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X Rebillard

Publications and source records attributed to X Rebillard.

13 recordsLinked to original sources

[5 alpha-reductase and prostate].

The human prostate is a complex organ composed of four glandular zones that differ in their histology and biology. In addition to this anatomical organization, the prostate is mainly composed of epithelial and mesenchymal tissues. Two pathologies affect the growth of the prostate: cancer and benign prostatic hyperplasia. Anatomical and pathological studies have shown that stromal enlargement is the first step in the process of BPH and that both transition and periurethral regions are the exclusive sites of origin. Because the first step of androgen action is the reduction of testosterone into dihydrotestosterone by the 5 alpha-reductase, it have been postulated that modification of this enzymatic activity may play an important role in BPH development. However DHT production alone cannot explain the hyperplastic development of the gland. Thus it has also been postulated that androgen-growth factor interaction may be an important feature of this growth: these growth factors include the IGF axis. An interaction between androgen pathway and sympathethic system, via alpha-adrenoreceptor may also be suspected.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Effect of finasteride (Proscar) on the proliferation of cultured epithelial and stromal cells from normal and hyperplastic human prostates.

Finasteride is a potent 5 alpha-reductase inhibitor which has proven useful in the clinical management of benign prostatic hyperplasia. To determine a potential mode of action for finasteride in prostatic cell proliferation, we have studied the incorporation of [3H]-thymidine into the DNA of cultured epithelial and stromal cells from normal and hyperplastic human prostates. The effects of short treatment with 10(-9) M and 10(-6) M finasteride (48 hrs.) on the incorporation of labelled thymidine were studied. A significant effect of finasteride on prostatic cell proliferation was observed at 10(-6) M for both epithelium and stroma from normal prostate: the rate of thymidine incorporation decreased to 80 +/- 3% (p < 0.001) and 55 +/- 10% (p < 0.01), respectively, compared to the control cells. As observed for normal prostates, this rate of thymidine incorporation was less for hyperplastic epithelium (70 +/- 4%, p < 0.001) than that observed for the hyperplastic stroma (74 +/- 4%, p < 0.01). These data clearly demonstrate that the reduction of the prostate volume observed in BPH treatment by finasteride is partly due to an inhibition of cell proliferation. However, the absence of complete inhibition of cell proliferation at 10(-6) M, a concentration known to strongly inhibit the 5 alpha-reductase activity, supports the hypothesis that factors other than DHT are necessary to induce prostatic cell proliferation.

Adult↗

Nuclear localization of the testis determining gene product SRY.

We have studied the expression of the human SRY protein (termed p27SRY) in two different cell lines by using specific antibodies. Confocal microscopy enabled us to localize p27SRY precisely in the nucleus in a discrete punctuate pattern. Furthermore, through microinjection experiments, we have demonstrated that the localization of the p27SRY protein into the nucleus was an event involving the NH2-terminal part of the high mobility group (HMG) domain. With the help of several synthetic peptides and various p27SRY mutants, we have characterized a bipartite basic motif in this part of the protein corresponding to a nuclear localization signal. This nuclear localization signal appears to be highly conserved in SRY box- and HMB box-containing proteins, suggesting common properties of nuclear targeting within the HMG box protein family.

Amino Acid Sequence↗

Cathepsin D cytosolic assay and immunohistochemical quantification in human prostate tumors.

We quantified cathepsin D by immunoradiometric assay (IRMA) and quantitative immunohistochemistry in fifteen human prostate cancers, seventeen BPH, and nine normal prostates. The cytosolic cathepsin D concentration was higher in prostatic carcinoma (mean: 31.5 pmol/mg cytosol proteins; range: 10.2-66.2) than in normal prostate (16.0 pmol/mg cytosol proteins; 7.2-25.5; P = 0.01). Prostatic hyperplasia showed intermediate values (20.2 pmol/mg cytosol proteins; 7.6-33.9). Immunostaining of cathepsin D and prostatic acid phosphatase on serial frozen sections of prostate tissues was only observed in glandular epithelial cells. Immunostaining was quantified by computer-assisted image analysis as an quantitative immuno-cytochemical score (QIC score) expressed in arbitrary units (A.U.). QIC scores for cathepsin D were dispersed and had a tendency to be higher in benign prostatic hyperplasia (mean: 178.3 A.U.; range: 95-297) compared to normal prostate (85.2 A.U.; 2-173 P < 0.01) and prostatic carcinoma (90.0 A.U.; 21-179 P = 0.0002). Prostatic cathepsin D levels in cytosols or immunostaining sections were independent of other clinicobiological parameters.

Acid Phosphatase↗

Adrenergic receptors on smooth muscle cells isolated from human penile corpus cavernosum.

The effect of the alpha-adrenergic blocker moxisylyte was examined on smooth muscle cells isolated from human corpus cavernosum, and compared with that of other adrenergic agents and papaverine. Isolated smooth muscle cells were shown to contract (reduction of the mean cell length) under noradrenaline and carbachol stimulations in a time-dependent and concentration-dependent manner (maximum at 30 seconds, EC50 [noradrenaline] = 5 nM., EC50 [carbachol] = 1 nM.). The contractile effect of noradrenaline was dose-dependently inhibited by moxisylyte (IC50 = 0.5 +/- 0.2 microM.) and by prazosin (IC50 = 0.9 +/- 0.2 microM.). The dose-response curves were parallel and no statistically significant difference could be shown between the IC50 values. The alpha 2-adrenergic antagonist tolazoline also inhibited noradrenaline-induced contraction, whereas the alpha-adrenergic agonist methoxamine did not change the mean cell length. As expected, isoproterenol caused relaxation of noradrenaline-precontracted cells by interaction with a beta 2-adrenergic receptor. Papaverine was also found to inhibit the contraction induced by noradrenaline in a dose-dependent manner (IC50 = 2 +/- 0.3 nM.). Tritiated-dihydroergocryptine (3H-DHE) specific binding was competitively inhibited by moxisylyte and prazosin with the same IC50 value of 0.01 microM. Methoxamine and tolazoline also inhibited this binding with lower affinity (IC50 = 0.1 +/- 0.02 microM.), while isoproterenol did not change specific binding. Scatchard plots from saturation experiments with 3H-DHE and with 3H-N-methyl scopolamine revealed the presence of 15 times more adrenergic than muscarinic binding sites (650,000 and 45,000 sites per cell, respectively). Together, these data support evidence for the presence of postsynaptic alpha 1-adrenergic receptors on smooth muscle cells from human corpus cavernosum. These receptors are coupled with the contraction of the cell and are blocked by the alpha 1-adrenergic antagonists moxisylyte or prazosin. They also show that the phosphodiesterase inhibitor papaverine and the beta-adrenergic agonist isoproterenol induced relaxation. This model constitutes a new approach to study the potential targets of the adrenergic agents in the erectile tissue.

Dose-Response Relationship, Drug↗

[Cancer of the testis after Hodgkin's disease. Apropos of 2 cases].

We report about two cases of cancer of the testis occurring 2 and 7 years after Hodgkin's disease treated with combined chemotherapy and radiation therapy. From an etiopathogenic point of view, this association may, of course, be accidental, but it may also have an iatrogenic origin or be caused by contiguous carcinogenesis, or even by an immune deficiency. In addition to orchidectomy, the therapeutic history of these patients requires an adaptation of the treatment of their tumors of the testes.

Adult↗

[Coronary ischemia after kidney transplantation in patients over 60 years of age].

Many elderly patients (aged over 60) are waiting for renal allograft but are considered a risk population for myocardial infarction or sudden cardiac death. Between 1987 and January 1st, 1990, 22 elderly patients (16 men and 6 women; mean age 63.4 +/- 0.7 years; range 60-69 years) underwent cadaveric kidney transplantation. Twenty patients had been on haemodialysis for 4.8 +/- 1 years (range: 1-16.3), one had been on peritoneal dialysis for 5 years and one had developed chronic rejection of a previous cadaveric allograft. Among these 22 patients, 6 (27 percent) developed antibodies directed against the random lymphocyte panel and one had a second transplant. Cardiovascular risk factors were systematically estimated, including medical history, cervical arterial Doppler, echocardiography and stress thallium testing (STT). Coronary angiography was performed if there was evidence of myocardial ischaemia. STT did not show any coronary disease in 16 patients and was not maximal (less than 60 percent of maximal theoretical stress) in 4 patients. In 2 patients, STT showed myocardial ischaemia: one, with a history of angina, underwent coronary angiography and angioplasty; the other had silent ischaemia and refused coronary angiography. Two patients died of myocardial infarction. One of them was the patient with silent ischaemia and positive STT test. The patient with angioplasty had a successful transplantation 20 months later, without any cardiovascular complication. After 9 to 32 months of follow-up, 19 patients have functioning allografts (mean serum creatinine level 151 +/- 6 mumol/l). One patient lost his kidney from urinary fistula. Eight patients (36 percent) developed acute rejection and all responded to intravenous corticosteroids. No immunological transplant loss was observed. After 18 months, the graft actuarial survival rate was 85 percent. We conclude that elderly patients free of clinical or silent myocardial ischaemia are good transplant recipients. The cardiovascular risk could be prevented by using STT during the pretransplant screening. If the STT is not maximal or shows coronary ischaemia, coronary angiography is mandatory.

Actuarial Analysis↗

Discrimination between tumour and normal cells by staining with 3,4,5,6,16,17-hexadehydro-16-(methoxycarbonyl)-19 alpha-methyl-20 alpha-oxayohimbanium: the uracil ring as a target for the specific interaction between RNA(s) and the fluorescent probe.

3,4,5,6,16,17-Hexadehydro-16-(methoxycarbonyl)-19 alpha-methyl-20 alpha-oxayohimbanium (Alstonine) is a fluorescent alcaloid which has been known to stain tumour cells more efficiently than normal ones. In this paper the spectral properties of Alstonine were first investigated and its capability for preferential staining of tumour cells verified in culture using SK-OV-3 cells as tumour cells and Mouse 3T3 fibroblasts as controls. Then interactions between Alstonine and biological macromolecules were investigated to provide the rationale for preferential labelling. Molecular filtration techniques have demonstrated that binding occurs only with RNA molecules. Similar experiments were performed with different isopolynucleotides to find an explanation for that specificity. They provide evidence that binding occurs only in the presence of a uridyl ring. This is consistent with the specificity of the linkage to RNA. As the linkage of Alstonine with RNA did not induce any shift or obvious change in the intensity of its fluorescence spectrum, it is concluded that the binding might involve the side chain of the fluorescent compound.

3T3 Cells↗