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Biomedical subjects

W E Farnsworth

Publications and source records attributed to W E Farnsworth.

At least 19 recordsLinked to original sources
PubMed1991

Prostate plasma membrane receptor: a hypothesis.

Based on 50 years of emerging knowledge about and changing views of prostate biochemistry and physiology and especially on the belief that there is an underlying mechanism of androgen control, the hypothesis is developed and tested that the rates of proliferation, biosynthesis, metabolism, and secretion are modulated through the hormone-sensitive Na, K-ATPase of the plasma membrane. These preliminary experiments, constituting a novel synthesis of technologies from endocrinology, intermediary metabolism, and membrane transport, attempt to explain the extraordinary production and secretion of citrate and how this may be coupled to sustaining prostate cell number and function. Attention is focused on learning where androgen is bound and how it interacts with the Na,K-ATPase. Both the dissimilar properties of epithelial and stromal cells in the separate regions of the acinus and the changing environment of growth factors in which these cells are bathed help account for their unlike reactivities during development and ongoing mature function. Little wonder that one hormone can have so many effects!

Androgens↗
PubMed1991

Training physicians to be doctors--teachers and healers, problem-solvers and decision-makers.

With the scientific advances made in medicine during the past 200 years, the training of physicians in America has changed from that of a mentor/apprenticeship relationship to one in which students are part of an impersonal, mass production process. From a historical perspective, it is contended that basic science and rote memorization of medical theory have subsumed the art of medicine. As a result, students are overloaded with irrelevant facts, few of which they carry over in their professional practice of medicine. To alter this teaching approach and, hence, the quality of physicians, medical school curricula should incorporate recommendations found in the General Professional Education of Physicians Report, among other sources. These recommendations, which have been incorporated successfully in the curriculum at the University of New Mexico School of Medicine, for example, include: establishing goals that may be coordinated interdepartmentally; reestablishing the physician/mentor for each student; using a small-group, interactive, problem-solving, clinically oriented approach to teaching; measuring each student's ability to not only retain knowledge but, more importantly, apply such information to actual clinical problem-solving and decision-making situations; admitting liberal arts graduates--not premedical students--to medical schools; and recruiting and training faculty members who have the time to each and the ability to emphasize biomedicine rather than their special discipline. These changes will make students more than physicians. They will be "real doctors," individuals who not only possess knowledge but can apply it in their daily practice of medicine.

Clinical Competence↗
PubMed1988

Prolactin effect on the permeability of human benign hyperplastic prostate to testosterone.

While it has been known for over 30 years that prolactin (Prl) synergizes with androgen in the support and stimulation of prostatic growth and metabolism, the evidence that this is accomplished through increasing access of the steroid to the cellular machinery of the gland has arisen only since about 1970. There is widespread uncertainty as to how the Prl effect takes place: by 1) increasing the free steroid concentration in the blood; 2) facilitating the uptake of protein-bound androgen; 3) increasing, by metabolism or receptor-binding, the concentration gradient that can support passive diffusion of the steroid across the plasma membrane; or 4) modification of the fluidity of the membrane itself to increase the solubility of the steroid in the lipoprotein and, thus, the ease of penetration of the cell. The present study attempted to learn if Prl is an effective stimulus of androgen uptake when the first three options are not operative. Using an equilibrium exchange procedure to track the uptake of [17 alpha-3H]-testosterone ([17 alpha-3H]-T) into minced benign hyperplastic human prostate tissue and the irreversible metabolism of the entering steroid to [17 alpha-3H]-dihydrotestosterone [17 alpha-3H]-DHT, it was found that the rate of production of the 5 alpha-reduced metabolite, during a 1-hr incubation in vitro, was directly proportional to the concentration of ovine Prl over the dose range of 0-160 ng/ml. The clinical significance of Prl mediation of steroid uptake is discussed, and suggestions are made as to how the Prl might alter the permeability of the plasma membrane.

Biological Transport↗
PubMed1985

Prolactin.

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Animals↗
PubMed1981

Interaction of prolactin and testosterone in the human prostate.

Three experiments were performed to determine whether human prolactin (hPr) affects prostatic uptake and metabolism of testosterone (T). 1) Patients with prostatic cancer were infused twice with radio-labelled androgens, the first time with basal hPR, the second time with oral thyrotrophin-releasing hormone (TRH)-elevated hPr. In 5/7, significant increases in metabolic clearance of dihydrotestosterone (DHT) and in conversion of T to DHT accompanied increased hPR. 2) The incorporation of labelled T into minced benign prostatic hypertrophy (BPH) tissue from subjects with high (40 ng/ml) hPR was measured and was found to be more than twice the uptake into tissue from those with low hPR (6.5 +/- 1.9 ng/ml). 3) Uptake and metabolism in vivo of a bolus of 3H-T by BPH and carcinomatous prostates was measured and was far greater in subjects whose hPR was elevated by chlorpromazine than in untreated controls. It is concluded that prolactin increases prostatic uptake and metabolism of T. It is suggested that the best management of prostatic cancer should include depletion of prolactin as well as androgen.

Dihydrotestosterone↗
PubMed1980

Comparative performance of three radioimmunoassays for prostatic acid phosphatase.

Three commercial radioimmunoassays and one enzymatic assay for prostatic acid phosphatase (PAP) have been tested on 122 patients to determine their relative specificity, sensitivity, and diagnostic value. Each of the three radioimmunoassays was found to have special merits. For distinguishing Stage IV prostatic cancer from normal patients without prostatic disease, the Smith Kline (SKF) and New England Nuclear (NEN) assays provide more significant differences. The SKF test also best distinguishes all stages of prostatic cancer from benign prostatic hyperplasia (BPH), but is inferior to the Malinckrodt (MAL) assay for contrasting Stage IV prostatic cancer from BPH. Values obtained with the NEN assay best distinguish the stages of prostatic cancer. Only with the MAL assay are significantly higher PAP values obtained in patients with metastases to bone than those without positive bone scans. Viewed from the point of sensitivity, the SKF assay proves best at all levels of specificity examined in detecting all stages (I-IV), and Stage IV prostatic cancer. By none of the assays can estrogenized Stage III and IV cancer patients be distinguished from those not on estrogen.

Acid Phosphatase↗
PubMed1979

Benign prostatic hyperplasia in an XX man.

A sixty-nine-year-old white phenotypic male who was being investigated for a myeloproliferative disorder, was found to have an XX karyotype in all cells examined in bone marrow, lymphocytes, and skin fibroblast cultures. Despite essentially no testosterone in the plasma, he also suffered from severe prostatic hyperplasia, a finding not reported previously in patients with this genotype. While endocrine studies showed normal follicle-stimulating hormone, the luteinizing hormone level was twice the upper limit of normal and estrogens were in the normal female range. Except for complete absence of Leydig cells, testicular histology resembled that usually found in Klinefelter syndrome. The patient died of the combined effects of the myeloproliferative disease and urinary tract obstruction. The mechanism of occurrence of the sex chromosome anomaly as well as the cause and implication of the unusual finding of prostatic hyperplasia are discussed.

Aged↗
PubMed1979

Derivation and determination of a human prostatic epithelial index.

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.

Arginase↗
PubMed1978

Factors underlying infertility in the alcoholic.

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.

Alcoholism↗
PubMed1977

Prolaction and prostate cancer.

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.

Bone Neoplasms↗
PubMed1977

Activities of the androgen-responsive receptor of the prostatic plasma membrane.

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.

Adenosine Triphosphatases↗
PubMed1976

A simple radioimmunoassay for plasma cortisol and 11-deoxycortisol (17, 21-dihydroxy-4-pregnene-3, 20-dione).

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.

17-Hydroxycorticosteroids↗
PubMed1976

Androgen of the human prostate.

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.

Androgens↗
PubMed1975

Role of lactogen in prostatic physiology.

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.

Acid Phosphatase↗
PubMed1975

Prostaglandin F2alpha and human prostatic affinity for testosterone.

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.

Dose-Response Relationship, Drug↗