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Biomedical subjects

C Benassayag

Publications and source records attributed to C Benassayag.

At least 19 recordsLinked to original sources
PubMed1992

In vivo transient rise in plasma free fatty acids alters the functional properties of alpha-fetoprotein.

Previous in vitro studies have shown that unsaturated fatty acids (UFA) induce conformational changes in rodent and human alpha-fetoprotein (AFP). To determine whether such changes in the binding and immunological properties of rat AFP also occur in vivo, plasma free fatty acid (FFA) concentrations were increased in young male rats (15, 21 and 28 days old) by acute i.v. injection of heparin (200 IU/kg). Plasma estrogens (estrone and estradiol) did not change after injection of heparin. There was a large increase in plasma FFA 10-20 min post-heparin injection, with a return to normal 60 min later. This transient rise in FFA plasma was associated with a 50% drop (P less than 0.001) in the binding of estradiol to rat AFP of 15-, 21- and 28-day-old rats by reducing the number of binding sites (P less than 0.001), leaving the affinity constant (Ka) unchanged. FFA extracts from post-heparin plasma induced similar changes in estradiol binding to purified rat AFP. The rise in plasma FFA induced a loss of AFP immunoreactivity, in 21- (P less than 0.001) and 28-day-old rats (P less than 0.001), but not in 15-day-old rats. This age-dependent response correlated with the FFA/AFP molar ratio (38 in 15-day-old rats, 388 in 21-day-old rats, and 5600 in 28-day-old rats). These results indicate that an in vivo rise in FFA induces rapid and reversible conformational changes in AFP which may modulate the endocrine and immune function of this oncofetal protein.

Animals↗
PubMed1992

Alterations in the concentrations and binding properties of sex steroid binding protein and corticosteroid-binding globulin in HIV+patients.

The abnormal concentrations of steroid hormones and free fatty acids in the plasma of HIV-infected subjects are associated with qualitative and quantitative alterations in two of the major steroid hormones carrier proteins, sex steroid-binding protein (SBP) and corticosteroid-binding globulin (CBG). The properties of SBP and CBG in the sera of two age-matched groups of 67 men healthy blood donors (controls) and 64 HIV+subjects: 11 CDC group II and III (ASY), 6 CDC group IVA and 47 groups IV C1+D (AIDS) were analyzed. The HIV+patients had SBP concentrations 39-51% above those of controls. The sera of AIDS patients had higher SBP association constants (Ka) for testosterone than did those of the II, III and IVA groups and controls. In contrast, the CBG concentrations in all the HIV+subjects were similar to those of the controls. However, the binding properties of HIV+CBG were abnormal: the Ka's for cortisol and 17 alpha hydroxyprogesterone binding were 50% below normal, while the number of binding sites was significantly higher. Such changes in these carrier proteins could result from conformational transitions; they may cause abnormal transfer of hormonal information and/or steroid hormones metabolism, thus modifying the impact of steroids on the immune response in HIV+subjects.

17-alpha-Hydroxyprogesterone↗
PubMed1992

Effect of the aromatase inhibitor, 4 hydroxyandrostenedione, on the endotoxin-induced changes in steroid hormones in male rats.

The increase in circulating estrogen concentrations that follows injection of Escherichia coli endotoxin (Endo) may be due to increased aromatase activity. We have therefore analysed the effect of the aromatase inhibitor, 4 hydroxyandrostenedione (4OHA) on the steroid hormone response of male rats, particularly the dramatic increase in estrogens and decrease in androgens, induced by Endo. The concentrations of corticosterone (B), progesterone (P4), 17 alpha hydroxyprogesterone (17 alpha OHP4), androstenedione (delta 4), testosterone (T), estrone (E1) and estradiol (E2) were determined 2 hours after injection of increasing doses of 4OHA with and without Endo. The increase in serum estrogen concentrations and drop in serum androgen levels in response to Endo were blocked by a single dose of 4OHA. The effect of 4OHA appeared to be dose dependent. Low doses (30 mg/kg and 50 mg/kg) induced significant changes in the estrogen and androgen responses, but the high dose (100 mg/kg) blocked all changes in sex steroids induced by Endo. 4OHA did not alter the Endo-induced changes in other steroids.

Analysis of Variance↗
PubMed1992

Relationship between changes in serum estrone levels and outcome in human males with septic shock.

The effect of septic shock on the production of estrogens, other steroid hormones, and gonadotropins in men was investigated. Two groups of male patients in the early septic shock were studied over 3 days following their admission to the Intensive Care Unit. Group I (n = 9) patients recovered and group II (n = 6) patients died. The simplified acute physiological score was 13.5 +/- 1.5 for group I and 21.2 +/- 2.3 for group II (P less than .05). In group I patients, estrogen levels (particularly E1) were high on day 1 and decreased progressively (day 1: 3,515 +/- 884 pmol/L, day 2: 2,450 +/- 292 pmol/L, and day 3: 1,043 +/- 255 pmol/L). In group II patients, estrone levels were as high as in group I on day 1, but increased throughout the 3 days (day 1: 3,250 +/- 1,200 pmol/L, day 2: 4,495 +/- 930 pmol/L, and day 3: 6,123 +/- 966 pmol/L). There were few changes in gonadotropins and other steroid hormones, except that the testosterone levels were below normal in both patient groups, while cortisol was elevated in group II. The changes in serum E1 may provide an accurate marker of individual outcome.

Aged↗
PubMed1991

Phytoestrogens: new ligands for rat and human alpha-fetoprotein.

The binding of the lignans, enterolactone, enterodiol, nordihydroguaiaretic acid (NDGA), and the isoflavonic phytoestrogen equol, to human and rat alpha-fetoprotein (AFP) was studied. They had differential inhibitory effects (NDGA greater than equol greater than enterolactone greater than enterodiol) on the binding of estrone and estradiol to rat AFP and the binding of unsaturated fatty acid to both rat and human AFP. Inhibition was dose-dependent. The apparent dissociation constants (Kd) for phytoestrogens binding to AFP were: Kd NDGA = 5 +/- 1.2.10(-7) M, Kd equol = 6.7 +/- 0.8.10(-6) M, Kd enterolactone = 1.7 +/- 0.4.10(-5) M and Kd enterodiol = 2.2 +/- 0.6.10(-5) M. The Kd for estrone binding to rat AFP was increased by increasing concentrations of equol, but the number of esterone binding sites remained unchanged. This, plus the results of double-reciprocal plots, suggests that they compete for the same site(s). NDGA also competitively inhibited estrone binding at low NDGA concentrations (increased Kd), but high concentrations induced conformational changes in rat AFP, as both Kd and the number of binding sites (n) were altered. Both rat and human AFPs underwent changes in electrophoretic behaviour and loss of immunoreactivity with increasing NDGA, suggesting that NDGA binding induces conformational changes in the AFPs. However, equol did not alter the electrophoretic or immunological properties of either rat or human AFP, providing further evidence for qualitative differences in the effects of these diphenols. These findings indicate that phytoestrogens could play a role in AFP-dependent normal and pathological growth and development.

4-Butyrolactone↗
PubMed1991

Endotoxin induced changes in serum estrogen in male rats: influence of testicular maturation.

The influence of acute endotoxin (Endo) administration on adrenal and testicular serum hormones, corticosterone (B), progesterone (P4), 17 alpha OH progesterone (17 alpha OH P4), androstenedione (delta 4), testosterone (T), estrone (E1) and estradiol (E2) was studied in male rats aged 8, 12 and 15 weeks. The present study confirms that the concentrations of circulating steroid hormones in male rats vary with age, and indicate that the adrenal glands mature before the testes. The steroid response to Endo is age-dependent. B, P4, 17 alpha OH P4 was increased and T decreased in all animals. But, there was a very significant increase in estrogens (E1 and E2) and a decrease in delta 4 only in male rats aged 12 weeks and over. The lack of an estrogen response to Endo injection in 8 week-old rats may indicate that the reduced sensitivity (refractory period) to Endo (which has been reported to last until 21 days of age) continues longer. The reduced sensitivity to Endo which occurs in young rats could be due in part to the absence of adrenal-testicular cooperation as a result of partial testicular immaturity.

17-alpha-Hydroxyprogesterone↗
PubMed1989

Conformational changes in rodent and human alpha-fetoprotein: influence of fatty acids.

Binding, spectral and immunological studies were performed to demonstrate the conformational changes in rodent and human alpha-fetoprotein (AFP) induced by a free fatty acid environment. Scatchard analysis of estradiol (E2) binding to purified rat AFP indicated that unsaturated fatty acids changed the number of binding E2 sites and the apparent E2 equilibrium dissociation constant which varied non-linearly with docosahexaenoic acid concentration. UV spectral analysis of rodent and human AFPs showed that the absorbance minimum of AFP incubated with unsaturated fatty acid (L-AFP) was red-shifted, broadened and less pronounced than that of purified native AFP (N-AFP). Immunochemical studies with specific polyclonal antibodies to purified rodent and human AFPs (N-AFP antibodies) showed that these proteins lost immunoreactivity after incubation with unsaturated fatty acid. N-AFP antibodies recognized fewer epitopes on L-AFP than on N-AFP, whatever the species. Specific anti-rat L-AFP antibodies were used to demonstrate specific epitopes on rat L-AFP. Rat L-AFP antibodies did not recognize rat N-AFP. Saturated fatty acids were without effect on the binding, spectral and immunological properties of rodent and human AFPs. RIA or ELISA values for human AFP from fetal serum, hepatoma serum, and cord serum, were reduced 80, 50 and 5%, respectively, by unsaturated fatty acids. This decrease correlated with the relative percentage of polyunsaturated fatty acid in each biological fluid. Such results indicate that an unsaturated fatty acid environment induces conformational changes in AFP which may modulate the endocrine and immune functions of this protein.

Animals↗
PubMed1989

Anatomical and surgical particularities of cholesteatomas in children.

In children, cholesteatoma is closely related to dysfunction of the eustachian tube and evolves inside a malleable temporal bone. The importance of auditory and speech functions in such patients has caused us to use a very particular clinical philosophy. At the present time we have studied 154 cases of cholesteatomas in children under 15 years old. The following three points have been shown: the pathogenesis of a cholesteatoma can be of the primary type, secondary (due to an unfavorable extension of retraction pocket or to squamous cell migration) or even be iatrogenic; anatomical and clinical findings (with X-ray studies) predicate the treatment used; surgical treatment frequently requires a "second-look" operation.

Adolescent↗
PubMed1989

Aesthetic surgery for microtia.

We describe here a technique for reconstruction of the external ear based upon an autogenous costal cartilage graft which is inserted into a cutaneous pocket dissected in the auricular area. Three subsequent procedures are then performed: rotation of the ear-lobe; reconstruction of the tragus; and elevation of the auricle. The ideal age for reconstruction is about 7 years. This technique was originally described by Brent, who has a very extensive experience with this kind of surgery. Skin deficiencies can be overcome by using either a temporo-parietal fascial flap or a skin expander.

Cartilage↗
PubMed1989

[Contribution of immunohistochemistry to the diagnosis of cervicofacial cancers].

In spite of classical morphological studies, a good number of cervico-facial cancers remain classified as undifferentiated. Thanks to the use of intracellular antigens, immunohistochemistry (IHC) allows for a differentiation of tumoral growths. 33 patients were used in this study within the last three years. After studying the different markers used, the authors consider their specificity and their reactivity, than their respective usefulness in the three main diagnostic cancer of the face. In 22 patients, IHC alone allowed a diagnosis and a specific therapeutic orientation. Material, technical and human demands must be considered along with the efficacity to the technique.

Antibodies, Monoclonal↗
PubMed1989

[Use of a temporoparietal fascial flap in difficult reconstructions of the external ear].

Temporo parietal fascial flap is a way of total ear reconstruction when there is not a sufficient quantity of available skin in auricular region. This flap very thin, supplied by superficial temporal vessels is located above the auricle and can cover the framework's convolutions. This technique has been well described by Burt Brent. Our experience is based upon 12 total ear reconstruction with this kind of flap. When there is an extreme skin shortage, but of good quality, we discuss the technique of skin expander.

Ear, External↗
PubMed1979

Relations between fatty acids and oestrogen binding properties of pure rat alpha 1-foetoprotein.

A delipidation procedure based on treatment with charcoal at pH 3 has been applied to highly purified rat alpha 1-foetoprotein preparations. The oestrogen binding properties of the delipidated proteins have been studied with an equilibrium dialysis technique, and compared with the properties of the untreated foetal protein, as well as those of preparations reconstituted from the defatted alpha 1-foetoprotein and the removed lipids. An important increase has been evidenced for the binding levels of oestrone, oestradiol-17 beta and diethylstilboestrol by the delipidated alpha 1-foetoprotein. A reversal of this effect has been obtained by incubating the delipidated protein either with the lipids extracted from the purified alpha 1-foetoprotein or with a potent competitor of the rat alpha 1-foetoprotein-oestrogen interaction, designated as 'L', previously demonstrated and isolated from whole rat sera, and tentatively characterized as a mixture of fatty acids. Scatchard analysis of the oestrone and oestradiol-17 beta binding parameters show that the enhanced fixation of the hormones after defatting is primarily due to a two-fold increase of the apparent number of binding sites/mol alpha 1-foetoprotein. The results are interpreted in terms of the probable, at least partial, identity between the lipids closely associated with the pure alpha 1-foetoprotein and the fatty acid mixture 'L' isolated from whole sera. The possible biological role of complex interplay between oestrophilic alpha 1-foetoproteins, phenolsteroids and fatty acids in the control of oestrogen levels during development is discussed briefly.

Animals↗
PubMed1979

Ligand properties of diethylstilbestrol: studies with purified native and fatty acid-free rat alpha 1-fetoprotein and albumin.

We report the equilibrium binding parameters for the interactions of the estrogen analogue diethylstilbestrol (DES) with highly purified rat alpha 1-fetoprotein (AFP) and serum albumin preparations. At 25 degrees C and pH 7.4, an association constant (Ka) of about 1.5 X 10(6)M-1 and 2 sites/mole are measured with the DES-AFP system, whereas for the DES-albumin interaction, we find a Ka of approximately 2 X 10(5)M-1 and about 11 sites/mole of protein. The removal of fatty acids from pure AFP causes a reversible 3 fold increase of the number of DES binding sites; the same delipidation procedure applied to albumin slightly diminishes its DES binding parameters. We also demonstrate the capability of DES to displace competitively estradiol-17 beta (E2) from its high affinity sites on the estrophilic rat AFP. Finally, the binding behaviour of the two serum proteins towards the synthetic estrogen is compared to their interaction with the natural hormones. The physiological and pharmacological relevance of these data is discussed.

Animals↗
PubMed1977

Rat iso-alpha1-fetoproteins. Purification and interaction with estradiol-17beta.

The combination of polyacrylamide gel electrophoresis and Concanavalin-A-Sepharose affinity chromatography has permitted the isolation on a preparative scale, of four molecular forms of rat alpha 1-fetoprotein: a "slow" and a "fast" fraction, each separable into Concanavalin-A-adsorbed ("high carbohydrate", i.e. rich in accessible alphaD-Mannosyl and alphaD-Glu-cosyl residues) and a Concanavalin-A-non adsorbed ("low carbohydrate") fractions. These four iso-alpha 1-fetoproteins (iso-AFP) bind estradiol-17beta. However, they disclose differences in both their association constants and number of binding sites for this hormone. Very high affinity sites (10(9) are mainly located on the "slow-low carbohydrate" form. Low affinity, high capacity sites are preferentially located on the "high carbohydrate" form. These results confirm the molecular and functional heterogeneity of rat AFT and suggest that the carbohydrate moiety of the protein may have a role in estrogen-AFP interactions.

Animals↗
PubMed1977

Rat and human embryo and post-natal sera contain a potent endogenous competitor of estrogen-rat alpha-fetoprotein interactions.

A highly active inhibitor of the binding of estrone and estradiol-17beta to rat alpha-fetoprotein is demonstrated for the first time in embryo, immature and adult rat sera as well as in fetal and adult human sera. The competitive character and the narrow specificity of this inhibition effect is shown. The major compound responsible for this activity is isolated by successive column Sephadex LH20 and thin layer chromatography: it is characterized as a nonpolar, nonphenolic, dialysable and thermostable substance, unreactive towards anti-estrone and anti-estradiol-17beta antibodies. The possible biological role of an endogenous non-estrogen ligand of rodent fetoproteins is discussed.

Adrenalectomy↗