bluuebunny/crossref_metadata_2025 huggingface dataset:
On the first come–first served rule in multi‐echelon inventory control
Authors: Axsäter Sven
Published: February 2007

A two‐echelon distribution inventory system with a central warehouse and a number of retailers is considered. The retailers face stochastic demand and replenish from the warehouse, which, in turn, replenishes from an outside supplier. The system is reviewed continuously and demands that cannot be met directly are backordered. Standard holding and backorder costs are considered. In the literature on multi‐echelon inventory control it is standard to assume that backorders at the warehouse are served according to a first come–first served policy (FCFS). This allocation rule simplifies the analysis but is normally not optimal. It is shown that the FCFS rule can, in the worst case, lead to an asymptotically unbounded relative cost increase as the number of retailers approaches infinity. We also provide a new heuristic that will always give a reduction of the expected costs. A numerical study indicates that the average cost reduction when using the heuristic is about two percent. The suggested heuristic is also compared with two existing heuristics. © 2007 Wiley Periodicals, Inc. Naval Research Logistics, 2007
Effect of peroxide crosslinking on thermal and mechanical properties of poly(ε‐caprolactone)
Authors: Han Changyu , Ran Xianghai , Su Xuan , Zhang Kunyu , Liu Nanan , Dong Lisong
Published: February 2007

Poly(ε‐caprolactone) (PCL), a saturated polyester, derived from ring‐opening polymerization of ε‐caprolactone, was chemically crosslinked with various amounts of benzoyl peroxide (BPO) by a two‐step method by first evenly dispersing the BPO into the PCL matrix and then crosslinking at elevated temperature. The gel fraction increased with an increase in BPO content. The modified Charlesby–Pinner equation was used to calculate the ratio of chain scission and crosslinking. The results showed that both scission and crosslinking occurred, and that crosslinking predominated over scission. The number‐average molecular weight between the crosslinks determined by the rubber elasticity theory using the hot set test showed a decrease with increasing BPO content. The melting temperature and crystallinity decreased with an increase in BPO content, and the crystallization temperature increased after crosslinking. Dynamic mechanical analysis results showed a decrease in the glass transition temperature as a result of chemical crosslinking of PCL. This was explained by the observed reduction in crystallinity and the increase in free volume due to restrictions in chain packing. Moreover, Young's modulus and elongation at break generally decreased with an increase in BPO content, but the tensile strength first increased with BPO content up to 1.0 wt%, reached a maximum, and then decreased. Copyright © 2007 Society of Chemical Industry
Effects of 1,2‐butadiene on the anionic copolymerization of styrene and 1,3‐butadiene in the presence of polar additives
Authors: Wang Qiang , Liao Mingyi , Wang Yurong , Zhang Chunqing
Published: February 2007

1,2‐Butadiene is shown to be a chain terminating/transferring agent in butyllithium‐initiated diene polymerization. The influence of 1,2‐butadiene on the anionic copolymerization of 1,3‐butadiene and styrene is investigated using n‐butyllithium as initiator and tetrahydrofuran or N,N,N′,N′‐tetramethylethylenediamine as polar additive. A decrease of copolymerization rate is observed on the addition of 1,2‐butadiene. On introducing 1,2‐butadiene, the number average molecular weight (Mn) decreases and the molecular weight distribution broadens. The vinyl content of copolymer increases slightly with an increase of 1,2‐butadiene. During the copolymerization, 1,2‐butadiene in the presence of a high ratio of polar additives to n‐butyllithium greatly decreases the copolymerization rate, resulting in a lower value of Mn and a narrower molecular weight distribution than that found for a low ratio of polar additives to n‐butyllithium. This evolution can be explained by the base‐catalyzed isomerization of 1,2‐butadiene to form 1‐butylene in the presence of polar additives. With an increasing amount of 1,2‐butadiene, the vulcanized rubber exhibits an increased rolling resistance and a reduced wet skid resistance owing to the decrease of coupling efficiency. These results further indicate the activity of alkynyllithium derivatives produced by the reaction of alkyllithium and 1‐butyne is less than that of the alkyllithium. Copyright © 2007 Society of Chemical Industry
First identification of biradicals during thermal [2π + 2π] cyclopolymerization of trifluorovinyl aromatic ethers
Authors: Mifsud Nicolas , Mellon Veronique , Jin Jianyong , Topping Chris M , Echegoyen Luis , Smith Dennis W
Published: February 2007

The thermal cyclopolymerization of three trifluorovinyl aromatic ether monomers 1,1,1‐tris (4‐trifluorovinyloxyphenyl)ethane (1), 4,4′‐bis(4‐trifluorovinyloxy)biphenyl (2) and 2,2‐bis(4‐trifluorovinyloxy‐ phenyl)‐1,1,1,3,3,3‐hexafluoropropane (3) were monitored in situ using time‐resolved electron paramagnetic resonance spectroscopy over a temperature range of 150–210 °C. The signals observed during the early stages of perfluorocyclobutyl polymer production suggest the formation of a triplet state corresponding to the proposed biradical intermediate with a strong dipole–dipole interaction. A doublet splitting shows the presence of hyperfine coupling due to fluorine. The characterization of radical species formed during the polymerization of monomer 1 using model compounds and polymerization kinetics of monomer 2 are also presented. Copyright © 2007 Society of Chemical Industry
Dynamic light scattering and rheology studies of aqueous solutions of amphiphilic sodium maleate containing copolymers
Authors: Di Cola Emanuela , Waigh Thomas A. , Colby Ralph H.
Published: February 2007

Light scattering techniques, video particle‐tracking microrheology, and bulk rheology were employed to examine the structure and dynamics of a series of alternating sodium maleate copolymers with moderately hydrophobic comonomers (diisobutylene, styrene, and isobutylene) in aqueous solutions. The scaling dependence of the specific viscosity (ηsp) on the polyelectrolyte concentration (c) was studied with and without added salt; similar trends were found in both conventional rheology and particle‐tracking microrheology measurements, showing good performance of the technique with flexible polyelectrolytes. Furthermore, with dynamic light scattering performed in high added salt conditions, we examined the behavior of the amplitude of the fast mode, which is in agreement with scaling predictions. In contrast, the slow modes are not understood and display three separate behaviors for the wavevectorqdependence of the decay rate (Γ), depending on the comonomer; superdiffusive (Γ∼q2.7, isobutylene) possibly because of sticky aggregates, wavevector independent (Γ∼q0, styrene) most likely because of coupled polyion‐ion diffusion and diffusive (Γ∼q2.0, diisobutylene) presumably because these aggregates are not sticky. The hydrophobicity of the comonomer appears to switch the aggregation process between “open,” “closed,” and “non” association for isobutylene, diisobutylene, and styrene respectively. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 774–785, 2007
An exploratory, interview study of oncology patients' and health‐care staff experiences of discussing resuscitation
Authors: Cox Karen , Wilson E. , Jones L. , Fyfe D.
Published: February 2007

There is little research about how patients and their families would like discussions surrounding resuscitation to take place. The purpose of this exploratory study was to investigate the experience of a discussion of resuscitation from the perspective of the participants. In‐depth interviews were undertaken with 21 patients, of whom nine were interviewed together with a relative and 14 staff in an oncology setting. Data were analysed using a constant comparative method and coded using NVIVO qualitative data analysis software. Patients appeared to be accepting resuscitation discussions as necessary and important. A minority felt that the timing of the discussion could have been better, particularly if they were newly diagnosed or had recently commenced treatment. Relatives generally found the discussions more difficult and felt that discussions should take place much closer to death. Patients identified that they needed time and privacy during the discussion. Staff identified a need to present a sensitive and individualised discussion which took into account the key elements of timing, place, space, manner and pace. Patients acknowledged that the resuscitation discussion enabled them to begin to address issues relating to dying and end of life. For staff on‐going communication skills training and support in this area were seen as important but often overlooked parts of the process. Copyright © 2007 John Wiley & Sons, Ltd.
Plasma estradiol, free testosterone, sex hormone binding globulin binding capacity, and prolactin in benign prostatic hyperplasia and prostatic cancer
Authors: Rannikko Sakari , Adlercreutz Herman
Published: February 2007

The nature of hormonal changes with age and the possible role of these changes in the development of benign prostatic hyperplasia (BPH) and prostatic cancer (PC) were studied by assaying the plasma levels of total and free testosterone (T), estradiol (E2), prolactin, and sex hormone binding globulin binding capacity (SHBG) in 20 normal healthy men aged 40‐59 years, in 30 patients with BPH aged 63‐79 years, and in 30 patients with PC of similar height, weight, and age as the BPH patients. The mean E2 was highly significantly (P < 0.0005) lower in the PC patients and in the young controls than in the BPH patients. The mean free T was significantly higher in the young controls than in the BPH patients (P < 0.025) and PC patients (P < 0.0005). The PC patients had a slightly lower (P < 0.05) mean free T and mean E2/free T ratio than the BPH patients. The mean E2/free T ratio was significantly higher in the BPH patients (P < 0.0005) and in the PC patients (P < 0.0025) than in the young controls. It seems possible that the observed age‐dependent significant increase in plasma estrogen concentration in the BPH patients may act as a protective factor against prostatic cancer.
Development of an in vitro clonogenic assay for the R3327 rat prostatic adenocarcinoma permits comparison of the proliferative potential of the R3327, R3327A, and R3327AT tumors
Authors: Dibner Julia J. , Nakeff Alexander
Published: February 2007

The R3327 class of rat prostate tumors consists of both the androgen‐dependent R3327 adenocarcinoma and androgen‐independent sublines, the R3327At spindle cell tumor, and the R3327A, a squamous cell carcinoma. We have developed in vitro clonogenic cell assays to measure and compare systematically the proliferative potential of these tumors following various monodispersion techniques. Linear relationships between the number of monodispersed tumor cells cultured at low cell density and the number of colonies formed 10 days later establish these assays as the first quantitative cellular approach to those proliferative subpopulations ultimately responsible for the growth of these tumors.

We have chosen the name colony forming cell‐prostatic adenocarcinoma (CFC‐PA) to refer to the members of the proliferative subpopulation of the R3327 tumor. An ultrastructurd comparison of R3327 adenocarcinoma tissue sections with the cells produced during culture provides evidence that the cells of the proliferative subpopulation may be derived from the acinar epithelium of the tumor.
Suppression of antibody response of male mice exposed to diethylstilbestrol or estramustine phosphate (estracytR)
Authors: Haukaas Svein A.
Published: February 2007

The effects of treatment of male mice with diethylstilbestrol (DES) or estramustine phosphate (EMP) on the primary antibody response to sheep red blood cells (SRBC) and lipopolysaccharide (LPS) were investigated using a hemolytic plaque assay for enumeration of antibody‐producing cells. DES treatment at a daily dose of 1.4 or 5.6 mg/kg from 2 days prior to and up to 3 days after immunization significantly reduced the number of anti‐SRBC as well as anti‐LPS‐producing cells per 106 spleen cells. The 100 mg/kg EMP given as daily intraperitoneal injections significantly diminished the antibody response to both SRBC and LPS. No alteration in the number of anti‐SRBC‐producing cells per 106 spleen cells was detected in spleens from mice receiving 30 mg/kg/day EMP, while the number of anti‐LPS‐producing cells was reduced.

The immunoregulatory effects of EMP are apparently not a pure estrogen effect, since treatment with doses of estradiol‐17β equivalent to the amounts of estradiol linked to the cytotoxic moiety in 100 mg/kg/day of EMP were without effect. EMP‐induced functional impairment in the T‐cell population is inferred from the reduced ability of adoptively transferred T cells from EMP‐exposed animals to support an antibody response to SRBC in syngeneic nude mice.
Prostate cancer and the multiple primary malignant neoplasm syndrome
Authors: Ray P. , Guinan P. , Sharifi R. , Mouli K. , Shaw M.
Published: February 2007

In an attempt to evaluate the relationship of prostate cancer to the multiple primary malignant neoplasm syndrome, 626 prostate cancer cases were reviewed. Patients with one malignant tumor appear to be no more at risk of developing a prostate cancer than individuals who have never had a tumor.
Primary explant culture: An in vitro model of the human prostate
Authors: Merchant Donald J. , Clarke S. M. , Ives K. , Harris S.
Published: February 2007

Human prostate tissue gave rise to essentially pure cultures of basal cells in vitro. Careful analysis by phase‐contrast microscopy and photography suggested that these cells attempt to differentiate into secretory acinar cells. This was confirmed by immunocytochemical analysis for prekeratin which is present only in basal cells in situ and for prostatic acid phosphatase, prostate‐specific antigen, and prostate fluid antigen, which are present only in secretory acinar cells in situ.
Carcinoma of the prostate: Results of post‐irradiation biopsy
Authors: Freiha F. S. , Bagshaw M. A.
Published: February 2007

One hundred and forty‐six patients with clinically localized carcinoma of the prostate were surgically staged and treated with external beam irradiation to the prostate and to the lymph node‐bearing areas. Sixty‐four (44%) of these patients had needle biopsy of the prostate 18 months or more following completion of therapy. Thirty‐nine (61%) of the biopsies were interpreted as positive and 25 (39%) as negative. Twenty‐eight (72%) of the 39 patients with a positive biopsy have subsequently developed metastases as compared to only 6 of 25 (24%) of the patients with a negative biopsy. It is concluded that an apparently positive postirradiation biopsy is likely to indicate active disease and identifies patients at a higher risk for development of metastases. Other details of staging, grading, and outcomes that compare these two groups are discussed.
International overview on the treatment of prostate cancer–scandinavian experience
Authors: Könyves I. , Andersson L.
Published: February 2007

The Scandinavian countries, especially Sweden and Norway, have a high incidence of prostate cancer. The tumor classification has been mainly uniform in recent years, according to the TNM system. Transrectal fine‐needle biopsy and cytologic malignancy grading were introduced in Sweden and were gradually accepted in other countries. The treatment of prostate cancer has been mainly conservative as it is in most parts of Europe. For a long period endocrine therapy was given in the vast majority of cases. In recent years radiotherapy has also been used in cancer of low differentiation with no evidence of dissemination. In poorly differentiated and disseminated disease, Estracyt is the standard therapy. Estracyt is also given in disseminated carcinoma nonresponsive to ordinary hormone therapy. In this category of patients other chemotherapy is the second therapeutic alternative. Various techniques of endocrine therapy, chemotherapy, and radical surgery are subject to controlled trials.
Surgical staging in carcinoma of the prostate: The RTOG experience
Authors: Pilepich M. V. , Asbell S. O. , Mulholland G. S. , Pajak T.
Published: February 2007

One hundred thirty‐six patients with carcinoma of the prostate entered on phase III RTOG studies (RTOG 75–06 and RTOG 77–06) between 1976 and the end of 1980 underwent staging lymphadenectomy prior to irradiation. The operative reports and histological findings have been reviewed in order to determine the patterns of intrapelvic tumor spread and to correlate the type of surgical procedure and the extent of lymphatic dissection with the incidence and type of postirradiation complications (primarily genital and lower extremity lymphedema). The surgical procedures were classified into three categories according to extent: 1) biopsy only, 2) limited (diagnostic) dissection, and 3) complete (therapeutic) dissection. The incidence of postirradiation lymphedema was found to be strongly dependent upon the extent of dissection. Patients undergoing limited (diagnostic) dissection followed by pelvic irradiation have a 25–30% risk of developing this debilitating complication. In patients undergoing complete (therapeutic) dissection followed by pelvic irradiation lymphedema has been observed in 66% of cases.
A mobile mass screening unit for prostatic disease
Authors: Watanabe Hiroki , Ohe Hiroshi , Inaba Tadashi , Itakura Yasuhiro , Saitoh Masahito , Nakao Masahiro
Published: February 2007

A mobile unit for mass screening of prostatic disease using transrectal ultrasonotomography was developed in December 1980. In the following years we screened 1,396 males over 55 years of age. We have detected 463 cases [33.2%] of benign prostatic hypertrophy [BPH] and eight cases [0.6%] of prostatic cancer. The detection rate of BPH and malignancy of the prostate was shown to be very high. Thus, the unit promises to be of value in preventative medicine projects for prostatic disease in Japan.
The use of radioactive 7α, 17α‐dimethyl‐19‐nortestosterone (mibolerone) in the assay of androgen receptors
Authors: Schilling Karen , Liao Shutsung
Published: February 2007

Tritiated 7α, 17α‐dimethyl‐19‐nortestosterone (DMNT; mibolerone), a synthetic androgen stable to metabolic conversion in the rat ventral prostate, is an excellent radioactive ligand for the quantitation and characterization of androgen receptors in prostate, liver, and cultured cells. DMNT is more receptor‐selective than 17α‐methyl‐17β‐hydroxy‐estra‐4,9,11‐trien‐3‐one (R1881); DMNT interacts with glucocorticoid and progestin receptors much less strongly than R1881. Unlike 5α‐dihydrotestosterone, DMNT does not bind tightly to testosterone‐estradiol binding globulin of human serum. The hydroxylapatite‐filter assay we employed can clearly distinguish between DMNT binding to androgen receptors of rat ventral prostate and interaction of DMNT with androgen binding protein of epididymides. The prostate cytosol (3H)DMNT‐receptor complex sediments in two forms (4 and 8 S) in a low salt medium. In 0.4 M KCl, both the prostate cytosol and nuclear (3H)DMNT‐receptor complexes migrated as 3–4 S components. The formation of both the cytosol and nuclear DMNT‐receptor complexes is inhibited by antiandrogens and 17β‐estradiol.
Action of prolactin in regressing prostate: Independent of action mediated by androgen receptors
Authors: Assimos Dean , Smith Cornelius , Lee Chung , Grayhack John T.
Published: February 2007

Hyperprolactinemia, achieved by grafting pituitaries under the renal capsule, has been shown to cause a delay in the rate of castration‐induced prostatic regression in rats. The mechanism of this prolactin action is not established, although it has been suggested that the action of prolactin in the rat prostate is mediated through the action of androgen. To explore the possibility that a small amount of residual endogenous androgen present in the prostate at the time of castration acts synergistically with prolactin to cause this delay in prostatic regression, Flutamide has been used in the present study in an attempt to inhibit this residual androgen effect by blocking its interaction with androgen receptors. Two experiments were conducted. In experiment 1, daily sc injections of Flutamide (25 mg/kg) for 7 days to castrated rats supplemented with dihydrotestosterone‐filled silastic tubing either 1 or 4 cm long completely suppressed both prostatic weight and protein content to the level that was normally observed in castrated rats receiving empty tubings. Furthermore, treatment of Flutamide to castrated rats did not cause an increase in prostatic weight and protein content over those of castrated rats treated with the vehicle only. These results indicate that Flutamide, at this dosage, is a potent antiandrogen and that the compound itself does not have any androgenic activity in the rat prostate. In experiment 2, adult male rats were castrated and received two female pituitaries grafted under the renal capsule. One week later, their serum prolactin levels increased from 20±3 ng/ml to 102±8 ng ml. This elevated level of serum prolactin was associated with a delay in the rate of prostatic regression. Administration of Flutamide, at a dose (25 mg/kg) which completely suppressed prostatic growth, failed to inhibit the delay in prostatic regression in castrated rats bearing the pituitary grafts. Since Flutamide inhibits the androgen action in the prostate by blocking the binding of intracellular dihydrotestosterone to androgen receptors, the failure of Flutamide to block the effect of prolactin suggests that the prolactin action in regressing prostates is not mediated by androgen receptors.
Effects of diethylstilbestrol and estramustine phosphate (estracyt) on natural killer cell activity and tumor susceptibility in male mice
Authors: Kalland Terje , Haukaas Svein A.
Published: February 2007

The effects of estramustine phosphate (EMP) and diethylstilbestrol (DES) on natural killer (NK) cell activity, tumor growth, and artificial metastases were investigated in male C57BL/6 mice. Kinetic analysis and studies at the single‐cell level indicated that EMP did not influence the number of NK cells but interfered with their lytic activity thereby reducing the actual killer capacity. NK cells from EMP‐exposed animals responded normally to the interferon inducer Poly I:C which restored NK activity to control levels. Spleen cells from DES‐treated animals had lytic activity comparable to that of control animals. However, more detailed analysis showed that DES reduced the number of lymphocytes able to recognize target cells, while the individual NK cell had an increased lytic activity and recycling capacity. Moreover, NK cells from DES‐treated animals were refractory to poly‐I:C stimulation, suggesting that they were prestimulated in vivo. The pertubations of the NK cell system induced by both EMP and DES were reversible and normalization of NK activity was reached within a week. The incidence of tumor takes after subcutaneous inoculation of the syngeneic Lewis lung carcinoma was increased in EMP as well as DES‐treated animals. Artificial lung metastasis produced by intravenous injection of the same tumor was increased in EMP but not in DES‐exposed animals.
Promotional effects of testosterone and dietary fat on prostate carcinogenesis in genetically susceptible rats
Authors: Pollard Morris , Luckert Phyllis H.
Published: February 2007

Germfree (GF) Lobund strain Wistar (LW) rats, fed vegetable diet L‐485, have developed prostate adenocarcinomas spontaneously (10% incidence) at average age 34 months. Conventional LW rats, implanted with testosterone at age 4 months, developed a higher incidence of prostate cancer after an average interval of 14 months: 24% had developed gross tumors, and 40% when it included microscopic tumors. Preliminary results indicate that testosterone‐treated LW rats that were fed the same diet, which was supplemented with corn oil up to 20% fat, developed prostate cancer after intervals of 6–12 months.

Aged GF Sprague‐Dawley (SD) rats have not developed prostate cancer spontaneously. Conventional SD rats fed diet L‐485 and treated with testosterone developed only prostatitis.

Experimental designs should consider genetic susceptibility as a basic prerequisite for studies on experimental prostate cancer.
Nutrition and prostate cancer: A case‐control study
Authors: Heshmat Martin Y. , Kaul Lalita , Kovi Joseph , Jackson Marvin A. , Jackson Aaron G. , Jones George W. , Edson Mitchell , Enterline John P. , Worrell Roger G. , Perry Sophie L.
Published: February 2007

This one‐to‐one, age‐ and race‐matched case‐control study involved 181 histologically confirmed black prostate cancer patients and 181 controls seen at three major hospitals in Washington, DC, during the period 1979–1982. Personal interviews were conducted to obtain the number of times food items of specified serving size were consumed per week by cases and controls during the age periods 30–49 and 50 years and older. Then the average daily consumption of each of 18 nutrients per 1,000 calories was calculated. There was risk enhancement associated with increased intake of proteins, total fat, saturated fat, oleic acid, and vitamin A during the age period 30–49 years. The association was highly significant for vitamin A and approached statistical significance for the other four nutrients. A hypothesis based on disturbance of the zinc‐retinol binding protein‐vitamin A axis was put forward to explain the relative risk enhancement effect of vitamin A on prostate cancer.
DHT in prostate cancer tissue— a guide to management and therapy
Authors: Geller Jack , Albert Jerry D.
Published: February 2007

In 24 untreated stage D2 prostate cancer patients with prostate DHT levels greater than 2.5 ng/g, 20 initially responded to therapy with partial objective progression (POR) or were objectively stable (OS) for 12 or more months while four patients relapsed in less than 1 year. Of eight patients with prostate DHT levels less than 2.0 ng/g, five had either objective progression or were objectively stable for 6 months or less; two other patients have completed remissions ranging from 16 to 24 months while one patient remains objectively stable for 21 months to date.

DHT concentrations were also measured in prostate tissue of patients with advanced prostate cancer in relapse following either DES or castration with or without estrogen therapy. Although castration, medical or surgical, usually leads to DHT concentrations of less than 2.4 ng/g, two out of 20 surgical castrates and four out of nine estrogen‐treated patients had values above this level. These differences suggest that (1) increased tissue DHT levels of DES‐treated patients may be due to inadequate dosage or decreased compliance, and (2) increased tissue DHT concentrations greater than 2.4 ng/g in castrates suggests an adrenal cortical androgen contribution to the prostate DHT level.

These studies suggest that DHT measurements in prostate cancer tissue are of value in predicting response in untreated prostate cancer patients and of directing therapy in patients who are in relapse after orchiectomy or estrogen therapy.
Efficacy of (D‐Leu6)‐Des Gly‐NH210‐LHRH ethylamide against prostatic cancer
Authors: Yamanaka Hidetoshi , Makino Takeo , Yajima Hisanori , Saruki Kazuhisa , Shida Keizo
Published: February 2007

Twenty‐two patients with prostatic cancer were treated for 12 to 52 weeks with the luteinizing hormone‐releasing hormone agonist, (D‐Leu6)‐des Gly‐NH210‐LHRH ethylamide (leuprolide). The clinical efficacy of leuprolide was evaluated at 12 weeks according to NPCP criteria. All seven patients with Stage B and C disease demonstrated a partial objective regression. The objective response rate in 12 previously untreated Stage D patients was 92% (partial regression: 5; stable disease: 6). In three relapsing Stage D patients, one demonstrated stable disease and two failed to respond to leuprolide therapy. Even though the dose of leuprolide used in this study was high, no serious side effects were observed in any patients. There was a large increase in serum FSH and LH levels during the first few days of treatment, but serum FSH and LH levels fell below the initial levels by 1 and 2 weeks, respectively. Serum testosterone fell to less than 1 ng/ml within 3 weeks, and at 12 weeks it was 7.99% of the initial level. The present study shows that chronic administration of leuprolide in high doses can safely and effectively reduce the level of serum testosterone in patients with prostatic cancer.
The effects of estradiol‐17β on the ultrastructure and subcellular distribution of zinc in the prostatic epithelium of castrated rats
Authors: Timms B. G. , Chandler J. A.
Published: February 2007

Male Sprague‐Dawley rats, previously castrated for a 7‐day period, were maintained on either a low or high dose of estradiol‐17β for 3 days. Some areas of the prostatic epithelium in the lateral lobe exhibited the ultrastructural characteristics of the untreated, intact animals in response to the small dose of estrogen. The ventral lobe by comparison was not similarly affected. This stimulation in the lateral prostate was not reflected by comparable changes in the subcellular distribution of zinc.
Identification of prostate and other cancers by two‐dimensional protein electrophoresis
Authors: Anderson Kenning M.
Published: February 2007

Some cancers are so undifferentiated as to preclude their identification, and this hinders selection of an appropriate therapy. The systematic analysis and cataloguing of electrophoresed proteins from identified cancers and their comparison with the protein patterns from histologically indeterminate cancers should provide a general means of identifying the latter.
Secretion of bromide by the canine prostate
Authors: Smith Emil R. , Ilievski Vladimir
Published: February 2007

Four dogs with surgically produced prostatic fistulas were given single oral doses of 1.13 gm of sodium bromide daily for five consecutive days. Two days later the mean (± SE) serum level of bromide was 28.0 ± 4.0 meq/L and the serum chloride level had decreased from a pretreatment value of 112.5 ± 1.0 meq/L to 86.5 ± 3.7 meq/L; in the basal prostatic secretion, the mean prostatic fluid to serum (PF/S) ratios for bromide and chloride were 0.56 ± 0.15 and 0.53 ± 0.11, respectively, and were not different (P > 0.05, paired t‐test); at higher rates of secretion provoked by intravenous pilocarpine the corresponding PF/S ratios of 1.48 ± 0.04 and 1.32 ± 0.01 were significantly different (P < 0.05, paired t‐test). It is concluded that the processes involved in forming the basal and pilocarpine‐induced prostatic secretions must differ and that the ability of the chloride‐transporting system to transport bromide is slightly greater than that for chloride. Because it may impair sperm motility, bromide secreted in prostatic fluid potentially could adversely affect reproduction.
Zinc and cadmium concentrations in whole tissue and in separated epithelium and stroma from human benign prostatic hypertrophic glands
Authors: Lahtonen Riitta
Published: February 2007

Prostate tissues from patients with benign prostatic hypertrophy were separated into epithelial and stromal components and the concentrations of zinc and cadmium were determined in these two fractions and in whole tissue by atomic absorption spectrophotometry. The concentrations of testosterone and 5α‐dihydrotestosterone (5α‐DHT) were determined by radioimmunoassays. The concentration of zinc was found to be significantly greater (P < .001) in epithelial than in stromal preparations: 17.32 ± 1.15 vs 7.29 ± 0.53 μmol/g dry weight (SEM, n = 15). The concentrations of cadmium in epithelium, 9.55 ± 1.31 μmol/g dry weight (SEM, n = 15) and in stroma, 6.65 ± 1.06 μmol/g dry weight (SEM, n = 15), did not differ significantly. The concentrations of zinc and cadmium in whole tissues were 13.88 ± 1.70 μmol/g dry weight and 8.85 ± 1.53 μmol/g dry weight, respectively (SEM, n = 15).

In epithelial preparations, cadmium and testosterone were inversely correlated, but no other correlations were noted between metal and androgen concentrations in whole tissue, stroma, or epithelium.

The results of the present study indicate that zinc preferably resides in the epithelium of human prostatic tissue, particularly in BPH, although the stroma also contains significant amounts of this metal. Cadmium appears to be more evenly distributed between the epithelium and stroma of prostatic tissue and previous findings of high cadmium concentrations in hypertrophic and carcinomatous prostatic tissue were not confirmed.
Nuclear androgen receptor content in biopsy specimens from histologically normal, hyperplastic, and cancerous human prostatic tissue
Authors: van Aubel O. G. J. M. , Bolt‐de Vries J. , Blankenstein M. A. , Kate F. J. W. , Schröder F. H.
Published: February 2007

Androgen receptors (ARn) were assayed in nuclear extracts of prostatic biopsies from 60 patients with benign prostatic hyperplasia (BPH) and 82 patients with prostatic cancer (PC), with an exchange assay using heparin extraction, labelling with 3H‐R1881, and protamine sulphate precipitation. The content of ARn of BPH biopsies (38 ± 34 fmol/mg protein [mean ± SD]; n = 70) was not different from that of PC biopsies (39 ± 32 fmol/mg protein; n = 115). Biopsies showing essentially normal prostatic tissue had a lower ARn content (12 ± 13 fmol/mg protein; n = 6). The content of ARn was independent of the age of the patient and of the histological grade of the carcinomas. A considerable variation in ARn content within tumors of individual patients was found, indicating that ARn are not uniformly distributed over prostatic tissue; ie, cells with high and low receptor content may coexist in different proportions in different regions of the prostate. Therefore, assays on multiple biopsies may be required for a proper estimation of the mean receptor content. The question remains, however, whether the behavior of the tumor is adequately predicted by the mean receptor level or, for instance, by the region with the lowest receptor content.
Inhibition of androgen metabolism in stroma and epithelium of the human benign prostatic hyperplasia by progesterone, estrone, and estradiol
Authors: Krieg Michael , Schlenker Arvid , Voigt Klaus‐Dieter
Published: February 2007

It has been shown that progesterone, estrone, and estradiol are present in significant amounts in the human benign prostatic hyperplasia (BPH). Therefore it was of interest to determine the inhibitory effect of these steroids on the 5α‐reductase and 3α(β)‐hydroxysteroiddehydrogenase (HSDH) activities, the enzymes responsible for the conversion of testosterone to 5α‐dihydrotestosterone (DHT), and DHT to 3α(β)‐androstanediols, respectively. The enzyme inhibition was analyzed in vitro by measuring the 5α‐reductase in the presence of either progesterone, estrone, or estradiol, using testosterone as substrate. The DHT was used as substrate for HSDH. The metabolites were quantified by t.l.c. The main results were as follows: (1) Concerning 5α‐reductase in BPH, the mean inhibitor constants (K1; μM) of progesterone, estrone, and estradiol were 0.11, 15.5, and 5.1, respectively. (2) Analyzing epithelium and stroma of BPH separately, the inhibition of 5α‐reductase resulted in nearly identical K1′S. (3) Concerning HSDH in BPH, the mean K1s of progesterone, estrone, and estradiol were 169, 63, and 192, respectively. (4) Analyzing epithelium and stroma of BPH separately, the inhibition of HSDH led to nearly identical K1′s. (5) The kinetic parameters (KM, Vmax) of the 5α‐reduction of progesterone and testosterone were nearly identical. These results led to the suggestion that the endogenous concentrations of progesterone, estrone, and estradiol have no significant inhibitory effect on the 5α‐reductase and HSDH in vivo. Furthermore, the nearly identical inhibitor constants found for both enzymes in epithelium and stroma of BPH indicate that in both compartments the 5α‐reductase and HSDH are qualitatively identical.
Tissue interactions and prostatic growth: II. Morphological and biochemical characterization of adult mouse prostatic hyperplasia induced by fetal urogenital sinus implants
Authors: Miller Gary J. , Runner Meredith N. , Chung Leland W. K.
Published: February 2007

Current hypotheses regarding the causes of human benign prostatic hyperplasia have implicated both steroid hormone imbalance and tissue interactions. To examine the role of the latter we have further investigated the phenomenon of urogenital sinus‐induced hyperplasia of the adult mouse ventral prostate. Urogenital sinuses (UGS) or purified urogenital mesenchyme (UGM) from C3H mice were implanted into the ventral prostates or coagulating glands of 50‐ to 90‐day‐old BALB/c‐nu/nu hosts. The animals were sacrificed at 15, 30, and 180 days postimplantation to establish time dependence. Wet weight and DNA content were used as measures of net growth. Glucose phosphate isomerase (GPI) isozyme analysis was used to determine the relative contributions of C3H and BALB/c cells to the enlarged chimeric ventral prostates. It was determined that the induced growth is time‐dependent and that the UGS induces 2‐ to 4‐fold more growth than UGM. GPI analysis shows that UGM‐induced growth was composed primarily of host‐derived cells whereas the UGS is composed nearly equally of host‐ and implant‐derived cells. Histologie analysis reveals that the UGS implants induce marked epithelial proliferation. The proliferating glands occur in clusters, and the epithelium within the glands appears cribriform. Foci of postobstructive cystic atrophy are also found. Remnants of the implanted UGS are still present even at 180 days postimplantation. UGM‐induced growth is of a more subtle nature and appears morphologically similar to the sham‐operated controls. In view of the morphologic similarity with human disease, as well as the time and hormonal dependence of UGS‐induced ventral prostatic hyperplasia, this model represents the basis for a unified hypothesis regarding the roles of tissue interaction and hormonal milieu in human benign prostatic hyperplasia.
Tissue polypeptide antigen (TPA) as a prognostic aid in human prostatic carcinoma
Authors: Lewenhaupt Arvid , Ekman Peter , Eneroth Peter , Nilsson Bo , Nordstrom Lennart
Published: February 2007

Serum levels of tissue polypeptide antigen (TPA) and prostatic acid phosphatase (PAP) in serum, the presence or absence of skeletal metastases, tumor grade, patient age, and erythrocyte sedimentation rate (ESR) were determined in 50 patients with prostatic adenocarcinoma before onset of any therapy. Crude survival rates were estimated for a 5‐year period after the time of diagnosis. The prognostic value was estimated by means of the log rank test and multivariate life table analysis. The TPA, PAP, tumor stage, and ESR all appeared to be useful as prognostic markers. Tumor grade and patient age were not significantly related to crude survival. The TPA proved to be the most reliable prognostic marker in single test estimates as well as in a multivariate life table analysis (p < 0.01).
Characterization of the heterogeneity of R3327 rat prostatic tumors derived from single‐cell clones
Authors: Thompson Sue Ann , Johnson Michael P. , Heidger Paul M. , Lubaroff David M.
Published: February 2007

Prostatic adenocarcinoma is characterized by cellular diversity, which is well demonstrated in the Dunning R3327 rat prostatic adenocarcinoma. This heterogeneity may arise from epigenetic influences, ie, cellular adaptation or selection, and/or from genetic changes. To investigate the question of genetic instability, four tissue culture cell lines were derived from single cells isolated from the uncloned late (UCL) passage of the Dunning R3327H prostate cell culture. Each of these clonally derived tissue cultures was injected into castrated and intact young adult male rats for tumor production. Uncloned early (UCE) and UCL passage tissue cultures were also propagated as solid tumors. Tumors and the cultures from which they were derived were examined for evidence of phenotypic and genetic changes using morphological and cytometric methods. Transmission and scanning electron microscopy revealed only slight differences among the cell cultures. A single population of diploid cells was demonstrated in each of the cell cultures by propidium iodide staining and subsequent flow cytometric measurement of DNA content/nucleus. Tumors of unicellular as well as multicellular origin exhibited extreme heterogeneity of histological features, both among animals as well as within a single tumor. Tumors were surveyed and tissue types were characterized and cataloged. Clone 3 was generally better differentiated than the others; tumors from castrated animals were better differentiated than those from intact animals. Flow cytometry revealed multiple hyperdiploid cell populations that were variable from one sample to another. We concluded that changes in genotype as well as phenotype occurred in the tumors derived from single cells. Some of these changes may have occurred in the cells while still in culture.
The antigenic relatedness of proteins from human and simian prostate fluid
Authors: Carter Donald B. , Timmins James G. , Adams Lonnie D. , Lewis Ronald W. , Karr James P. , Resnick Martin I. , Buhl Allen E.
Published: February 2007

Two‐dimensional electophoretic analysis of human prostate fluid reveals an abundant protein migrating to a molecular weight of 15 kD and an isoelectric point of 5.5. Polyclonal antibodies were raised specifically to microgram quantities of electrophoresed, excised, and eluted PSP15 (prostate secretory protein). Western immunoblot analysis using these antibodies showed they ot only react to PSP15, but cross‐react with simian prostate and human seminal fluid proteins of similar molecular weights. Two‐dimensional gel immunoblots strongly suggest that the seminal protein and PSP15 are the same, thereby providing a more accessible source of the protein. The antibody to the human PSP15 cross‐reacted with neither prostate fluid from the ventral lobe of the rat prostate nor the prostate fluid from the beagle dog.
The effect of 5α‐androstane‐3α, 17β‐diol and 17β‐estradiol on the adult and immature chacma baboon prostate
Authors: De Klerk Daniel P. , Human H. J. , De Klerk J. N.
Published: February 2007

We have studied the Chacma baboon prostate in an attempt to develop a primate model of benign prostatic hyperplasia. Anatomically, the baboon prostate can be divided into caudal, cranial, and prostatic urethral segments. A peri‐urethral group of glands has been identified in the prostatic urethra. Following treatment with either 5α‐androstane‐3α, 17β‐diol or 17β‐estradiol, or the hormones in combination, the mature baboon prostate showed very little response by gravimetric or morphometric analysis. In contrast, the stimulatory effect of 5α‐androstane‐3α, 17β‐diol on the caudal lobe of the immature baboon prostate and the prostatic urethral segment (a structure that is largely fibromuscular) was potentiated by the addition of 17β‐estradiol. The weight of the immature baboon cranial prostate was increased by 5α‐androstane‐3α, 17β‐diol treatment, but 17β estradiol did not potentiate androgen‐induced growth. By morphometric analysis it could be shown that both the epithelial and stromal component of the immature baboon caudal prostate responded to 5α‐androstane‐3α, 17β‐diol (androstanediol) treatment and that the addition of 17β‐estradiol had a slight, but significant, potentiating effect on the androstanediol‐induced increase of epithelial volume.
Long‐term follow‐up of patients with advanced prostatic carcinoma treated with either buserelin (HOE 766) or orchiectomy: Classification of variables associated with disease outcome
Authors: Koutsilieris Michael , Tolis George
Published: February 2007

We compared the clinical efficacy and safety of Buserelin treatment versus orchiectomy in 29 patients with newly diagnosed advanced prostatic cancer. There was no significant difference between the two treatment modalities in 1) reduction of plasma testosterone to below 100 ng/dl after 8 weeks, 2) objective clinical response rates in patients with stage D2 carcinoma, 3) induction of complete remission in patients with stages C and D1 carcinoma, or 4) relapse rates and death rates in patients with stage D2 carcinoma. After scoring stage D2 disease according to our aggressiveness analysis system, we found that patients with less aggressive neoplasms displayed a qualitatively better response and more prolonged remission. These data and the absence of estrogenic effects confirm Buserelin as a favorable alternative to orchiectomy in the treatment of prostatic cancer. Additionally, the study demonstrates the importance of considering the heterogeneity of the aggressiveness of stage D2 disease in assessing the benefits of clinical trials in prostatic carcinoma.
Cellular response to androgen depletion and repletion in the rat ventral prostate: Autoradiography and morphometric analysis
Authors: English Hugh F. , Santen Richard J. , Drago Joseph R.
Published: February 2007

The effect of androgen depletion/repletion on the cell types of the rat ventral prostate has been studied using light microscope autoradiography and morphometric analysis. All prostatic cells were assigned to one of the following groups: epithelial, endothelial, stromal (periacinar), or stromal (interacinar). With the exception of the latter group, the numbers of all other cell types were significantly reduced by androgen depletion (castration), and increased by repletion thereafter. During the repletion period, the labeling index of all cell types rose in parallel and peaked 72 hours postinitiation of androgen replacement. The size of the proliferating pool just prior to the peak day was determined. Forty‐five percent of the total prostatic cell population was found to be labeled. The epithelial cell group contained the greatest proportion of labeled cells, but significant percentages occurred in the other types. These results precisely define the temporal effects of androgen replacement on prostatic cell population dynamics in the castrate rat.
Immunoelectron microscopic demonstration of prostatic acid phosphatase in human hyperplastic prostate
Authors: Song Guo‐Xing , Lin Chin‐Tarng , Wu Jang‐Yen , Lam Kwok‐Wai , Li Chin‐Yang , Yam Lung T.
Published: February 2007

Immunoelectron microscopic studies were done on prostatic tissues obtained from patients with benign hyperplasia. Rabbit IgG‐peroxidase conjugate against purified human prostatic acid phosphatase band 2 (HPAP‐2) was used for studies. Under the light microscope, the columnar secretory epithelia of prostatic glands showed different intensity and distribution of immunostaining whereas the basal cells were unstained. Under the electron microscope, the secretory epithelial cells often showed electron‐dense reaction product in the Golgi apparatus and secretory vesicles and vacuoles, and only sparingly in the cisternae of nuclear envelope and rough ER. Sometimes, fusion of secretory vacuolar membrane and plasma membrane and discharge of the vacuolar contents into the extracellular space were noted. The surfaces of microvilli at the apical portion of the columnar epithelia and the lumen of the glandular acini always showed reaction product. These findings suggest that HPAP‐2 may be synthesized in the rough ER and transported to the Golgi apparatus where it is concentrated and transferred to the secretory vesicles and vacuoles. HPAP‐2 is finally discharged into the extracellular spaces through exocytosis, a secretory mechanism similar to that of other secretory proteins.