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Biomedical subjects

C Sultan

Publications and source records attributed to C Sultan.

At least 163 records · Page 9Linked to original sources
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

[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↗
PubMed1985

[Hormonal evaluation in male infertility].

Recent progress in the study of the hormonal regulation of spermatogenesis justifies endocrine examination in the case of male sterility. The most important complementary investigation are the assays of FSH, LH and plasmatic testosterone. Radioimmunoassay of FSH is the fundamental examination, since this hormone is considered to be an indicator of germinal function. Thus, in the case of oligospermia, or even azoospermia, FSH assay is decisive. When the FSH levels (in conjunction with LH levels) are high and combined with azoospermia, there is a possibility of testicular dysgenesis linked with a karyotype anomaly (XXY etc.). In some cases the germinal affection is secondary to cryptorchidism, orchitis, torsion, medicinal alteration, or radiotherapy. Decreased testosterone values combined with an insufficient FSH and LH response to stimulation tests indicate a gonadotrophic deficit, which is the best indication for substitution therapy using gonadotrophins or LH-RH. An increase in LH, contrasting with a normal FSH value, evokes the exceptional case of a disturbance of androgen receptivity. Normal FSH (and LH) values suggest excretory sterility. Lastly, when hyperprolactinemia is suspected, an assay of plasmatic prolactin is necessary. A "simple" hormonal evaluation allows a routine etiological approach to the diagnosis of sterility, and is thus an important element in the investigative strategy applied to male sterility, used along with the other complementary and indispensible examinations.

Estradiol↗
PubMed1984

Specific 5 alpha-dihydrotestosterone receptor and 5 alpha-reductase activity in human amniotic fluid cells.

A macromolecular component which specifically binds tritium-labeled-dihydrotestosterone is present in cultured amniotic fluid cells. The androgen-binding complex is characterized by a 3.6S sedimentation coefficient, an apparent dissociation constant of 1 nmol/L, a mean binding capacity of 243 +/- 140 fmol/mg of DNA, and a specificity for testosterone and dihydrotestosterone. Similar properties have been reported for the androgen receptor of the fetal genital skin fibroblast, which suggests that the tritium-labeled-dihydrotestosterone-binding component in amniotic fluid cells is the androgen receptor. Amniotic fluid cell monolayers incubated with serum-free medium containing testosterone are able to transform testosterone into dihydrotestosterone. The 5 alpha-reduced product has been characterized by thin-layer chromatography and capillary column gas-liquid chromatography. Androgen receptors and 5 alpha-reductase activity are expressed in amniotic fluid cells. The prenatal diagnosis of 5 alpha-reductase deficiency or complete androgen insensitivity syndrome (testicular feminization) is thus theoretically possible and obviously prenatal testing would be indicated in the family at high risk.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1984

Inhibition of androgen metabolism and binding by a liposterolic extract of "Serenoa repens B" in human foreskin fibroblasts.

We previously suggested [Steroids 33, (1979) 3; Steroids 37, (1981) 6] that cultured genital skin fibroblasts should prove useful for screening of potential antiandrogens in human and living target cells. "Serenoa repens" lipidic extract (S.R.E.) was recently reported (Br. J. Pharmacol., in press) to inhibit androgen action in animals. The present investigation was designed to study the antiandrogenicity of this compound in human cells: we therefore analyzed the effects of S.R.E. on the intracellular conversion of testosterone (T) to 5 alpha-reduced derivatives, and we investigated interaction of S.R.E. with the intracellular androgen-receptor complex. Since the chemical structure of the active component of S.R.E. is still unknown, results are expressed in U/ml (one unit is defined as the amount of S.R.E. required to inhibit 50% of the specific binding (IC50) of [3H]1881 to rat prostate cytosol). S.R.E. at different dilutions (5.7 to 28.6 U/ml) is added to culture media containing [3H]T or [3H]dihydrotestosterone (DHT) and incubated at 37 degrees C with cultured fibroblasts. 28.6 U/ml S.R.E. significantly alters the formation of DHT and strongly inhibits 3 ketosteroid reductase mediated conversion of DHT to 5 alpha-androstane-3 alpha, 17 beta-diol, characterized radiochemically by thin-layer chromatography. S.R.E. is a good competitor for the whole cell androgen receptor: 7.1 U/ml S.R.E. gives 50% inhibition of the binding of 2 X 10(-9) M [3H]DHT to its receptor. Competitive binding assays after cell fractionation indicate that S.R.E. is less potent in nuclear than in cytosol receptors. Sucrose gradient centrifugation of the radioactive cell lysate of fibroblasts demonstrates that 28.6 U/ml S.R.E. abolishes 70% of the 3.6 S receptor-complex radioactive peak. The present studies show that S.R.E. inhibits 5 alpha-reductase, 3-ketosteroid reductase and receptor binding of androgens in cultured human foreskin fibroblasts. As the search for the ideal antiandrogen continues, S.R.E. appears to be a new type of antiandrogenic compound as therapeutics for the treatment of benign prostatic hypertrophy, hirsutism and so forth.

Adult↗
PubMed1984

Binding of Permixon, a new treatment for prostatic benign hyperplasia, to the cytosolic androgen receptor in the rat prostate.

The benign hyperplasia of the prostate is a manifestation of aging, involving the accumulation, within the gland, of dihydrotestosterone, the probable mediator of the hyperplasia. Binding studies were performed on the cytosolic androgenic receptor of the rat prostate using [3H]methyltrienolone as a ligand. The binding of [3H]methyltrienolone at 5 nM, was inhibited by various drugs, such as methyltrienolone and cyproterone acetate. Permixon, a liposterolic extract of the plant, Serenoa Repens B, inhibits competitively the binding to the cytosolic receptor of the rat prostate. Various vegetable and mineral oils, the plant steroid: beta sitosterol and the antiprostatic drug: Tadenan, were all found to be inactive. The antiprostatic activity of Permixon shown in animal studies and controlled clinical trials, may thus result from a direct action at the cytosolic receptor.

Animals↗
PubMed1984

Cobalamin (vitamin B12) and B12 binding proteins in hypereosinophilic syndromes and secondary eosinophilia.

Serum cobalamin (vitamin B12) and unsaturated B12 binding capacity (UBBC) have been measured in 24 cases of hypereosinophilia: 16 were cases of hypereosinophilic syndrome (HES) and 8 of secondary eosinophilia. The two groups were similar with respect to absolute eosinophil counts. Serum cobalamin and UBBC were found to be markedly increased in most cases of HES and normal in secondary eosinophilia. This elevation of UBBC was mainly related to the increase of R binders (transcobalamins I and III). The elevated serum cobalamin and R binders in HES were due neither to a higher intracellular content of R binders nor to an increased release of these binders from eosinophils of HES. Pure fractions of eosinophils obtained from HES and secondary eosinophilia did not exhibit any difference in vitamin B12 binders. On the other hand, neutrophil-rich fractions from the same patients showed a higher content of intracellular B12 binding proteins than pure eosinophil fractions, irrespective of the cause of eosinophilia. These findings suggest that the increased serum vitamin B12 and UBBC could reflect an expanded pool of both eosinophils and neutrophils in HES and, thus, provide an additional argument for the inclusion of this syndrome in the group of myeloproliferative disorders.

Eosinophilia↗
PubMed1983

Incomplete androgen insensitivity syndrome: partially masculinized genitalia in two patients with absence of androgen receptor in cultured fibroblasts.

In male pseudo-hermaphroditism due to end organ unresponsiveness, partial androgen insensitivity can usually be related to low but detectable dihydrotestosterone (DHT) binding activity in cultured sexual skin fibroblasts. We have studied two patients with partial virilization and total absence of androgen receptors in cultured fibroblasts. A lack of DHT binding could be related to a selection of a fibroblast strain with no androgen receptor activity, to insufficient sensitivity of the method in detecting very low receptor concentrations or to an instability of the receptor or the androgen-receptor complex. However, these observations raise the question of masculinization of external genitalia with undetectable androgen receptor.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1983

Haematological features of primary myelodysplastic syndromes (PMDS) at initial presentation: a study of 118 cases.

The haematological features of 118 cases of primary myelodysplastic syndromes (PMDS) were reviewed to see how these could be related and classified according to the recent FAB proposals. A majority of the cases were elderly who presented with a macrocytic or normocytic anaemia and reticulocytopenia. Cases of acquired idiopathic sideroblastic anaemia (AISA) usually had normal leucocyte and platelet counts, erythroid hyperplasia, marked dyserythropoiesis and more than 20% ringed sideroblasts. Cases of refractory anaemia with excess of blasts (RAEB) had frequent neutropenia and thrombopenia usually with prominent dysgranulopoiesis and dysthrombopoiesis. Refractory anaemia or refractory cytopenia appeared morphologically to be a heterogeneous group. Leukaemic transformation did not occur in any of these 16 cases of AISA whereas six of the 34 cases of RAEB transformed into acute leukaemia. It appears that the cases of PMDS present with well defined haematological features which permit recognition of different groups; these latter groups appear to be morphologically and prognostically distinct.

Adult↗
PubMed1983

Prevalence and distribution of ringed sideroblasts in primary myelodysplastic syndromes.

In order to determine the prevalence and percentage distribution of ringed sideroblasts in primary myelodysplastic syndromes, the results of Prussian blue staining were analysed in 133 cases. Ringed sideroblasts ranging from 1 to 86% of cells were found in 76 (57%) cases. The cases of primary myelodysplastic syndrome corresponding to the group entitled "acquired idiopathic sideroblastic anaemia" had between 21 and 86% ringed sideroblasts; these were also found in 40% (26/65) cases corresponding to refractory anaemia with excess of blasts. Seven of the 22 cases having morphological features of refractory anaemia with excess of blasts in transformation had ringed sideroblasts. It would appear that cases of acquired idiopathic sideroblastic anaemia have at least 20% ringed sideroblasts; they also seem to occur frequently in refractory anaemia with excess of blasts.

Anemia, Aplastic↗
PubMed1983

[Metabolism of dihydrotestosterone in cultured skin fibroblasts: reduction to 5 alpha-androstane-3 alpha, 17 beta-diol].

Reduction of dihydrotestosterone into 5 alpha-androstan-3 alpha, 17 beta diol by 3 alpha hydroxysteroid dehydrogenase was studied in human cultured skin fibroblasts. Characterization of the 3 alpha diol was performed by gas-liquid chromatography coupled with mass spectrometry. Sex skin fibroblasts enzyme has the same Km (9.10 X 10(-6) M) as that of non sex skin fibroblasts (8.75 X 10(-6) M). On the other hand, reduction of DHT is 3 times higher in sex skin fibroblasts (Vmax = 223.9) than in non sex skin fibroblasts (Vmax = 87.9). Thus, human culturel fibroblasts appear again to be an useful tool for the study of a key-enzyme of androgen metabolism in target cells.

Androstane-3,17-diol↗