Carcinoma oesophagus--an unusual presentation.

We report a 32 years old female who had carcinoma of the oesophagus and who presented with unusual features.

Effect of cyclosporine on steroidogenesis in rat Leydig cells.

Cyclosporine induces hypoandrogenism in adult male rats. In order to assess whether this effect of CsA may be due to a direct inhibitory effect on Leydig cell function, CsA (0, 50, 500, and 5000 ng/ml) was added to a collagenase-dispersed mixed Leydig cell preparation and incubated with and without hCG (0, 0.1, 0.

Effects of gonadotropin-releasing hormone analogs on cis-platinum-induced spermatogenic damage.

In order to test the hypothesis that pretreatment with gonadotropin-releasing hormone (GnRH) analogs might ameliorate cytotoxic drug-induced testicular damage, mature male Wistar rats were pretreated for 2 weeks with a GnRH superactive agonist or a pure GnRH antagonist prior to, and for 1 week after, a 5 mg/kg intraperitoneal dose of cis-platinum. Despite inhibition of testicular function by both GnRH analogs prior to cis-platinum administration, there was no evidence of protection or enhanced recovery of spermatogenesis at 6 and 12 weeks after cis-platinum treatment, and spermatogenesis was significantly further depressed at both time-points by both GnRH agonist and antagonist pretreatment. This suggests that pretreatment with GnRH analogs in the rat does not protect spermatogenesis from cis-platinum-induced testicular damage within up to two spermatogenic cycles and that hypogonadism at the time of cytotoxic drug treatments may aggravate testicular damage.

Effects of cyclosporine on the hypothalamic-pituitary-gonadal axis in the male rat: mechanism of action.

In the intact adult male rat, cyclosporine (CsA) induces a significant decrease in serum testosterone (T), serum LH, and intratesticular T. To elucidate the mechanism of action of this CsA-induced hypogonadotropic hypogonadism, castrated male rats were treated with oral CsA (30 mg/kg.day) or vehicle alone, and serum LH was measured after 1, 2, and 4 weeks of treatment.

Reversibility of cyclosporine-induced hypoandrogenism in rats.

In an attempt to determine whether the inhibition of the hypothalamic-pituitary-testicular axis induced by oral cyclosporine (CsA) is reversible, intact adult male rats were treated with 30 mg/kg oral CsA daily for 4 weeks, and then vehicle (orange juice) for the next 4 weeks. A second group of animals (control) was fed orange juice throughout the entire 8 weeks of the experiment. Serum testosterone (T) was decreased significantly (P less than 0.

Cyclosporine inhibits testosterone biosynthesis in the rat testis.

To determine whether the immunosuppressive agent cyclosporine (CsA) has an effect on testicular androgen function in the male rat, four groups of adult animals were treated daily for 28 days with either orange juice or three doses of CsA (7.5, 15, or 30 mg/kg X day). Twenty-four hours after the last dose of CsA, the animals were killed and the following parameters were measured: testis, seminal vesicle, and ventral prostate weights; serum levels of CsA, creatinine, testosterone (T), and LH; and intratesticular levels of pregnenolone, progesterone, 17 alpha-hydroxyprogesterone, androstenedione, and T.

Inhibition of testicular testosterone biosynthesis following experimental varicocele in rats.

In an attempt to determine whether defective testicular testosterone (T) biosynthesis may be associated with a varicocele, an experimental study was performed in adult rats whereby a unilateral left varicocele was surgically created. At 2, 4, 8, and 12 wk following the creation of the varicocele, intratesticular T as well as the activities of three (17 alpha-hydroxylase, 17,20-desmolase, and 17 beta-hydroxysteroid dehydrogenase) of the five enzymes in the delta 4 pathway of testicular T biosynthesis were measured. Intratesticular T (ng/g testis +/- SEM) in the left testis decreased significantly from 121 +/- 21 in the control group to 59 +/- 8 in the two-wk varicocele group (p less than 0.

Lack of a direct effect of gonadotropin hormone-releasing hormone agonist on human testicular steroidogenesis.

In an attempt to determine whether the chronic administration of GnRH agonist (GnRH-A) has a direct inhibitory effect on testicular steroidogenesis in the human, the testes of four men with disseminated prostatic cancer who were treated with GnRH-A daily for at least 1 yr were assayed for intratesticular pregnenolone (5-pregnen-3 beta-ol-20-one), progesterone, dehydroepiandrosterone, 17 alpha-hydroxypregnenolone (5-pregnen-3 beta 17 alpha-diol-20-one), 17 alpha-hydroxyprogesterone, androstenedione, and testosterone (T). In addition, testicular 17 alpha-hydroxylase, 17,20-desmolase, and 17 beta-hydroxysteroid dehydrogenase enzyme activities of the delta 4 pathway were measured. These intratesticular steroids and enzyme activities from four GnRH-A-treated patients were compared to those in five men (controls) who were orchiectomized as the primary treatment for their disseminated prostatic cancer and in three other men who were treated for 3-12 months with GnRH-A daily but received, in addition to the daily GnRH-A, 1000 IUhCG, im, every other day for 3 days immediately before their salvage orchiectomy, which was performed when their disease progressed.

Mechanism of inhibition of human testicular steroidogenesis by oral ketoconazole.

To determine the antisteroidogenic effect of ketoconazole (KTZ) in the human testis, we measured the plasma delta 5-pregnenolone, delta 5-17 alpha-hydroxypregnenolone, dehydroepiandrosterone (DHEA), progesterone, 17 alpha-hydroxyprogesterone, androstenedione (A), and testosterone (T) concentrations in three men with previously untreated metastatic prostate cancer at various time intervals for 24 h before and 48 h after the administration of 200 mg oral KTZ every 8 h. The adrenal glands of these three patients were suppressed (as measured by the plasma cortisol levels) by the administration of 1.0 mg dexamethasone daily for 7 days before and during the study.

Luteinizing hormone and follicle-stimulating hormone responses to intransal gonadotropin-releasing hormone.

For determination of the dose-response relationships of plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to the intranasal administration of gonadotropin-releasing hormone (GnRH), normal adult men were administered doses of 100, 200, 400, and 800 micrograms of GnRH on separate days, and plasma LH and FSH were measured before and after nasal insufflation of GnRH. Plasma LH was increased after a minimum dose of 200 micrograms GnRH. Median peak plasma LH levels occurred 30 minutes after intranasal GnRH and followed a log-dose relationship.

Hormonal effects of ketoconazole in vivo in the male rat: mechanism of action.

Ketoconazole, an antifungal agent, has been shown to lower serum testosterone (T) in man. Measurements of circulating precursors of T suggest that ketoconazole may inhibit 17,20-desmolase activity in the testis. To further elucidate its mechanism of action in vivo, we studied its effects on the pituitary-gonadal axis in the male rate.

Effect of in vitro ketoconazole on steroid production in rat testis.

In an attempt to confirm where in the testosterone (T) biosynthetic pathway of the rat testis ketoconazole (KTZ) inhibits T production, rat testicular mince was incubated with either 10 micrograms/ml or 100 micrograms/ml KTZ in the presence and absence of hCG (1 IU), and intratesticular pregnenolone (delta 5P), progesterone (P), 17-alpha-hydroxyprogesterone (17 alpha-HP), androstenedione (A) and testosterone (T) were assayed. In the absence of hCG, 10 micrograms/ml KTZ was sufficient to reduce intratesticular T by 80%. At this concentration of KTZ, intratesticular 17 alpha-HP (ng/g testis, mean +/- SEM) increased from 0.

Assay system for simultaneous measurement of three steroidogenic enzyme activities in rat and human testis--effect of human chorionic gonadotropin.

An assay system that measures the enzymatic activities (17 alpha-hydroxylase, 17,20-desmolase, and 17 beta-hydroxysteroid dehydrogenase) in the delta 4 pathway of testosterone biosynthesis using rat and human testicular homogenate was examined. This system involves the simultaneous separation of the steroid intermediates by a three-step TLC procedure. The observed Rf values were 0.

Impaired testosterone biosynthesis in cryptorchidism.

In an attempt to determine whether the production and synthesis of testosterone (T) by the testis is impaired by the cryptorchid state, the ability of the cryptorchid rat testis to form T was assessed at various time periods into adulthood after the surgical induction of cryptorchidism in the newborn period. The intratesticular T content of the descended testis rose from 0.3 ng/testis at 14 days of age to 71.

In vitro inhibition of testosterone biosynthesis by ketoconazole.

Oral ketoconazole has been demonstrated to lower plasma testosterone in man. Measurement of blood precursors of testosterone suggest that ketoconazole may have its effect inhibiting the 17,20-desmolase enzyme within the testis. To substantiate this, a series of in vitro experiments was conducted using the rat testis to determine where in the testosterone biosynthetic pathway ketoconazole has its effect.

Differential turnover of methyl groups on methyl-accepting membrane proteins of irreversibly sickled erythrocytes.

Methyl group turnover rates for specific methyl-accepting membrane proteins in intact irreversibly sickled cells (ISCs) have been determined. The turnover of methyl groups on all methyl acceptor membrane proteins carboxylmethylated in ISCs is not concerted but proceeds in an ordered sequence which is markedly different from that exhibited by unfractionated normal erythrocytes (AA). In ISCs methyl group turnover based on initial demethylation rate constants is most rapid for membrane polypeptides migrating in sodium dodecyl sulfate at 30,000-39,000 Da, 40,000-55,000 Da, polypeptides comigrating with cytoskeletal component band 4.

Phospholipid methylation of kidney cortex brush border membranes. Effect on fluidity and transport.

Exposure of intact brush border membrane vesicles of hog kidney cortex to cholesterol oxidase resulted in 24% oxidation of membrane cholesterol compared with more than 95% oxidation of cholesterol in lipids isolated from membranes, showing that cholesterol is asymmetrically distributed in membranes. Phospholipase C, hydrolyzed 76% of phosphatidylcholine and 10-12% phosphatidylethanolamine while phosphatidylserine was not hydrolyzed, thus indicating that majority of phosphatidylcholine is present on the outer surface of these vesicles while phosphatidylethanolamine and phosphatidylserine are present on the inner surface. Methylation of phospholipids in brush border membrane with S-adenosyl-[methyl-3H]methionine resulted in the formation of phosphatidyl-N-monomethylethanolamine, phosphatidyl-N,N]dimethylethanolamine and phosphatidylcholine from endogenous phosphatidylethanolamine.

Proteoliposome interaction with human erythrocyte membranes. Functional implantation of gamma-glutamyl transpeptidase.

The transfer of detergent solubilized and purified gamma-glutamyl transpeptidase (gamma-GTase), of hog kidney cortex, from proteoliposomes into human erythrocyte ghost membranes has been studied. The transfer of gamma-glutamyl transpeptidase was observed upon incubation of gamma-GTase incorporated dipalmitoylphosphatidylcholine vesicles with erythrocyte ghost membranes at 37 degrees C for 12 h. The extent of transfer was dependent upon the fluidity of donor proteoliposomes, being more when dipalmitoylphosphatidylcholine proteoliposomes were used compared to dimyristoylphosphatidylcholine, and intermediate values were observed when binary mixtures of DMPC and DPPC were used.