Characterization and measurement of androgen receptors in human prostatic tissue.
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Biomedical subjects
Publications and source records attributed to L L Hicks.
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The potent synthetic androgen methytrienolone (R 1881), which does not bind to serum proteins, was utilized to characterize binding to receptors in human androgen responsive tissues. Cytosol extracts prepared from hypertrophic prostates (BPH) were utilized as the source of receptor for the initial studies. High affinity binding was detected in the cytosol of 29 of 30 samples of BPH (average number of binding sites, 45.8+/-4.7 fmol/mg of protein; dissociation constant, 0.9+/-0.2 nM). This binding had the characteristics of a receptor: heat lability, precipitability by 0-33% ammonium sulfate and by protamine sulfate, and 8S sedimentation coefficient. High affinity binding was also detected in cytosol prepared from seminal vesicle, epididymis, and genital skin but not in non-genital skin or muscle. However, similar binding was demonstrated in the cytosol of human uterus. The steroid specificities of binding to the cytosol of male tissues of accessory reproduction and of uterus were similar in that progestational agents were more effective competitors than natural androgens. Binding specificities in cytosol prepared from genital skin were distinctly different and were similar to those of ventral prostate from the castrated rat in that dihydrotestosterone was much more potent than progestins in competition. Thus binding of R 1881 to the cytosol of prostate, epididymis, and seminal vesicle has some characteristics of binding to a progesterone receptor. When the nuclear extract from BPH was analyzed, high affinity binding was demonstrated that conformed to the specificities of binding to an androgen receptor. Here dihydrotestosterone was a more potent competitor than progestational agents. Similar patterns of binding were detected in the crude nuclear extracts from seminal vesicle, epididymis, and genital skin but not in uterus, muscle, or non-genital skin. We conclude that the androgen receptor is not demonstrable in the cytosol of prostate, epididymis, or seminal vesicle of non-castrated men but can be measured in the cytosol of genital skin and the nuclear extracts of androgen responsive tissues. Because steroid hormones exert their major influence within the nucleus of target tissues, the measurement of nuclear receptor may provide valuable insight into the regulation of growth of target tissues.
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The binding of 3H-R 1881 to cytosol prepared from benign and malignant prostatic neoplasms has been investigated. We have demonstrated that high affinity binding of 3H-R 1881 is present in cytosol preparations of benign prostatic hyperplasia, in specimens of prostatic cancer obtained from patients prior to hormonal therapy and in carcinoma of the prostate metastatic to lymph nodes. In addition, high affinity binding was present in all specimens of prostatic cancer from patients who had objective evidence of progressive metastatic disease after an initial response to hormonal therapy. Until greater numbers of patients have been studied the significance of these findings can only be speculative. Because the binding of 3H-R 1881 may measure androgen and progesterone receptors future investigations must include careful steroid specificity studies. Finally, because steroidal hormones exert their major influence within the nucleus of target tissues the measurement of nuclear receptor content may provide a more accurate means to predict the hormonal responsiveness of prostatic cancer.
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In the name of costing accuracy, nurses are asked to track inventory use on per treatment basis when more significant costs, such as general overhead and nursing salaries, are usually allocated to patients or treatments on an average cost basis. Accurate treatment costing and financial viability require analysis of all resources actually consumed in treatment delivery, including nursing services and inventory. More precise costing information enables more profitable decisions as is demonstrated by comparing the ratio-of-cost-to-treatment method (aggregate costing) with alternative activity-based costing methods (ABC). Nurses must participate in this costing process to assure that capitation bids are based upon accurate costs rather than simple averages.
In 1994 12.7% of the population was 65 and over, while 10.6% were 85 and over. Expenditures for nursing homes reached $72.3 billion in 1994 (much of which is tax-supported) accounting for 8.7% of all personal health money spent. Data from the 1993 Missouri Medicaid cost reports for 403 nursing homes were reviewed to determine differences in costs per resident day (PRD) and discover which factors most influenced these differences. Mid-sized facilities with 60-120 beds reported the lowest resident-related PRD costs. PRD expenses for aides and orderlies were higher in tax-exempt facilities, which was thought to be related to their "more altruistic" mission. Investor-owned facilities showed significantly greater administrative costs PRD, which may relate to higher administrative salaries and fancier offices. The authors suggest further study that would incorporate location, occupancy rate, quality of care, case mix, and payer mix data.