PubMed Health⌕ Search

Biomedical subjects

F Galtier

Publications and source records attributed to F Galtier.

14 recordsLinked to original sources
PubMed2006

Resting energy expenditure and fuel metabolism following laparoscopic adjustable gastric banding in severely obese women: relationships with excess weight lost.

BACKGROUND: Although adjustable gastric banding is increasingly proposed for massively obese patients, little is known about the modifications of resting metabolic rate and substrate oxidation or about metabolic determinants of weight loss following this type of bariatric surgery. OBJECTIVES: To evaluate the relationships between excess weight loss, resting metabolic rate (RMR) and substrate oxidation, and to identify metabolic predictive factors of weight loss after adjustable gastric banding. SUBJECTS: Seventy-three obese nondiabetic women aged 39.1+/-10.4 years (18.4-64.8). DESIGN: Resting metabolic rate and substrate oxidation (indirect calorimetry), body composition (bio-impedance), lipid profile and insulin sensitivity indexes were assessed before and after (13.3+/-6.0 months, range 6.0-31.1) adjustable gastric banding. Patients were classified according to postsurgery time: group A (6-12 months, n=39); group B (12-18 months, n=21); group C (>18 months, n=13). Metabolic parameters associated with the percentage of excess weight lost (EWL) 1 year after surgery were analyzed in univariate and multivariate regressions. RESULTS: Mean weight loss was 26.2+/-11.4 kg. Mean fat mass loss was 17.3+/-8.1 kg. All biological parameters associated with excess weight improved after surgery. Excess weight lost at 1 year was 45.9+/-17.1% in group A, 47.4+/-17.1% in group B and 51.4+/-18.5% in group C (P=NS). Resting metabolic rate/fat-free mass (FFM) slightly decreased (28.9+/-3.26 vs 30.3+/-2.8, P<0.00001) and RMR/body weight slightly increased (18.5+/-2.8 vs 17.3+/-1.9, P<0.00001) after surgery. Respiratory quotient (0.81+/-0.06 vs 0.82+/-0.05) and FFM-adjusted lipid oxidation (1.10+/-0.41 vs 1.05+/-0.33 mg/min/kg FFM) were not significantly modified after surgery. In multiple linear regression analysis, difference in RMR/body weight, difference in energy sparing, baseline BMI and postsurgery time, were significantly and independently correlated with EWL (total R2=72.5%). CONCLUSIONS: Adjustable gastric banding promotes gradual but sustained weight loss and is associated with long-term conservation of lipid oxidation and energy expenditure. The individual variability in energy sparing mechanisms predicts weight loss during the first year after surgery.

Adolescent↗
PubMed2005

Anti-growth factor activities of benzothiophenes in human breast cancer cells.

We have tested the effects of two Eli-Lilly compounds, LY 117, 018 and raloxifene, on E2-regulated and IGF-I-induced proliferation or AP-1 activity in human breast cancer cells. We now demonstrate that both molecules have strong antiestrogenic and anti-growth factor inhibitory effects in MCF7 cells. They were as potent as ICI 182, 780 and more efficient than OH-Tam to prevent estradiol action whereas their inhibition on IGF-I stimulation was less than with ICI 182, 780 and equivalent to that of OH-Tam. Moreover, raloxifene was the most efficient molecule to prevent IGF-I-induced AP-1 activity, with a significant effect observed with a concentration as low as 5 x 10(-11)M in the presence of IGF-I alone. Similar dose-response curves were obtained with a combined treatment of IGF-I and E2 with a 2log shift. Their action on IGF-I-induced proliferation was completely abrogated in MCF7 transfectants in which the expression of an antiestrogen-regulated protein tyrosine phosphatase, PTPL1, was abolished by antisense RNA transfection. Accordingly, they were both able to dose-dependently regulate the expression of PTPL1 and to interfere with the PI3-K/Akt pathway by drastically decreasing Akt phosphorylation exclusively in wild-type PTPL1 expressing cells. Our data altogether demonstrate that raloxifene has a potent inhibitory effect on IGF-I action, with a drastic effect on AP-1 triggered responses as well as on Akt phosphorylation, suggesting that it might be a useful therapeutic agent in tumors in which these signalling pathways become constitutively active.

Breast Neoplasms↗
PubMed2001

Characterization of the physical interaction between estrogen receptor alpha and JUN proteins.

Activated estrogen receptor alpha (ERalpha) modulates transcription triggered by the transcription factor activator protein-1 (AP-1), which consists of Jun-Jun homodimers and Jun-Fos heterodimers. Previous studies have demonstrated that the interference occurs without binding of ERalpha to DNA but probably results from protein.protein interactions. However, involvement of a direct interaction between ERalpha and AP-1 is still debated. Using glutathione S-transferase pull-down assays, we demonstrated that ERalpha bound directly to c-Jun and JunB but not to FOS family members, in a ligand-independent manner. The interaction could occur when c-Jun was bound onto DNA, as shown in a protein-protein-DNA assay. It implicated the C-terminal part of c-Jun and amino acids 259-302 present in the ERalpha hinge domain. ERalpha but not an ERalpha mutant deleted of amino acids 250-303 (ER241G), also associated with c-Jun in intact cells, in the presence of estradiol, as shown by two-hybrid and coimmunoprecipitation assays. We also show that ERalpha, c-Jun, and the p160 coactivator GRIP1 can form a multiprotein complex in vitro and in intact cells and that the ERalpha.c-Jun interaction could be crucial for the stability of this complex. VP16-ERalpha and c-Jun, which both interact with GRIP1, had synergistic effect on GAL4-GRIP1-induced transcription in the presence of estradiol, and this synergistic effect was not observed with the ERalpha mutant VP16-ER241G or when c-Fos, which bound GRIP1 but not ERalpha, was used instead of c-Jun. Finally, ER241G was inefficient for regulation of AP-1 activity, and an ERalpha truncation mutant encompassing the hinge domain had a dominant negative effect on ERalpha action. These results altogether demonstrate that ERalpha can bind to c-Jun in vitro and in intact cells and that this interaction, by stabilizing a multiprotein complex containing p160 coactivator, is likely to be involved in estradiol regulation of AP-1 responses.

Animals↗
PubMed1998

FRA-1 expression level modulates regulation of activator protein-1 activity by estradiol in breast cancer cells.

We compared the effect of estradiol on activator protein-1 (AP-1) activity in estrogen receptor positive (ER alpha+) and estrogen receptor negative (ER alpha-) human breast cancer cell lines transiently transfected with the AP-1-responsive reporter plasmid AP-1-TK-CAT and an ER alpha expression vector. While estradiol increased AP-1 activity in the ER alpha+ cell lines MCF7, ZR75.1, and T47D, it decreased (MDA-MB231 and BT20 cells) or had no significant effect (MDA-MB435 cells) on AP-1-mediated transcription in ER alpha- cells. Estradiol also inhibited AP-1 activity in ER alpha-MDA-MB231 cells stably transfected with ER alpha and in which ER alpha levels are close to those found in MCF7. Use of ER alpha mutant expression vectors demonstrated that the DNA-binding domain of ER alpha was needed for stimulation or inhibition of AP-1 activity by estradiol but suggested that ER alpha binding to estrogen-responsive elements was not required for these effects. Changes in regulation paralleled quantitative and qualitative changes in protein binding to AP-1 sites, as demonstrated by gel shift assay: protein binding was greater and DNA/protein complexes migrated faster for ER alpha--than for ER alpha+ cells. In fact, by Northern blot, a high level of Fra-1 mRNA was found in BT20 and MDA-MB231 cells as compared with ER alpha+ cells, and MDA-MB435 cells showed an intermediary level of expression. The differential expression of Fra-1 in MCF7 and MDA-MB231 cells was confirmed at the protein level by supershift experiments. In addition, overexpression of Fra-1 in MCF7 cells decreased the positive effect of estradiol while inhibition of Fra-1 expression in MDA-MB231 cells, by transient transfection of the Fra-1 antisense expression vector, abolished the negative effect of the hormone. In conclusion, we demonstrated that ER alpha- breast cancer cell lines differ from ER+ cells by a high level of AP-1 DNA-binding activity due, at least in part, to high Fra-1 constitutive expression. High Fra-1 concentration is crucial for the negative regulation of AP-1 activity by estradiol and thus may take part in estradiol-induced inhibition of cell proliferation in ER alpha- breast cancer cells transfected with ER alpha expression construct.

Blotting, Northern↗
PubMed1994

Differential effect of forms A and B of human progesterone receptor on estradiol-dependent transcription.

In addition to stimulation of the target gene fatty-acid synthetase, the synthetic progestin R5020 strongly inhibited estradiol-induced pS2 and cathepsin D mRNA levels in MCF7 human breast cancer cells as shown by Northern blot analysis. Inhibition was half-maximal with 30 pM R5020, and the antiprogestin RU486 had only a weak effect. Two human progesterone receptor isoforms have been described; isoform A is a truncated form of isoform B and lacks the 164 N-terminal amino acids. We hypothesized that the two isoforms could have a differential capacity to transrepress estrogen-induced responses. Therefore, in MDA-MB231 cells containing no progesterone and estrogen receptors, we transiently transfected progesterone receptor expression vectors coding for form B (hPR1 or hPR0) or form A (hPR2) along with the estrogen receptor expression vector HEO. We show that R5020 inhibited estradiol-induced transcription of the pS2-CAT reporter plasmid only in cells selectively expressing isoform B. The same results were obtained when progesterone receptor isoforms were overexpressed in MCF7, Ishikawa, HeLa, or NIH-3T3 cells. Transrepression was dependent on the promoter context since the extent of inhibition by isoform B was higher when evaluated with pS2 or cathepsin D nonpalindromic estrogen-responsive element-mediated transcription than with the perfect palindromic form of the vitellogenin gene. Isoform A was inefficient regardless of the reporter construct used. Inhibition varied with the isoform ratio, and isoform B had a dominant effect, with > 70% inhibition measured in cells transfected with the same amount of both progesterone receptor isoforms. Progestin repressed only one of the two transcription activation functions of the estrogen receptor, AF-2, which corresponds to the hormone-binding domain. We conclude that differential expression of progesterone receptor isoforms could be responsible for a tissue-specific inhibition of estrogen target genes by progestins.

3T3 Cells↗
PubMed1993

Synthetic antiestrogens modulate induction of pS2 and cathepsin-D messenger ribonucleic acid by growth factors and adenosine 3',5'-monophosphate in MCF7 cells.

In MCF7 human breast cancer cells, the antiestrogens 4-hydroxy-tamoxifen and ICI 164,384 inhibit the mitogenic activity of epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I). These growth factors also stimulate the expression of cathepsin-D and pS2 genes. Therefore, we studied the effects of antiestrogens on growth factor induction of pS2 and cathepsin-D mRNA. The two antiestrogens strongly inhibited the transcriptional induction of pS2 by growth factors. On the contrary, estradiol and IGF-I or EGF had an additive effect on pS2 mRNA accumulation. Growth factor induction of cathepsin-D was also inhibited by ICI 164,384. By contrast, 4-hydroxytamoxifen had an agonist effect on cathepsin-D and an additive effect on IGF-I-induced mRNA. When 12-O-tetradecanoylphorbol-13-acetate or 8-bromo-cAMP (8-Br-cAMP) was used instead of growth factors, similar effects of 4-hydroxytamoxifen and ICI 164,384 were obtained on pS2 (12-O-tetradecanoylphorbol-13-acetate and 8-Br-cAMP) and cathepsin-D (8-Br-cAMP) induction. A mechanism based on the classical competitive inhibition by antiestrogens of estrogen binding and action on the estrogen receptor was very unlikely, as 1) no antigrowth factor activity was obtained with R5020, which was a potent inhibitor of estrogen induction of pS2 and cathepsin-D mRNA; 2) in the Ishikawa endometrial cancer cell line, the cathepsin-D gene is unresponsive to estrogen, but was inhibited by antiestrogen after its induction by EGF or 8-Br-cAMP; and 3) the residual estrogen concentration in cells was too low to induce the expression of estrogen-specific genes. However, antiestrogens did not inhibit the expression of all genes induced by growth factors, as they were without effect on IGF-I induction of glyceraldehyde-3-phosphate dehydrogenase mRNA. These results demonstrate that antiestrogens can modulate the transcription of some growth factor-induced genes and strongly suggest that this effect is not due to interference with residual estrogens.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1993

[Post-traumatic awakening and "child of the night"].

Clinical configuration of borderline period of awakening is described based on the triangular relation (Patient, Family, Care Team) beginning during coma. The possible suffering before awakening (regressive attitude, downfall of immune defences, and so on ...) evokes a sort of reply of trauma and the hypothesis that mechanisms of "negative hallucination" play a part in post-traumatic amnesia.

Amnesia↗
PubMed1993

[Plea for interactive rehabilitation during coma].

The question of head trauma reasons, and the shock of traditional family and therapeutic references, make the authors examine clinic coma evolution till awakening. From signs of libidinal values collected by care-team, another way during coma and till life recovery, is rebuilt.

Brain Injuries↗
PubMed1991

The anti-progestin RU486 stabilizes the progestin-induced fatty acid synthetase mRNA but does not stimulate its transcription.

Progestins induce fatty acid synthetase (FAS) in breast cancer cell lines, both increasing its gene transcription and mRNA stabilization (Joyeux, C., Rochefort, H., and Chalbos, D. (1989) Mol. Endocrinol. 4, 681-686). In vitro run-on transcription assays show that RU486, in contrast to progestin, inhibits FAS transcription by 40-50%. Moreover and surprisingly, anti-progestin RU486 also stabilizes FAS mRNA 3- to 4-fold in MCF7 cells as measured by chase experiments in the presence of actinomycin D or cordycepin or after short cell labeling with [3H]uridine. Dexamethasone is inefficient in increasing the half-life of FAS mRNA in MCF7 cells. RU486 had no effect on MDA-MB 231 cells which contain glucocorticoid but no progesterone receptors, indicating that the progesterone receptor is implicated in this regulation. RU486-induced mRNA stabilization allows delayed accumulation of FAS mRNA. These results indicate that the progesterone receptor can be activated separately to stimulate gene transcription or stabilize mRNA.

Cell Line↗
PubMed1990

Regulation of fatty acid synthetase by progesterone in normal and tumoral human mammary glands.

Progesterone and estrogens play an important role in the control of growth, differentiation and function of mammary epithelial cells. Their mechanism of action can be studied in human metastatic breast cancer cell lines (MCF7, T47D, ZR75-1...) that contain progesterone and estrogen receptors. We used this system to try to define progestin-regulated human genes which would permit to study progestin-regulation of gene expression in cell culture and to develop clinical markers of progestin-responsiveness. This paper summarizes our investigation of the progestin-regulated 250K protein, recently identified as human fatty acid synthetase (FAS).

Breast↗