Search PubMed⌕ Search

Biomedical subjects

C Aubert

Publications and source records attributed to C Aubert.

At least 73 records · Page 4Linked to original sources
PubMed1989

Reversibility of para-chlorophenylalanine-induced insomnia by intrahypothalamic microinjection of L-5-hydroxytryptophan.

Para-chlorophenylalanine, a blocker of serotonin biosynthesis by inhibiting tryptophan hydroxylase, induced total insomnia which was accompanied in cat by a permanent discharge of ponto-geniculo-occipital activity. L-5-Hydroxytryptophan microinjection (1-4 micrograms/0.5 microliters) in the anterior hypothalamus 72 h after para-chlorophenylalanine administration, restored both slow wave sleep and paradoxical sleep with variable latencies for each state of sleep. On the contrary, ponto-geniculo-occipital activity was never suppressed. The hypnogenic effects of L-5-hydroxytryptophan were always followed by a return of the para-chlorophenylalanine-induced insomnia. On the other hand, the temperature recording did not show any alteration of the cerebral temperature after para-chlorophenylalanine treatment but the subsequent L-5-hydroxytryptophan microinjection was followed by hyperthermia. Using immunohistochemistry for serotonin after intrahypothalamic L-5-hydroxytryptophan microinjection in parachlorophenylalanine-pretreated cat, we defined a restricted region of the anterior hypothalamus possibly responsible for the hypnogenic effect. This region included the lateral hypothalamus and the anterior hypothalamic area. It is suggested that the reversible hypersomnia after L-5-hydroxytryptophan microinjection in the anterior hypothalamus in para-chlorophenylalanine-pretreated cat is due to a neurohormonal action of serotonin: serotonin could act upon the anterior hypothalamus which secondarily inhibits a waking system located in the ventrolateral hypothalamus leading to the appearance of paradoxical sleep.

5-Hydroxytryptophan↗
PubMed1989

Long-lasting insomnia induced by preoptic neuron lesions and its transient reversal by muscimol injection into the posterior hypothalamus in the cat.

In order to analyse the role of the anterior hypothalamus in the regulation of the sleep-waking cycle we made bilateral neuronal lesions at different levels of the anterior hypothalamus in cats, by means of microinjections of a cell-specific neurotoxin:ibotenic acid. These lesions resulted in severe insomnia in eight cats. This insomnia was characterized by a large decrease or even disappearance of paradoxical sleep and deep slow wave sleep and, to a lesser extent, by a decrease of light slow wave sleep, for 2-3 weeks. In the other five animals, we observed a large reduction of deep slow wave sleep (0-40% of control level), but a less intensive decrease of time spent in paradoxical sleep (50-75% of control level) and no marked effect on light slow wave sleep. During the first 3-6 postoperative days we also noticed hyperthermia in all cats; thereafter, the animals presented only a slight increase in brain temperature which did not appear to trigger the sleep impairment. Histological analysis of the different lesions revealed that the insomnia could be attributed to neuronal cell body destruction in the mediobasal part of the anterior hypothalamus covering; the medial preoptic area and a narrow portion of the lateral preoptic area as well as a restricted part of the anterior hypothalamic nucleus. In order to investigate the putative role of the posterior hypothalamic structures in the mechanism of insomnia after lesion of the mediobasal preoptic area neurons we injected an agonist of GABA into the ventrolateral part of the posterior hypothalamus to locally depress the neuronal activity. The bilateral intracerebral microinjection of muscimol (0.5-5 micrograms) induced a transient intensive hypersomnia (slow wave sleep and paradoxical sleep). These findings indicate that neuronal cell loss in the mediobasal preoptic area induced a long lasting insomnia. Thus, it may be hypothesized that the integrity of this structure is necessary for sleep appearance. Finally, our data are in keeping with an intrahypothalamic regulation of the sleep-waking cycle.

Animals↗
PubMed1989

Molecular cloning of the complete genome of Theiler's virus, strain DA, and production of infectious transcripts.

We constructed a complete cDNA clone of the genome of Theiler's virus strain DA in a Bluescript plasmid. This recombinant plasmid, called pTMDA, was used to synthesize full length RNA transcripts of the viral insert. The RNA was infectious for BHK cells. Virus R1-DA, obtained from transfected BHK cells, caused the biphasic disease classically observed with this strain of Theiler's virus. SJL/J mice did not show clinical symptoms during the first week following intracranial inoculation, although viral antigens were found in a few neurons of brain and spinal cord. By 45 days post-inoculation, the mice had developed a chronic demyelinating disease and viral RNA and antigens could be found only in spinal cord white matter in areas surrounded by inflammatory infiltrates. At this stage no RNA or antigens were found in neurons. Therefore the phenotype of R1-DA was indistinguishable from that of genuine DA Theiler's virus.

Animals↗
PubMed1989

[Early adjuvant intraportal chemotherapy with 5-fluorouracil after hepatic resection of colorectal metastasis: a preliminary clinical and pharmacokinetic study].

Intraportal continuous infusion of 5-FU (600 mg/m2/24 h during 7 days) was administered in the immediate postoperative course of 6 consecutive patients with colorectal metastases resected for cure (one segmentectomy and 5 nonanatomical local resections). One month later, a systemic continuous infusion of 5-FU was delivered at the same dose. The tolerance of intraportal chemotherapy was good despite 2 patients with mild digestive toxicity. The plasma concentrations of both unchanged 5-FU and 5,6-dihydro-5-FU (the primary metabolite of 5-FU), were determined in 2 patients using Gas Chromatography--Mass Spectrometry. The 5-FU clearance was higher after intraportal infusion than after systemic infusion (x 1.5 to 3). Hepatic extraction was variable (0.32-0.70) and lower than in reported experimental data on dogs (0.90-0.99). 5,6-dihydro-5-FU concentrations were constantly higher than 5-FU concentrations in plasma. The patient with lower hepatic extraction had the higher 5,6-dihydro-5-FU plasma concentrations. These findings suggest a predominant extrahepatic formation of plasmatic 5,6-dihydro-5-FU.

Adult↗
PubMed1988

[Chlamydia TWAR respiratory infection in cytomegalovirus infection].

A middle-aged male smoker with cytomegalovirus infection developed a respiratory tract infection, mostly bronchitis, associated with a low Chlamydia psittaci titer and a high C. trachomatis titer in indirect immunofluorescence tests. This situation, previously encountered in children and elderly people having no contact with birds and no genital infection, was reminiscent of the TWAR strains interhuman infections described by Grayston and Wang. A serum sample was therefore sent to Proff. Grayston's laboratory where it was found to be highly reactive in the specific microimmunofluorescence test against a reference TWAR strain. This shows that TWAR infections are present in France. Although TWAR strains are regarded as forming a special morphological entity within the C. psittaci group, the serological data available seem to indicate that they might be discussed on the basis of a high prevalence of C. trachomatis titers in the group indirect immunofluorescence reactions now being used. However, TWAR infections need to be reinvestigated as soon as TWAR antigens become available in this country under license from the Seattle University, Washington.

Adult↗
PubMed1988

Detection of a low frequency of activated ras genes in human melanomas using a tumorigenicity assay.

We have used an assay combining DNA-mediated gene transfer and tumorigenicity in Swiss athymic mice to look for activated ras genes in solid human sporadic melanomas. This assay can detect ras oncogenes mutated at codons 12, 13, or 61. We examined a panel of 13 independent surgical specimens of primary tumors and metastases. No H- or K-ras oncogenes were detected; an N-ras oncogene, mutated at codon 61, was identified in one of the 13 samples. No N-ras genes mutated at codon 13 were detected. Thus, the tumorigenicity assay detects a low frequency of ras gene activation in melanomas.

Amino Acid Sequence↗
PubMed1988

Expression of Theiler's murine encephalomyelitis virus protease 3C and polymerase 3D in Escherichia coli and characterization of monospecific sera.

Defined DNA fragments of cloned Theiler's murine encephalomyelitis virus genome were used to construct procaryotic recombinant plasmids expressing viral genes 3C and 3D. In these plasmids (pEX-EMBL vectors), viral sequences are fused in-phase behind the Escherichia coli lac Z' gene which is under the control of the inducible lambda Pr promoter. Partially purified fusion proteins were used to immunize Balb/c mice. Sera monospecific for the viral protease 3C and polymerase 3D were obtained. These sera detected their corresponding antigens in situ in infected BHK cells using immunocytochemical reactions.

3C Viral Proteases↗
PubMed1987

Identification of Theiler's virus infected cells in the central nervous system of the mouse during demyelinating disease.

Theiler's virus is a picornavirus responsible for a persistent, demyelinating infection of mouse central nervous system. We examined the nature of infected cells during the course of this disease using a simultaneous immunoperoxidase-in situ hybridization assay. Cell types were identified with antigenic markers and infected cells were recognized by the presence of viral RNA. We found that, depending on the animal, approximately 10% of infected cells were migroglia-macrophages, 5 to 10% were astrocytes and 25 to 40% were oligodendrocytes. Approximately half of the infected cells could not be identified.

Animals↗
PubMed1986

Simultaneous determination of tropatepine and its major metabolites by high-performance liquid chromatographic-mass spectrometric identification. Application to metabolic and kinetic studies.

Tropatepine is used to combat against extrapyramidal syndrome induced by neuroleptic drugs. A high-performance liquid chromatographic method was proposed for the simultaneous determination of tropatepine and its potential metabolites in biological fluids. After double extraction of compounds in hexane and back-extraction in hydrochloric acid, the chromatographic separation was performed on a reversed-phase column with an acetonitrile--perchlorate buffer mixture as mobile phase. Compounds were detected at 229 nm and the detection limit was about 15 ng/ml. The method was applied to bile and urine samples collected in rats, after a single high oral dose of 100 mg/kg of tropatepine hydrochloride. Gas chromatography-mass spectrometry was used for identification of the potential metabolites. Nortropatepine and tropatepine S-oxide were identified in this way, and it seemed that tropatepine was subjected to a large and intense metabolic process. The analytical procedure and the results of the metabolic investigation were applied to a preliminary pharmacokinetic study in patients undergoing long-term oral therapy with tropatepine.

Animals↗
PubMed1986

Plasma quantification of quazepam and its 2-oxo and N-desmethyl metabolites by capillary gas chromatography.

The authors have developed a gas chromatographic method for the simultaneous quantification of quazepam in plasma and its two main metabolites, 2-oxoquazepam and N-desmethylquazepam. This method involves an extraction from plasma using butyl acetate, and an analysis by electron-capture detection on a CP-Sil 5 WSCOT capillary column. Intra- and inter-day precision and accuracy were better than 10% for each of these three compounds, even near their detection limit estimated at 0.2 ng/ml. Linearity proved satisfactory between 0.2 and 60-70 ng/ml. For endogenous plasma components, adequate specificity was achieved. Despite some inconveniences, a long analysis time, a progressive saturation of the column owing to a low oven temperature, and a relatively short life-span of the CP-Sil 5 columns, this method was the only one available in the literature for the quantification of quazepam and its metabolites from the same plasma sample. It was successfully applied to phase I studies in healthy volunteers.

Anti-Anxiety Agents↗
PubMed1986

Demyelinating lesions due to Theiler's virus are associated with ongoing central nervous system infection.

We used in situ hybridization and immunocytochemistry to look for a correlation between virus expression and white matter lesions during late demyelinating disease due to persistent Theiler's virus infection. We found the following. (i) Tissue lesions developed at the site of virus infection. This correlation was not explained by infection of lymphocytes and macrophages. (ii) Large differences in the extent of pathology existed between mice. The amount of inflammation paralleled the number of cells containing viral RNA or viral capsid antigens. (iii) C57BL/6 mice, which are resistant to demyelination, were able to eradicate the infection. Our results are strongly in favor of a mechanism of demyelination in which viral gene products play a central role.

Animals↗