Biomedical subjects
Publications and source records attributed to W E Farnsworth.
The approximate percentage of epithelium (Iepith) in a sample of human prostate tissue can be estimated by assaying the specific activity of epithelial marker enzymes, beta-glucuronidase or arginase. There is a good correlation between epithelial density and beta-glucuronidase activity per unit of tissue protein.
In an effort to identify the factor(s) contributing to loss in sexual competence in alcoholics, a pilot study was made of the interrelationships of hepatic disease, plasma hormone levels and importnce in 35 male patients in an alcohol unit. Contrary to previous reports, impotence was not a direct concomitant of hepatic disease, elevated sex hormone-binding globulin capacity or hyperestrinism. The most significant aberration found was a nearly 30% lower mean free testosterone concentration which appeared to be secondary to a mean total testosterone concentration 20% below that of the subjects with normal sexual function. We conclude from this that impotence results from testicular secretion impaired by the action of alcohol or its metabolite, acetaldehyde.
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The efficacy of treating carcinoma of the prostate with levodopa (L-dopa), a known inhibitor of prolactin secretion, has been tested in 11 Stage D patients who were refractory to conventional modalities. Relief of bone pain and recovery of mobility was excellent in 6, fair in 2, questionable in 1, and nonexistent in 2. Acid phosphatase, where initially found to be elevated, was reduced to normal limits.
Evidence of the presence of an androgen-activated "gatekeeper" receptor in the human prostate plasma membrane is presented. Not only does testosterone in vitro very rapidly accelerate uptake of alpha-aminoisobutyric acid into prostate slices but also its metabolite, dihydrotestosterone, greatly increases the rates of phosphorylation and dephosphorylation of the cation-dependent ATPase of isolated membranes. The relationship of this regulatory unit to prostatic physiologic processes is discussed.
A simple procedure for the measurement of cortisol and 11-deoxycortisol in plasma or serum is described. One-half ml. of plasma is extracted with methylene chloride. Separation of cortisol and deoxycortisol is achieved by a Sephadex LH-20 mini-column. The assay itself is achieved by the use of a commercially available cortisol kit employing rabbit anti-cortisol coated tubes. This antibody exhibits a 20% crossreactivity with 11-deoxycortisol. This procedure is extremely useful in the assessment of a pituitary-adrenal reserve in the Metyrapone test.
The relationship between the concentrations of total and apparent free testosterone in the plasma and the levels of testosterone (T), dihydrotestosterone (DHT) and 5 alpha-androstan-3-alpha, 17 beta-diol (DIOL) in 13 benign hypertrophic and 6 carcinomatous prostates was studied. The androgen concentration within both types of glands was nearly 4-fold that in the blood but bore no direct relationship to the blood level. About 75% of the androgen in the tissue was DHT. The most striking finding was that, in spite of a 25.5% less concentrated pool of apparent free testosterone in the blood, the level of T and its metabolites in the cancer tissue was 29% above that in the samples of benign hypertrophic prostate.
Lactogen causes binding of testosterone to human prostate and therapy increases steroid enhancement of acid phosphatase activity of the tissue. Diminished response to steroid of tissue treated with lactogen antibody is interpreted as evidence of inactivation of endogenous lactogen associated with the tissue. This is the first time that steroid-lactogen-phosphatase interaction has been demonstrated in vitro.
Earlier work had shown that the lactogen, LTH and HPL, foster testosterone binding by the prostate. This study was undertaken to see if prostaglandin F2alpha would oppose the effect of the lactogen on the prostate as it does the luteotrophic action of the hormone on the corpus luteum. When it was found instead that the PGF increases steroid binding and that its interaction with lactogen was neither antagonistic nor additive, attention was directed to further characterization of prostaglandin's effect. A dosage/response study of F2alpha alone showed that concentrations of 4 ng/ml and 40 ng/ml increased binding but that 400 ng/ml did not. Glands with stromal hyperplasia and/or inflammation were not responsive than those with epithelial hyperplasia. Assays of water extracts of the tissue revealed concentrations of about 340 ng of F2alpha per gram fresh weight and that the concentration varied inversely as the beta-glucuronidase activity. If the enzyme level is considered an index of the epithelial cell density within the specimen, the inverse relationship suggest a non-epithelial (stromal) site of prostaglandin concentration.
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