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Biomedical subjects

M Benahmed

Publications and source records attributed to M Benahmed.

At least 91 records · Page 5Linked to original sources
PubMed1989

[Cardiac toxicity of 5-fluorouracil].

A 67 year-old patient receives 5-fluorouracil for vocal chord cancer. During the perfusion, atypical angina pain occurs, accompanied with offset of ST above the baseline in standard leads and in V4 through V6. The pain subsides spontaneously in 45 minutes. These ECG alterations are followed 48 hours later by diffuse inverted T waves with lengthened QT. Cardiac ultrasonography and isotopic angiography do not show any abnormality of the left ventricular function, but myocardial tomoscintigraphy with labelled thallium show a lower hypofixation on exertion. The cardiac toxicity of 5-fluorouracil is in frequent. It is usually believed that it involves a coronary spasm, as suggested by the ECG tracing in the reported cases. The incident, which may be painful or painless, may result in a myocardial infarction or even sudden death during the perfusion. Therefore, it is advisable to discontinue the treatment as soon as an angina-type pain occurs.

Aged↗
PubMed1988

Evidence for a FSH dependent secretion of a receptor reactive transforming growth factor beta-like material by immature Sertoli cells in primary culture.

Type beta Transforming Growth Factor (TGF beta)-like activity was identified in conditioned medium obtained from immature porcine Sertoli cell-enriched cultures using the following criteria: (i) stimulation of anchorage independent growth of mesenchymal cell lines, (ii) competition with pure human TGF beta in a radioreceptor assay. The secretion of the receptor reactive TGF beta-like material in Sertoli cell conditioned medium is decreased to very low or undetectable levels by Follicle Stimulating Hormone, one of the major hormones involved in the physiological testicular activities. The effects of this factor are probably exerted in the context of the local control of the male gonad functions.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1988

Direct regulating effects of transforming growth factor beta on the Leydig cell steroidogenesis in primary culture.

The effect of transforming growth factor beta on testicular steroidogenesis was studied by using a model of immature porcine Leydig cells cultured in a chemically defined medium. Leydig cells were cultured in the presence of human or porcine purified TGF beta and the following parameters were measured: cell proliferation, LH/hCG binding, and hCG-stimulated steroid hormone productions (DHEA, DHEAS and testosterone). Whereas TGF beta from the two sources had no effect on Leydig cell multiplication, it markedly inhibited LH/hCG-stimulated DHEA and DHEAS in a time- and dose-dependent manner. The maximal inhibitory effect of this peptide on LH/hCG binding (65% decrease), hCG-stimulated DHEA (77% decrease) and DHEAS (92% decrease) productions was observed with 2 ng/ml for 48 h of treatment. In contrast, TGF beta exerted a biphasic effect on hCG-stimulated testosterone production: stimulating (110% increase) until 2 ng/ml and inhibiting (35% decrease) for higher concentrations. [125I]TGF beta was cross-linked to Leydig cells using disuccinimidyl suberate; cells affinity labelled with [125I]TGF beta exhibit a major labelled band of approx 280 kDa, which has the properties expected from a TGF beta receptor. These data demonstrate that TGF beta is a direct potent regulator of Leydig cell steroidogenic function and its effects are probably mediated via a specific receptor.

Androgens↗
PubMed1988

Fibroblast growth factor is a regulator of testosterone secretion in cultured immature Leydig cells.

The regulatory effect of fibroblast growth factor (FGF) on testosterone secretion was studied by using a model of immature porcine Leydig cells cultured in serum-free defined medium. FGF enhanced in a dose-dependent manner hCG-stimulated testosterone secretion (ED50 = 11 ng/ml FGF). The stimulatory effect of FGF on testosterone accumulation was time dependent; testosterone increased to a maximal value at 24 h treatment and then dramatically declined to near control value following 48 and 72 h treatment with FGF; such a decline was not related to FGF degradation in culture medium. Although FGF increased maximal secretion of testosterone, it did not affect the human chorionic gonadotrophin (hCG) concentrations required for maximal and half-maximal secretion of testosterone (1 and 0.2 ng/ml hCG, respectively). These effects of FGF are probably exerted in the context of the local control of testicular steroidogenesis.

Animals↗
PubMed1987

Somatomedin C/insulin-like growth factor 1 as a possible intratesticular regulator of Leydig cell activity.

By using immature porcine Sertoli cells cultured in serum-free defined medium, we report that Sertoli cell-conditioned medium (SCCM) contains immunoreactive somatomedin C/insulin-like growth factor 1 (ir-SmC/IGF 1) which dilutes in parallel with purified human SmC/IGF 1. The release of ir-SmC/IGF 1 in the culture medium was dependent on the exposure time to Sertoli cells: no measurable ir-SmC/IGF 1 at 8 h, 12.1 +/- 1.2 ng/10(6) cells at 24 h and 33.9 +/- 5.3 ng/10(6) cells at 48 h of incubation. Moreover, ir-SmC/IGF 1 was also evidenced in SCCM following high performance liquid chromatography using a muC18 Bondapak column; ir-SmC/IGF 1 Sertoli cell-conditioned medium co-eluted with pure human SmC/IGF, suggesting a high homology between the two peptides. The effects of SmC/IGF 1 on testicular steroidogenesis were studied by incubating immature porcine Leydig cells with a biosynthetic human SmC/IGF 1. SmC/IGF 1 exerted a dose- and time-dependent stimulating effect on Leydig cell function with a maximal response at 50 ng/ml after 48 h of treatment. SmC/IGF 1 increased both LH/hCG binding (4.3-fold), basal testosterone (4-fold) and DHAS- and hCG-stimulated testosterone and DHAS (dehydroepiandrosterone sulfate) production (15.5- and 6.4-fold respectively). The slight effect of SmC/IGF 1 (100 ng for 48 h) on cell number (1.3-fold) and incorporation of [3H]thymidine into DNA (1.5-fold) in comparison with the high steroidogenic effect, supports the concept that SmC/IGF 1 acts as a cytodifferentiative factor rather than as a growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Somatomedin C/insulin-like growth factor 1: an intratesticular differentiative factor of Leydig cells?

By using immature porcine Sertoli cells cultured in serum-free defined medium, we report that medium conditioned by Sertoli cells contained immunoreactive somatomedin C/insulin-like growth factor 1 (SmC/IGF1) measured following acidic gel filtration. The release of this immunoreactive SmC/IGF1 was slightly increased following Sertoli cell treatment with fibroblast growth factor but not with follicle-stimulating hormone or growth hormone. On the other hand, human biosynthetic SmC/IGF1 exerts a potent stimulatory effect on Leydig cell differentiated functions such as LH/hCG-binding (greater than 4-fold) and hCG-stimulated testosterone secretion (greater than 15-fold). This effect was dose and time dependent and the maximal increase of Leydig cell function was observed following 48 h treatment with 50 ng/ml SmC/IGF1. The steroidogenic action of the peptide was not related to Leydig cell growth since both cell number and 3H-thymidine incorporation into DNA were not or slightly (approximately equal to 1.5-fold) increased in the optimal conditions with SmC/IGF1 treatment (100 ng/ml for 48 h). Moreover, the concomitant treatment of Leydig cells by both arabinoside C (10(-5) M), a DNA synthesis inhibitor, and SmC/IGF1 did not modify the stimulating effect of the peptide on LH/hCG-binding and hCG-stimulated testosterone production. Taken together, the present findings support the concept that Sertoli cell derived SmC/IGF1 could be a potent regulator of Leydig cell differentiated functions.

Animals↗
PubMed1986

Evidence for a Sertoli cell, FSH-suppressible inhibiting factor(s) of testicular steroidogenic activity.

By using a model of immature porcine Leydig and Sertoli cells cultured in serum free defined medium, we evidenced a paracrine control of Leydig cell steroidogenic activity by Sertoli cells via a secreted inhibiting protein(s). This protein(s), partially purified using gel filtration (M.W. 20,000-30,000) suppresses the steroidogenic responsiveness to LH/hCG by decreasing the specific LH/hCG binding (52% decrease) and hormone steroid biosynthesis (73% decrease) at a level(s) located between cAMP production and pregnenolone formation. The suppression of this inhibitor(s) by FSH, in a dose dependent manner, is one mechanism by which FSH "sensitizes" Leydig cell response to LH/hCG stimulation.

Animals↗
PubMed1986

Paracrine control of Leydig cell activity by FSH dependent proteins from Sertoli cells: an in vitro study.

The regulating effect of follicle-stimulating hormone (FSH) on Leydig cell function was studied using a model of immature porcine Leydig and Sertoli cells cultured in a hormone supplemented defined medium. FSH pretreatment for 2 days of Leydig cells cultured alone was with no effect. FSH pretreatment of Leydig cells cocultured with Sertoli cells increases Leydig cell activity in an FSH dose-dependent manner with a maximal effect observed at 50 ng/ml porcine FSH (pFSH). Leydig cells cultured for 2 days in conditioned medium (CM) by FSH stimulated (FSH-CM) Sertoli cells, as compared to CM by unstimulated (control) (C-CM) Sertoli cells show an increase of their activity with a maximal effect observed at 50 ng/ml pFSH. Leydig cells cultured in CM as compared to non CM, show a marked development of organelles (smooth endoplasmic reticulum and mitochondria) involved in the steroidogenic activity. The activity of FSH-CM as compared to C-CM on Leydig cell function was non dialyzable and trypsin sensitive. These data suggest that Sertoli cells exert a regulatory action on Leydig cell steroidogenic activity via FSH dependent secreted proteins.

Animals↗
PubMed1986

Cis platine (CDDP) in continuous intravenous ambulatory infusion: a new method of administration.

Twenty-three patients with metastatic tumors received multiple chemotherapy regimens which included CIS platine (CDDP) by continuous ambulatory infusion for 4 successive days at a rate of 25 mg/m2/day repeated every 4 weeks. Continuous infusion was provided by an external disposable pump, the "Infusor," which delivers the drug in a volume of 48 ml at a constant rate of 2 ml/hour, in conjunction with oral hydration and antiemetics. No incident detrimental to the patient was recorded. The average duration of the infusions was 23 hr. Only 22% of the patients had minor nausea and vomiting, and 1 case of functional renal insufficiency (4%) was easily corrected by simple intravenous hydration. A randomized study is ongoing to compare continuous perfusion with standard infusion for efficiency, side effects and response rate. Patients with "Infusor" are treated at home under Minitel supervision.

Cisplatin↗
PubMed1986

[Somatomedin C: a factor of the differentiation of adrenal cortex cells].

Using a model of bovine adrenocortical cells cultured in a chemically defined medium, we have shown that pure biosynthetic IGF 1/SmC increases adrenal steroidogenic function. The treatment with increasing concentrations of SmC (0-200 ng/ml) increases the AII binding and synergizes the effect of AII on steroidogenesis. The maximal effect is observed with 50 ng/ml SmC for 48 hrs. This effect of SmC could not be attributable to a mitotic effect, since 100 ng/ml of SmC for 48 hrs., induced a very slight increase in DNA synthesis (X 1.2) without any modification of corticoadrenal cell number. Insulin mimics the steroidogenic effect of SmC, but only at high concentrations. The effects of these two hormones are not additive, suggesting a common step in their mechanism of action. In summary, SmC exerts a direct cytodifferentiating effect on adrenal steroidogenesis.

Adrenal Cortex↗
PubMed1985

FSH regulates cultured Leydig cell function via Sertoli cell proteins: an in vitro study.

The effects of follicular stimulating hormone (FSH) on testicular steroidogenic activity has been studied by testing the capacity of conditioned medium (CM) by both unstimulated (control) Sertoli cells (C-CM) and FSH stimulated Sertoli cells (FSH-CM) to influence porcine cultured Leydig cell activity. Leydig cells cultured in FSH-CM for 48 hrs, as compared to C-CM, show a significant (P less than 0.05) increase in [125I]-hCG binding (150% +/- 4) and hCG-stimulated testosterone (T) secretion (266% +/- 42). In addition, the stimulating effect of FSH-CM on Leydig cell function as compared to C-CM, is trypsin sensitive, non dialyzable, heat stable, acid resistant and is chromatographed following gel filtration (Sephadex G 100) into two different peaks of activity. These data suggest that FSH regulates Leydig cell function via (at least two types of) Sertoli cell secreted proteins.

Animals↗
PubMed1985

Cultured Sertoli cell-mediated FSH stimulatory effect on Leydig cell steroidogenesis.

To determine the precise role of Sertoli cells in the stimulating effects of follicle stimulating hormone (FSH) on Leydig cell activity, porcine purified Leydig and Sertoli cells were cultured separately or together in a chemically defined medium in the absence or presence of porcine, FSH 50 ng/ml. Leydig cell activity was evaluated using two parameters: human chorionic gonadotropin (hCG) binding sites; and hCG-stimulated cAMP production and testosterone secretion. First, it was found that FSH increases Leydig cell activity in crude Leydig cell preparations (40-60% of Leydig cells), whereas it exerts no effect on purified Leydig cells (greater than 90% of Leydig cells). Second, FSH stimulates the activity of Leydig cells cocultured with Sertoli cells, whereas it remains without effect on purified Leydig cells cultured alone. This stimulating effect of FSH on Leydig cell activity is dependent on the Sertoli cell number in the coculture. These data 1) show that the stimulating effect of FSH on Leydig cell function is mediated by Sertoli cells and 2) support the concept of local control of Leydig cell function originating from Sertoli cells.

Animals↗
PubMed1985

[Chemotherapy by ambulatory continuous infusion using a portable pump: a feasibility trial].

43 metastatic cancer patients received 190 portable infusors over 24 hours or more. This portable infusor is a disposable material made by Travenol which operates without outside energy. The drug in an elastomere balloon reservoir is injected about 24 hours at a rate of 2 ml/hour. We used various drugs: CDDP, bleomycin, 5 fluorouracil, aracytine, velbe, voltarene. The patients were under hospital observation and received their treatment without any incident due to the pump itself. The patients who had already been perfused with the usual technique greatly appreciated the comfort of this light portable device. Our next step will permit us to estimate the use of these infusors by patients at home.

Ambulatory Care↗
PubMed1984

Interactions between immature porcine Leydig and Sertoli cells in vitro. An ultrastructural and biochemical study.

Interactions between Leydig and Sertoli cells, as well as a stimulatory effect of FSH on Leydig cell activity, have been reported in many studies. In order to investigate these interactions, the ultrastructure of immature pig Leydig cells under different culture conditions has been studied. When cultured alone in a chemically defined medium, there is a marked regression of the Leydig cell smooth endoplasmic reticulum and a swelling of the mitochondria. Addition of FSH or hCG does not prevent these phenomena. Co-culturing of Leydig cells with Sertoli cells from the same animal maintains the smooth endoplasmic reticulum at the level seen in vivo and in freshly isolated Leydig cells. The addition of FSH to the co-culture stimulates its development and increases Leydig cell activity, as assessed by an increase in hCG binding sites and an increased steroidogenic response to hCG. These results suggest that Sertoli cells exert a trophic effect on Leydig cells, and that the stimulatory effect of FSH on Leydig cell function is mediated via the Sertoli cells. These results reinforce the concept of a local regulatory control of Leydig cell steroidogenesis.

Animals↗
PubMed1983

[Modulation of Leydig cell activity by Sertoli cell: an in vitro study].

In vivo studies indicate that FSH can modulate Leydig cells steroidogenic activity. However, in the testis only Sertoli cells contain specific FSH receptors. In order to clarify the mechanism by which FSH exerts this effect on testicular steroidogenesis, purified Pig Leydig and Sertoli cells were cultured alone or in co-culture. Leydig cell activity has been evaluated by two parameters: 1. hCG-stimulated testosterone secretion. 2. LH/hCG binding sites. FSH does not stimulate these two parameters of purified Leydig cells when cultured alone. On the other hand, when Leydig cells are co-cultured with Sertoli cells, FSH significantly increases these two parameters of Leydig cell function. These results suggest that the effect of FSH on Leydig cells is not direct but mediated by Sertoli cells.

Animals↗