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Biomedical subjects

J T Grayhack

Publications and source records attributed to J T Grayhack.

At least 37 records · Page 2Linked to original sources

DNA profile of nephrogenic adenoma assessed by flow cytometry.

Nephrogenic adenoma is a metaplastic condition which usually involves the bladder urothelium within the clinical setting of chronic inflammation. Its presentation/endoscopic appearance may mimic bladder cancer and a premalignant potential has been speculated. DNA flow cytometry performed on involved bladder tissue revealed a diploid phenotype exhibiting low proliferative activity. These findings are most suggestive of a benign process.

Adenoma↗

Benign prostatic hyperplasia. The scope of the problem.

BACKGROUND: The prevalence and incidence of clinical problems secondary to and associated with benign prostatic hyperplasia (BPH) are of increasing concern as the population ages. METHODS: Selected published reports using anatomical and clinical criteria to identify BPH and its clinical sequelae were reviewed. RESULTS: The following observations seem to reflect the current state of knowledge: (1) BPH develops with increasing frequency as men age; (2) BPH causes significant pathologic changes in the urinary tract of some patients and symptoms in others; and (3) other identifiable or cryptic etiologic factors may be the predominant cause of identical voiding dysfunction in patients with BPH. CONCLUSION: Essential information about factors initiating and promoting development of BPH, the exact mechanisms by which BPH alters voiding mechanisms, and definitive diagnostic criteria to establish the role of BPH in clinical changes are lacking. Progress in these problem areas is essential to guide appropriate clinical management.

Adult↗

A local direct effect of pituitary graft on growth of the lateral prostate in rats.

Prolactin and testosterone are synergistic in stimulating growth of the rat prostate. The lateral lobe is more sensitive to this synergism than the ventral and dorsal lobes. To investigate whether prolactin acts directly in the rat prostate or indirectly through another systemic mediator, anterior pituitary grafts (1 mm3) were implanted in the lateral prostate of castrated Sprague-Dawley rats in whom a 0.5 cm or 1.0 cm testosterone-filled silastic tubing was implanted subcutaneously at the same time. Rats were randomly assigned to receive either the pituitary or a muscle chip of similar size grafted beneath the fascia lateral to the lateral prostate. Twenty-one days later, serum prolactin levels were not elevated in pituitary-grafted animals and were not significantly different from those in muscle-grafted rats. The mean lateral prostate weight on the grafted side in pituitary-implanted rats with 1.0 cm testosterone tubing was 43% heavier than either that of the contralateral side or the corresponding weights in muscle-implanted rats. In pituitary-implanted rats with 0.5 cm testosterone tubing, the mean lateral prostate weight on the grafted side was 60% heavier than either that of the contralateral side or that of the corresponding weights in muscle-implanted rats. The weight of the ventral and dorsal lobes of the prostate was not significantly affected by the presence of pituitary grafts in one of the lateral lobes. The local effect of prolactin on the lateral prostate was further demonstrated by an overall decline in tissue concentrations of dihydrotestosterone in the grafted side. These results provided evidence to indicate that there was a direct effect of prolactin on growth of the lateral prostate in rats.

Animals↗

Evidence for a non-androgenic role of testis and epididymis in androgen-supported growth of the rat ventral prostate.

A widely held view is that the role of testis in prostatic growth is through its ability to secrete androgen. Our earlier observation suggested a non-androgenic role for the testis, and perhaps the epididymis, in promoting growth of the ventral prostate in rats. The present study was conducted to evaluate the separate role of the testis and the epididymis in this phenomenon. In the first study, increasing quantities of silastic tubing filled with crystalline testosterone were implanted into adult Sprague-Dawley rats at the time of bilateral epididymo-orchiectomy or sham-operation. Twenty-eight days later, growth of the ventral prostate, as determined by fresh weight, DNA, and protein content, was significantly greater in sham-operated rats than in those receiving combined epididymo-orchiectomy, confirming our previous observation using dihydrotestosterone. In the second and third studies, rats were subjected to selective surgical procedures to evaluate the independent role of the testis and the epididymis. At the same time, 12 cm silastic tubing filled with testosterone or dihydrotestosterone were implanted subcutaneously into each of these animals for 28 days. Results indicated that the ventral prostate was significantly smaller in rats receiving the combined epididymo-orchiectomy than that of sham-operated controls. Simple orchiectomy or simple epididymectomy resulted in an increased weight of the ventral prostate between the two values obtained from the above two groups. Ligation of either the efferent duct or the vas deferens yielded ventral prostatic weights comparable to the androgen-treated, sham-operated controls. These results indicated that in order to achieve a maximal effect on androgen-supported growth of the ventral prostate, the presence of both the testis and the epididymis is required.

Androgens↗

Advanced prostatic carcinoma. Early versus late endocrine therapy.

Since the landmark observations of Huggins and Hodges in 1941, androgen deprivation has been the mainstay of treatment for advanced-stage prostate cancer. Although early, poorly controlled studies suggested enhanced survival with hormonal therapy, this view fell into disfavor as a result of the observations of the first and second VACURG studies. Recently, there has been a proliferation of experimental and clinical data supporting early androgen deprivation, including a reanalysis of the VACURG data, which suggests a survival advantage for younger patients with stage D disease and high-grade tumors who undergo androgen-ablative therapy at the time of diagnosis. The risk-benefit analysis presented in this review is strongly supportive of early hormonal therapy. Finally, long-term survival of patients with metastatic prostate cancer will require the development of novel treatment strategies effective against androgen-resistant tumor cells and their use in concert with early androgen deprivation.

Androgen Antagonists↗

Non-androgenic role of testis in enhancing ventral prostate growth in rats.

This study was conducted to investigate whether the testis, aside from its ability to secrete androgen, is able to promote prostatic growth in rats. Increasing quantities of silastic capsules filled with crystalline dihydrotestosterone (DHT) were implanted subcutaneously into adult Sprague-Dawley rats at the time of bilateral epididymo-orchiectomy or sham operation on the testes. Control animals received empty capsules. Twenty-eight days later, the growth of the ventral prostate as measured by wet weight, DNA, and protein content per prostate was significantly greater in rats with intact testes than in orchiectomized rats. An overall increased growth was noted at all doses of exogenous DHT administered. Serum levels of luteinizing hormone in animals treated with DHT were undetectable. Serum levels of testosterone in intact rats treated with DHT were not significantly different from those in castrated rats. These observations suggest a non-androgenic role for the testis and, perhaps, epididymis in promoting prostatic growth in rats, and are consistent with the concept that a non-androgenic substance, produced from the testis and/or epididymis, is able to enhance prostate growth induced by androgen stimulation. The possibility that this phenomenon may play a role in the benign growth of the prostate observed in aging human males with decreased blood levels of androgen warrants consideration.

Analysis of Variance↗

Elevated transferrin receptor content in human prostate cancer cell lines assessed in vitro and in vivo.

Transferrin receptors (TfR) were measured in benign and malignant prostatic cells by performing Scatchard analysis following the administration of 125I-transferrin. Established human prostate cancer cell lines (PC-3 and DU-145) as well as biologically aggressive variants (PC-3 ASC and PC-3 DES) were shown to possess significant levels of high affinity TfR when assessed in vitro. In contrast, TfR content was negligible in cultured stromal cell fractions derived from human benign prostatic hyperplasia (BPH) specimens. Scatchard analysis was also performed on in vivo derived prostatic tissues: tumors resulting from the subcutaneous xenografting of PC-3 ASC cells into athymic, nude mice and fresh BPH surgical specimens. These tissues were dissociated and their stromal and epithelial components separated. TfR were only detected in the epithelial component of both malignant and benign epithelial cells. PC-3 ASC tumor cells exhibited TfR levels comparable to their in vitro expression and these levels were 10-fold greater than in the BPH cells. These findings suggest that elevated TfRs may serve as another useful marker of the transformed phenotype within human prostate tumor systems.

Animals↗

Radiographic assessment of the vesicourethral anastomosis directing early decatheterization following nerve-sparing radical retropubic prostatectomy.

Early decatheterization directed by postoperative gravity cystography in 55 consecutive radical prostatectomy patients is described. The catheter-free status was 22 per cent by postoperative day 8, 62 per cent by postoperative day 11 and 80 per cent by postoperative day 14. Cystograms performed beginning on postoperative day 7 identified 3 groups of patients and dictated their management: 1) no extravasation resulting in immediate catheter removal (36 patients), 2) moderate extravasation requiring repeat cystography leading to decatheterization by postoperative day 15 (9 patients) and 3) severe extravasation necessitating prolonged catheter drainage (8 patients). A decatheterization protocol is presented.

Adenocarcinoma↗

Carcinoma of the prostate. Hormonal therapy.

A selective review of the literature regarding hormonal therapy for patients with carcinoma of the prostate is presented to assess the current status of the following: therapeutic advantages, disadvantages and risks of alternate approaches to hormonal therapy; observations to predict the magnitude and duration of response to therapy; indications for initiating hormone therapy; the short-term and long-term effects of therapy; and role of hormone therapy in patients with recurrent tumor activity after initial hormonal measures.

Adrenalectomy↗

Two-dimensional characterization of prostatic acid phosphatase, prostatic specific antigen and prostate binding protein in expressed prostatic fluid.

Specimens of pooled prostatic fluid, collected by rectal massage from men under 50 years of age with no apparent prostatic disorders, were subjected to two-dimensional gel electrophoresis to study the composition of its proteins. In a preliminary study, a total of 57 major protein groups were detected. In the present study, we attempted to identify, in the two-dimensional gels, those that are related to prostate-associated proteins, i.e., prostatic acid phosphatase (PAP), prostatic specific antigen (PSA), and prostate binding protein (PBP). Individual proteins were recognized by the procedure of Western Blot using specific antisera with peroxidase-antiperoxidase as the staining reagent. Each protein spot in the two-dimensional gel was expressed, along the abscissa, by its isoelectric point (pI) and, along the ordinate, by the molecular weight (MW). PAP consisted of a train of more than ten protein spots that occupied an area in the gel from pI 7.0, MW 45,000 to pI 6.0, MW 50,000. Four protein spots with a MW of 34,000 and a pI range of 8.2-8.8 were identified as PSA. PBP was observed as having three protein spots that were located at pI 5.6-6.6 with a single MW of 15,000. For PAP and PSA, additional protein spots with lower MWs also stained positively with the specific antisera, suggestive of the presence of degradative products of these proteins. Following the removal of the serum-related proteins by an extensive absorption with anti-human serum antibody by affinity chromatography, the prostatic fluid contained 27 major groups of non-serum proteins. These non-serum proteins in the prostatic fluid included PAP, PSA, PBP, and their related smaller molecular species. These results indicate that the prostatic fluid contains PAP, PSA, PBP and that their presence and the patterns of their distribution in the two-dimensional gels should be considered as the characteristic property of the prostatic secretions.

Acid Phosphatase↗

Adjuvant radiation therapy in stages C and D1 prostatic adenocarcinoma: preliminary results.

Twenty patients with adenocarcinoma of the prostate underwent postradical prostatectomy adjuvant external beam megavoltage radiation therapy because of periprostatic disease in histologic evaluation of the resected specimen. Fourteen of these patients had pathologic Stage C and 6 pathologic Stage D1 disease. Treatment in most patients consisted of 5,000 rad delivered to the true pelvis. The five-year recurrence-free survival was 75 per cent for pathologic Stage C and 41 per cent for Stage D1 disease. The median time to first evidence of treatment failure was fifty months for D1 patients and has not been reached by the C group. Minor complications occurred in 85 per cent of patients and major complications in 5 per cent. In 1 patient with mild, postoperative stress incontinence total urinary incontinence developed after radiation therapy. These preliminary observations suggest a prolonged disease-free interval with an acceptable morbidity is obtained utilizing this regimen.

Adenocarcinoma↗

The natural history of simple renal cysts: a preliminary study.

We examined the natural history of simple renal cysts in 59 patients followed periodically with renal ultrasonography. Using the parameters of cyst diameter and number we grouped the patients according to the differing natural history of the cystic lesions. The results indicate that simple cysts tend to progress in number rather than size. Furthermore, 3 patients had independent solid or complex lesions. The only patient explored had an adenocarcinoma of the kidney. Periodic reevaluation of patients with an ultrasonic diagnosis of simple renal cyst warrants serious consideration.

Adult↗

Metabolic action of prolactin in regressing prostate: independent of androgen action.

The mechanism of the observed synergistic effect of prolactin and androgen on the lateral lobe of the rat prostate is not established. The observation that prolactin alone delayed the rate of loss of weight, protein, and DNA of the lateral lobe in castrated rats has led us to question the assumption that the effect of prolactin is produced by a modification of recognized androgen-induced intracellular changes. The present study was conducted to explore whether or not the sites of prolactin action in the rat prostate coincided with those recognized as the androgen effect. Two anterior pituitaries from female donors were grafted under the right renal capsule of adult male Sprague-Dawley rats. Seven days later, bilateral orchiectomy and unilateral nephrectomy were performed in these rats. In one half of the animals, the kidney bearing the pituitary grafts was removed. In the other half, the contralateral kidney was removed. Seven days following the orchiectomy-nephrectomy, animals bearing the pituitary grafts had a higher level of serum prolactin (93 +/- 7 ng/ml, mean +/- SE) than in those without the graft (26 +/- 3 ng/ml). This condition of hyperprolactinemia was associated with the delay of castration-induced regression in the lateral prostate. The rate of protein degradation, as judged by the amount of radioactivity remaining in the tissue following a single i.v. pulse of 3H-leucine 24 hr before orchiectomy-nephrectomy, was significantly slower in the lateral prostate in graft-bearing animals than in those without grafts. However, the rate of protein synthesis, as judged by both in vitro and in vivo incorporation of 3H-leucine into the protein fractions of the prostate, was not significantly different between the two groups. Nor was the total activity of cathespin D in the lateral prostate different. These results were not consistent with parameters known as the effect mediated through androgen-controlled mechanisms. We therefore conclude that the action of prolactin in the regressing rat prostate is probably not mediated through the action of androgen.

Androgens↗

Epididymal metastasis from prostatic carcinoma.

A case of epididymal metastasis from carcinoma of the prostate with an unusual presentation is reported. A review of the literature disclosed only 10 reported cases of this rare finding. A mechanism for the method of metastasis in this patient is proposed.

Adenocarcinoma↗