Search PubMed⌕ Search

Biomedical subjects

C Sultan

Publications and source records attributed to C Sultan.

At least 145 records · Page 8Linked to original sources

Stimulation of aromatase activity by dihydrotestosterone in human skin fibroblasts.

In order to study the regulation of aromatase activity by androgens in cultured fibroblasts derived from genital skin of normal prepubertal boys, aromatase activity was evaluated in the presence of various concentrations of non-aromatizable androgen DHT(5 alpha-dihydrotestosterone). The estrogen formation was assayed by an enzymatic method, after 24 h incubation of the cells with 10(-6) M androstenedione. Aromatase activity was stimulated 3- to 20-fold by DHT at concentrations 10(-10) and 10(-9) M. It was necessary to preincubate the cells with DHT for 48 h in order to bring about this stimulation. The stimulatory effect was not significant after preincubation for only 24 h. The basal value of aromatase activity was in the range of 8 +/- 1.2 pmol/mg protein/day (mean +/- SEM), while the maximal stimulation 1043 +/- 46 pmol/mg protein/day was obtained at the concentration of 10(-8) M DHT. This stimulation was partially blocked with cyproterone acetate at level of 20 +/- 4 pmol/mg protein/day; stimulation of aromatase activity by DHT could thus be mediated by the androgen receptor. This stimulatory effect was prevented by incubation of the cells with cycloheximide or actinomycin D, suggesting that DHT acts to increase aromatase activity in cultured fibroblasts by inducing the synthesis of new proteinaceous material. In vitro regulation of aromatase activity by androgens could contribute to a new approach to the extraglandular formation of estrogen.

Aromatase↗

Evaluation of androgen action on fibroblast growth by flow cytometry.

The action of androgen (dihydrotestosterone-DHT-) on fibroblast growth was evaluated by 3H thymidine incorporation in DNA, by DNA assay using 3-5 diaminobenzoic acid fixation, and by a more sophisticated technique: flow cytometry. Cell DNA and proteins were stained with propidium iodide and fluorescein isothyocyanate, respectively. We did not observe any detectable DNA variation when fibroblats were incubated in the presence of DHT. Moreover, DHT did not modify DNA and protein distribution, either in the total cell cycle or in each phase of the cell cycle. These results suggest that androgens do not induce total protein synthesis nor increase DNA in target cells. It is likely that they induce specific protein synthesis.

Cell Cycle↗

Stimulatory effects of androgens on normal children's bone marrow in culture: effects on BFU-E, CFU-E, and uroporphyrinogen I synthase activity.

We studied the effect of natural and synthetic androgens on children's erythropoietic precursor cells in culture. Cultures of normal marrow were carried out according to a miniaturized methylcellulose method in the presence of erythropoietin. We then evaluated the effects of testosterone, nortestosterone, fluoxymesterone and etiocholanolone (10(-9)-10(-6) M) on erythroid colony-forming units (CFU-E) and burst-forming units (BFU-E). Androgen-induced growth of erythroid progenitors was quantified by directly scoring colonies and by a biochemical determination of the uroporphyrinogen I synthase activity (UROS). We observed a significant increase (p less than or equal to 0.05) in the number of CFU-E and BFU-E and in the UROS activity of derived colonies in the presence of androgens (10(-8) or 10(-7)M). This microculture assay could be useful not only to study the effect of androgens on erythroid progenitor cells in culture, but also to predict the best androgenic treatment of anemia in children and adults.

Ammonia-Lyases↗

Free and total plasma testosterone in men and women with acne.

Androgens are important in the pathogenesis of acne, and free testosterone in the serum is regarded as the biologically active component. In this study, serum free and total testosterone levels were measured in men (34) and women (14), suffering from acne but otherwise healthy. The plasma values for both groups of patients did not differ significantly from those of the age matched control groups.

Acne Vulgaris↗

[Collagen and steroid hormones].

The authors analyse the effects of steroid hormones on collagen, from up to date datas previously published and personal works. Glucocorticoids have catabolic effects; their molecular effects are reviewed. Conversely, oestrogens and androgens have an anabolic effect.

Androgens↗

Androgen receptors and partial androgen insensitivity in male pseudohermaphroditism.

Male pseudohermaphroditism can occur either as a result of inadequate fetal androgen secretion or ineffective androgen action. Partial androgen insensitivity syndrome is related to a decrease in the binding capacity of target cells androgen receptors. However, the biochemical expression of these syndromes is variable: although a low concentration of androgen receptors is observed in 75% of the cases, a normal binding capacity is sometimes reported. If the presence of androgen receptors is necessary for hormonal action, it is not sufficient since the receptor has to conserve its functional integrity. Several qualitative abnormalities of the androgen receptor have been described and could thus explain the disturbance in the androgen mechanism of action. The study of androgen-dependent proteins and other androgen-receptor "markers" should offer the clinician a better management of partial androgen insensitivity and allow, in amniotic or trophoblastic cells, a prenatal diagnosis of androgen resistance in high-risk families.

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

[Dysmenorrhea in the female adolescent. Clinical, biological and therapeutic data].

The physiology and pathology of dysmenorrhea in adolescent girls has become clear in the past 5 years. Although the prime cause of the disorder has not been identified, the obvious rise in PGF2 alpha prostaglandins is an objective biologic sign. As a result, more specific treatment has become possible with more definite and established care of this "condition" which is often distressing to the teenage girl affected.

Adolescent↗

[Physiopathology of sex differentiation anomalies].

In addition to the conventional classification, based on the nature of the gonads, it is possible to compile a physiopathologic classification based instead on the mass of androgens secreted by the fetal testicle, the receptivity of the target tissues and the coexistence of estrogen and androgen secretion.

Androgens↗

Inhibition, post-hydroxymethylglutaryl-CoA regulation and relation to cell growth of cholesterol biosynthesis in cultured human skin fibroblasts.

Cholesterol biosynthesis in cultured human skin fibroblasts was studied by [14C]acetic acid incorporation into non-saponifiable lipids and quantification of labeled cholesterol among its precursors. Synthesis was slow, in spite of a high 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA) activity and led to an accumulation of unexpected non-polar metabolites identified as C-30 sterones, but not C-27 sterol precursors. This supports a post-HMG-CoA regulation at the lanosterol demethylation step. Cholesterol biosynthesis was stimulated by cell culture in lipid depleted medium and was inhibited by pentadecane-2-one which acts mainly at two post-HMG-CoA steps: lanosterol demethylation and lathosterol isomerisation to cholesterol. A parallel pentadecane-2-one inhibition of cell growth was also observed, even when cells were cultured in the presence of whole serum. This indicates the existence of a relationship between endogenous cholesterol synthesis and cell growth and sheds additional light on the role of post-HMG-CoA regulation in this phenomenon.

Acetates↗

Myelodysplastic syndrome or acute myeloid leukemia? A study of 28 cases presenting with borderline features.

Some patients present borderline features between acute myeloid leukemia (AML) and typical myelodysplastic syndromes (MDS): an excess of blasts insufficient to conclusively diagnose AML, yet above the figures usually compatible with MDS or the presence of Auer rods associated with a moderate excess of blasts. This presents considerable difficulties in diagnosis and management. The authors studied 28 such cases using the French-American-British Co-operative Group (FAB) classification, which groups them into a separate category termed "refractory anemia with excess of blasts in transformation" (RAEB-T). This was found to be a heterogenous group. Certain patients (4/28) had a previously established myelodysplasia, but most presented directly as RAEB-T. Two very different pictures emerged: a few patients (4/28) were young, with presentation and evolution similar to classic AML, for whom combination chemotherapy was effective; the majority (20/28) were older, with more varied clinical and cytologic presentation, for whom chemotherapy was of little effect and who presented a picture resembling classic RAEB with a median survival of 10 months.

Adolescent↗

Testosterone secretion is severely impaired after hepatectomy in rat, dog and man.

In 90%-hepatectomized rats, the plasma testosterone level (0.34 +/- 0.07 ng.ml, mean +/- SEM) is significantly lower (P less than 0.001) than in sham operated male rats (1.7 +/- 0.26 ng.ml, mean +/- SEM). In dogs, after 90% hepatectomy, the mean plasma testosterone concentration fell to 1/10 of the plasma testosterone level measured in sham operated animals either 24 or 72 h after surgery. In hepatectomized men, plasma testosterone is markedly decreased in contrast to what is observed after duodeno-pancreatectomy performed under the same conditions of anesthesia. These results suggest that 90% hepatectomy severely alters the Leydig cell function.

Animals↗

Evaluation of the interest in ordering the leucocyte differential count.

The development of technical innovations which has taken place during the last 10 years in the medical field, has resulted in a rapid growth of laboratory investigations. The diffusion of these techniques has induced the systemacy in the prescription of certain tests without reconsidering the information they give. The analysis that has been made in Henri Mondor Hospital on the case of the white blood cells differential deals with this question. Has the white blood cells differential to be considered as a systematic test? What are the technological implications at stake? Can we propose strategies in this field for the use of equipment? A study has been made in order to answer these different questions. The study concerns 1514 requests for hematologic tests and 863 patients in order to characterize the prescriptions, to measure their interest and to evaluate their opportuneness. Furthermore, the contribution of decision-making aids in rationalizing the prescriptions has been evaluated in parallel to this study.

Blood Cell Count↗

Testosterone-producing hepatoblastoma in a 3-year-old boy with precocious puberty.

The syndrome of isosexual precocious puberty (PP) associated with a primary malignant hepatic tumor is rare and previously reported in only 17 cases with poor prognosis. Twelve cases are well-documented gonadotropin-producing tumors. We here describe a new case of virilizing hepatoblastoma in a 2-year-10-month-old boy with evidence of testosterone (T) production by the tumor itself, and survival with a 3 1/2-year follow-up after an extended right hepatic lobectomy. Preoperative laboratory findings showed high levels of serum alpha-fetoprotein (AFP) and T:350,000 ng/mL and 4.92 ng/mL, respectively, which normalized after surgery. There was no circulating gonadotropin nor stimulation of the hypothalamic-pituitary axis. Testicular biopsy showed neither interstitial-cell maturation nor Leydig-cell hyperplasia. Moreover, demonstration of T secretion by tumor cells and T synthesis in presence of C14 progesterone was performed in an in vitro culture system. These data seem to provide supportive evidence of a T-producing hepatoblastoma.

Carcinoma, Hepatocellular↗

Increased peripheral aromatase activity in prepubertal children with partial androgen insensitivity syndrome.

It has been suggested that rate of estrogen formation was higher in patients with androgen insensitivity syndrome (AIS). This work was designed to find out if peripheral aromatase activity could be related to a defect in androgen action in prepubertal children with male pseudohermaphroditism. Fibroblast estrogen production was assayed by a highly specific enzymatic determination. Foreskin fibroblast strains were raised from 17 children with partial androgen insensitivity (PAIS) as defined by dihydrotestosterone binding activity in cells. Results are expressed as pmol estrogens/mg proteins synthetized/day when cultured fibroblasts are incubated with D4-androstenedione. In normal prepubertal boys (n = 19), aromatase activity ranged between 5 and 10 pmol estrogens/mg proteins/day, while in postpubertal boys it varied between 15 and 34 pmol estrogens/mg proteins/day. In prepubertal boys with PAIS (n = 17) aromatase activity is highly elevated: 19.4 +/- 8.4 pmol/mg proteins/day. These results show that (a) peripheral aromatase activity is low before puberty and (b) fibroblast estrogen synthesis is significantly (p less than 0.001) increased in prepubertal children with PAIS. Our data suggest that low utilization of androgens by target cells stimulates the production of estrogen. Peripheral aromatase activity can thus be considered as a 'marker' of androgen insensitivity in prepubertal children with male pseudohermaphroditism.

Androgens↗

Criteria for the diagnosis of acute leukemia of megakaryocyte lineage (M7). A report of the French-American-British Cooperative Group.

For the diagnosis of M7, the bone marrow aspirate shows a leukemic cell infiltrate that comprises 30% or more of all cells. These cells are identified as being of megakaryocyte lineage by the platelet peroxidase reaction on electron microscopy or by tests with monoclonal or polyclonal platelet-specific antibodies. Myelofibrosis or increased bone marrow reticulin are a prominent aspect in most patients with M7. In patients with increased reticulin, the bone marrow sample may be difficult to obtain and the counts done on the marrow films may be misleading. In these patients, the diagnosis of M7 should be based on excellent bone marrow biopsy sections that show an excess of blasts and, at times, increased numbers of maturing megakaryocytes; and on the presence of unequivocal megakaryoblasts in the peripheral blood or bone marrow (or both) as shown by immunologic techniques.

Acute Disease↗

[Demonstration of a nuclear androgen receptor in erythroblasts obtained by culture of human bone marrow].

The new techniques of culture of bone marrow have shown that androgens and 5 beta steroids exert a direct effect on erythroid precursor cells from human or animal bone marrow. By contrast, the mechanisms of the intracellular actions of those compounds are poorly understood. Tritiated methyltrienolone (R 1881), a synthetic androgen that highly binds to androgen receptor, has been used for the study of a binding activity in nuclear extracts of cultured erythroblasts from human bone marrow. The nuclear extracts contain binding sites saturable at low concentrations of 3H-R 1881 (20-30 nM). Scatchard analysis revealed that the R 1881-nuclear complex has a dissociation constant (Kd) of 25-50 nM, and the number of binding sites was 235-370 fmoles/mg protein. The complex sedimented on 5-20% sucrose gradient in the 3.9 S region and 5 beta dihydrotestosterone compete strongly with R 1881 for binding sites. This binding component has characteristics of high affinity, low-capacity, sedimentation behaviour, and specificity commonly attributed to "androgen receptors".

Binding, Competitive↗