bluuebunny/crossref_metadata_2025 huggingface dataset:
Response criteria for the prostate of the USA national prostatic cancer project
Authors: Murphy G. P. , Slack N. H.
Published: February 2007

Response criteria developed by the National Prostatic Cancer Project to evaluate chemotherapy for advanced disease and as an adjuvant in early disease are described. Subjective and objective procedures and tests are used to compare pre‐and post‐treatment disease activity in advanced disease. These patients enter trials in demonstrated progression; hence stabilization of activity was considered a category of objective response. Other response categories include the rare complete response and less rare partial regression, with progression for non‐responders. In adjuvant studies response indicators are the incidence of recurring disease and length of disease‐free‐interval.
Solid‐phase immunofluorescent and immunoadsorbent assays of serum prostatic acid phosphatase
Authors: Lee C. L. , Wang M. C. , Killian C. S. , Slack N. H. , Murphy G. P. , Chu T. M.
Published: February 2007

Human prostatic acid phosphatase was purified to homogeneity from malignant prostatic tissue by Tween 80 extraction and 40‐75% ammonium sulfate precipitation, followed by Con A‐Sepharose, DEAE‐cellulose, and gel filtration chromatography. A specific antiserum was raised by immunizing female goats or rabbits with the purified enzyme. This antiserum did not cross‐react with the acid phosphatase of other human tissues. Two immunochemical methods, a solid‐phase fluorescent immunoassay and a solid‐phase immunoadsorbent assay, were developed. The IgG antibody fraction from antiprostatic acid phosphatase was conjugated to CNBr‐activated Sepharose 4B, which was then used in the two immunoassays to separate serum prostatic acid phosphatase from other acid phosphatases or serum proteins. The enzyme activity was subsequently measured by incubating the solid‐phase bound prostatic acid phosphatase with α‐naphthyl phosphate and quantitating the fluorescent product with a spectrophotofluorometer (immunofluorometric assay) or quantitating the α‐naphthol‐FRBS colored complex with a spectrophotometer (immunoadsorbent assay). The sensitivity of this immunofluorometric assay was 60 pg/ml, more sensitive than other immunoassays. The results obtained from clinical evaluation indicate that serum prostatic acid phosphatase in prostate cancer can be detected in significant percentage with early stages of prostatic cancer. The sensitivity of the immunoadsorbent assay was 0.22 IU/l of enzyme activity or 0.88 ng of prostatic acid phosphatase protein per ml serum. Initial clinical evaluation demonstrated that 19 of 25 patients with early stages of prostate cancer and 12 of 14 patients with metastatic prostate cancer exhibited an elevated serum PAP level (over all 79%), as compared with only six and eight patients respectively (overall 35%), by a conventional chemical method.
Counterimmunoelectrophoretic studies of serum prostatic acid phosphatase
Authors: Romas Nicholas A. , Hsu Konrad C. , Ng Po Ying , Pitts Melvin , Tomashefsky Philip , Tannenbaum Myron
Published: February 2007

A counterimmunoelectrophoretic (CIEP) assay for the specific determination of prostatic acid phosphatase (PAP) is described. PAP was obtained from benign human prostatic tissue and a specific antiserum to this enzyme was produced in rabbits and goats. The lowest detectable activity of PAP was at 0.3 IU/l or 4 ng./0.1 ml. This CIEP method was compared to a standard biochemical method (Roy) on a wide spectrum of prostatic and nonprostatic disease. Nonprostatic malignancies and other disorders associated with hyperacidphosphatasemia by the biochemical method were found to be nonreactive for PAP by CIEP. Patients under treatment with various stages of prostatic carcinoma showed comparable elevations by both methods (35%). In untreated patients, the CIEP was statistically most sensitive in stage A (39% by CIEP and 14% by chemical).
The surface character of separated prostatic cells and cultured fibroblasts of prostatic tissue as determined by concanavalin‐A hemadsorption
Authors: Oishi K. , Romijn J. C. , Schroeder F. H.
Published: February 2007

Con A‐coated human type O red blood cells (indicator RBC) were used for ConA reactivity assay of separated epithelial cells and cultured fibroblasts of human prostatic tissue. The epithelial cells of carcinoma showed higher reactivity than those of normal tissue or hyperplastic tissue.

Although both cultured fibroblasts of PC and BPH are considered to be non‐malignant, it is clearly demonstrated that the PC fibroblasts have a malignant surface character in terms of ConA reactivity, whereas the BPH fibroblasts have a quite low ConA reactivity.

ConA‐mediated HAD appeared to be a useful tool to distinguish malignant epithelial cells of human prostate from non‐malignant ones. It still remains unknown whether the alteration of PC fibroblasts is the cause or the result of carcinogenic transformation of prostatic tissue.
Nitroimidazoles in the canine prostate, vagina, and urethra
Authors: Nielsen Ole S. , Frimodt‐Møller Niels , Maigaard Svend , Madsen Paul O.
Published: February 2007

Diffusion of metronidazole and tinidazole in canine prostatic secretion was studied and compared to the diffusion of metronidazole into the canine vagina. This particular comparison was made because prostatic secretion represents an acidic environment in contrast to the canine vagina which has a basic pH.

Metronidazole reached significantly higher concentrations in the prostatic secretion (PS) than in plasma (P). No differences were found in the concentrations of tinidazole in P and PS. Plasma and prostatic interstitial fluid (PIF) concentrations of both drugs showed no differences either. However, the PS/P and PIF/P ratios of metronidazole were significantly higher than the corresponding ratios of tinidazole. Metronidazole concentrations in the canine vagina and urethra were significantly lower than the plasma concentrations, possibly because of the basic pH environment. These findings suggest a possible advantage in using metronidazole over tinidazole in aerobic and Trichomonas vaginalis prostatitis and vaginitis in acidic environments. However, clinical studies comparing the two drugs should be carried out in order to establish if this is of clinical importance.
Creatine kinase BB and other markers of prostatic carcinoma
Authors: Silverman Lawrence M. , Chapman John F. , Jones Marcie E. , Dermer Gerald B. , Pullano Thaddeus , Tökes Zoltȧn A.
Published: February 2007

Creatine kinase BB has been described to be elevated in the serum of patients with prostate cancer. The incidence of abnormal serum levels correlates with the degree of differentiation of the tumor; that is, the more poorly differentiated tumors are associated most frequently with elevated CK‐BB levels. We have recently described two additional findings which involve CK‐BB in prostate cancer: 1) the finding of abnormally migrating CK‐BB bands reported to be IgG‐CK‐BB complexes in several Stage D patients and in 2/3 Stage B patients following 125I implants, and 2) significant differences between CK‐BB purified from prostatic fluid from CK‐BB of brain origin. In particular, we find two bands of prostatic CK‐BB following purification as compared to a single band from brain, when the same purification protocol is used. While further characterization of these differences is proceeding, the two bands of CK‐BB are being used to develop a prostate‐specific antiserum for use in immunoassays to detect prostate cancer in conjunction with other traditional markers such as prostatic acid phosphatase. If serum detection of tumor markers is to be efficacious, tumor marker panels such as CK‐BB and prostatic acid phosphatase may provide a significant advantage over individual markers.
Leukocyte migration inhibition assay in patients with prostate adenocarcinoma
Authors: Wright George L. , Schellhammer Paul F. , Faulconer Robert J. , Reid James W. , Brassil Diane N. , Sieg Susan M.
Published: February 2007

The leukocyte migration inhibition (LMI) assay was used to determine the cell‐mediated immune reactivity of prostate cancer patients to putative tumor antigens present in potassium chloride extracts of surgically removed prostate tumor tissue. Using an extract prepared from prostate tumor tissue, inhibition of leukocyte migration was found more frequently in prostate tumor patients (61%) than in patients with benign prostate hyperplasia (37%), patients with nonprostate cancers (26%), or normal donors (10%). Control extracts prepared from normal prostate tissue, benign prostate hyperplasia tissue, and unrelated tumor tissue were statistically less reactive in the LMI assay than the prostate tumor extract when reacted against leukocytes from prostate tumor patients. These results suggest that the LMI assay might be potentially useful for measuring the tumor‐directed, cell‐mediated immune responses in patients with prostate cancer.
Metioprim‐sulphadiazine distribution in the canine prostate
Authors: Iversen Peter , Nielsen Ole S. , Vergin Hartmut , Madsen Paul O.
Published: February 2007

Constant infusion experiments with metioprim and sulphadiazine were performed in four anesthesized dogs to determine the drugs' concentrations in prostatic secretion, prostatic interstitial fluid, prostatic tissue, urine, and serum. Metioprim showed a specific affinity for the prostate gland, whereas sulphadiazine, as expected, demonstrated lower values in prostatic secretion and tissue than in serum. The prostatic secretion: serum and prostatic tissue:serum ratios using a high‐pressure liquid chromatography assay of metioprim were 7.3 and 4.0, respectively. Furthermore, metioprim showed 3.6 to 5.7 times higher concentrations in the organs of the urogenital system, liver, lung, and pancreas than in serum. We suggest that metioprim may be useful in the treatment of bacterial prostatitis, considering its spectrum of antibacterial activity and the data presented in this study.
Fluid imbibition as a factor in estrogen‐induced increase of prostatic weight in castrated rats
Authors: Corrales J. J. , Kadohama N. , Chai L. S. , Hoisaeter P. A. , Hampton M. T. , Murphy G. P. , Sandberg A. A.
Published: February 2007

The mechanism by which estrogens inhibit castration atrophy has been investigated morphologically and biochemically utilizing ventral prostate from Copenhagen rats. The suppression of weight loss and gross edematous appearance of the prostate associated with the in vivo effect of 17β‐estradiol (E2) could not be accounted for by DNA and protein synthesis. Increase in the fluid content in the tissues was confirmed by demonstration of significant increase in the ratio of wet/dry tissue weights. Light microscopy demonstrated that the main effects were on the stroma, characterized by large inter‐glandular areas almost totally devoid of collagen resulting in an edematous appearance. Electron microscope studies showed an abundance of fluid localized adjacent to the capillary endothelium and some red blood cells indicating disturbances in capillary permeability. The combination of a prolactin secretion inhibiting agent with E2 partially prevented the fluid accumulation and weight increase produced by E2 alone, indicating an involvement of prolactin in the estrogen effect. Differences in blood prolactin concentration between strains of rats may influence the sensitivity of the prostate to estrogens.
Hormonal control of accessory sex organ fibromuscular stroma
Authors: Mariotti Angelo , Mawhinney Michael
Published: February 2007

Using the surgically separated epithelium and muscle preparation of the guinea pig seminal vesicle, quantitative determinations were made of the hormonal sensitivities of three components of male accessory sex organ fibromuscular stroma. The parameters measured were epithelial collagen, muscle tissue cell number, and muscle tissue collagen.

Epithelial collagen increased approximately tenfold between one week of age and adulthood. This growth was completely prevented by castration and was sustained at normal levels by maintenance of prepubertal castrates with dihydrotestosterone (DHT). Castration of adult animals reduced epithelial collagen 40%; such reductions were prevented by DHT treatment. Estrogen treatment of adult castrates, either alone or in combination with DHT, had no anabolic effect on the epithelium. In all of these studies, changes in epithelial collagen correlated with changes in epithelial wet weight, DNA content, and RNA/DNA.

From 1 week of age to adulthood, growth of seminal vesicle muscle involved marked increases in wet weight, DNA content, RNA/DNA, and collagen content. Increments in all parameters were prevented by prepubertal castration and were sustained at normal levels in castrates by DHT treatment. However, in adult animals, muscle DNA content and collagen levels were insensitive to castration and androgen replacement; only tissue weight and cell size (RNA/DNA) were androgen sensitive. Estrogen treatment of adult castrates caused supranormal increases in muscle DNA and collagen; changes in collagen were irreversible. The effects of simultaneous treatment of DHT and estrogen did not differ from those of DHT alone.

Therefore, normal postnatal development of the stromal components, epithelial collagen, muscle cells, and muscle collagen was androgen dependent, but in adult animals, only epithelial collagen retained androgenic sensitivity. Estrogen induced supranormal and irreversible growths in the muscle.
On the presence of prostatic secretion protein in rat seminal fluid
Authors: Borgström Eric , Pousette Åke , Björk Per , Högberg Bertil , Carlström Kjell , Sundelin Birgitta , Gustafsson Jan‐Åke
Published: February 2007

The copulating plug collected from the tip of the penis from rats immediately after decapitation contains a protein very similar and probably identical to PSP (prostatic secretion protein); this protein has earlier been purified from rat prostatic cytosol and characterized. The protein present in the copulating plug interacts with [3H]estramustine and binds to the antibody raised against rat PSP. The concentration of the protein in the copulating plug is 400 ng/mg of total protein, when measured using the radio immunoassay technique developed earlier for measurement of PSP in rat prostate. The [3H]estramustine–protein complex formed in a preparation of the copulating plug has an apparent molecular weight of about 50,000 and a sedimentation coefficient of about 3S when analyzed using sucrose density gradient centrifugation. The complex was retained on Concanavallin‐A Sepharose indicating that the protein is a glycoprotein. Binding of the complex was also observed on hydroxylapatite and DEAE‐Sephadex columns, from which it ws eluted at 0.18 M KC1. Light microscope autoradiograms of rat sperms incubated with 125I‐labeled PSP indicated that PSP is bound to all parts of the sperms. A macromolecule interacting with the PSP‐antibodies is also present in human seminal fluid but at a concentration considerably lower than in rat seminal fluid. The present study shows that a macromolecule probably identical to prostatic secretion protein is present in the copulating plug from the rat. The biological role of this protein in normal male fertility is discussed.
Acute therapy with megestrol acetate decreases nuclear and cytosol androgen receptors in human BPH tissue
Authors: Geller Jack , Albert Jerry , Geller Suzanne
Published: February 2007

This study measures the effect of megestrol acetate (Megace), a progestational antiandrogen, on nuclear and cytosol receptor concentrations in human BPH prostates. Prostatic tissue was obtained at surgery from both untreated patients with BPH and patients pretreated for three to eleven days with 120 to 160 mg of Megace daily; tissues were homogenized and separated into cytosol and crude nuclear fractions. Cytosol and salt extractable nuclear fractions were subjected to saturation analysis with 3H R1881 over the range of 0.5 to 10 nmoles in exchange reactions for 20 hours at 15°C.

Cytosol receptor concentration decreased significantly from 32.7 to 8.7 femtomoles per mg protein (P <0.05); nuclear receptor also was significantly reduced from 317 to 43.8 femtomoles (fmole) per mg DNA (P < .001). Plasma testosterone also decreased significantly from 3.65 to 1.01 ng/ml in Megace‐treated patients. These effects of Megace on receptor concentration appear to be qualitatively quite different from those reported following castration in animals or following high‐dose estrogen therapy in humans. The mechanism of action of Megace in decreasing both cytosol and nuclear androgen receptor concentrations is unknown. It is possible that decrease in receptor concentration is secondary to either the progestational or antiandrogenic effects of Megace. These possibilities are currently under study.
Influence of pituitary and adrenocortical hormones on prostatic secretion protein, a major protein in rat prostate
Authors: Pousette Å. , Björk P. , Carlström K. , Forsgren B. , Högberg B. , Gustafsson J.‐Å.
Published: February 2007

Prostatic secretion protein (PSP) is an androgen‐sensitive, quantitatively important protein in rat ventral prostate which has been shown to inhibit the nuclear uptake and decrease the DNA‐binding capacity of the androgen‐receptor complex. In the present study, the influence of the pituitary, adrenals, and gonads on the concentration of PSP in the prostate was studied. Hypophysectomy decreased the concentration of PSP to about 10% of the control level, an effect similar to that obtained by castration. No effects on prostatic wet weight or PSP concentration were observed following substitution of hypophysectomized rats with human growth hormone, rat prolactin, or rat growth hormone. On the other hand, PSP concentration as well as wet weight of the prostate were normalized in hypophysectomized rats after administration of testosterone propionate. These results are in line with a direct extrahypophyseal effect of androgens on the prostate. Adrenalectomy did not affect the concentration of PSP, nor the wet weight of the prostate. Administration of estramustine decreased the wet weight of the prostate but did not affect the prostatic concentration of PSP in normal rats. Combined treatment with testosterone propionate and estramustine seemed to increase both the wet weight and the concentration of PSP more than administration of testosterone propionate alone. These results indicate a synergistic effect between estramustine and testosterone propionate.
Effect of diethylstilbestrol and estramustine phosphate (estracyt®) on delayed hypersensitivity response to oxazolone in male mice
Authors: Haukaas Svein A. , Kalland Terje
Published: February 2007

The effects of diethylstilbestrol (DES) and estramustine phosphate (EMP) on delayed hypersensitivity response (DTH) to oxazolone in male mice were investigated using a radioisotopic ear method. DES significantly inhibited the ability to express a DTH response and was most effective when given during the effector phase of the reaction. EMP had no effects when the animals were exposed to the drug during the effector phase, while it resulted in a strong and dose‐dependent depression of the DTH response when applied in the sensitization phase. Possible involvement of suppressor cells was investigated by pretreatment of animals with cyclophosphamide or by adoptive transfer of tentative suppressor cells from spleen, lymph nodes, or peritoneal cavity. However, no evidence of cellular or humoral suppressor factors induced by drug treatment was found.
Estramustine phosphate (estracyt®) treatment of T3–T4 prostatic carcinoma
Authors: Veronesi Andrea , Zattoni Filiberto , Frustaci Sergio , Galligioni Enzo , Tirelli Umberto , Trovó Gaetano , Tumolo Salvatore , Merlo Alberto , Artuso Giorgio , Cosciani‐Cunico Sergio , Grigoletto Eligio
Published: February 2007

From September, 1978, to November, 1980, 69 consecutive patients with locally advanced (T3‐T4) prostatic adenocarcinoma, with or without distant metastases, were treated with oral estramustine phosphate. Dosage was 15 mg/kg/day for 2 months, followed by 5 mg/kg/day until progression. In the 48 evaluable patients with progressive disease at entry in the study, 1 complete response, 7 partial responses, 31 disease stabilizations, and 9 progressions were encountered (81.2% NPCP response rate). Karnofsky performance status equal to or less than 50 was predictive of poor response to estramustine phosphate.

In the 10 evaluable patients with stabilized disease at entry in the study after orchiectomy, 2 complete responses, 4 partial responses, 3 disease stabilization, and 1 progression were noted.

The major side effects observed were gynecomastia, nausea, and vomiting.
Isolation, characterization, and spontaneous interconversion of two forms of human prostatic acid phosphatase
Authors: McTigue John J. , Van Etten Robert L.
Published: February 2007

Starting with human prostatic acid phosphatase (HPAP) purified by affinity chromatography on Sepharose‐bound N‐(6‐aminohexyl)tartramic acid [Van Etten, R. L. and Saini, M. S. (1978) Clin. Chem. 24, 1525], two forms of the enzyme can be separated by gradient elution DEAE‐cellulose chromatography. The two enzyme forms are electrophoretically distinguishable on high pH gels. Under some conditions of storage one of these forms undergoes a conversion to the other. Both forms have identical amino acid compositions and Vmax values with typical substrates, but differences are observed in circular dichroism spectra, relative fluorescence intensities, Km values, and carbohydrate composition. It is concluded that the two forms differ only in the structure of their (nonphosphorylated) carbohydrate side chains. In view of the possible interconversion of the two forms upon storage, caution must be observed in any attempt to attach clinical significance to the relative amounts of the two forms.
Transurethral resection of the prostate for chronic bacterial prostatitis
Authors: Barnes Roger W. , Hadley Henry L. , O'Donoghue E. P. N.
Published: February 2007

Forty‐nine patients with chronic bacterial prostatitis causing symptoms and receiving routine accepted treatment for many months or years, without permanent relief, were treated by transurethral prostatic resection (TURP). The purpose of the surgery was to remove the gland down to the true capsule (radical TURP). The patients' own appraisal of the results, the absence of symptoms and of infection, indicate 67% had a good result when assessed 1 year following surgery; 21% were improved and 12% received no benefit. Transurethral resection is recommended in selected cases and when the surgeon is able to remove all of the glandular tissue without causing large perforations through the true capsule. Acceptable results have been achieved in two‐thirds of cases. There was no mortality and insignificant morbidity. Patients experiencing no benefit and those who were only improved but not cured were either poorly selected or infected prostatic tissue was not removed.
The type of current frequency used in transurethral resection of prostate (TURP) affects the androgen receptor
Authors: Albert Jerry , Geller Jack , Nachtsheim Daniel A.
Published: February 2007

Blended Bovie current No. 2 destroys androgen receptor in both cytosol and nuclear extracts of prostate tissue. No significant difference was noted in either nuclear or cytosol receptor concentrations between openly resected and electroresected specimens when Bovie current No. 1 was used with cutting loops No. 26 or larger, although total androgen receptor (cytosol plus nuclear) was significantly reduced in the electroresected specimens. The androgen receptor method used is highly reliable for prostate obtained by either open resection or electroresection using pure cutting currents, although receptor concentrations in samples obtained by the two methods probably should not be combined or compared.
Whither pelvic lymphadenectomy in prostatic cancer?
Authors: Pollen Jeffrey J.
Published: February 2007

In the last decade pelvic lymphadenectomy has gained in popularity as a staging maneuver designed to improve the selection of patients with localized prostatic cancer for curative treatment, by uncovering lymph node metastases. The presence of tumor in the regional nodes portends substantial risk for the later appearance of distant metastases. With rare exceptions, lymphadenectomy is widely regarded as a staging procedure without therapeutic benefits. Unfortunately, the operation as routinely performed carries a significant complication rate. The survival results of total prostatectomy for well‐selected nodules of prostatic cancer are excellent without preliminary lymphadenectomy. The morbidity of lymphadenectomy is compounded by superimposed external irradiation. Because of the low complication rate from external radiation alone, it is suggested that patients selected for pelvic radiation be spared the discomfort of lymphadenectomy. Clinical trials of adjuvant chemotherapy in patients with minimal nodal disease may answer the question of whether pelvic lymphadenectomy should ever be performed. It is predicted that noninvasive imaging will improve to the point that staging lymphadenectomy may be relegated to the surgical archives.
Histologic grading and the practicing urologist
Authors: Albertsen Peter
Published: February 2007

Over the past 60 years, pathologists have identified three histologic features, tumor volume, glandular differentiation, and nuclear anaplasia, as important prognosticators of the malignant potential of prostatic adenocarcinoma. Several histologic grading systems have emerged to assess these morphological and cytological features, but problems with objectivity and reproducibility have been encountered. The failure of grading systems to predict accurately the malignant potential of individual tumors and the paucity of therapeutic options available have prevented many urologists from adopting these systems. Recent progress among stage A lesions has highlighted the clinical relevance of histologic grading systems, but advances are needed in prognostic techniques and therapeutic modalities before the practicing urologist can apply histologic information clinically among the majority of his patients.
Significance of prostatic biopsies after radiation therapy for carcinoma of the prostate
Authors: Herr Harry W. , Whitmore Willet F.
Published: February 2007

The significance of a prostatic biopsy after radiation therapy for prostatic cancer is at present uncertain. Criteria for interpreting residual tumor cells as viable and, more important, determining whether such cells are biologically capable of local growth and/or subsequent dissemination, by histological evaluation, require further clinical correlation and studies designed to better characterize biological behavior and growth potential of neoplastic cells in general and how this may or may not be altered by irradiation. A positive biopsy after radiation therapy must be regarded, however, as ominous simply because its potential significance is yet to be determined. Prostatic biopsies may predict treatment failure in general, but their significance relative to an individual patient requires correlation with 1) tumor stage, grade, size, and site of the original tumor; 2) technique of biopsy, number of cores obtained, and the location relative to the original tumor; 3) time interval of biopsy after treatment and whether biopsy is performed on one or more occasions; 4) circumstances (clinical progression or clinical regression) at the time of biopsy; and 5) treatment artifacts regarding dose delivered and distribution, which is especially important with regard to interstitial irradiation.
Phenotypic modulation of the canine prostate after long‐term treatment with androgens and estrogens
Authors: Aumüller G. , Funke P. J. , Hahn A. , Hoffbauer G. , Tunn U. , Neumann F.
Published: February 2007

Fine structural alterations of the canine prostate induced by long‐term treatment of castrated adult animals with estrogens and/or androgens and also in combination with antiandrogens and/or antiestrogens for six months have been studied with particular respect to their topographic location within the gland. Three major patterns of structural responses of the epithelium have been distinguished: squamous metaplasia, atrophy, and hypertrophy, while in stroma, regression, hypertrophy, or sclerosis were observed. In addition to cellular alterations of stromal fibrocytes and smooth muscle cells, characteristic changes in the arrangement, distribution, and pattern of the different stromal elements occurred. General squamous metaplasia of the epithelium and regressive alterations of stromal cells were most obvious in animals treated with estradiol plus androstanediol. Atrophy of the epithelium and stromal sclerosis were the salient features of antiandrogen‐treated castrated animals, while hypertrophy or hyperplasia of both the epithelium and stroma was a major finding in andro‐stanediol‐substituted castrated animals. Combined treatment caused rather heterogeneous structural patterns seemingly dependent on the location within the gland. The results indicate that the prostatic epithelial cells dispose of a broad variety of structural reaction patterns that, in case of combined hormonal treatment, are expressed in a manner typical for their locations within the ductal system of the gland. However, with the exception of combined treatment with estradiol, tamoxifen, and androstanediol of castrated dogs, none of the experimental protocols used induced a morphologic response of the gland comparable to that seen in human benign prostatic hyperplasia. The canine prostate therefore is of rather limited value as a model for human BPH.
Blood hormone levels related to stages and grades of prostatic cancer
Authors: Høisaeter P. Å. , Haukaas S. , Bakke A. , Hoiem L. , Segadal E. , Thorsen T.
Published: February 2007

Human follicle stimulating hormone (FSH), human luteinizing hormone (LH), human prolactin, testosterone, estradiol, and sex hormone binding globulin (SHBG) were measured in the blood of 100 consecutive new patients with prostatic carcinoma. According to the VACURG classification, 14% of the patients were in Stage 1,25% in Stage 11, 25% in Stage III, and 36% in Stage IV. Within each stage the tumors were further subdivided into either highly, moderately, or poorly differentiated carcinomas. Thus the whole group consisted of 12 categories (stages and grades) of prostatic carcinoma. No specific hormonal pattern emerged which could distinguish any particular category or group of categories. We, therefore, conclude that single hormone measurements are of no practical value for diagnostic purposes related to staging and grading of prostatic carcinoma.
In vitro and in vivo effects of diethylstilbestrol and estramustine phosphate (estracyt®) on the mitogen responsiveness of human peripheral blood lymphocytes
Authors: Haukaas Svein , Høisaeter Per Åge , Kalland Terje
Published: February 2007

The responsiveness to diethylstilbestrol (DES) and estramustinephosphate (EMP) of human peripheral blood lymphocytes to T‐cell mitogens has been investigated in vitro and in vivo. EMP demonstrated potent inhibiton of both Con A‐and PHA‐induced lymphocyte proliferation in vitro, while it had no detectable effects when given to patients with cancer of the prostate. DES reduced the response to Con A in vitro, but had only marginal effects on PHA‐induced mitogen response. In contrast, the response to Con A was unaltered, while the response to PHA was significantly diminished after DES therapy in patients with prostatic cancer. This effect, however, was only seen when high doses of DES not included in conventional regimen were given. The proliferative response to T‐cell mitogens in patients with prostatic cancer was not affected by serum source in the assay, indicating the absence of humoral factors able to inhibit mitogen response in these patients.
Regional variations in the testicular dependence of prolactin binding and its possible relationship to castration‐induced involution in rat prostate gland
Authors: Witorsch Raphael J.
Published: February 2007

Prolactin binding sites of ventral, lateral, and dorsal lobes of rat prostate were examined immunohistochemically 1, 2, 4, and 8 days after castration or sham operation. In sham‐operated rats each lobe exhibited a distinct pattern of intracellular and intraluminal prolactin binding. A loss in proiactin binding from epithelial cells of ventral prostate, which was visualized postcastration, was quantitated with the aid of an image analyzer and then statistically evaluated. The proportion of ventral prostate epithelial cells devoid of prolactin binding increased from approximately 13% in sham‐operated rats to approximately 29% 1 day after castration, and reached a peak level of about 71% 4 days postcastration. No loss of prolactin binding was evident in either lateral or dorsal prostate up to 8 days postcastration. Direct measurement of epithelial cell heights and subsequent statistical evaluation revealed similar regional differences in the rates and extent of prostate involution. Eight days after castration ventral prostate epithelial cell heights decreased by 56% whereas lateral and dorsal lobe epithelial cells heights decreased about 25% and 14%, respectively. The apparent relationship between testicular dependence of prostatic prolactin binding and castration‐induced prostatic involution are discussed in terms of possible regional variations in the prolactin‐androgen interplay in prostate.
Epithelial and fibroblastoid cell lines derived from the normal canine prostate. II. Cell proliferation in response to steroid hormones
Authors: Eaton C. L. , Pierrepoint C. G.
Published: February 2007

Epithelial and fibroblastoid cell lines derived from the adult canine prostate, have been used as model systems in a preliminary study of the effects of steroid hormones on isolated cell populations. The mitogenic activities of various androgens and one estrogen were assessed during logarithmic growth in replicate subcultures by measurement of population size and radiolabeled nucleotide uptake in the presence of concentration ranges of these steroids. [H3]‐Leucine incorporation rate was used as an estimate of protein synthesis in the epithelial cell line during the latter phase of log growth. Of the androgens examined, elevated cell population growth rate was only demonstrated in either epithelial or fibroblastoid cell cultures supplemented with 5α‐androstane‐3α, 17β‐ and 17α‐diols at physiological concentrations. No significant qualitative differences were observed between individual prostatic cell types in their proliferative response to the androgens tested. Contrasting effects were observed in the growth rates of epithelial and fibroblastoid cell types in cultures supplemented with estradiol‐17β. This estrogen was significantly mitogenic in fibroblast cultures, but did not significantly affect epithelial proliferation at the concentrations studied. These results are reviewed with reference to current concepts of steroid action in the canine prostate. The importance of the characterization of culture conditions and procedures has been emphasized as a prerequisite to the study of cell proliferation, and potential mitogens, using cell culture models.

The relevance of these findings in the consideration of stromal‐epithelial interaction, and glandular differentiation, is discussed.
Abnormal levels of plasma hormones in men with prostate cancer: Evidence toward a “two‐disease” theory
Authors: Zumoff Barnett , Levin Joseph , Strain Gladys W. , Rosenfeld Robert S. , O'Connor John , Freed Selwyn Z. , Kream Jacob , Whitmore Willet S. , Fukushima David K. , Hellman Leon
Published: February 2007

The 24‐hr mean plasma concentrations of 13 hormones or hormone metabolites (cortisol, testosterone, dihydrotestosterone, dehydroisoandrosterone, dehydroisoandrosterone sulfate, androsterone, androsterone sulfate, estrone, thyroxine, triiodothyronine, LH, FSH, and prolactin) were measured in 16 rigorously screened patients (aged 55–80) with stage C or D prostate cancer and 36 normal men. Nine of the hormones showed no abnormalities in the patients but four (testosterone, dihydrotestosterone, cortisol, and estrone) showed abnormalities. Testosterone and dihydrotestosterone, which, respectively, decreased with age and showed no change with age in the normal men, rose sharply with age in the patients. The patients' curves crossed the normal curves at about age 65; patients 65 or above showed normal values while patients under age 65 showed significantly subnormal levels of both hormones: testosterone averaged 282 ng/dl in patients vs 434 ng/dl in controls (P < 0.0001) and dihydrotestosterone averaged 70 ng/dl in patients vs 99 ng/dl in controls (P <0.01). Cortisol, which was age invariant in the normal men, fell sharply with age in the patients; patients under 65 had significantly elevated levels (10.1 vs 6.9 μg/dl; P < 0.0001), while patients 65 or older had normal levels. Estrone levels were age invariant in both patients and controls, but the mean level in patients was markedly elevated (81 vs 47 pg/ml in controls; P < 0.001). The cortisol/testosterone ratio almost completely separated prostate cancer patients under 65 from normal men, but did not discriminate patients 65 or older from normal.

The findings indicate that prostate cancer patients under 65 differ markedly in their endogenous hormonal pattern from patients 65 or older. This leads us to propose a “two‐disease” theory of prostate cancer, with possible differences in genetic factors and prognosis.
Rapid endocrine effects of tamoxifen and testolactone in prostatic carcinoma patients
Authors: Leinonen Pekka , Bolton Nicholas J. , Kontturi Matti , Vihko Reijo
Published: February 2007

The short‐term (6‐day) endocrine effects of tamoxifen and testolactone were investigated in men with prostatic carcinoma. Tamoxifen treatment (20 mg/day) did not affect the gonado‐tropin levels, but it temporarily increased prolactin, induced sex hormone‐binding globulin production, and suppressed peripheral serum progesterone, 17‐hydroxyprogesterone, an‐drostenedione, testosterone, and 5α‐dihydrotestosterone concentrations. These changes were attributed to the estrogenic properties of tamoxifen, since no changes in peripheral serum estradiol concentrations were observed. Testolactone (1000 mg/day) decreased peripheral estradiol concentrations by 50% and increased the concentrations of the neutral steroids measured. The increases in serum FSH and LH were very small. This study corroborates the early estrogen‐like action of tamoxifen, and the experiment with testolactone further suggests that endogenous estradiol has physiological functions in man, regulating gonadotropin and androgen production.
Effect of perphenazine on growth and zinc‐65 uptake of the rat prostatic adenocarcinoma, R 3327
Authors: Rosoff Betty , Diamond Edward J.
Published: February 2007

Prolactin affects the growth and function of both normal and carcinatomous prostate tissue. Therefore, the effect of modifying prolactin secretion on the growth of the adenocarcinoma of the rat prostate (R3327) was studied, utilizing chronic administration of the dopamine antagonist perphenazine. At 4 and 8 weeks after tumor inoculation, perphenazine (0.5 and 1.0 mg per dose) was injected for 12–16 weeks. Tumors weighed at autopsy showed that the 0.5 mg dose resulted in significantly smaller and the 1.0 mg dose, in significantly larger tumors than the controls. Perphenazine at both doses increased serum prolactin, but the increase was greater when 0.5 mg was administered. There was a higher uptake of 65Zn when the tumor growth was inhibited as in the animal receiving 0.5 mg of perphenazine. Several possible explanations are offered for the results, including the fact that prolactin might follow a bell‐shaped curve in its effect on the tumor and that perphenazine might have other mechanisms of action besides dopamine antagonism.
Effects of androgens on the ultrastructure and subcellular zinc distribution in the prostatic epithelium of castrated rats
Authors: Timms B. G. , Chandler J. A.
Published: February 2007

Sprague Dawley rats were maintained on testosterone propionate or 5α‐dihydrotestosterone for 3 days following bilateral orchidectomy for a 7‐day period. Ultrastructural examination showed only partial recovery of the prostatic epithelium with testosterone propionate while 5 α‐dihydrotestosterone caused the lateral and ventral lobes to revert to the appearance of control tissues. The latter metabolite induced greater stimulation of the prostate evidenced by increased mitotic division of the epithelial cells and an increased number of basal cells exhibiting ciliary formation was observed. Zinc concentrations in subcellular regions of both lateral and ventral prostate lobes were affected by the two androgens. Testosterone propionate was most effective in elevating zinc in the lateral lobe, particularly within the secretory components. In the ventral lobe both androgens caused an increase in subcellular zinc concentrations above control levels. The increase of nuclear and nucleolar zinc was related to the increase in nuclear activity and cellular response to the androgen administration.
Separation of acid phosphatases in the rat ventral prostate by gel filtration, isoelectric focusing, and chromatofocusing
Authors: Jauhiainen Anneli , Rytöluoto‐Kärkkäinen Raili , Vanha‐Perttula Tapani
Published: February 2007

Acid phosphatases of the rat ventral prostate were fractionated by gel filtration (GF) on Sepharose 6B, isoelectric focusing (IEF), and chromatofocusing (CF). In GF three activity peaks (GF‐1, GF‐2, GF‐3) were disclosed. They showed some differences in substrate preference when six substrates (p‐nitrophenyl phosphate; p‐NPP; phenolphthalein phosphate, Phe‐P: thymolphthalein phosphate, Tym‐P; α‐naphthyl phosphate, α‐NP; β‐naphthyl phosphate, β‐NP; naphthol ASBI phosphate, N‐ASBI‐P) were tested. Differences were also encountered in their sensitivity to tartrate and fluoride. IEF gave seven bands at different pI values (8.3, 8.1, 7.9, 7.1, 6.4, 5.5, and 5.0) with α‐NP and β‐NP but only four with N‐ASBI‐P. Four of the bands (8.3, 8.1, 7.9, 5.5) were sensitive to tartrate. In CF eight activity peaks (CF‐1 to CF‐8) were resolved with the six substrates. They differed from each other in pI values, pH optima, substrate preference, and modifier characteristics. Peaks CF‐1 (pI 8.3, pH 5.5), CF‐2 (pI 8.1, pH 4.2) and CF‐3 (pI 7.9, pH 4.2) had a large substrate spectrum and high sensitivity to tartrate and fluoride. CF‐4 (pI 7.1, pH 6.0) and CF‐7 (pI 5.5, pH 4.2) were low in activity, preferred α‐NP as substrate, and were moderately sensitive to tartrate. CF‐5 (pI 6.4, pH 5.5) and CF‐8 (pI 5.0, pH 5.0) were able to hydrolyse all substrates tested with moderate inhibition by tartrate. CF‐6 (pI 6.0, pH 5.0) showed a relative preference for p‐NPP and Phe‐P with no hydrolysis of N‐ASBI‐P and Tym‐P. Of these activities CF‐6 and CF‐7 were also clearly activated by Co2+. Peaks CF‐6 and CF‐7 appeared the most sensitive to p‐chloromercuribenzoate. It is concluded that activities CF‐1, CF‐2, and CF‐3 are lysosomal isoenzymes with minor structural differences. The others are possibly all nonlysosomal with greater biochemical differences. Some of them apparently represent the secretory form(s) of acid phosphatase in the rat ventral prostate.
Liarozole, an antitumor drug, modulates cytokeratin expression in the dunning AT‐6sq prostatic carcinoma through in situ accumulation of all‐trans‐retinoic acid
Authors: Smets G. , van Ginckel R. , Daneels G. , Moeremans M. , van Wauwe J. , Coene M.‐C. , Ramaekers F. C. S. , Schalken J. A. , Borgers M. , de Coster R.
Published: February 2007

Liarozole showed antitumoral activity in the Dunning AT‐6sq, an androgen‐independent rat prostate carcinoma. To investigate its potential mechanism of action, the effects of the drug doses (ranging from 3.75 to 80 mg/kg b.i.d.) on endogenous plasma and tissue all‐trans‐retinoic acid levels and on the differentiation status of the tumor cells were evaluated. To follow modulation of differentiation, cytokeratins were localized in the (un)treated tumors by immunocytochemistry and quantitatively determined by immunoblotting. Results showed that liarozole statistically significantly reduced tumor weight from 30 mg/kg upwards and induced accumulation of all‐trans‐retinoic acid both in plasma and tumors. In the tumors, a statistically significant accumulation was already noted from 7.5 mg liarozole/kg upwards. Concomitantly, the differentiation status shifted from a keratinizing towards a non‐keratinizing squamous carcinoma, which was further confirmed by the cytokeratin profile of the carcinoma (presence of CK 8, 10, 13, 14, 18, 19). Immunoblotting revealed an overall decrease in cytokeratin content, except for CK 8. These findings suggest that the antitumoral properties of liarozole might be related to an increase in the degree of tumor differentiation through accumulation of all‐trans‐retinoic acid. © 1995 Wiley‐Liss, Inc.
Mutagenesis data in the automated prediction of transmembrane helix dimers
Authors: Metcalf Douglas G. , Law Peter B. , DeGrado William F.
Published: February 2007

We present a molecular modeling protocol that selects modeled protein structures based on experimental mutagenesis results. The computed effect of a point mutation should be consistent with its experimental effect for correct models; mutations that do not affect protein stability and function should not affect the computed energy of a correct model while destabilizing mutations should have unfavorable computed energies. On the other hand, an incorrect model will likely display computed energies that are inconsistent with experimental results. We added terms to our energy function which penalize models that are inconsistent with experimental results. This creates a selective advantage for models that are consistent with experimental results in the Monte Carlo simulated annealing protocol we use to search conformational space. We calibrated our protocol to predict the structure of transmembrane helix dimers using glycophorin A as a model system. Inclusion of mutational data in this protocol compensates for the limitations of our force field and the limitations of our conformational search. We demonstrate an application of this structure prediction protocol by modeling the transmembrane region of the BNIP3 apoptosis factor. © 2007 Wiley‐Liss, Inc.
First principles study of small palladium cluster growth and isomerization
Authors: Luo Chen , Zhou Chenggang , Wu Jinping , Dhilip Kumar T. J. , Balakrishnan Naduvalath , Forrey Robert C. , Cheng Hansong
Published: February 2007

Structures and physical properties of small palladium clusters Pdn up to n = 15 and several selected larger clusters were studied using density functional theory under the generalized gradient approximation. It was found that small Pdn clusters begin to grow 3‐dimensionally at n = 4 and evolve into symmetric geometric configurations, such as icosahedral and fcc‐like, near n = 15. Several isomers with nearly degenerate average binding energies were found to coexist and the physical properties of these clusters were calculated. For several selected isomers, relatively moderate energy barriers for structural interchange for a given cluster size were found, implying that isomerization could readily occur under ambient conditions. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007