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Biomedical subjects

G Mercier

Publications and source records attributed to G Mercier.

At least 55 records · Page 3Linked to original sources
PubMed1998

Frequency of the C282Y mutation of hemochromatosis in five French populations.

Hereditary hemochromatosis mutation 845A (C282Y) in the HFE gene was recently described, and the C282Y frequencies were reported for various world populations. The aim of this study was to determine the Y allele frequencies of the C282Y mutation for five French populations. The most elevated value (= 5.6%) was obtained for Bretons, in accordance to the hypothesis indicating a Celtic origin of the hereditary hemochromatosis mutation.

Adult↗
PubMed1998

The use of nested RT-PCR of prostate-specific membrane antigen in blood cells: implications for the detection of haematogenous neoplastic cells in patients with prostate adenocarcinoma.

The aim of this study was to determine the presence of haematogenous neoplastic cells in patients with prostate cancer. Circulating prostate cells can be detected in cancer patients by using a nested-reverse transcriptase-polymerase chain reaction assay (RT-PCR), for prostate-specific membrane (PSM) antigen mRNA. This sensitive nested RT-PCR assay may play a crucial role in the administration of adjuvant therapy of patients with prostate adenocarcinoma.

Adenocarcinoma↗
PubMed1998

[Frequency of the coreceptor CCR5 gene delta 32 mutation in different French regions].

We studied the frequency of the coreceptor CCR5 gene delta 32 mutation on 1,836 DNA samples originating from ten French regions. This mutation confers, in the homozygous state, resistance to HIV-1 infection. For the whole territory, the mean percentage presence of the delta 32 mutation is 9.2%. The mutation is statistically more frequent in the north (11.2%) than in the south (6.3%) of the country; this differentiation corresponds probably to a gradient of decreasing frequencies of the delta 32 mutation in Europe.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Mutation analysis of the HLA-H gene in French hemochromatosis patients, and genetic counseling in families.

Mutation analysis of the HLA-H gene in French hemochromatosis patients and genetic counseling in families: Genotype analysis of 61 hemochromatosis patients living in France and 126 controls confirms that the disease is strongly associated with homozygosity for the mutation C282Y of the HLA-H gene: in our sample 67.2% patients, and none of the controls, carry two copies of the C282Y mutation; the frequency of the C282Y allele in a control population is 3.97%. A second variant (H63D) at the HLA-H gene is somehow more enriched (8.2%) in patient chromosomes that do not carry the C282Y mutation. The C282Y mutation was used in 10 hemochromatosis families for genetic counseling.

Amino Acid Substitution↗
PubMed1997

Detection of Borrelia burgdorferi DNA by polymerase chain reaction in urine specimens of patients with erythema migrans lesions.

A polymerase chain reaction (PCR) assay was developed for the detection of Borrelia burgdorferi-specific DNA in the urine of patients with erythema migrans (EM). The target for the PCR was a specific region of the flagellin gene, and DNA was extracted from urine by Chelex resin. The detection limit was 1-10 genomes of B. burgdorferi, B. garinii or B. afzelii. A prospective study was performed with 12 consecutively diagnosed patients with EM, to evaluate the PCR assay on clinical samples. Borrelia burgdorferi-specific DNA could be detected in urine specimens from the 12 patients with EM before antibiotic therapy. Five weeks after therapy all the patients were negative by PCR of urine. Results of the present study confirm that the described PCR assay is sensitive and that this sort of test allows monitoring of the efficacy of therapy in patients with early Lyme borreliosis.

Adult↗
PubMed1997

Influence of lipid diets on the number of metastases and ganglioside content of H59 variant tumors.

We investigated the influence of the fatty acid composition of the diet on the number of hepatic metastases and the ganglioside profile of the primary tumor and metastases. C57BL/6 female mice were fed different diets containing either no fats (TEK) or 8% of fish oil (POL), linseed oil (LIN), safflower oil (SAF) or beef tallow (BT) and were injected subcutaneously in the dorsum with H59 cells, a variant of the Lewis lung carcinoma (3LLc) that metastasizes preferentially to the liver. The omega3 polyunsaturated fatty acid (PUFA)-rich diets (LIN and POL) elicited more metastases than the omega6 PUFA-rich (SAF), fat-free (TEK), or saturated fats (BT) diets. However, dietary fat did not influence the ganglioside composition of either the primary tumors or the metastases, at least in the glucidic part. However, comparison of diets with low (TEK, SAF, and BT) and high (LIN and POL) number of metastases showed that the levels of G3 (which could be a second band of GM2) were greater in metastases of the latter group. This study showed that the H59 hepatic metastases contained more GM2 than the s.c. tumors, irrespective of diet or the number of metastases produced. The small differences in the ganglioside profiles observed in this study could have resulted from the limitations of the HPTLC method. A detailed analysis of the lipid chains, as well as glycolipids other than gangliosides, could give more information on changes resulting from different lipid diets.

Animals↗
PubMed1997

Evaluation of the potential carcinogenicity of 60 Hz linear sinusoidal continuous-wave magnetic fields in Fischer F344 rats.

Electric and magnetic fields (EMFs) associated with the production, transmission, and use of electricity are ubiquitous in industrialized societies. These fields are predominantly of low frequency (50/60 Hz) and are generally of low intensity. Review of the epidemiological evidence shows that the association between exposure to EMFs and cancer is weak and inconsistent, and generally fails to show a dose-response relationship. Moreover, in view of the methodological problems of these epidemiological studies, animal and laboratory studies are urgently needed to determine whether EMFs could be initiators and/or promoters of cancers. The objective of the present study was to determine whether chronic exposure to 60 Hz linear (single axis) sinusoidal, continuous-wave magnetic fields (MFs) of different intensities might increase the risk of leukemia and solid tumor development in rodents born and raised under these fields. Five groups of 50 female F344 rats were exposed for 20 h/day to 60 Hz MFs at intensities of <0.02 (sham controls), 2, 20, 200, and 2000 microT. Full body exposure to the different fields was administered for 104 wk starting from the prenatal period (2 days before birth) and continuing during lactation and weaning until late adult life. Body weight, survival, and clinical observations were evaluated in all groups of animals during in-life exposure. Necropsy was performed on all exposed and control animals that died, were found moribund, or were killed at termination of the study. To preserve and demonstrate the absence of any experimental bias, all clinical observations and pathological evaluations were conducted under "blinded" conditions. Fifty organs and tissues were evaluated in each animal, with special attention to the incidence of mononuclear cell leukemia, brain tumors, and mammary tumors. The findings from this chronic carcinogenicity study demonstrate that, under our defined experimental conditions, exposure to 60 Hz linear (single axis) sinusoidal, continuous wave MFs did not affect animal survival, solid tumor, or mononuclear cell leukemia development in female F344 rats. No statistically significant, consistent, positive dose-related trends with the number of tumor-bearing animals per study group could be attributed to MF exposure.

Age Factors↗
PubMed1997

The c-Jun-induced transformation process involves complex regulation of tenascin-C expression.

In cooperation with an activated ras oncogene, the site-dependent AP-1 transcription factor c-Jun transforms primary rat embryo fibroblasts (REF). Although signal transduction pathways leading to activation of c-Jun proteins have been extensively studied, little is known about c-Jun cellular targets. We identified c-Jun-upregulated cDNA clones homologous to the tenascin-C gene by differential screening of a cDNA library from REF. This tightly regulated gene encodes a rare extracellular matrix protein involved in cell attachment and migration and in the control of cell growth. Transient overexpression of c-Jun induced tenascin-C expression in primary REF and in FR3T3, an established fibroblast cell line. Surprisingly, tenascin-C synthesis was repressed after stable transformation by c-Jun compared to that in the nontransformed parental cells. As assessed by using the tenascin-C (-220 to +79) promoter fragment cloned in a reporter construct, the c-Jun-induced transient activation is mediated by two binding sites: one GCN4/AP-1-like site, at position -146, and one NF-kappaB site, at position -210. Furthermore, as demonstrated by gel shift experiments and cotransfections of the reporter plasmid and expression vectors encoding the p65 subunit of NF-kappaB and c-Jun, the two transcription factors bind and synergistically transactivate the tenascin-C promoter. We previously described two other extracellular matrix proteins, SPARC and thrombospondin-1, as c-Jun targets. Thus, our results strongly suggest that the regulation of the extracellular matrix composition plays a central role in c-Jun-induced transformation.

Animals↗
PubMed1996

Differential modulation of natural and adaptive immunity in Fischer rats exposed for 6 weeks to 60 Hz linear sinusoidal continuous-wave magnetic fields.

Two separate, independent experiments were conducted to evaluate the effect of 60 Hz linearly polarized, sinusoidal, continuous-wave magnetic fields (MFs) on immune system performances in rats born and raised under these fields. Each experiment lasted for 6 weeks. A total of 96 animals, divided into groups of eight animals each, was exposed for 20 h/day to MFs of different intensities, i.e., sham (< 0.02 microT) and 2, 20, 200, and 2000 microT. Another group of animals, which was housed in a separate room, served as cage controls (CC). These animals were exposed to ambient MFs of < 0.02 microT. The following immune responses were evaluated in both experiments total T and B cells; CD4+ and CD8+ subpopulation and natural killer (NK) cell activity in splenic lymphocytes; hydrogen peroxide (H2O2), nitrous oxide (NO), and tumor necrosis factor (TNF) production by peritoneal macrophages. Our results show that a 6 week exposure to MFs induced a significant decrease in the number of CD5+, CD4+, and CD8+ populations. These changes were even more significant in rats that were exposed to fields of 2000 microT. A lower, although significant, decrease in the CD5+ population was also observed in animals that were exposed to fields of 200 microT. Linear regression analysis demonstrated a dose effect with MF intensity. B lymphocyte (Ig+ cell) populations also showed a 12% decrease (P < .05) in the groups that were exposed to fields of 20 and 200 microT. However, these results were not significant, and no relation with MF intensities could be demonstrated. In contrast, evaluation of splenic NK cell activity revealed a 50% increase (P < .05) in animals that were exposed to fields of 2000 microT. No significant results were obtained from the evaluation of TNF activity and NO secretion in peritoneal macrophages. Phorbol 12-myristate 13-acetate (PMA)-stimulated and net H2O2 productions for a minor subpopulation of peritoneal cells showed positive dose-response correlations by linear regression analysis. Taken together, our results suggest that an in vivo exposure of rats for 6 weeks to 60 Hz MFs can induce significant immunological perturbations on effector cells of both natural and adaptive immunity in a dose-dependent fashion.

Animals↗
PubMed1996

A simplified semiquantitative determination of hepatitis C virus genome molecules by the end-point dilution method.

We describe a semiquantitative method to measure hepatitis C virus (HCV) viral particle numbers, by carrying out reverse-transcription polymerase chain reaction (RT-PCR) on serial dilutions of serum samples. The virus concentrations measured were 10(3)-10(6) viral particles ml-1 of serum. The method described is relatively quick, and the only required manipulation is dilution of the serum. An optimal RT-PCR method is used for diluted and undiluted samples.

Hepacivirus↗
PubMed1994

SPARC and thrombospondin genes are repressed by the c-jun oncogene in rat embryo fibroblasts.

The sequence-specific transcription factor c-Jun displays oncogenic potential in mammalian cells either in cooperation with activated Ras in primary embryonic fibroblasts or alone in established cell lines. Although pathways for signal transduction leading to activation of c-Jun proteins have been extensively studied, little is known about the events downstream of c-Jun stimulation. We isolated cellular genes that are targets of c-Jun by differential screening of a cDNA library from primary rat embryo fibroblasts. Two transcripts with sequences similar to known genes were repressed following transitory expression of a c-Jun-encoding vector. They correspond to the SPARC and thrombospondin 1 (TS1) genes, encoding extracellular matrix proteins. These genes are tightly regulated during embryogenesis and in adult tissues and are involved in the control of cell growth. c-Jun transitory repression of these two genes was demonstrated both in primary cells and in FR3T3, an established fibroblast cell line. The repression was also detected in FR3T3 derivatives stably transformed by c-Jun or Ras. Although c-Jun regulation of the TS1 gene was found at the promoter level, preliminary results strongly suggest that repression of SPARC and TS1 gene expression are mediated by a secreted factor. In contrast, expression of these genes was unaffected by transformation with oncogenes from DNA viruses. Our results identify new, specific, probably indirect c-Jun target genes and suggest previously unsuspected regulatory roles for SPARC and thrombospondin in the control of cell growth.

Animals↗
PubMed1994

Major factors influencing bacterial leaching of heavy metals (Cu and Zn) from anaerobic sludge.

Anaerobically digested sewage sludges were treated for heavy metal removal through a biological solubilization process called bacterial leaching (bioleaching). The solubilization of copper and zinc from these sludges is described in this study: using continuously stirred tank reactors with and without sludge recycling at different mean hydraulic residence times (1, 2, 3 and 4 days). Significant linear equations were established for the solubilization of zinc and copper according to relevant parameters: oxygen reduction potential (ORP), pH and residence time (t). Zinc solubilization was related to the residence time with a r2 (explained variance) of 0.82. Considering only t=2 and 3 days explained variance of 0.31 and 0.24 were found between zinc solubilization as a function of ORP and pH indicating a minor importance of those two factors for this metal in the range of pH and ORP experimented. Cu solubilization was weakly correlated to mean hydraulic residence time (r2=0.48), while it was highly correlated to ORP (r2=0.80) and pH (r2=0.62) considering only t of 2 and 3 days in the case of pH and ORP. The ORP dependence of Cu solubilization has been clearly demonstrated in this study. In addition to this, the importance of the substrate concentration for Cu solubilization has been confirmed. The hypothesis of a biological solubilization of Cu by the indirect mechanism has been supported. The results permit, under optimum conditions, the drawing of linear equations which will allow prediction of metal solubilization efficiencies from the parameters pH (Cu), ORP (Cu) and residence time (Cu and Zn), during the treatment. The linear regressions will be a useful tool for routine operation of the process.

Journal Article↗
PubMed1994

Differential effects of c-jun and CREB on c-AMP response element activation by Ha-ras.

We have previously shown that a Long Terminal Repeat (LTR) of the Intracisternal A-type Particle (IAP) element was activated by ras oncogenes. Here we show that, like the somatostatin CRE (som CRE) and the collagenase TPA Response Element (coll TRE), the IAP CRE is activated by c-jun and that Val 12 Ha-ras cooperates with c-jun to activate these motifs. Neither jun-B nor jun-D activated the IAP CRE, although they were able to act on the som CRE and the coll TRE and to synergize with ras. The CREB factor activated both CREs and modestly inhibited the coll TRE, but diminished the effect of ras on the coll TRE. Finally, forskolin was shown to cooperate with Ha-ras to activate the CRE and the coll TRE. Taken together, these results show that CREB is not involved in ras activation of the CRE and suggest that c-jun is at least one of the elements implicated in this phenomenon.

3T3 Cells↗
PubMed1991

Synthetic peptides corresponding to the F protein of RSV stimulate murine B and T cells but fail to confer protection.

We have previously located a major neutralization site of the fusion protein of respiratory syncytial virus (RSV) in the polypeptide region extending from amino acids Ile221 to Glu232. In this report, 8 peptides corresponding to the six major hydrophilic regions of the F1 subunit were selected to analyse their immunogenic and protective capacities as well as their ability to block the high neutralization activities of 4 monoclonal antibodies (MAbs). Only 5 of the 8 peptides tested induced specific antibodies while all induced an in vitro interleukin-2 response of splenocytes from immunized mice. Peptide 3 (Ile221-Phe237) was able to elicit neutralizing antibodies, confirming our previous hypothesis concerning the location of a neutralization site. However, immunization with the latter did not induce significant reduction of virus in lungs of BALB/c mice upon challenge, probably due to an inadequate level of circulating neutralizing antibodies. Interestingly, peptides 2 (Asn216-Glu232), 3 (Ile221-Phe237), and 5 (Ser275-Ile288) blocked in vitro neutralization by four different F1 specific MAbs. A hypothesis is proposed to explain these results.

Amino Acid Sequence↗
PubMed1991

ras oncogene activates the intracisternal A particle long terminal repeat promoter through a c-AMP response element.

To understand the mechanism responsible for the high expression of Intracisternal A Particles (IAP) in murine cells transformed by the Kirsten Mouse Sarcoma Virus (Ki-MSV), we have investigated the effect of p21ras on IAP transcription. By transient cotransfections of IAP LTR-CAT plasmids with v-Ki-ras and c-Ki-ras expression vectors, we have found that p21v-Ki-ras, and the p21c-Ki-ras to a lesser extent, stimulate the promoter activity of the 5' IAP LTR. We constructed several plasmids containing the CAT gene under control of IAP LTRs deleted in different regions. CAT assays demonstrate that the ras responsive sequence is a 16 bp oligonucleotide containing an effective c-AMP Response Element (CRE) TGACGTCA, which is located in the U3 region, 20 bp upstream of the CAAT box.

Animals↗