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Biomedical subjects

C Sultan

Publications and source records attributed to C Sultan.

At least 127 records · Page 7Linked to original sources
PubMed1987

Partial androgen receptor deficiency and mixed gonadal dysgenesis in Drash syndrome.

Drash syndrome associates a nephropathy characterized by a diffuse mesangial sclerosis of early onset, Wilms tumor, and male pseudohermaphroditism (MPH). A patient with Drash syndrome is reported with the following: karyotype 46,XY, external genitalia near normal female, mixed gonadal dysgenesis, severe androgen receptor deficiency demonstrated for the first time in this syndrome. The possibility of a common genetic denominator with the del 11p13 WAGR complex is suggested. MPH/nephroblastoma association is common. Androgen receptor deficiency has been observed in one case of each syndrome, respectively.

Disorders of Sex Development↗
PubMed1987

Determination of glycogen and enzymes of glycogen metabolism in human hair follicles.

The skin epithelium and its organelles use glycogen as well as glucose as source of energy. Therefore the characterisation of glycogen metabolism and the enzymes involved is important in the study of mechanisms regulating the normal or abnormal differentiation of skin organelles such as sebaceous glands and hair follicles. The present paper describes fluorimetric methods for the determination of glycogen and for the measurements of phosphorylase and phosphorylase kinase activity in one and the same lysate of minute tissue samples. The methods were tested for their suitability on freshly isolated human hair follicles and cultured hair follicle cells. The possible use of these techniques for studies on the pathophysiology of acne and hirsutism is discussed.

Cells, Cultured↗
PubMed1987

Bioluminescence: an improvement in the enzymatic assay of dehydroepiandrosterone sulfate in biological fluids.

Dehydroepiandrosterone sulfate (DHEAS) determination in biological fluids was carried out by enzymatic hydrolysis and conversion into estrogens [estrone (E1) and estradiol (E2)] by the multienzyme system of human placental microsomes. The enzymatic complex consists of sulfatase, 3 beta-hydroxysteroid oxido reductase and 5en----4en isomerase which converts DHEAS into androstenedione (A); the latter component is further converted into estrogens by the aromatase. The resulting estrogens were determined from the NADH formed by the transhydrogenation reactions of human placental dehydrogenase. NADH was measured by bioluminescence. As little as 4 pg was assayable by this rapid enzymatic method, with a coefficient of variation of 8%. The results are in good agreement with radioimmunoassay and the method is suitable for routine use.

Dehydroepiandrosterone↗
PubMed1987

[Somatomedin C/insulin-like growth factor I and in vitro erythropoiesis].

The effect of human somatomedin C/insulin-like growth factor I(SM-C/IGF-1) and human growth hormone (hGH) on colony formation by erythroid precursor cells (CFU-E and BFU-E) from children's bone marrow or blood was studied by methylcellulose cloning assay. We found that physiological concentrations of IGF-1, but not of hGH, stimulated erythropoiesis in vitro in the presence of erythropoietin, as demonstrated by the increased activity of a cytosolic enzyme of the heme pathway (uroporphyrinogen I synthase). The results suggest that IGF-I could be involved in the regulation of erythroid differentiation.

Bone Marrow↗
PubMed1987

Is increased 5 alpha-reductase activity a primary phenomenon in androgen-dependent skin disorders?

Testosterone metabolism was investigated in fractions of human skin, enriched in epidermis, dermis, sebaceous glands, and sweat glands, by histologic sectioning of skin punch biopsies, and the results were compared with two culturable skin cells, i.e., keratinocytes and fibroblasts. Since sebocytes could not be brought in culture, metabolism was also investigated in the hamster flank model. In the epidermal tissue of the skin biopsies the predominant metabolite was androstenedione, formed by the enzyme 17 beta-hydroxysteroid dehydrogenase. The same was true for cultured hair follicle keratinocytes. In the deeper skin layers the formation of androstenedione was markedly reduced, whereas the formation of 5 alpha-reduced metabolites was highly increased, with a maximum in the skin fractions containing large sebaceous glands. Cultured shoulder skin fibroblasts showed a markedly different testosterone metabolism compared with the sectioned skin biopsies, suggesting that dermal fibroblasts play a less important role in the overall skin testosterone metabolism. The present approach, allowing the comparison of testosterone metabolism in different substructures of the same skin biopsy provides new evidence that the high 5 alpha-reductase activity in the specific skin fractions must be mainly ascribed to the sebaceous glands. These results render a previous hypothesis, stating that the elevated level of 5 alpha-reductase and subsequent formation of dihydrotestosterone in androgenetic alopecia and acne (usually accompanied by seborrhea) could therefore simply be the consequence of sebaceous gland enlargement, much stronger. This hypothesis is further evaluated by quantitative correlation of sebaceous gland size with enzyme activity in the hamster flank model.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1987

Myelodysplastic syndromes.

The myelodysplastic syndromes (MDS) represent a group of syndromes having in common a defective production of one or more myeloid cell lines. They occur in patients which are more than 50 years old without any sex preponderance. The term MDS is replacing the obsolete and archaic term of 'preleukemia' and/or 'oligoblastic leukemia'. The more striking hematologic features are a discrepancy between a cellular bone marrow and a peripheral blood cytopenia. MDS may be idiopathic or secondary. Some of them precede or predispose to the subsequent development of an acute myeloid leukemia. A correct analysis of peripheral blood and bone marrow smears permits to classify MDS and to establish some prognostic features. Some syndromes are easily recognizable such as acquired idiopathic sideroblastic anemia, refractory anemia with excess of blasts, pure refractory cytopenia and acute myelodysplasia with myelofibrosis. Nevertheless this classification does not cover all these syndromes. Some of them with borderline features will be discussed separately. An analysis of a large series of MDS recently published in the literature will be presented as well as nosologic problems which arise. A conceptual effort should be made to recognize and evaluate the MDS.

Humans↗
PubMed1987

Insulin-like growth factor I stimulates human erythroid colony formation in vitro.

The effects of human GH and insulin-like growth factor I on the proliferation and differentiation of erythroid progenitor cells from the bone marrow and peripheral blood of children were studied in a hormone-depleted culture system. Growth of erythroid progenitors was quantified by directly scoring colonies and by biochemical determination of the activity of a cytosolic enzyme of the heme pathway, uroporphyrinogen I synthase. In the presence of erythropoietin, high concentrations (50-100 ng/mL) of human GH induced an increase in the number of erythroid colonies (and their uroporphyrinogen I synthase activity) formed by bone marrow or peripheral blood erythroid precursors. In the same conditions, physiological concentrations of insulin-like growth factor I (0.5-1 ng/mL) stimulated erythroid cell growth and differentiation (P less than 0.03) from bone marrow or peripheral blood.

Bone Marrow Cells↗
PubMed1987

Gonadotropin and alpha-subunit secretion during long term pituitary suppression by D-Trp6-luteinizing hormone-releasing hormone microcapsules as treatment of precocious puberty.

Short term treatment with GnRH agonists has been reported to increase plasma gonadotropin alpha-subunit (Gn alpha) levels while decreasing plasma immunoreactive LH (IR-LH) levels. In this study we examined the effect of D-Trp6-LHRH (LHRH-A) in microcapsules (60 micrograms/kg, im, every 28 days for 1 yr) in 13 girls suffering from precocious puberty. Plasma IR-Gn alpha was measured by RIA; plasma IR-LH and IR-FSH were measured by both polyclonal RIAs and monoclonal immunoradiometric assays (IRMA). Before treatment, basal IR-LH and IR-FSH levels and peak responses to LHRH measured by both RIA and IRMA were similar, and the Gn alpha response paralleled that of LH. After the first injection of LHRH-A, RIA LH levels were significantly higher than pretreatment levels until day 21, while IRMA LH levels transiently increased, but returned to pretreatment levels by day 7 and became lower thereafter (P less than 0.005). Plasma IR-Gn alpha levels increased from days 3-21 (P less than 0.05). After 1.5 months of treatment, basal RIA LH levels remained detectable and not different from pretreatment levels; IRMA LH levels were very low. The mean RIA and IRMA LH responses to LHRH were decreased at 1.5 and 12 months (P less than 0.01). Basal plasma RIA and IRMA FSH levels were similar during treatment (P greater than 0.05) and significantly lower than pretreatment values (P less than 0.01). The mean RIA and IRMA FSH responses to LHRH decreased significantly at 1.5 months (P less than 0.001). After 12 months, both RIA and IRMA FSH responses were increased, but IRMA values were significantly lower than RIA values. A sustained increase in basal Gn alpha values occurred, but there was a tendency for the peak levels after LHRH treatment to decrease, becoming significantly lower than pretreatment peak levels after 1 yr. The chromatographic analysis on Sephadex G-100 of a pool of plasma samples collected during a LHRH test in three children treated for 6 months indicated that IR-Gn alpha coeluted with [125I]Gn alpha. The large discrepancy between RIA and IRMA LH values suggests the secretion of unusual LH molecules which are recognized by RIA but not by IRMA. The sustained release of large amounts of IR-Gn alpha indicates dissociated effects of LHRH-A on alpha- and beta-subunit secretion by the gonadotrophs. The sustained response of Gn alpha to LHRH demonstrates that gonadotroph cell LHRH receptors are still responsive to LHRH during treatment with a LHRH agonist.

Capsules↗
PubMed1987

[Surgical problems posed by abnormalities of testicular migration].

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.

Cryptorchidism↗
PubMed1987

[A computer program for recognition of normal and pathologic blood and bone marrow cells].

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.

Bayes Theorem↗
PubMed1987

[Reevaluation of strategies for the diagnosis of iron deficiencies].

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.

Anemia, Hypochromic↗
PubMed1986

Studies on the local activity of antiandrogens at the molecular and histological level.

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.

Androgen Antagonists↗
PubMed1986

A paediatric case of sideroblastic anaemia. Ultrastructural studies of erythroblasts cultured from marrow BFU-E in a methylcellulose micromethod.

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.

Anemia, Sideroblastic↗
PubMed1986

In vitro CFU-E and BFU-E responses to androgen in bone marrow from children with primary hypoproliferative anaemia: a possible therapeutic assay.

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.

Androgens↗
PubMed1986

Aromatase activity in human skin fibroblasts: characterization by an enzymatic method.

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.

Adipose Tissue↗