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Biomedical subjects

C Aussel

Publications and source records attributed to C Aussel.

At least 109 records · Page 6Linked to original sources

Interaction of retinoids and bilirubin with the binding of arachidonic acid to human alpha-fetoprotein.

Human alpha-fetoprotein (HAFP) has three binding sites for polyunsaturated fatty acids with association constant Ka = 1.8 X 10(7) M-1. One of these binding sites overlaps with a retinoid binding site with Ka = 2.6 X 10(6)M-1. Competition experiments with bilirubin showed that this compound does not compete neither with fatty acids nor with retinoids. Thus, the two bilirubin binding sites previously demonstrated appear as two additional binding sites on HAFP. Nevertheless, the close proximity of two fatty acid binding sites and two bilirubin binding sites resulted in a modification of the binding constants for fatty acids. It is hypothesised that the binding properties of HAFP reflect the three domain structures of the protein recently deduced from the study of the nucleotide sequence of HAFP mRNA and AFPcDNA segments.

Arachidonic Acid↗

Plasma amino acid pattern in burn subjects: influence of septicemia.

A comparison of plasma amino acid levels was made between two groups of burn subjects, septic and non-septic. On day 4 after injury, results do not show any differences between patients who later went on to develop sepsis on day 7 and those who remained non-septic. Similarly, no differences between these two groups were discernable on day 7. Thus metabolic variations induced by septicemia do not seem to modify the usual burn-induced amino acid variations; consequently, plasma amino acid determination in burn patients do not appear to predict septicemia.

Journal Article↗

Prostaglandin synthesis in human placenta and fetal membranes: partial inhibition by rat and human alpha-fetoproteins.

The conversion of exogenous arachidonic acid into prostaglandin E2 (PGE2) was studied in human placenta and fetal membranes microsomes Rat and human alpha-fetoproteins (AFPs) at 170 micrograms/ml in the incubation medium, a concentration that does not exceed the physiological concentration observed in rat and human body fluids during pregnancy, decreased by 75% and 90% respectively the amount of PGE2 synthesized. The regulation of PGs synthesis by AFPs can shed a new light on different aspects of the numerous physiological actions of AFPs previously described such as ovarian regulation of immunosuppressive activity.

Animals↗

Human alpha-fetoprotein-fatty acid interaction.

Human alpha-fetoprotein (AFP) is able to bind arachidonic acid with high affinity Ka = 10(7)M-1 and a limited number of binding sites NS = 3. Thirty different fatty acids were tested by competition using labelled arachidonic acid as tracer. This experiment demonstrated a great specificity for the fatty acid-AFP interaction. Only polyunsaturated long chain fatty acids were able to bind to AFP with high affinity. The metabolic products of arachidonic acid i.e. prostaglandins presented no affinity for the AFP molecule.

Arachidonic Acids↗

On rat alpha-fetoprotein as a fatty acid carrier. Influence of the structure of fatty acids.

Fatty acids interfere with rat alpha-fetoprotein-estrogen interaction. We present here a quantitative study of the association constants for the binding to alpha-fetoprotein of different fatty acids. It can be concluded that fatty acids bind more strongly if the number of carbon atoms increases with the number of double bonds. The maximum binding ability occurred with the C20 fatty acids having three or four double bonds. As these fatty acids are the precursors in the synthesis of prostaglandins, we tested some compounds in this series and showed that prostaglandins presented no particular affinity for rat alpha-fetoprotein.

Animals↗

Inhibition of rat alpha-fetoprotein-estrogen interaction by adult rat ovarian extracts--role of unsaturated fatty acids.

Thin layer chromatography with four different solvent systems enabled us to show that ovarian extracts contained nonesterified unsaturated fatty acids able to compete with estradiol on the alpha-fetoprotein binding site. Gas chromatography demonstrated a high level of oleic and linoleic acids and the presence of arachidonic acid, a strong competitor of the rat alpha-fetoprotein-estrogen interaction. Arachidonic acid is a precursor of prostaglandins thus we suggest that its binding to AFP might play a role in the AFP-mediated ovarian regulation previously demonstrated.

Animals↗

Comparative binding properties of rat and human alpha-fetoproteins for arachidonic acid and estradiol.

Rat and human alpha-fetoproteins, (AFP) were able to bind arachidonic acid with high affinity (Ka = 10(7) to 10(8) M-1). Nevertheless, a great difference was found in the binding capacity of these two proteins. Rat AFP was shown to possess one high affinity binding site and several (12-13) low affinity sites while human AFP presented three equivalent binding sites for polyunsaturated fatty acids. Estrogenic hormones compete with fatty acids bound to the high affinity binding site of rat AFP but remained unable to displace arachidonic acid bound to the human one.

Animals↗

Immunolocalization of alpha-fetoprotein in the ovary and hypophysis of immature female rats.

Alpha-fetoprotein (AFP), an oestrogen-binding protein, has been localized in the ovary and hypophysis of prepuberal rats. In the ovary, AFP was localized in secondary follicles, its distribution being limited to the liquor folliculi and the zona pellucida. In the hypophysis, AFP was only found in blood vessels. The intra-ovarian localization of the protein is consistent with our previous hypothesis that AFP might act as a regulator of ovarian activity by decreasing the local free oestradiol level.

Animals↗

Role of alpha-fetoprotein (AFP) in the regulation of ovarian activity during hepatocarcinogenesis and post-natal development.

N-fluorenylacetamide produces an augmentation of serum AFP which is accompanied by a drastic decrease of ovarian activity. A passive augmentation of the AFP level of adult rats, produced by injection of this protein provokes the same phenomenon: i.e. a decrease of follicular maturation, a decrease number of corpora lutea and finally a drop in the plasma progesterone level. The study of ovarian post-natal development shows that ovarian maturity occurs on the 35th day of life when AFP level reaches its adult serum concentration. These facts support the hypothesis that AFP plays a role in the regulation of ovaries during the sexual maturation of the female rat.

Animals↗

Sex steroid hormones levels and testicular activity during hepatocarcinogenesis by N-2-fluorenylacetamide.

During hepatocarcinogenesis by N-2-fluorenylacetamide, the hormonal status of male Sprague-Dawley rats is modified. The testes present a reduced activity which is evidenced by a decreased spermatogenetic activity accompanied by a drastic decrease of the plasma testosterone level. In contrast, plasma progesterone and estradiol-17 beta levels were not modified despite the 80 fold augmentation of alpha-fetoprotein, an estrogen binding protein synthesized during liver carcinogenesis.

2-Acetylaminofluorene↗

Thyroid activity during hepatocarcinogenesis by N-2-fluorenylacetamide in the male rat.

During chemical hepatocarcinogenesis by N-2-fluorenylacetamide, the hormonal status of male Sprague Dawley rats is modified. The histological study of the thyroid gland demonstrates a decreased activity evidenced by an augmentation of the follicle size and a reduced size of follicular epithelium. The level of T3 and T4 reflects in part this decreased activity. Comparison with female rats treated in the same conditions shows an opposite effect of N-2-fluorenylacetamide. Indeed in the female, the thyroid gland presented an hyperactive state accompanied by a drastic decrease of serum T3 and T4. This difference in thyroid activity might take an important part in the mechanism responsible for the sex difference in liver cancer induction by N-2-fluorenylacetamide.

2-Acetylaminofluorene↗

[Physiological role of alpha-fetoprotein. Effect of the injection of purified AFP on the ovarian activity of the adult female rat].

Alpha-fetoprotein injected in normal adult female Rats produced a decrease in ovarian activity. The histological study of the ovaries showed that the number of maturing follicles as well as the number of corpora lutea were lowered in AFP-treated Rats, but not in albumin-treated control animals. The serum level of progesterone was also largely decreased by AFP injections. A possible role of AFP in the regulation of the ovarian activity during pregnancy and post natal sexual development is proposed.

Animals↗

Thyroid activity during hepatocarcinogenesis by N-2-fluorenylacetamide.

During chemical carcinogenesis by N-2-fluorenylacetamide, the hormonal status of female Sprague Dawley rats is largely modified. Thyroids present a modified activity which is evidenced by the histological study as well as T4 and T3 assays. In hypophysis, thyrotropic cells were found in an hyperactive state, a fact which is in agreement with the changes observed in thyroid follicles size and epithelial cells demonstrating an hyperactivity of thyroid glands. Despite this histological result, T4 serum level was lowered. T3 level was also decreased but to a lesser extent. We suggest that the low thyroid hormone level play a role in the relative protection of females versus males toward liver cancer induction by chemicals.

2-Acetylaminofluorene↗

In vivo regulation of ovarian activity by alpha-fetoprotein.

Adult female rats, each injected with 760 microgram alpha-fetoprotein (AFP) weekly, presented after the third week a decrease of ovarian activity evidenced by a decreased number of maturing follicles, corpora lutea, and a drop in ovarian weight. The level of progesterone was low and agreed with the decreased number of corpora lutea. Conversely, total and free estradiol-17 beta levels remained normal despite the known ability of AFP to bind estrogenic hormones. A regulatory role of AFP during the postnatal stage of sexual maturation is proposed.

Animals↗