plus maze. Naloxone (0.3 mg/kg SC) but not delta selective antagonists, blocked the various responses induced by DAGO.

Animals↗
PubMed1991

[Demonstration of the excitatory effect of the thalamo-subthalamic efferent from the parafascicular nucleus].

The synaptic effect of the projection from an intralaminar thalamic structure, the parafascicular nucleus, to the subthalamic nucleus was investigated through extracellular recordings of subthalamic unit activities. Electrical stimulation of the parafascicular nucleus caused a complex response with two successive excitatory phases. The first excitation was assumed to be monosynaptically driven since it was not affected by pallidal lesion or transsection of the internal capsule. Pharmacological activation of the parafascicular neurons through microinjections of carbachol elicited a prolonged increase in the subthalamic discharge rate. These results suggest that the intralaminar parafascicular nucleus contributes to the activation of subthalamic neurons.

Animals↗
PubMed1990

Excitatory influence of rat subthalamic nucleus to substantia nigra pars reticulata and the pallidal complex: electrophysiological data.

By selective chemical stimulation of the subthalamic nucleus (STh) with the gamma-aminobutyric acid (GABA) antagonist bicuculline, we have studied the effect of its projections to the target nuclei. Results show that bicuculline (0.39 mM) produced a mean activation of 358% in subthalamic neurons. Most of the cells recorded in the substantia nigra pars reticulata (SNpr), the entopenduncular nucleus (EP), and the globus pallidus (GP) were also significantly activated. In the substantia nigra pars compacta (SNpc), slight and opposite changes were produced: half of the cells were activated and half were inhibited. In the striatum, 3 types of responses were recorded: activation, inhibition, and biphasic effect. Inhibition of subthalamic neurons by local microinjection of muscimol (0.95 mM), produced reductions in the neuronal activity of cells in the SNpr, the EP, and the GP. These results suggest that the STh conveys an important and permanent excitatory influence onto its target nuclei. In another set of experiments, in order to investigate whether or not the STh utilizes glutamate for neurotransmission in the SNpr, we injected the glutamate receptor antagonist kynurenic acid (2.6 mM) into the SNpr, later followed by an injection of bicuculline in the STh. Kynurenic acid alone produced a mean inhibition of 30% in non-dopaminergic nigral cells, and antagonized the subsequent bicuculline-induced activating effect of the STh. These results further confirm recent data showing that the STh exerts an excitatory action on its efferent structures, and provide new evidence for glutamatergic transmission in subthalamic projections.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effects induced by chronic treatment with selective D1 or D2 antagonists on open-field behavior and colonic temperature.

We have studied the behavioral responses in open-field and the changes in body temperature induced after chronic treatment with a selective D1 antagonist, SCH 23390, a selective D2+ antagonist, sulpiride, or a non specific but preferential D2 antagonist, haloperidol. After chronic treatment with SCH 23390 or sulpiride, rats were challenged with SKF 38393, selective D1 agonist, or LY 171555, selective D2 agonist, in order to study the responses of D1 and D2 stimulation. After chronic SCH 23390, an increase of the locomotion and of the number of rears were observed whereas, no changes were induced by chronic sulpiride or haloperidol. Acute treatment with sulpiride blocked the hyperlocomotion induced by chronic SCH 23390. In naive rats acute administration of SKF 38393 or LY 171555 did not produce any change in locomotion or rearing. In rats treated chronically with SCH 23390 this acute administration of LY 171555 induced an increase of the number of squares and of the number of rears. In these animals, acute administration of SKF 38393 also augmented the number of squares crossed. In contrast, chronic sulpiride did not modify behavioral responses obtained after acute SKF 38393 or LY 171555. Colonic temperature was not changed after acute SKF 38393 while acute LY 171555 induced a hypothermia. Chronic sulpiride did not modify the responses of SKF 38393 or LY 171555, but an increase in body temperature was observed after acute SKF 38393 in animals chronically treated with SCH 23390. The present results support a different behavioral expression of D1 and D2 supersensitivity in rats. Furthermore, chronic treatment with a D1 antagonist induced facilitatory effects on D2 behavioral responses; however, these D1-D2 interactions were not observed in body temperature responses.

Animals↗