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Biomedical subjects

S Geller

Publications and source records attributed to S Geller.

At least 37 records · Page 2Linked to original sources

Acute therapy with megestrol acetate decreases nuclear and cytosol androgen receptors in human BPH tissue.

This study measures the effect of megestrol acetate (Megace), a progestational antiandrogen, on nuclear and cytosol receptor concentrations in human BPH prostates. Prostatic tissue was obtained at surgery from both untreated patients with BPH and patients pretreated for three to eleven days with 120 to 160 mg of Megace daily; tissues were homogenized and separated into cytosol and crude nuclear fractions. Cytosol and salt extractable nuclear fractions were subjected to saturation analysis with 3H R1881 over the range of 0.5 to 10 nmoles in exchange reactions for 20 hours at 15 degrees C. Cytosol receptor concentration decreased significantly from 32.7 to 8.7 femtomoles per mg protein (P less than 0.05); nuclear receptor also was significantly reduced from 317 to 43.8 femtomoles (fmole) per mg DNA (P less than .001). Plasma testosterone also decreased significantly from 3.65 to 1.01 ng/ml in Megace-treated patients. These effects of Megace on receptor concentration appear to be qualitatively quite different from those reported following castration in animals or following high-dose estrogen therapy in humans. The mechanism of action of Megace in decreasing both cytosol and nuclear androgen receptor concentrations is unknown. It is possible that decrease in receptor concentration is secondary to either the progestational or antiandrogenic effects of Megace. These possibilities are currently under study.

Cell Nucleus↗

Tissue carcinoembryonic antigen, dysplasia, and disease duration in colonic inflammatory bowel disease.

Tissue carcinoembryonic antigen (CEA) was studied in five groups of patients: eight ulcerative colitis patients with mild or no dysplasia, five ulcerative colitis patients with severe dysplasia, seven Crohn's disease patients with nondiseased colon, nine Crohn's disease patients with diseased colon, and 18 colorectal cancer patients from the noncancerous colon resection margins. CEA levels were significantly lower in the normal colon Crohn's group than all other groups (p less than 0.05). CEA levels were significantly higher in the severe dysplasia ulcerative colitis group than all other groups (p less than 0.05). The Crohn's disease patients with diseased colon, the ulcerative colitis patients with mild or no dysplasia, and the colorectal cancer group with noncancerous colon all had similar intermediate CEA levels.

Carcinoembryonic Antigen↗

Medical castration of males with megestrol acetate and small doses of diethylstilbestrol.

An alternative program for medical castration for treatment of prostate cancer has been developed using a progestational antiandrogen, megestrol acetate (MA), in combination with small doses of diethylstilbestrol (DES; 0.1 mg/day). The administration of MA (40-80 mg/day) with 0.1 mg DES to nine patients resulted in castrate levels of plasma testosterone (less than 0.4 ng/ml) and significant suppression of both FSH and LH (P less than 0.05) for up to 12 months. Although large clinical trials must ultimately establish its safety, clinical side effects of this combined therapy to date have consisted of mild gynecomastia in two patients. The symptoms did not necessitate discontinuing the medications. It is concluded that the use of 0.1 mg DES with a minimum of 40 mg/day MA results in medical castration with sustained suppression of plasma testosterone. Because of the possible additional therapeutic advantage of blockade of intracellular androgen-mediated action by MA in androgen-dependent tumors, this combined therapy should be further explored as a possible initial treatment of choice for advanced prostate cancer.

Castration↗

FSH and LH pituitary reserve and output in the postmenopause.

FSH and LH basal levels and their cumulative responses following LH-RH administration were determined along with plasma estradiol levels in postmenopausal patients. 89 postmenopausal patients were studied. They were divided into four groups according to the time elapsed since their menopause. Group I being less than 2 yr postmenopausal, Group II between 2 and 5 yr, Group III 5--10 yr and Group IV 10 yr or more postmenopausal. Blood was drawn before a bolus intravenous injection of 100 micrograms of LH-RH was given and at different time intervals after the injection. FSH, LH and plasma estradiol were assayed. FSH and LH cumulative responses after LH-RH (CR) and total cumulative responses (TCR), as defined by the surface area comprised between the tracing and a horizontal line drawn through the basal level (CR) or the X-axis (TCR) were calculated by planimetry. The basal levels of FSH tend to increase with age, with a maximum in the 3rd age group and a decline thereafter. A similar trend, though less outspoken, was seen in the LH basal levels. FSH cumulative responses after LH-RH (as expressed by the mean increment (delta), maintained over the 2 h duration of the test) were significantly lower than the corresponding FSH basal levels and appeared to remain at the same level throughout postmenopause. In contrast, LH cumulative responses after LH-RH, expressed in the same way, compared with corresponding LH basal levels. They were highest in the younger age group, associated with still appreciable estradiol levels and declined in the subsequent age groups. LH-TCR and LH-TCR : FSH-TCR ratio showed a similar trend as LH cumulative responses. It is suggested that this peculiar pattern, is related to estradiol levels.

Age Factors↗

Delay of gratification: decisional self-control and experience with delay intervals.

Actual and verbally reported decisional self-control choices (e.g., 1 penny now or 2 pennies in 1 minute) were obtained from 40 retarded adolescents who participated in a sheltered workshop. Prior to each of their eight choices, one-half of the students experienced the same time interval that was included in the choice for that day (e.g., 1 minute). Analysis of the number of actual and reported delay choices yielded a significant effect for experience, with the treatment group making more delay choices. In addition to suggesting that decisional self-control can be facilitated by prior exposure to delay intervals, the results indicated that verbally reported choices can be used as a reliable and valid indication of actual choices.

Adolescent↗

A method for tissue extraction and determination of prostate concentrations of endogenous androgens by radioimmunoassay.

A method for simultaneously determining concentrations of major androgens in prostate has been developed. Extraction techniques used to isolate the androgens from minced tissue include homogenization with high-speed blades in Delsal's solvent mixture, adsorption to silica gel, followed by column and one thin-layer chromatography (TLC). Radioimmunoassays (RIA) of small aliquots of TLC eluates are used to quantitate picogram amounts of 5alpha-dihydrotestosterone (DHT) and 5alpha-androstanediols (Diol) and to estimate testosterone (T) and androstenedione (Ad). Contamination of blanks was reduced to RIA sensitivity limits primarily by treatment of glassware in a self-cleaning oven. The specificity of the method for each androgen was established by TLC separations of known prostate metabolites, antisera specificities, and parallelism of sample aliquots to androgen RIA standards. The overall precision, in terms of coefficients of variation, was 21% for DHT and 24% for Diol. T and Ad could not be measured with acceptable precision because their very low concentrations in prostate (less than or equal 0.5 ng/g tissue) were less than RIA sensitivity limits. Accuracy studies indicated recoveries ranging from 96% for Diol to 121% for DHT. In human benign hypertrophic prostate tissue, DHT averaged 153 ng/g soluble protein (5.8 ng/g tissue) which was 17 times higher than values obtained in human spleen and kidney; Diol in prostate showed no consistent differences from values noted in kidney or spleen.

Androgens↗