Symposium on Uropathology. Introduction: Measurement of genitourinary diseases.
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Biomedical subjects
Publications and source records attributed to M Tannenbaum.
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Acid phosphatase was the first "tumor marker" to be measured in the blood, and over 40 years have passed since an elevation of the serum acid phosphatase level was observed in patients with prostatic carcinoma. However, significant elevations in the level of this enzyme have been observed in other diseases, as well as elevations of other tissue phosphatases. Many improvements in the colorimetric technique have been introduced, but none has been used successfully to detect the tissue origin of this ubiquitous enzyme. The finding that prostatic acid phosphatase is antigenically distinct from acid phosphatase of other tissues opened a new horizon in the measurement of acid phosphatase in prostatic cancer. On the basis of this immunochemical specificity, several immunoassays have been employed for determining the prostatic acid phosphatase level.
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Comparisons of the bone marrow and serum acid phosphatase values obtained by counterimmunoelectrophoresis and the Roy biochemical test were made in 72 patients with and in 13 patients without prostatic cancer. The counter-immunoelectrophoresis test, when positive at more than 1 international unit per liter, showed only 4.4% falsely positive results. The Roy biochemical test, which uses sodium thymolphthalein monophosphate as the substrate, had 65% falsely positive bone marrow acid phosphatase levels. Conflicting reports regarding the value of bone marrow acid phosphatase determinations in patients with prostatic cancer result from the use of non-specific substrates in biochemical methods for measurement and from the trauma incidental to bone marrow aspiration, which releases many non-prostatic acid phosphatase enzymes. The use of immunoassay such as counter-immunoelectrophoresis minimizes this source of error.
Dog prostates under defined hormonal influences were investigated by light microscopy (LM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The normal acinar cell apices exhibited well-developed, densely packed microvilli. TEM demonstrated numerous secretory granules, indicating a high secretory activity. Following castration, the acinar cells of the dog prostate showed rounded apices. Most of the microvilli disappeared and only knob-like protrusions were seen. Castrated dogs following administration of 3 alpha-androstandiol showed fewer microvilli than the controls; however, a well-developed undulating surface could be observed. Castrated dogs given 3 alpha-androstandiol and cyproterone acetate showed almost completely atrophic glandular cells. Prostates of dogs with spontaneous benign prostatic hyperplasia (BPH) were characterized by pleomorphism of cell shapes and surfaces. The different hormonal influences induced changes of the prostatic surface structures and secretory activity.
Man, dog, rat and mouse prostatic glandular cells were compared by light microscopy (LM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). In rodents and dogs, a merocrine secretion exists, and in these species the undulating surface represented a confluence of secretory granules. The prominent secretory blebs observed in dog and human benign prostatic hyperplasia (BPH) corresponded to apocrine secretions. Also variations in the amount of secretory activity were seen. Androgenic hormones were responsible for the differentiation of the prostatic epithelial cells during development. Therefore, an absence of microvilli as well as the appearance of ruffles, microplicae, and bare cells were seen in the prepuberal and castrated rat. In the elderly rat and in human BPH, a pleomorphism of the apical cell surface was evident.
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An immunochemical method for detection of prostatic acid phosphatase is described. Acid phosphatase was obtained from benign human prostatic tissue. A specific antiserum to this enzyme was produced in rabbits. A counter immunoelectrophoretic method utilizing the specific antiserum with a chemical staining technique has been developed. Clinical trials have indicated the usefulness of this method for the specific determination of prostatic acid phosphatase.
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The possible activation of immunologic defenses against tumor by local ultrasonic irradiation was investigated. Sonication of one tumor of a dual implant destroyed that tumor only with no contralateral effect. Injection of tumor cells previously sonicated in vivo did not induced immunity to subsequent challenge with live cells. Immunofluorescent staining of host kidneys for antibody complexes was negative. It was concluded that sonication was only effective when directly applied to the tumor.
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Paired Wistar-Furth male rats were implanted subcutaneously with the Furth-Columbia rat Wilms' tumor. Seven days after implantation the tumors were either subjected to therapeutic ultrasound irradiation or were left as untreated controls. On the ninth day after implantation the animals were sacrificed, and suspensions of cells were made from the excised tumors by trypsinization. The cells were counted using trypan blue dye as an indicator of viability. New rats were then implanted with cells either from sonicated tumors or cells from controls. In half the recipient animals the suspensions were matched by total cell count. In the other half of the rats cell counts were matches for viability by the dye exclusion test. Tumors developed in a total of 8 of 11 rats receiving control cells and they died. A palpable tumor did not develop in any rat receiving cells fromsonicated tumors during the ninety-day study period. Surviving rats were challenged with Wilms' tumor by trocar implant. Tumor developed in all recipients, and they died.
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