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S Fournier

Publications and source records attributed to S Fournier.

At least 91 records · Page 5Linked to original sources
PubMed1988

Calmodulin-binding proteins in chromaffin cell plasma membranes.

Calmodulin-binding proteins present in chromaffin cell plasma membranes were isolated and directly compared with calmodulin-binding proteins present in chromaffin granule membranes. Chromaffin cell plasma membranes were prepared using Cytodex 1 microcarriers. Marker enzyme studies on this preparation showed a nine- to 10-fold plasma membrane enrichment over cell homogenates and a low contamination of these plasma membranes by subcellular organelles. Plasma membranes prepared in this manner were solubilized with Triton X-100 and applied to a calmodulin-affinity column in the presence of calcium. Several major calmodulin-binding proteins (240, 105, and 65 kilodaltons) were eluted by an EGTA-containing buffer. 125I-Calmodulin overlay experiments on nitrocellulose sheets containing both chromaffin plasma and granule membranes showed that these two membranes have several calmodulin-binding proteins in common (65, 60, 53, and 50 kilodaltons), as well as unique calmodulin-binding proteins (34 kilodaltons in granule membranes and 240 and 160 kilodaltons in plasma membranes). The 65-kilodalton calmodulin-binding protein present in both membrane types was shown to consist of two isoforms (pI 6.0 and 6.2) by two-dimensional gel electrophoresis. Previous experiments from our laboratory, using two monoclonal antibodies (mAb 30 and mAb 48) specific for a rat brain synaptic vesicle membrane protein (p65), showed that the monoclonal antibodies reacted with a 65-kilodalton calmodulin-binding protein present in at least three neurosecretory vesicles (chromaffin granules, neurohypophyseal granules, and rat brain synaptic vesicles). When these monoclonal antibodies were tested on chromaffin cell plasma membranes and calmodulin-binding proteins isolated from these membranes, they recognized a 65-kilodalton protein. These results indicate that an immunologically identical calmodulin-binding protein is expressed in both chromaffin granule membranes (as well as other secretory vesicle membranes) and chromaffin cell plasma membranes, thus suggesting a possible role for this protein in granule/plasma membrane interaction.

Adrenal Medulla↗
PubMed1988

A similar calmodulin-binding protein expressed in chromaffin, synaptic, and neurohypophyseal secretory vesicles.

The presence of calmodulin-binding proteins in three neurosecretory vesicles (bovine adrenal chromaffin granules, bovine posterior pituitary secretory granules, and rat brain synaptic vesicles) was investigated. When detergent-solubilized membrane proteins from each type of secretory organelle were applied to calmodulin-affinity columns in the presence of calcium, several calmodulin-binding proteins were retained and these were eluted by EGTA from the columns. In all three membranes, a 65-kilodalton (63 kilodaltons in rat brain synaptic vesicles) and a 53-kilodalton protein were found consistently in the EGTA eluate. 125I-Calmodulin overlay tests on nitrocellulose sheets containing transferred chromaffin and posterior pituitary secretory granule membrane proteins showed a similarity in the protein bands labeled with radioactive calmodulin. In the presence of 10(-4) M calcium, eight major protein bands (240, 180, 145, 125, 65, 60, 53, and 49 kilodaltons) were labeled with 125I-calmodulin. The presence of 10 microM trifluoperazine (a calmodulin antagonist) significantly reduced this labeling, while no labeling was seen in the presence of 1 mM EGTA. Two monoclonal antibodies (mAb 30, mAb 48), previously shown to react with a cholinergic synaptic vesicle membrane protein of approximate molecular mass of 65 kilodaltons, were tested on total membrane proteins from the three different secretory vesicles and on calmodulin-binding proteins isolated from these membranes using calmodulin-affinity chromatography. Both monoclonal antibodies reacted with a 65-kilodalton protein present in membranes from chromaffin and posterior pituitary secretory granules and with a 63-kilodalton protein present in rat brain synaptic vesicle membranes. When the immunoblotting was repeated on secretory vesicle membrane calmodulin-binding proteins isolated by calmodulin-affinity chromatography, an identical staining pattern was obtained. These results clearly indicate that an immunologically identical calmodulin-binding protein is expressed in at least three different neurosecretory vesicle types, thus suggesting a common role for this protein in secretory vesicle function.

Adrenal Glands↗
PubMed1987

Molecular cloning and sequence of the cDNA for a 94-amino-acid seminal plasma protein secreted by the human prostate.

The precursor to a seminal plasma protein reported to have inhibin-like activity was characterized through cDNA cloning and sequencing. It is a 114-amino-acid polypeptide which differs from its seminal plasma derivative mainly by the presence of a 20-residue amino-terminal extension, a putative signal sequence, carrying a possible N-glycosylation site. The protein is specified by a single gene per haploid genome. Its mRNA is detectable in the prostate but not in the testis, which suggests that it is primarily a prostatic secretory protein.

Amino Acid Sequence↗
PubMed1987

[Atypical hyperplasias of the endometrium].

A review of the literature concerning atypical hyperplasias of the endometrium is presented. The new pathological classifications differentiate structural abnormalities from cellular abnormalities. For atypical hyperplasias with cellular abnormalities, similar classifications to that of Richard for the cervix have been proposed: Intra Endometrial Neoplasia (IEN) grades I to III. Evolution of these lesions toward endometrial adenocarcinoma must guide the treatment. In prospective studies, atypical hyperplasias with structural abnormalities evolve into adenocarcinoma in 1.6 to 22 per cent of the cases. In atypical hyperplasia with cellular abnormalities, they evolve into adenocarcinoma in 23 to 57 per cent of the cases, according to the authors. Total hysterectomy is the treatment which is the most suitable for atypical hyperplasias with cellular abnormalities. Continuous progestational medications before menopause and the same given intermittently before menopause, represent the possible medical treatments.

Carcinoma in Situ↗
PubMed1986

Suicide attempts in hypo-oestrogenic phases of the menstrual cycle.

The phase of the menstrual cycle in women who had attempted suicide was determined by structured interview. 108 young women were investigated within 24 h of the attempt. Patients were grouped according to menstrual week and whether they used oral contraception (OC) (n = 73) or not (n = 35). In OC non-users suicide attempts were associated with low plasma oestradiol: they tended to happen during the first week of the menstrual cycle (42%) and after the fourth week (12%). Frequency of suicide attempts did not vary significantly during the menstrual cycle in OC users. In OC non-users, low oestradiol production may predispose to depression and attempted suicide.

Adult↗
PubMed1986

Modulation of the nicotinic alpha-bungarotoxin site in chromaffin cells in culture by a factor(s) endogenous to neuronal tissue.

An endogenous factor(s) which affects the in vitro binding of (alpha-BGT) to rat brain membranes has previously been found in brain supernatant. This fraction, as well as a partially purified preparation of this material from bovine brain, is here shown to affect the binding of alpha-BGT to chromaffin cell membranes. To study possible long term effects, the supernatant extract was added to adrenal medullary chromaffin cells in culture. The cells were incubated for several days and at the end of this time, the medium bathing the cells, which contained the endogenous factor(s), was removed and alpha-BGT binding to the cells measured. Binding to control cultures had shown that alpha-BGT bound to the chromaffin cells in a saturable manner, with high affinity (Kd = 1.5 nM) and the specificity of a nicotinic receptor ligand. After incubation of the cells with supernatant factor, a marked decline in the number of alpha-BGT binding sites was observed with no change in affinity. This does not appear to be due to a detrimental effect on the cells as cell number did not appear to be decreased in the cultures preincubated with the supernatant extract and the DNA and protein content were similar in the control and treated cultures. The possibility that there was some non-specific detrimental effect to the chromaffin cell membrane was considered; however, the stimulated release of noradrenaline from the cells was not affected by treatment of the cultures in the presence of the supernatant fractions. In addition, tyrosine hydroxylase activity was significantly increased in the treated cultures. D-Tubo-curarine, an antagonist at the acetylcholine receptor, caused an increase in alpha-BGT binding after 7 days of treatment, while the agonist nicotine and choline had no effect. These results suggest that in brain supernatant there may exist an endogenous factor(s), which may function in the regulation of the nicotinic-like alpha-BGT receptors in neuronal cell.

Adrenal Medulla↗
PubMed1986

[Estradiol-progesterone interaction in normal and pathological human breast cells].

In most target tissues of the female genital tract, an adequate cell differentiation can be obtained with the successive and synergistic action of estradiol (E2) and progesterone (P), essentially because the progesterone receptor (PR) synthesis implicates the previous action of E2 via its E2 receptor (ER). In normal breast, E2 stimulates the growth of the ductal system whereas the development of acini depends on P secretion. In other words, when E2 plus P are secreted by the ovaries in balanced proportions, the two hormones permit a complete and harmonious development of the mammary gland. The antiestrogenic activity of P is carried out through the decrease of ER resynthesis and stimulation of 17 beta-hydroxysteroid dehydrogenase enzyme activity, which transforms E2 into its less active metabolite estrone (E1) in the target cells. These biochemical events are well documented concerning the endometrium. They have also been observed in normal mammary cells in primary cultures as well as in breast fibroadenomas with high epithelial cellularity. Moreover, data from literature indicate that E2 could be both a direct and indirect factor of cell multiplication in cancerous cell lines. P as well as progestins have the opposite effect. Recent results from this laboratory indicate that E2 and P also have antagonistic effects on the cell multiplication of normal human mammary cells in primary culture. Therefore, the hypothesis that a lack of P during a long period of the female genital like could be a factor in the promotion of breast cancer must be considered.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

[Evaluation of 17-beta-hydroxysteroid dehydrogenase activity as a marker of the hormone dependence of breast cancers].

Intratumoral activity of the enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) was measured in 55 patients with breast cancer (17 pre- and 38 post-menopausal) before and/or after 8 days of a progestin treatment (lynestrenol 10 mg/day). In 12 patients the 17 beta-HSD ability to be stimulated was compared to estradiol and progesterone receptor (ER and PR) levels. In premenopausal patients 17 beta-HSD was higher when tumorectomy was performed in the luteal phase than in the follicular phase. In post-menopausal patients, 17 beta-HSD is higher after progestin treatment. However 17 beta-HSD stimulation by lynestrenol depends on receptor levels. It is most after markedly stimulated in ER+ PR+ tumors. It remains low in ER- PR- tumors. In conclusion, intratumoral measurement of the progesterone dependent enzyme (17 beta-HSD) in breast cancer after progestin treatment provides a fine and reliable index of the presence and functional character of PR and hormone dependence of the tumor.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

Estradiol 17 beta-hydroxysteroid dehydrogenase, a marker of breast cancer hormone dependency.

Intratumoral activity of the progesterone-dependent enzyme 17 beta-hydroxysteroid dehydrogenase (E2DH) was measured in 114 patients with breast cancer (33 pre- and 81 postmenopausal) before and/or after 8 days of a progestin treatment (lynestrenol, 10 mg/day). In 12 postmenopausal patients, the ability of E2DH to be stimulated by lynestrenol was compared to estradiol receptor (ER) and progesterone receptor (PR) levels. In premenopausal patients, E2DH was higher when tumors were excised in the luteal phase than when excised in the follicular phase. In postmenopausal patients, E2DH was higher after progestin treatment. However, E2DH stimulation by lynestrenol depended on receptor levels. It was most often markedly stimulated in ER-positive, PR-positive tumors. It remained low in ER-negative, PR-negative tumors. Intratumoral measurement of the progesterone-dependent enzyme E2DH in breast cancer after progestin treatment could therefore provide a fine and reliable index of the presence and functional character of PR and hormone dependency of the tumor.

17-Hydroxysteroid Dehydrogenases↗
PubMed1984

Biochemical characterization of 17 beta-hydroxysteroid dehydrogenase in human meningioma.

17 beta-Hydroxysteroid dehydrogenase (E2-DH) activity was characterized on a semipurified microsomal preparation of human meningioma tissue (mean Km of 2 microM and Vmax of 500 pmol/mg protein/10 min) and then assayed in 49 meningioma specimens with high progesterone receptor and low estrogen receptor levels. Of these 49 tumors, 36% contained an E2-DH activity greater than 1,000 pmol/mg protein/10 min and similar to that of uterine myometrium. In this limited series of tumors, no correlation between E2-DH activity and progesterone receptor levels was noted.

17-Hydroxysteroid Dehydrogenases↗
PubMed1983

Role of mast cell mediators in pathogenesis of anaphylactic gastric ulcer.

In an attempt to elucidate the pathophysiological mechanisms of gastric anaphylactic ulcer we measured tritiated thymidine incorporation in gastric cells, their mitotic rate and the degranulation of mast cells in the preulcerous phase. The results showed that there is a highly significant increase in cell turnover and mast cell degranulation in the mucosa of sensitized animals. Changes were found at the site of ovalbumin challenge, where point ulceration occurred within 48-72 h. The tissue culture studies demonstrated that the mucosa of sensitized animals produces significantly more histamine when challenged with ovalbumin than the mucosa of nonsensitized animals. Addition of histamine to the tissue culture medium in which normal gastric mucosa was cultured led to an increase in [3H]-thymidine uptake at low concentration, and a decrease at high concentration. Serotonin added to the culture medium had no significant effect on [3H]-thymidine uptake, but heparin at high concentration was found to have a stimulatory effect. These studies show that anaphylactic gastric ulceration is associated with an increase in mucosal cell turnover, and that the mast cell mediator responsible for this increase may be histamine.

Anaphylaxis↗
PubMed1983

[Steroid hormone receptors in benign breast diseases].

Benign breast diseases generally occur in women with progesterone insufficiency and an unopposed estrogen status. This hormonal imbalance is also a main risk factor for breast cancer in the long run. The presence of estradiol and progesterone receptors in benign breast disease are additional proof of their hormone dependence. The level of receptors is higher when the epithelial cellularity is high and also in more recent lesions, and younger women. The level and subcellular location of the receptors also depend on the endogenous secretion of steroids: their level varies throughout the menstrual cycle, and it is maximal at the end of the follicular phase, due to the high estradiol secretion. The cytosol and nuclear level and location of the receptors are also modified by hormonal therapy: estrogen-progestagens given as a contraceptive, or progestins given as a substitutive and antiestrogen therapy. These modifications constitute a biochemical basis for the hormonal progestagen treatment of benign breast diseases.

Adenofibroma↗
PubMed1982

Estradiol 17 beta-hydroxysteroid dehydrogenase activity in human breast fibroadenomas.

In the human endometrium, the presence of the progesterone-dependent enzyme 17 beta-hydroxysteroid dehydrogenase (E2DH) permits the conversion of an active estrogen, estradiol, into a less active one, estrone. This E2DH activity contributes to the antiestrogenic properties of progesterone. In the present study, E2DH activity was assayed in 54 surgically removed fibroadenomas. This benign breast disease was chosen since it offers rather homogeneous epithelial concentrations and still remains close to normal breast tissue from a pathological and hormonal point of view. E2DH activity was highest in fibroadenomas with high epithelial cell density. In addition, in these high epithelial cell density fibroadenomas (n = 18), E2DH activity increased markedly throughout the luteal phase of the menstrual cycle. Thus, it was 3- to 4-fold higher in fibroadenomas removed at the end of the luteal phase (1520 +/- 166 fmol/mg protein.h) than in those obtained during the follicular phase (375 +/- 95 fmol/mg protein.h). In addition, a striking increase in E2DH activity was observed in fibroadenomas from 5 patients treated with oral progestins (4080 +/- 650 fmol/mg protein.h) and 3 patients receiving progesterone topically applied upon the breast (3830 +/- 475 fmol/mg protein.h). E2DH activity, therefore, appears to be an important mechanism involved in the control by progesterone of estradiol action in breast tissue, as it is in the endometrium. It is also a good index of cellular differentiation and progesterone action at the molecular level. It is hypothesized that E2DH activity might be a specific marker of progesterone receptor itself and could be proposed in the evaluation of the hormone dependence of human breast tissue.

17-Hydroxysteroid Dehydrogenases↗