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Biomedical subjects

G André

Publications and source records attributed to G André.

At least 19 recordsLinked to original sources
PubMed2005

[Actions of a 19-norprogesterone derivative on mammary gland: nomegestrol acetate].

UNLABELLED: As the biological effects of progestins vary according to their molecular structure, it becomes essential to differentiate the various types of progestins, particularly with regard to the breast. OBJECTIVE: The purpose of this review was to gather published data on the effects of a 19-norprogesterone derivative, nomegestrol acetate, on the breast. Materials and methods. All experimental and clinical published studies reporting data in the literature on nomegestrol acetate and breast were reviewed. RESULTS: In experiments on steroid receptors, it was shown that nomegestrol acetate presents a high binding specificity and affinity for progesterone receptors, notably in normal and cancerous human breast tissues. It sharply inhibits synthesis of progesterone receptors in hormone-dependent T-47D human breast cancer cells grown in an estrogenic culture medium, thereby demonstrating its strong progestational activity. On the other hand, it does not bind to estrogen receptors and lacks any estrogenic potential, confirmed by the lack of induction of alkaline phosphatase activity of endometrial Ishikawa cells. Estrogen-induced synthesis of estrogen receptors is also inhibited by nomegestrol acetate, a major determinant of its strong intrinsic anti-estrogenic activity. Unlike androgenic progestins (e.g. 19-nortestosterone derivatives and medroxyprogesterone acetate) which may act indirectly on the breast by inducing modifications of sex hormone binding globulin (SHBG) and insulin-like growth factor-I (IGF-I), nomegestrol acetate is devoid of any androgenic activity. In studies carried out on the effects of progestins on enzyme activities involved in estradiol (E2) formation in breast tissue, nomegestrol acetate can control E2 levels in breast cancer tissue in vitro: it inhibits estrone sulfatase activity that converts estrone sulfate (E1S) to estrone (E1) and inhibits 17beta-hydroxysteroid dehydrogenase type 1 activity that converts E1 to E2, resulting in blockade of E2 bioformation in MCF-7 and T-47D human breast cancer cells. It also stimulates sulfotransferase activity and subsequently the transformation of non conjugated estrogens E1 and E2 into biologically inactive estrogen sulfates. In vitro studies on cell proliferation have demonstrated that nomegestrol acetate, on the one hand, is unable to stimulate proliferation of MCF-7 cells cultured in a medium devoid of estrogens and, on the other hand, can exert antiproliferative effects on T-47D cells grown in an estrogenic environment. Furthermore, studies on mammary apoptosis have shown that the withdrawal of nomegestrol acetate induces apoptosis peak of normal human breast epithelial cells in vitro and in vivo. In clinical trials carried out with premenopausal women, nomegestrol acetate administered in antigonadotropic sequence has demonstrated its efficacy in the treatment of cyclical mastodynia and early onset benign breast diseases. With postmenopausal hormone replacement therapy (HRT) combining estrogen and nomegestrol acetate, clinical trial results showed low incidence of mastodynia while under treatment as well as moderate increase in mammographic density, particularly with continuous combined regimens, however rapidly reversed by a short-term suspension of HRT. Noclinical data with this progestagen is available on breast cancer risk. CONCLUSION: In addition to efficacy on mastodynia, in vitro and in vivo study results support the good tolerance of nomegestrol acetate on breast, in the short and medium term.

Apoptosis↗
PubMed2005

Effect of rumen-degradable protein balance and forage type on bulk milk urea concentration and emission of ammonia from dairy cow houses.

As the Dutch government and dairy farming sector have given priority to reducing ammonia emission, the effect of diet on the ammonia emission from dairy cow barns was studied. In addition, the usefulness of milk urea content as an indicator of emission reduction was evaluated. An experiment was carried out with a herd of 55 to 57 Holstein-Friesian dairy cows housed in a naturally ventilated barn with cubicles and a slatted floor. The experiment was designed as a 3 x 3 factorial trial and repeated 3 times. During the experiment, cows were confined to the barn (no grazing) and were fed ensiled forages and additional concentrates. The default forage was grass silage. The nutritional experimental factors were: (1) rumen-degradable protein balance of the ration for lactating cows with 3 levels (0, 500, and 1000 g/cow per d), and (2) proportion of corn silage in the forage ration for lactating cows with 3 levels (0, 50, and 100%) of forage dry matter intake. Several series of dynamic regression models were fitted. One of these models explained emission of ammonia by the nutritional factors and the temperature; another model explained ammonia emission by the bulk milk urea content and the temperature. The ammonia emission from the barn increased when levels of rumen-degradable protein balance increased. Furthermore, at a given level of rumen-degradable protein balance, the emission of ammonia correlated positively with the corn silage content in the forage ration. However, this correlation was not causal, but was the result of interaction between corn silage proportion and intake of ileal digestible protein. The bulk milk urea content and the temperature correlated strongly with the ammonia emission from the barn; the selected model accounted for 76% of the variance in emission. It was concluded that the emission of ammonia from naturally ventilated dairy cow barns was strongly influenced by diet. The emission can be reduced approximately 50% by reducing the rumen-degradable protein balance of the ration from 1000 to 0 g/cow per d. The milk urea content is a good indicator of emission reduction.

Ammonia↗
PubMed2004

Putative implication of alpha-amylase loop 7 in the mechanism of substrate binding and reaction products release.

Alpha-amylases are widespread endo-enzymes involved in the hydrolysis of internal alpha-(1,4) glycosidic linkages of starch polymers. Molecular modeling of amylose-amylase interactions is a step toward enzymatic mechanism understanding and rational design of new enzymes. From the crystallographic complex of barley alpha-amylase AMY2-acarbose, the static aspects of amylose-amylase docking have been characterized with a model of maltododecaose (DP12) (G. André, A. Buléon, R. Haser, and V. Tran, Biopolymers 1999, Vol. 50, pp. 751-762; G. André and V. Tran, Special Publication no. 246 1999, The Royal Society of Chemistry, H. J. Gilbert, G. J. Davies, B. Henrissat, and B. Svensson, Eds., Cambridge, pp. 165-174). These studies, consistent with the experimental subsite mapping (K. Bak-Jensen, G. André, V. Tran, and B. Svensson, Journal of Biological Chemistry, to be published), propose a propagation scheme for an amylose chain in the active cleft of AMY2. The topographical overview of alpha-amylases identified loop 7 as a conserved segment flanking the active site. Since some crystallographic experiments suspected its high flexibility, its putative motion was explored through a robotic scheme, an alternate route to dynamics simulations that consume CPU time. The present article describes the characteristics of the flexibility of loop 7: location and motion in AMY2. A back-and-forth motion with a large amplitude of more than 0.6 nm was evaluated. This movement could be triggered by two hinge residues. It results in the loop flipping over the active site to enhance the docking of the native helical substrate through specific interactions, it positions the catalytic residues, it distorts the substrate towards its transition state geometry, and finally monitors the release of the products after hydrolysis. The residues involved in the process are now rational mutation points in the hands of molecular biologists.

Animals↗
PubMed2003

Computational and experimental studies of the catalytic mechanism of Thermobifida fusca cellulase Cel6A (E2).

Mutagenesis experiments suggest that Asp79 in cellulase Cel6A (E2) from Thermobifida fusca has a catalytic role, in spite of the fact that this residue is more than 13 A from the scissile bond in models of the enzyme-substrate complex built upon the crystal structure of the protein. This suggests that there is a substantial conformational shift in the protein upon substrate binding. Molecular mechanics simulations were used to investigate possible alternate conformations of the protein bound to a tetrasaccharide substrate, primarily involving shifts of the loop containing Asp79, and to model the role of water in the active site complex for both the native conformation and alternative low-energy conformations. Several alternative conformations of reasonable energy have been identified, including one in which the overall energy of the enzyme-substrate complex in solution is lower than that of the conformation in the crystal structure. This conformation was found to be stable in molecular dynamics simulations with a cellotetraose substrate and water. In simulations of the substrate complexed with the native protein conformation, the sugar ring in the -1 binding site was observed to make a spontaneous transition from the (4)C(1) conformation to a twist-boat conformer, consistent with generally accepted glycosidase mechanisms. Also, from these simulations Tyr73 and Arg78 were found to have important roles in the active site. Based on the results of these various MD simulations, a new catalytic mechanism is proposed. Using this mechanism, predictions about the effects of changes in Arg78 were made which were confirmed by site-directed mutagenesis.

Actinomycetales↗
PubMed2002

Microphase separation in Pr0.67Ca0.33MnO3 by small-angle neutron scattering.

We have evidenced by small-angle neutron scattering at low temperature the coexistence of ferromagnetism (F) and antiferromagnetism (AF) in Pr0.67Ca0.33MnO3. The results are compared to those obtained in Pr0.80Ca0.20MnO3 and Pr0.63Ca0.37MnO3, which are F and AF, respectively. Quantitative analysis shows that the small-angle scattering is not due to a mesoscopic mixing but to a nanoscopic electronic and magnetic "red cabbage" structure, in which the ferromagnetic phase exists in the form of thin layers in the AF matrix (stripes or 2D "sheets").

Journal Article↗
PubMed2002

First-order transition in the spin dynamics of geometrically frustrated Yb2Ti2O7.

Using neutron diffraction, 170Yb Mössbauer and muon spin relaxation spectroscopies, we have examined the pyrochlore Yb2Ti2O7, where the Yb3+S' = 1/2 ground state has planar anisotropy. Below approximately 0.24 K, the temperature of the known specific-heat lambda transition, there is no long range magnetic order. We show that the transition corresponds to a first-order change in the fluctuation rate of the Yb3+ spins. Above the transition temperature, the rate, in the GHz range, follows a thermal excitation law, whereas below, the rate, in the MHz range, is temperature independent, indicative of a quantum fluctuation regime.

Journal Article↗
PubMed2001

Magnetic ordering and phase transition in MnO embedded in a porous glass.

We present the results of a neutron diffraction study of the antiferromagnet MnO embedded in a porous glass. The type of magnetic ordering and the structural distortion are similar to those of the bulk, but the ordered magnetic moment of 3.84(4)muB/ion is strongly reduced and the Néel temperature is enhanced. The magnetic transition is second order, in contrast to the first order transition of the bulk. The size of the magnetic region is smaller than the average size of the nanoparticles. The reasons for this behavior are discussed.

Journal Article↗
PubMed2000

Neuroprotective effects of chronic estradiol benzoate treatment on hippocampal cell loss induced by status epilepticus in the female rat.

Neuroprotective properties of estrogen are supported by extensive experimental evidence. In this study, the effects of estrogen were examined on the neurodegeneration secondary to status epilepticus induced by kainic acid in the rat. Chronic supplementation of ovariectomized rats with estradiol benzoate (20 microg/day) did not modify the expression of seizures monitored by electroencephalography, but significantly reduced cellular loss in the hippocampus. This neuroprotection was in particular observed in the dentate hilus and CA3 pyramidal layer when treatment with estradiol benzoate was started five days before status epilepticus induction. These findings suggest that estrogen can exert neuroprotective effects in a model of status epilepticus, in the absence of anti-epileptic properties.

Animals↗
PubMed1999

Amylose chain behavior in an interacting context. III. Complete occupancy of the AMY2 barley alpha-amylase cleft and comparison with biochemical data.

In the first two papers of this series, the tools necessary to evaluate substrate ring deformations were developed, and then the modeling of short amylose fragments (maltotriose and maltopentaose) inside the catalytic site of barley alpha-amylase was performed. In this third paper, this docking has been extended to the whole catalytic cleft. A systematic approach to extend the substrate was used on the reducing side from the previous enzyme/pentasaccharide complex. However, due to the lack of an obvious subsite at the nonreducing side, an alternate protocol has been chosen that incorporates biochemical information on the enzyme and features on the substrate shape as well. As a net result, ten subsites have been located consistent with the distribution of Ajandouz et al. (E. H. Ajandouz, J. Abe, B. Svensson, and G. Marchis-Mouren, Biochimica Biophysica Acta, 1992, Vol. 1159, pp. 193-202) and corresponding binding energies were estimated. Among them, two extreme subsites (-6) and (+4), with stacking residues Y104 and Y211, respectively, have strong affinities with glucose rings added to the substrate. No other deformation has been found for the new glucose rings added to the substrate; therefore, only ring A of the DP 10 fragment has a flexible form when interacting with the inner stacking residues Y51. Global conservation of the helical shape of the substrate can be postulated in spite of its significant distortion at subsite (-1).

Amylose↗
PubMed1994

[A "no-bleeding" substitute hormone treatment with an oral microdose progesterone. A prospective multicenter study].

AIMS: Study of influence of different sequences of oral micronized progesterone (Pg) on endometrial morphology and the incidence of bleeding. DESIGN: Prospective comparative multicentric study conducted in 101 post-menopausal patients. PATIENTS AND METHODS: 98 patients who did not wish any regular withdrawal bleeding were given percutaneous oestradiol 17-beta (E2) (1.5 mg/d) associated with micronized Pg (100 mg/d) at bedtime during either 21 out of 28 days (group I), or 25 days per calendar month (group III), during a minimum of 6 months. For those wishing withdrawal bleeding (n = 3), E2 (3 mg/d) during 25 days was associated with Pg (300 mg/d) from the 16th to the 25th day of the month (group III). Endometrial biopsies were performed after 6 months of the same treatment and blindly analysed; transvaginal ultrasonography (measurement of endometrial mucosa thickness) was done in case of insufficient amount of tissue. RESULTS: Groups I and II: 61% of the endometrium were quiescent without mitosis, 23% were slightly active with rare mitoses, 8% partly secretory and 4% subatrophic. Sampling was inadequate in the remaining 4%. Mitotic activity of glands was low on the overall samplings (average < 0.53/1,000 cells). The average mucosa thickness was at 3.9 mm. No bleeding (spotting or withdrawal bleeding) occurred in 73.3% and 82.1% of cycles at the 3rd and 6th months of administration, respectively. Group III: endometrium were quiescent or slightly active and combined with frequent withdrawal bleeding. CONCLUSIONS: A relatively low dose of oral progesterone (100 mg/d) combined with E2 during 21d/28d or 25 d/month efficiently controls proliferation, induces a very low endometrial cyclic activity--while reducing spottings--and maintains an amenorrhea in the majority of women. This simple treatment is likely to improve compliance.

Administration, Cutaneous↗
PubMed1993

[Amenorrhea during menopausal hormone replacement therapy with a percutaneous estradiol and oral micronized progesterone combination].

The effects of oral micronized progesterone-administered at a low dose-on the endometrium and on bleeding pattern have been evaluated during a multicenter study in which 101 patients were involved. For a minimum of 6 months, patients who did not wish to have withdrawal bleeding (98) received the association of 17 beta-percutaneous estradiol (1.5 mg/d) and oral micronized progesterone (100 mg/d, at bedtime) during 25 days per month (or 21 d/28). The few women (3) who wished regular bleeding were given progesterone (300 mg/d) with estradiol (3 mg/d), from the 16th to the 25th of the month. No hyperplasia was observed among the endometrial biopsies performed after 6 months minimum of treatment. 8% of the endometria were partially secretory, 4% were sub-atrophic, 23% were mildly active with rare mitoses and 61% were quiescent without mitoses. The remaining 4% were considered inadequate. Mitotic activity of the glands was minimal in all samplings (mean < 0.53/1,000 cells). The average thickness of the mucosa was measured by ultrasonography at 3.9 mm, in the cases of insufficient samplings. No bleeding (or spotting, or cyclic bleeding) occurred in 73.3% and 80.9% of the cycles, in the 3rd and 6th month of therapy. Therefore a low dose of oral Pg (100 mg/d) combined with E2 during 25 days/month efficiently controls endometrial proliferation, while allowing a very weak cyclic activity. This situation makes it possible to minimize spottings and to maintain an amenorrhea in the majority of patients, thus letting us hoping for an improvement in the observance of this simplified therapy.

Administration, Oral↗
PubMed1992

A new variant of Glanzmann's thrombasthenia (Strasbourg I). Platelets with functionally defective glycoprotein IIb-IIIa complexes and a glycoprotein IIIa 214Arg----214Trp mutation.

We describe a new variant of Glanzmann's thrombasthenia (variant Strasbourg I). The patient (M.S.) showed an absence of platelet aggregation to ADP, thrombin, and collagen, and a decreased clot retraction. Platelet fibrinogen was approximately 20% of normal levels. ADP-stimulated platelets bound markedly reduced amounts of soluble fibrinogen and platelet adhesion to surface-bound fibrinogen was defective. Normal to subnormal amounts of glycoprotein (GP) IIb-IIIa (alpha IIb beta 3) complexes, the platelet fibrinogen receptor, were revealed by SDS-PAGE, crossed immunoelectrophoresis, and antibody binding. However, the complexes were unusually sensitive to dissociation with EDTA at room temperature. Furthermore, flow cytometry showed that the platelets failed to bind the activation-dependent monoclonal antibody, PAC-1, after stimulation. In contrast, an RGDS-containing peptide induced significant binding of the anti-ligand-induced binding site antibody, D3GP3, suggesting the presence of a functional RGD binding domain on the patient's GPIIb-IIIa complex. Sequence analysis was performed after polymerase chain reaction amplification of selected patient's GPIIIa exons, and of the patient's platelet GPIIb and GPIIIa mRNAs. A point mutation (C to T) was localized in exon D (iv) of GPIIIa that resulted in an 214Arg to 214Trp amino acid substitution. The defect has been inherited from the parents who are heterozygous for the same mutation. This substitution points to an essential amino acid in a region of GPIIIa involved in the binding of fibrinogen and influencing the Ca(2+)-dependent stability of the GPIIb-IIIa complex.

Adult↗
PubMed1991

On the use of apparent kinetic parameters for immobilized enzyme with uncompetitive substrate inhibition [corrected].

The use of a simple rate equation with apparent parameters to describe the kinetic behavior of an immobilized enzyme with uncompetitive [corrected] substrate inhibition was assessed. To do so, the reaction rate was calculated as a function of the interfacial substrate concentration, and the results were used to identify the apparent kinetic parameters by nonlinear regression. This procedure was repeated for different values of the diffusional constraints and of the inhibition constant. The equation using apparent parameters can describe the global kinetic behavior, provided that the diffusional and inhibitory constraints are not too high. When the constraints are high, a Michaelis-Menten equation can be used to model the kinetics for interfacial concentrations lower than the concentration leading to the maximum reaction rate.

Enzymes, Immobilized↗
PubMed1989

Simple high performance liquid chromatography methods for monitoring lipase reactions.

This paper describes three simple high performance liquid chromatography methods to separate mixtures of free fatty acids, mixtures of different triglycerides and mixtures of all fat classes (monoglycerides, diglycerides, triglycerides and free fatty acids). It is possible with our methods to identify and quantify each peak of the chromatogram. These methods have been designed to monitor lipase reactions. Using a first set of conditions, we have been able to separate five fatty acids: linolenic, linoleic, palmitic, oleic and stearic, without any specific preparation of the samples. With a second set of conditions, we showed that the same mobile phase and the same column could separate both triglyceride species and fat classes. However, in the latter case, a flow gradient was used.

Chromatography, High Pressure Liquid↗