Biomedical subjects
Publications and source records attributed to C Sultan.
Based on their experience and on a review of the literature, the authors study the surgical aspects of the undescended testis. A precise definition excluding the retractile testis is essential. Although the understanding of the pathogenesis remained incomplete, the present data give support to an early orchidopexy performed by a specialized surgeon following the failure of a human chorionic gonadotropin test.
Explore the source record for details and available documents.
A computer program to identify normal and pathological blood and marrow cells is presented. It requires an analysis of cellular morphology according to ten simple criteria. These criteria are treated by the Bayesian method; then the program offers, in decreasing order, the cells which are best classified. The responses are analyzed and discussed. This program seems to be well suitable to a computer-assisted teaching (CAT) of cytology. It supplements effectively the traditional methods.
Serum ferritin has been assayed by two methods. Radio-Immunology and Enzymo-Immunology in two group of young females. Iron deficiency is considered as unequivocal if serum ferritin is lower than 20 micrograms/l whatever the method used analysis of red cell indices in iron deficient females has shown that anemia, hypochromia and microcytosis are very late events and that their sensitivity for the diagnosis if iron deficiency is very poor.
Explore the source record for details and available documents.
A partial androgen receptor defect was found in a boy with male pseudohermaphroditism and an 11p13 deletion. We hypothesize that a gene responsible for the function or structure of androgen receptors might be localized in the 11p13 band or in close proximity to it.
Androgen dependent skin disorders are important in clinical practice. Effective topical antiandrogens would lead to a breakthrough in their treatment. Although many attempts have been performed to develop such compounds, major successes have not been forthcoming. In the present study three existing antiandrogenic molecules have been compared with regard to their effect on androgen metabolism, receptor competition and on histological parameters in the hamster flank organ test. It appears that the effect on the hamster pigmented spot can be predicted on the basis of molecular mechanism. However, the effects on histological parameters are apparently dependent on additional factors such as metabolism of the active substance before reaching the sebaceous structure or limited penetration through the skin surface. The results indicate that in the development of new antiandrogens pre-screening can be performed with the aid of metabolic and receptor studies, while the histological parameters in the hamster flank organ test provide an animal model with a good predictive value.
We examined the morphological and functional characteristics of erythroblasts derived from marrow erythroid progenitor cells grown in a methylcellulose microculture, which were taken from a female child with rare atypical sideroblastic anaemia (SA) partially responsive to pyridoxine. Colony formation was within the normal range in three successive cultures (median values: 82.25 CFU-E and 16.4 BFU-E derived colonies/6.6 X 10(4) cells) compared to growth by normal cells (65-315 CFU-E and 9-40 BFU-E). We evaluated in vitro differentiation by biochemical microassay of a cytosol enzyme involved in the haem pathway: uroporphyrinogen I synthase (UROS). The UROS values in the erythroid colonies from SA marrow were at the lowere end of the normal range (median values: 6.7 +/- 0.3 and 14.4 +/- 3.8 pmol uroporphyrinogen/h in CFU-E and BFU-E-derived colonies respectively versus 17.4 +/- 7.3 and 25 +/- 7.2 pmol/h in CFU-E and BFU-E colonies from normal subjects. Ultrastructural examination of the SA erythroblasts from non-cultured bone marrow or derived from cultured BFU-E revealed the characteristic deposition of iron in mitochondria around the nucleus of most cells (ringed sideroblasts). However, the majority of cultured cells had marked dyserythropoietic features, with a large number of bilobulated or trilobulated erythroblasts, multiple cytoplasmic vacuoles, numerous abnormalities of the nucleus, and excessive membrane material beneath the plasma membrane, all features difficult to observe in non-cultured marrows.
The effects of natural and synthetic androgens on erythroid colony formation in children's bone marrow cultures were studied using a methylcellulose microculture assay. In an attempt to predict the clinical response to androgens in two children with Fanconi anaemia (FA) and two children with Diamond-Blackfan syndrome (DB), we tested the hormonal stimulation of testosterone, nortestosterone and etiocholanolone on CFU-E, BFU-E and uroporphyrinogen I synthase activity (UROS). We observed that colony formation and UROS activity were reduced when compared to values obtained with normal children's bone marrow cultures. The addition of steroids to the cultures significantly enhanced the numbers of CFU-E and BFU-E derived colonies and their UROS activity in marrow from patients with FA and one patient with DB. The strong depletion of marrow progenitor cells in the unresponsive marrow from child 4 with DB could explain the absence of hormonal response. Whereas the responsiveness to steroids varied according to the individual, the in vitro testing of erythroid differentiation in the presence of androgens theoretically may lead to an effective prediction of response to therapy in children with hypoplastic anaemia.
Human skin fibroblasts were incubated for 24 h with 10(-6) M androstenedione and the estrone + estradiol released in the culture medium were measured by an enzymatic assay. Aromatase activity was expressed as pmol (estrone + estradiol) formed in the medium per mg cell protein per day. Using this method we were able to investigate the kinetic properties of aromatase in different cell strains and its stimulation by dexamethasone. Values of 92 nM and 9.1 pmol/mg protein/day were obtained respectively for Km and Vmax in cultured fibroblasts derived from genital skin of normal prepubertal subjects. In patients with complete androgen insensitivity syndrome CAIS, the Km was 156 nM and the Vmax 42 pmol/mg protein/day. Aromatase activity varied from 7.9 +/- 1.2 pmol/mg protein/day (mean +/- SD; n = 19) in normal prepubertal boys to 24.5 +/- 4.7 pmol/mg protein/day (mean +/- SD; n = 11) in those from normal postpubertal boys. The values were even higher in fibroblasts cultured from genital skin of prepubertal patients with CAIS. Cell concentrations did not modify the pattern of estrogen formation and aromatase activity did not vary with serial subcultures. The stimulatory effect of dexamethasone on aromatase activity in cultured fibroblasts was measured after preincubation of the cells for 48 h with dexamethasone, by determining estrogen formation after 24 h incubation of the cells with androstenedione 10(-6) M using this enzymatic method. This data suggest that aromatase activity measured in cultured fibroblasts could be a useful tool for studying extraglandular estrogen formation in physiological and pathological conditions.
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.
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.
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.
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.
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.
Explore the source record for details and available documents.
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.
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.