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Biomedical subjects

C Chauvin

Publications and source records attributed to C Chauvin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Lack of correlation between apoptosis and DNA single-strand breaks in X-irradiated human peripheral blood mononuclear cells in the course of ageing.

The dependence on age of both the basal and the X-radiation-induced levels of apoptosis was examined in human peripheral blood mononuclear cells (PBMC). In the same samples, the base value and the extent of induced DNA single-strand breaks were determined, using a sensitive and fast microplate assay. PBMC were isolated from blood of donors of various age groups (20-30, 40-60 and > 70 years of age) and X-irradiated ex vivo using a 6 MV linear accelerator to give a total exposure of 4 Gy. The mean basal levels of apoptosis in PBMC from donors in the 40-60 year age group and the > 70 year age group were found to be only slightly higher (by 20-10%) compared to that of the 20-30 year age group, whereas the extent of DNA damage strongly and significantly (P < 0.01) increased with age by up to 2-fold. In contrast to the extent of induced DNA damage, which steadily increased in the course of ageing by up to 1.8-fold, there was only a transient increase in the level of induced apoptosis to 1.5-fold in PBMC from X-irradiated blood (4 Gy photons) from donors aged 40-60 followed by a decrease to 0.9-fold in PBMC from old donors (>70), compared to age group 20-30. The results show that X-ray-induced apoptosis and DNA damage in PBMC are not correlated during ageing.

Aging↗
PubMed1998

In vivo hypoxic exposure impairs metabolic adaptations to a 48 hour fast in rats.

Hypoxia is well known to affect carbohydrate metabolism through its action on liver function and thus on glucose homeostasis. The aim of this study was to examine the carbohydrate, lipid and protein metabolic responses to 48 h of hypoxia, as well as the hormonal adaptations using both normoxic controls and hypoxic animals in the fasted state to standardize for the marked hypophagia observed in response to hypoxia. Hypoxia exposure (inspiratory oxygen fraction (FI,O2) = 0.1) resulted in a greater weight loss (-23 +/- 3.6% versus -16 +/- 2% in controls, p<0.001). Hypoxia plus fasting led to a significant increase in plasma glucose, lactate, insulin and catecholamine concentrations, while the increase in free fatty acid and beta-hydroxybutyrate was abolished. Changes in plasma amino acid patterns were not affected by hypoxia. Liver glycogen depletion was significantly less pronounced in the hypoxic group, while phosphoenolpyruvate carboxykinase (a key enzyme of liver gluconeogenesis) activity and transcription enhancements were abolished by hypoxia. Overall, hypoxic exposure in rats fasted for 48 h resulted in a unique pattern that differed from responses to injury or fasting per se. Oxygen seems to play a central role in the metabolic adaptation to fasting, from gene expression to weight loss. Since hypoxaemia associated with fasting has detrimental effects on nutritional balance, the present observations may be clinically relevant in the setting of acute exacerbation with hypoxaemia for chronic respiratory disease.

Adaptation, Physiological↗
PubMed1996

The inhibition of phosphoenolpyruvate carboxykinase following in vivo chronic phenobarbital treatment in the rat is due to a post-translational event.

Chronic treatment of rats with phenobarbital has been reported to decrease gluconeogenesis in rat hepatocytes by a 50% inhibition of phosphoenolpyruvate (P-pyruvate) carboxykinase activity [Argaud, D., Halimi, S., Catelloni, F. & Leverve, X. (1991) Biochem. J. 280, 663-669]. Contrary to the current knowledge of P-pyruvate carboxykinase regulation, we failed to find a diminution of either P-pyruvate carboxykinase protein (by using a polyclonal antibody) or P-pyruvate carboxykinase mRNA, in the liver of rats treated with phenobarbital for 2 weeks. Kinetic studies of P-pyruvate carboxykinase activity, measured by either carboxylation of P-pyruvate or decarboxylation of oxaloacetate, revealed a decrease in both V(max) and Km after phenobarbital treatment, whereas the nutritional state affected only the V(max), as expected. Assessment of P-pyruvate carboxykinase specificity was confirmed by the full inhibition of the enzyme with its specific inhibitor 3-mercaptopicolinate in the micromolar range. P-Pyruvate carboxykinase, purified either by ammonium sulfate fractionation or by immunoprecipitation, exhibited a similar decrease in affinity after phenobarbital treatment. Although the molecular mass does not appear to be altered, the pH sensitivity to 3-mercaptopicolinate inhibition and the enzyme recovery after immunoprecipitation both seemed to be affected. This leads us to propose that the effect of chronic phenobarbital treatment on P-pyruvate carboxykinase activity is not the result of transcriptional regulation but is exerted at the post-translational level.

Animal Nutritional Physiological Phenomena↗
PubMed1995

Mechanism of gluconeogenesis inhibition in rat hepatocytes isolated after in vivo hypoxia.

Gluconeogenesis was studied in hepatocytes isolated from fasted rats submitted to 24 h of hypoxic exposure (inspired O2 fraction 0.1) or to room air. Hepatocytes from hypoxic rats compared with controls exhibited a lower gluconeogenic rate with lactate (5.1 +/- 0.3 vs. 7.2 +/- 0.3 mumol.min-1.g dry cells-1, P < 0.001) but not with dihydroxyacetone (9.1 +/- 0.3 vs. 9.4 +/- 0.4 mumol.min-1.g dry cells-1), suggesting involvement of the phosphoenolpyruvate-pyruvate cycle. Experiments with perifused hepatocytes from hypoxic and control rats showed a single relationship between phosphoenolpyruvate and glucose flux (JGlc) but two different curves when cytosolic oxalacetate was plotted against JGlc. The decreased phosphoenolpyruvate carboxykinase (PEPCK) activity in the hypoxic group (9.0 +/- 0.9 vs. 16.2 +/- 1.9 nmol.min-1.mg protein-1, P < 001) without change in the Michaelis constant further settled the involvement of this step. The significant decrease in PEPCK mRNA levels in livers from hypoxic rats led us to propose that in vivo hypoxic exposure inhibits gluconeogenesis at the PEPCK level by decreasing PEPCK gene transcription.

Adenine Nucleotides↗
PubMed1993

A study of the expression of four chemoresistance-related genes in human primary and metastatic brain tumours.

We investigated four mechanisms of intrinsic chemoresistance in a series of 67 human brain tumours including 31 gliomas (one grade I ganglioglioma, nine grade II and 10 grade III astrocytomas, 11 glioblastomas), 13 cerebral metastases, one medulloblastoma, one malignant teratoma, three ependymomas and 18 meningiomas. We studied four genes by northern blotting: multidrug-resistance (MDR 1), glutathione-s transferase (GST pi), dihydrofolate reductase (DHFR), and topoisomerase II (Topo II). The Topo II gene was absent in the normal adult brain (100%) and in 64% of the tumour samples tested. A second gene, GST pi, was found to be overexpressed in 38% of brain tumours. The two other chemoresistance-related genes were occasionally overexpressed in brain tumours (2% for MDR1, 9% for DHFR). Our results provide evidence that chemoresistance is intrinsic to the brain tissue and seems likely to be a multifactorial process.

Blotting, Northern↗
PubMed1992

EGF receptor amplification and expression in human brain tumours.

Human epidermal growth factor receptor (EGFr) gene amplification, rearrangements and expression were studied in tumours of the human nervous system. EGFr gene amplification was studied in 46 brain tumours. Gene expression was analysed by northern blot in 37 tumours and binding of its protein to EGF in 27 tumours. The EGFr gene was simultaneously amplified (with arrangements in 12.5% of gliomas) and overexpressed in 53% (9/17) of malignant gliomas, but never in meningiomas. In five high grade gliomas, amplification was always associated with a high level of receptors. However, since high amounts of EGF receptors found in one glioma were not the result of gene amplification, several systems of deregulation in EGFr production may exist and could be located at translational and/or post-translational levels.

Adolescent↗
PubMed1992

[The EGF receptor pathway in human cerebral tumors].

The epidermal growth factor receptor gene is the most frequently involved proto-oncogene in human glial brain tumors, in the present series in agreement with previous reports in literature. It is therefore important to study this gene from DNA to the protein product. The vicinity of cystic fluid (C.F.) to tumor cells of the cystic wall has suggested investigation of possible "E.G.F.-like" autocrine activities in C.F. In 40% of gliomas, E.G.F.-R. gene is amplified and overexpressed. This is never observed in low grade astrocytomas. In 12% of the cases, mutations of the E.G.F.-R. gene are observed. In correlation with genomic abnormalities, E.G.F.-R. is immunoprecipitated in 40% gliomas. The basal phosphorylation of the receptor is increased in 50% gliomas. In C.F., unexpectedly, E.G.F.-R. phosphorylation inhibitory effect is observed. Its biochemical analysis suggests an anti-tyrosine kinase activity. The observation of anti-tyrosine kinase activity in C.Fs suggests the presence of negative modulatory factors of the proto-oncogene activation in tumor tissues. This could have therapeutical interest.

Blotting, Northern↗
PubMed1991

Human gliomas and epileptic foci express high levels of a mRNA related to rat testicular sulfated glycoprotein 2, a purported marker of cell death.

Clone pTB16 has been isolated by differential screening of a human glioma cDNA library. Northern blot analysis has shown that pTB16 expression is several times (greater than 11-fold) higher in gliomas than in a primitive neuroectodermal tumor. This observation was supported by in situ hybridization and extended to nine other gliomas. Expression was virtually absent in adenocarcinoma cells metastasized to brain. Malignant gliomas showed stronger hybridization than benign gliomas, while blood capillaries did not show hybridization. pTB16 mRNA was also shown to be expressed in established glioma cell lines and at high levels in epileptic foci, indicating that expression of the gene may be limited to certain cell types and that its upregulation is not merely a consequence of cellular proliferation. Nucleotide sequence analysis identified pTB16 as the human counterpart for rat testicular sulfated glycoprotein 2 (SGP-2), whose function in the reproductive system remains unknown. Although SGP-2 transcripts, and hence pTB16, were recently shown to be increased in neurodegenerative diseases such as scrapie in hamsters and Alzheimer disease in humans, our observations with brain tumors and epilepsy are suggestive of a role for pTB16 in neuropathologies in general and support the hypothesis of its involvement in tissue remodeling and cell death.

Blotting, Northern↗
PubMed1991

Activation of myc gene family in human lung carcinomas and during heterotransplantation into nude mice.

myc gene family activation (c-myc, L-myc, and N-myc) was examined in 26 human lung carcinomas and in their corresponding xenografts in nude mice. Of the 16 neuroendocrine (NE) carcinomas studied, amplification was observed in 4 with a c-myc probe and in 1 with both L- and N-myc probes. Overexpression was found in 1 of 7 cases studied for c-myc mRNA, in 1 of 7 cases for N-myc, and in 2 of 7 cases for L-myc. Of the 10 non-small cell lung carcinomas studied, only c-myc was amplified in 1 case and overexpressed in 5 of 7 cases. These results suggest that L- and N-myc gene activation are restricted to NE carcinomas. Over-expression of the myc gene without amplification was detected in 36% of cases. During heterotransplantation, there was a 27% change in myc gene abnormality and a 57% increase in myc expression levels, mostly in NE carcinomas (5 of 7; 71%). In a total of 42 xenografted lung carcinomas studied, 45% amplification and 77% overexpression of one of the myc genes were detected with a high prevalence of L-myc overexpression in NE carcinomas (50%) and of c-myc overexpression in non-small cell lung carcinomas (66%). Finally, 19 of 26 (73%) tumors are growing in nude mice with no myc gene amplification and 43% with no myc mRNA overexpression. Thus myc gene activation is not strictly required for heterotransplantation but seems to be a favorable factor in the maintenance and progression of lung carcinomas in vivo.

Animals↗
PubMed1991

[Detection of homologous oncogene sequences in the genome of Plasmodium falciparum].

Homologous sequences of the acute RNA tumor virus oncogenes have been found to be highly conserved within vertebrates, insects and yeasts. In the present work, seven different oncogene DNA sequences have been used as probes to search for homologous sequences in the DNA of the protozoan Plasmodium falciparum. Both the v-fms v-Ha ras probes hybridized P. falciparum DNA. The oncogene study will allow an understanding of the biology of the parasite and particularly the host-parasite relationships which allow P. falciparum to develop, keeping the established harmony between the parasite and his host.

Animals↗
PubMed1990

Analysis of the activation of the myc family oncogene and of its stability over time in xenografted human lung carcinomas.

In order to validate the use of the nude mouse as a model for studying lung cancers, 21 different lung cancers were xenografted onto nude mice and the tumoral DNA and RNA were analyzed for abnormality in the myc family genes (c-myc, L-myc, and N-myc). Six of 14 small cell lung cancers (SCLC) showed a 4-35-fold amplification for L-myc, 5 of 7 non-SCLC a 3-5-fold amplification for c-myc, and 1 of 14 SCLC an 80-fold amplification for N-myc. Of the 7 SCLC with amplified L- or N-myc oncogenes, 4 were of the small and large histological type, while only 5 of the 21 cases studied were of the small and large type. All xenografted tumors with amplification of one of the myc genes showed overexpression of the related mRNA. Overexpression without amplification of the myc genes was observed for 3 SCLC and 2 non-SCLC. These results indicate that the L-myc gene seems to be associated with the small and large phenotype in SCLC, whereas c-myc seems to be implicated in non-SCLC. Of the 21 lung cancers studied 14 were analyzed for myc family gene activation for serial passages into nude mice. No variation of DNA amplification was observed during long-term growth in nude mice for any of the myc oncogenes. Changes in the level of mRNA expression were observed only for c-myc; a beginning of expression in one SCLC and an increase in expression in one non-SCLC were noted in late passages when compared with early ones. The nude mouse is therefore a valuable model for the study of lung cancers "over a 4-year period at least."

Animals↗
PubMed1990

Failure to detect viral genomic sequences of three viruses (herpes simplex, simian virus 40 and adenovirus) in human and rat brain tumors.

Little is known about oncogenesis in brain tumors. Viruses are thought to be involved in some neurological diseases, the presence of subfractions of viral DNA has been reported in various circumstances and the oncogenicity of some viruses has been demonstrated in animal experiments. The discovery of homologies between retroviral oncogenes and normal cellular genes (proto-oncogenes) has stimulated once again the search for viral responsibility in oncogenesis. Having a large bank of tumor material available, we systematically examined 39 brain tumors using Southern blot hybridization with DNAs of three viruses, known to be involved in neurological diseases: herpes simplex virus (HSV), simian virus 40 (SV40) and adenovirus type 2 (Ad2). We detected no homology between the DNAs of the examined material and the viral DNA probes. We compare these negative results with those of other published studies and discuss the experimental conditions, with special reference to the possibility of non-specific hybridization, which could account for the positive results reported. The present negative results could be interpreted either as absence of involvement of the three investigated viruses in brain tumor oncogenesis, or an indirect involvement through a hit-and-run mechanism or a highly dispersed state of the viral sequences among the host genome, which would prevent hybridization with the probe, as it has been supposed to be the case during the latency phase of herpes virus.

Adenoviridae↗
PubMed1989

[Prolonged hepatitis due to ajmaline--description of a case and review of the literature].

A 60 years old woman was admitted for jaundice and fever which appeared after a treatment with ajmaline-butabarbital for two-weeks. Abdominal ultrasound examination and endoscopic retrograde cholangiography were normal. Mitochondrial antibodies were absent. Jaundice persisted for three years, associated with diffuse cutaneous xanthomatosis. Five years later, alkaline phosphatases remained elevated. A liver biopsy showed vanishing interlobular bile ducts with centrolobular cholestasis and ductular proliferation. We suggest that ajmaline can induce long lasting cholestasis due to damage to the intrahepatic bile ducts. The responsibility of butabarbital and the relationship with primary biliary cirrhosis are discussed.

Ajmaline↗
PubMed1989

[Post-puberty anorexia nervosa].

Post-puberty anorexia nervosa requires a thorough clinical study to facilitate its diagnosis and its early treatment. Longitudinal studies have demonstrated that good results usually depend on the speed of medical intervention (preferably with admission to hospital) and to the duration of treatment. The fact that certain cases result in death is too often due to excessive intensive care. Infusions must be avoided at all costs and should be replaced by forcible feeding if absolutely necessary. Finally, a better approach to, and a better understanding of adolescents should contribute to the prevention of anorexia nervosa.

Adolescent↗
PubMed1987

[Multiple correlative studies of stereotaxic biopsies of brain tumors].

The opportunity of having several samples at the same site which could be spatially localized allows an intensive exploitation of stereotactic biopsies of brain tumors: the pathological data may be correlated to other measures, performed at the same site (electrical impedance X ray absorption coefficient) or on other samples (NMR relaxation times, water content, nucleic acids). These samples are available for oncology experiments in cellular biology (cell cultures, grafts on nude mice) or in molecular biology (DNA and RNA hybridization with specific nucleic acid probes). We were therefore able: 1) to study the diagnostic homologies between pathology and histology examinations; 2) to show that T1 and T2 NMR relaxation times are 2 times longer in tumor tissues than in normal brain; 3) to show that the electrical impedance is decreased by a factor 2 in brain tumors; 4) to show the absence of integrated viral genomic sequences and the existence of oncogenes association patterns in brain tumors by hybridization of specific sequences; 5) to establish permanent cell lines, the tumorigenicity of which is assayed by grafting on nude mice. Therefore, stereotactic biopsies appear to be, provided they are intensively and rationally exploited, a major research tool in an area which remains unsensitive to the various therapeutic approaches.

Animals↗
PubMed1985

[How many cirrhotic patients may receive propranolol after digestive hemorrhage?].

The aim of the present study was to evaluate how many cirrhotics may receive propranolol after upper gastrointestinal bleeding. One hundred and twelve patients were consecutively admitted in a digestive intensive care unit during a two-year study, for bleeding of esophageal (63 p. 100) or gastric (4 p. 100) varices, or acute gastric erosions (33 p. 100). Twenty-one per cent of patients were initially class A (Child's classification). 26 p. 100 were B, and 53 p. 100 were C. Eighteen patients (16 p. 100) died within the first 10 days. Eighty patients (71 p. 100) did not receive propranolol because of: a) contraindication for this drug (asthma, heart failure, diabetes, n = 25); b) carcinoma, mainly of the liver (n = 11); c) foreseeable lack of compliance with the treatment (n = 8); d) criteria for which the efficacy of propranolol has not been demonstrated (small esophageal varices, jaundice, or ascites, n = 36). Only 14 patients (13 p. 100) received propranolol therapy: 5 stopped their treatment, 3 because of gastrointestinal rebleeding. Our experience suggests that propranolol can be used only in a few cirrhotics for prevention of recurrent gastrointestinal bleeding.

Adult↗
PubMed1983

Localization of the coding region for a 35000 Dalton polypeptide on the genome of herpes simplex virus type 2.

The cloned BglII N fragment of herpes simplex virus type 2 (HSV-2) DNA has been shown to code for a 35K polypeptide. Subfragments made by cleavage with XhoI, BamHI, SstII and XorII were then cloned and used with RNA extracted from HSV-2-infected cells for mRNA selection and in vitro protein synthesis. We found that the major translation product of such hybrid-selected mRNA has a molecular weight of 35 000. By further mapping, DNA coding sequences for this mRNA were located within the region of BglII N, at approximately 0.585 to 0.596 genome map units. DNA sequences complementary to mRNA encoding a 56K polypeptide were located between 0.607 and 0.612 map units.

Chromosome Mapping↗