bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental health science research and human risk assessment
Authors: Olden Kenneth , Klein Jean‐Louis
Published: February 2007

Environmental health science research, with its focus on fundamental science and disease prevention, is important for the development of rational and cost‐effective public health and regulatory policies related to environmental protection. Environmentally related diseases are preventable, yet they impose a major burden on society in terms of human suffering and costs related to health care. Similarly, the expenditure of hundreds of billions of dollars for regulatory compliance is a major economic concern. There is considerable debate regarding current regulatory risk assessment practices for environmental agents. Implicit in all risk assessment schemes is the need to extrapolate from high‐exposure studies to low‐exposure situations and from known risks in rodents to probable risks in people. Both extrapolations are fraught with uncertainties. These uncertainties are accommodated in risk‐assessment schemes by the incorporation of arbitrary “safety factors” and other default approaches. Since these factors are not derived experimentally, they may overestimate or under estimate actual risks. Risk‐assessment methodology, its relevance to the human condition, and its use in protecting human health will greatly improve when our expanding knowledge of the basic biology of environmental effects is incorporated into toxicological testing and risk‐assessment schemes. Moreover, exciting opportunities now exist to advance our understanding of the environmental and genetic bases of many common diseases and to design effective prevention and interventi on strategies to combat their development. This report discusses some of the current opportunities and challenges.© 1995 Wiley‐Liss, Inc
Strain‐dependent differences in DNA synthesis and gene expression in the regenerating livers of C57BL/6J and C3H/HeJ mice
Authors: Bennett L. Michelle , Farnham Peggy J. , Drinkwater Norman R.
Published: February 2007

C3H/HeJ(C3H) mice are approximately 50‐fold more susceptible to liver‐tumor induction than C57BL/6J(B6) mice. This difference in susceptibility is a consequence of allelic differences in hepatocarcinogen sensitivity(Hcs) genes that control the growth of preneoplastic lesions in the liver. We have shown previously that these two strains differ in their responses to partial hepatectomy, which acts as a promoter of hepatocarcinogenesis in B6 mice but not in C3H mice. To determine whether there are also strain‐specific differences in normal regulation of hepatic growth, we compared liver regeneration in C3H and B6 mice at the levels of DNA synthesis and gene expression. Partial hepatectomy induced a cascade of controlled events resulting in the regeneration of the liver to its original mass 11 d after surgery. We observed a two‐fold greater level of DNA synthesis in C3H mice relative to B6 mice during the first peak of DNA synthesis, which occurred 35 h after hepatectomy in both strains. While the c‐fos transcript was readily induced in both strains, there was a reduction in the expression of the late response genes E2F1 and dihydrofolate reductase in the livers of B6 mice when compared with the expression of these transcripts in the livers of C3H mice. The differential regulation of E2F1 between B6 and C3H mice may indicate that the Hcs genes and E2F1 function in the same signal‐transduction pathway of normal growth control.© 1995 Wiley‐Liss, Inc
Integrated capacity, demand, and production planning with subcontracting and overtime options
Authors: Merzifonluoğlu Yasemin , Geunes Joseph , Romeijn H.E.
Published: February 2007

Models for integrated production and demand planning decisions can serve to improve a producer's ability to effectively match demand requirements with production capabilities. In contexts with price‐sensitive demands, economies of scale in production, and multiple capacity options, such integrated planning problems can quickly become complex. To address these complexities, this paper provides profit‐maximizing production planning models for determining optimal demand and internal production capacity levels under price‐sensitive deterministic demands, with subcontracting and overtime options. The models determine a producer's optimal price, production, inventory, subcontracting, overtime, and internal capacity levels, while accounting for production economies of scale and capacity costs through concave cost functions. We use polyhedral properties and dynamic programming techniques to provide polynomial‐time solution approaches for obtaining an optimal solution for this class of problems when the internal capacity level is time‐invariant. © 2007 Wiley Periodicals, Inc. Naval Research Logistics, 2007
Die Geschichte der Therapie von Fettstoffwechselstörungen. Verhältnismäßig kurz und spannend
Authors: Bernschneider‐Reif Sabine
Published: February 2007

Die Geschichte der effektiven Therapie der Fettstoffwechselstörungen, wie sie hier am Beispiel wesentlicher Wirkstoffgruppen dargestellt wurde, ist kurz und aus pharmaziehistorischer Sicht bislang wenig untersucht. Viele Wirkstoffe wurden bis in die jüngere Zeit angewandt, ohne dass man den Wirkmechanismus kannte. Der Überblick zeigt, dass erst durch eine enge interdisziplinäre Zusammenarbeit bahnbrechende Fortschritte erreicht werden konnten – die Klärung der pathophysiologischen Grundlagen war dabei so wichtig, dass zwei Nobelpreise vergeben wurden. Die Komplexität des Stoffwechselgeschehens und die vielfältigen Möglichkeiten, in dieses Einzugreifen bieten bis heute Raum für Neuentwicklungen, oft auch – wie etwa bei der Nikotinsäure – auf der Basis lange bekannter Substanzen. Die kritischen Diskussionen, die sich zu einer Reihe von Substanzen über die Jahrzehnte ergaben, machen diese Therapeutika auch wissenschaftshistorisch zu einem sehr interessanten Gebiet.
Pflanzliche ω3‐ und ω6‐Fettsäuren: Wissenswertes zu Pflanzenölen
Authors: Metzner Christine , Lüder Wolfgang
Published: February 2007

Die mehrfach ungesättigten Fettsäuren (PUFA) LA und ALA können vom menschlichen Organismus nicht synthetisiert werden und sind deshalb für ihn essenziell. Während der Schwangerschaft sind auch die ω6‐Polyalkenfettsäure AA und die ω3‐Polyalkenfettsäure DHA konditionell essenziell. Die längerkettigen PUFAs werden durch Elongation und Desaturation gebildet. Die Konversionsrate von ALA wird durch die Zufuhrmengen reguliert und liegt bei 5 bis 10 %. Dieser “Sicherheitsstoffwechsel” ermöglicht es, dass auch Menschen, die keinen Fisch essen, mit den längerkettigen Fischölfettsäuren EPA und DHA versorgt werden.

AA und EPA sind Precursoren der Eicosanoide der 6‐er‐ bzw. der 3‐er‐Reihe. Da beide PUFAs um die gleichen Enzymsysteme konkurrieren, führt eine Erhöhung der ALA‐ und/oder eine reduzierte LA‐Zufuhr zu einer verminderten endogenen AA‐Bildung, wodurch das entzündliche und thrombotische Risiko und in Folge das kardiovaskuläre Risiko gesenkt wird.

Entscheidend für die gesundheitsfördernden Effekte der pflanzlichen PUFAs ist das Verhältnis von ω6‐ zu ω3‐Polyalkenfettsäuren bzw. von LA zu ALA. Für gesunde Personen ist im Nahrungsfett ein LA‐/ALA‐Quotient = 5:1 und für Personen mit metabolischem Syndrom oder deren Einzelkomponenten sowie für Personen mit chronisch‐entzündlichen Erkrankungen von 4 bis 3:1 anzustreben. Pro Tag sollten ca. 2 g ALA (20 g Rapsöl) und 7 bis maximal 10 g LA mit der Nahrung zugeführt werden. Um diese Vorgaben zu erreichen, sind ALA‐reiche Pflanzenöle/Lebensmittel zu präferieren, beispielsweise Lein‐, Raps‐ und Walnussöl, Erdnüsse und Walnüsse. Aus ernährungsmedizinischer Sicht (Energieproblem durch Fettzufuhr) kann es erforderlich sein, ALA zu supplementieren. Den ALA‐Supplementen sollten antioxidative Substanzen (Vitamine E und C, Flavonoide) zur Verminderung der exogenen und endogenen Lipidperoxidation zugesetzt werden. Obwohl ALA in ca. 10 % zu länger kettigen Fettsäuren EPA konvertiert wird, ist trotzdem ein Verzehr von fetten Seefischen zweimal pro Woche oder ein Fischöl‐Supplement in Kapselform (maximal 1 g pro Tag) zu empfehlen; letzteres unter ärztlicher Kontrolle.
Grüner Tee gegen AIDS?
Authors: Schäfer Sandra , Golks Ilka , Müller Carolin , Hartung Andrea
Published: February 2007

Grüner Tee ist weltweit eines der am meisten konsumierten Getränke. Und er soll eine wahre Wunderwaffe sein gegen verschiedenste Krankheiten, darunter so prominente wie Krebs und kardiovaskuläre Erkrankungen. Kürzlich kam dann noch das Tüpfelchen auf dem “i” dazu: Er soll auch vor einer Infektion mit HIV schützen!
Attitudes to prenatal testing and termination of pregnancy for fetal abnormality: a comparison of white and Pakistani women in the UK
Authors: Hewison Jenny , Green Josephine M. , Ahmed Shenaz , Cuckle Howard S. , Hirst Janet , Hucknall Clare , Thornton Jim G.
Published: February 2007

Objectives

To compare the attitudes of women from two different ethnic backgrounds to prenatal testing for a range of conditions, and to see if “clusters” of attitudes to different conditions could be identified, for which prenatal testing might be offered as a package.

Methods

Four hundred and twenty white and Pakistani women living in the UK were surveyed about their attitudes to prenatal testing and termination for 30 different fetal conditions. All participants had recently had a baby.

Results

Pakistani women held more favourable attitudes to prenatal testing, but less favourable attitudes to termination than their white counterparts. Both groups were most in favour of termination for the same four conditions: anencephaly, trisomy 13 or 18, quadriplegia, Duchenne muscular dystrophy. The rank ordering of conditions was also similar. Only 4% of Pakistani and 2% of white women wanted no prenatal testing at all. Fewer than a quarter of participants would consider a termination of pregnancy for 85% of the conditions, but only 25% of Pakistani women and 6% of white women would consider termination for none of the conditions. More advanced statistical analyses were used to measure how closely associated the 30 conditions were in respondents' answers. These analyses identified a principal dimension, reflecting the overall perceived seriousness of the conditions, and a cluster of severely disabling conditions—anencephaly, trisomy 13 or 18, quadriplegia, Duchenne muscular dystrophy, and severe learning difficulties—which stood out from the rest. Even within this cluster there remained a considerable amount of individual variation.

Conclusion

Women in the study wanted to make up their own minds about the conditions that to them merited testing or termination. These findings have implications for obtaining informed consent. Copyright © 2007 John Wiley & Sons, Ltd.
Indomethacin decreases both prolactin binding and membrane fluidity of ventral and dorso‐lateral lobes of rat prostate gland
Authors: Dave Jitendra R. , Witorsch Raphael J.
Published: February 2007

The objective of these studies was to examine the effects of in vivo treatment with indomethacin, a prostaglandin synthesis inhibitor, on prolactin binding activity and fluidity in membrane preparations of rat prostate gland. Adult male rats were treated with vehicle or either of two doses of indomethacin (3.8 μg/g body weight or 7.5 μg/g body weight) every 8 hr for 1, 2, and 3 days. Indomethacin treatment decreased prolactin binding in rat ventral and dorso‐lateral lobes of prostate gland in a time and dose‐dependent fashion. In ventral prostate membranes the higher dose of indomethacin decreased prolactin binding by approximately 80% after 3 days of treatment. Prolactin binding to membrane preparations from dorso‐lateral prostate gland of control animals was 10% of that observed for ventral prostate and decreased to undetectable levels within 24–48 hr after the start of indomethacin treatment. Scatchard analysis of the prolactin binding of ventral prostate indicated that indomethacin treatment decreased the number of prolactin binding sites rather than the apparent affinity constant. Prostatic membrane fluidity was measured by a fluorescence polarization technique. Dorso‐lateral prostate membrane preparations were found to have a higher membrane fluidity than those observed for ventral prostate membranes. The effects of indomethacin on membrane fluidity paralleled that of prolactin binding. Both ventral and dorso‐lateral prostatic membrane fluidity decreased after indomethacin treatment in a time and dose‐dependent manner. These simultaneous effects of indomethacin on prostatic prolactin binding and fluidity suggest that these phenomena are interrelated and that prostaglandins are involved in the maintenance of prolactin receptors in vivo.
Studies on the structural basis of the heterogeneity of human prostatic and seminal acid phosphatases
Authors: Taga Eulazio M. , Moore D. Lane , Van Etten Robert L.
Published: February 2007

We studied possible causes of the electrophoretic heterogcncity of the acid phosphatase (EC 3.1.3.2) purified by affinity chromatography from human prostate and human seminal fluid. The isoelectric focusing pattern in polyacrylamide gel shows numerous bands in the pH range 4.0–5.2 and 5.5–5.9. Treatment with neuraminidaae under conditions shown to cause complete removal of sialic acid does not abolish the observed heterogeneity. Although there is a change of the more acidic forms to ones having more basic pI values, at least 4 distinct bands remain. Structural differences at thr amino terminal end can be ruled out as the cause of the remaining electrophoretic heterogeneity. Lysine is shown to be the amino terminal amino acid for both the prostatic and seminal fluid enzymes. The bequences of the first 23 amino acids are shown to be identical for the prostatic and seminal fluid acid phosphatases. The functional enzyme contains no metal ion but it can be stoichiometrically inactivated by cupric ion.
Evidence against a zinc binding peptide in pilocarpine‐stimulated canine prostatic secretions
Authors: Parrish Richard F. , Perinetti Enrique P. , Fair William R.
Published: February 2007

Pilocarpine‐stimulated canine prostatic secretions were subjected to gel filtration chromatography over Sephadex G‐100 and Bio Gel P‐4. Free zinc and the zinc in pilocarpine‐stimulated canine prostatic secretions were observed to elute in the same fractions from the Sephadex G‐100 column. In addition, Sephadex G‐100 chromatography could not resolve free zinc from the small peptide bacitracin. However, a column packed with Bio Gel P‐4 could resolve free zinc and bacitracin. When pilocarpine‐stimulated canine prostatic secretions were chromatographed over the Bio Gel P‐4 column, the major portion of the zinc eluted in the same fractions as did free zinc. No zinc was observed in the fractions where the small peptide bacitracin was found to elute. These results indicate that contrary to a previous report, zinc in pilocarpine‐stimualted canine prostatic secretions was not bound to an eight amino acid peptide, but, rather, behaved chromatographically like free zinc.
Epidemiologic observations from the American College of Surgeons' survey on prostate cancer
Authors: Mettlin Curtis , Natarajan Nachimuthu
Published: February 2007

Data on the incidence and mortality from prostate cancer are available in this country and others, but there are few sources of information relating to widely prevalent clinical practices. The long‐ and short‐term prostate cancer surveys conducted by the Commission on Cancer of the American College of Surgeons offer a system of assessing patterns of cancer patient care in a large number of hospitals in the United States. Data from the Surveillance, Epidemiology, and End Results (SEER) System indicate that at every age blacks experience greater rates of incidence and mortality than whites. Comparisons of modes of diagnosis reported for black and white patients for 1974 and 1979 from the American College of Surgeons surveys show little difference between these groups, indicating that the excess in incidence among blacks is not attributable to differential patterns of diagnosis. The survey results also indicate that white patients appear to have a slight survival advantage in stages B, C, and D. The lower survival appears to be the product of relatively advanced stage of the disease rather than the result of biologically more malignant nature of prostate cancer in the blacks.
Use of urinary hydroxyproline excretion as a tumor marker in diagnosis and follow‐up of prostatic carcinoma
Authors: Mooppan M. M. Unni , Kim Hong , Wang Jen C. , Tobin Mark S. , Wax Sandor H.
Published: February 2007

Urinary hydroxyproline/creatinine ratio was measured in 49 patients of prostatic carcinoma and 13 patients with benign prostatic hypertrophy, the latter group serving as controls. The results show that it is a very sensitive indicator of osseous metastases in prostatic carcinoma. The ratio was also measured in 18 patients of prostatic carcinoma with bony metastases before commencement of treatment and during treatment. The results show that the elevated pretreatment values were significantly reduced in those who responded to therapy whereas in nonresponders, the values remained high. Changes in urinary hydroxyproline appeared to reflect the nature of response to treatment better than other parameters.
Distribution of quinoline carboxylic acid derivatives in the dog prostate
Authors: Jensen Klaus M.‐E. , Madsen Paul O.
Published: February 2007

The distribution in the prostate of norfloxacin and rosoxacin, both quinoline carboxylic acid derivatives, was investigated in an experimental dog model. The concentrations in prostatic interstitial fluid (PIF) and prostatic secretion (PS) of both antimicrobials were lower than the corresponding plasma (P) concentrations, as might be expected for acidic compounds. Norfloxacin achieved significantly higher PS/P and PIF/P ratios than rosoxacin following intravenous infusion; there were no differences between the two drugs in the various tissue/plasma ratios. The concentrations of both norfloxacin and rosoxacin in PIF, PS, and urine were in the minimal inhibitory range for most gram‐negative pathogens causing bacterial prostatitis and urinary tract infections. Clinical trials may be warranted for both drugs.
Carcinoma of the prostate: Clinical and pathological staging and prognosis
Authors: Gibbons Robert P. , Elder Jack S. , Wheelis Roger F. , Correa Roy J. , Brannen George E.
Published: February 2007

Clinical and pathological staging furnishes valuable information upon which the clinician can base his treatment and compare results. Staging refinements occur as we learn inore about the natural history of the disease and thc efficacy of our treatment. We observed that clinical stage B patients with minimal (less than twice normal) elevation of the serum acid phosphatase have similar pathologic stage B (75%) and disease‐free survival rates following total prostatectomy as stage B patients with normal acid phosphatases.

Intraglandular crystalloids were found in 26% of clinical stage 8 patients treated by total prostatectomy, and none of this subgroup of patients has had a recurrence of disease.

Pathologic staging frequently confirms the presence of a greater extent of tumor than was clinically anticipated. In general, prognosis for patients with a small tumor mass will be more favorable than that for patients with a large tumor mass. Staging permits the estimation of prognosis of groups of patients with similar tumor burdens; however, the survival of an individual within any such group is unpredictable.
Radical prostatectomy with preservation of sexual function: Anatomical and pathological considerations
Authors: Walsh Patrick C. , Lepor Herbert , Eggleston Joseph C.
Published: February 2007

The technique for radical retropubic prostatectomy has been modified to avoid injury to the branches of the pelvic plexus that innervate the corpora cavernosa. The surgical procedure is based on an understanding of the anatomical relationships between the branches of the pelvic plexus that innervate the corpora cavernosa, the capsular branches of the prostatic vessels that provide the scaffolding for these nerves, and the lateral pelvic fascia. The modifications involve two steps in the procedure: 1) the incision in the lateral pelvic fascia is placed anterior to the neurovascular bundle, which is located dorsolateral to the prostate along the pelvic sidewall; 2) the lateral pedicle is divided close to the prostate to avoid injury to the branches of the pelvic plexus that accompany the capsular vessels of the prostate. Pathologic evaluation of 16 prostatic specimens removed by this modified procedure demonstrated no compromise in the adequacy of the surgical margins. Postoperative sexual function was evaluated in 12 men who underwent the procedure 2‐10 months previously. All have experienced erections and six have achieved successful vaginal penetration and orgasm. Of the six patients with sexual partners who have been followed 6 months or longer, five (83%) are fully potent. These data indicate that it is possible to cure localized prostatic cancer with surgery and maintain postoperative sexual function.
Prostate cancer and impotence
Authors: Zorgniotti Adrian W.
Published: February 2007

Impotence in patients is most probably age‐related in the untreated case. The therapy of prostate cancer presents many hazards to the retention of sexual function which should be obvious to most urologists. What is now apparent is that surgical treatment of the disease does not necessarily cause impotence in all who were potent before the start of treatment. Documentation during history taking is essential. Increased awareness of the increased chances of retaining potency by physicians and patients will lead to improved results.
Physicochemical characterization of the androgen receptor from hyperplastic human prostate
Authors: Murthy L. R. , Chang C. H. , Rowley D. R. , Scardino P. T. , Tindall D. J.
Published: February 2007

In this manuscript we have characterized the androgen receptor from human benign prostatic hypertrophied (BPH) tissue. BPH tissue was obtained fresh from surgery, ground, and frozen in liquid nitrogen. Tissue was homogenized in 10 mM Tes buffer (pH 7.4 at 25°C) containing 0.25 M sucrose, 20 mM Na2MoO4, 12 mM monothioglycerol, and 1.5 mM EDTA. Cytosol was labeled with (3H)‐R1881 (0.5–10 nM) ± a 100‐fold excess of R1881 and a 500‐fold excess of triamcinolone acetonide to identify specific androgen receptor sites. An exchange assay was developed, whereby maximum binding was achieved by raising the temperature to 30°C for 15 min. A high‐affinity binding protein was detected (Kd = 1.3 ± 0.8 nM) which had a binding capacity of 15 ± 7 fmol/mg protein. Binding was specific for androgens with the following Ki (nM) values: R1881 (0.09), dihydrotestosterone (6), testosterone (50), progesterone (92), estradiol (100), epitestosterone (860), and cortisol (> 1,000). Under high ionic conditions the sedimentation coefficient of the receptor was 4.1 S. Higher S values were not observed in the presence of the following protein inhibitors: leupeptin (20 or 150 μM), iodoacetamide (10 mM), DFP (5 mM), PMSF (1 mM), bacitracin (0.1 mM), antipain (0.1 mM), aprotinin (1 TIU/ml). Gel filtration analysis revealed a Stokes radius of 6.5 nm. These data indicate a Mr of 120,000 and a f/fo of 2.01. The receptor eluted from a chromatofocusing column at a pH of 6.8. The receptor bound to phosphocellulose and DNA cellulose after being heat‐treated for 15 min at 30°C. These results suggest that BPH tissue contains an androgen receptor which is similar to receptors in other androgen‐responsive tissues.
Heterogeneity of steroid binding sites in prostatic carcinoma: Morphological demonstration and clinical implications
Authors: Pertschuk Louis P. , Eisenberg Karen B. , Macchia Richard J. , Feldman Joseph G.
Published: February 2007

Prostatic neoplasms were studied for estrogen binding using four methods. Two employed fluorescent estrogen histochemical ligands, one was a new immunocytochemical technique using specific monoclonal antibodies to human estrophilin, and the last procedure was conventional biochemical dextran‐coated charcoal assay. Results indicated that the fluorescent ligands recognized closely associated but separate estrogen‐binding sites (putative type II sites) which in turn differed from the binding site measured biochemically. Studies with the monoclonal antibodies were nearly always negative, suggesting that prostatic estrogen receptor might vary antigenically from that present in breast and endometrium. Histochemical and biochemical androgen‐binding studies were also compared and showed a close association. In the prediction of hormonal response in advanced prostate cancer both showed high sensitivity and low specificity. The addition of estrogen‐binding data did not improve the predictive value of the androgen‐binding histochemical assay. However, combining results of the biochemical and histochemical androgen‐binding assays resulted in significant improvement of the specificity without loss of sensitivity, suggesting that there is a degree of positive interaction between the binding sites assayed by the two methods.
Effect of long‐term hyperprolactinemia on the prolactin receptor content of the rat ventral prostate
Authors: Blankenstein M. A. , Bolt Vries J. ‐De , Coert A. , Nievelstein H. , Schröder F. H.
Published: February 2007

The rat ventral prostate contains prolactin receptors, and during sexual maturation prolactin stimulates the growth of this gland. The aim of the present investigation was to evaluate whether prolactin is involved in the regulation of the number of its own receptor sites in the rat ventral prostate. To this end, the content of prolactin receptors was estimated in prostate membranes of control and chronically hyperprolactinemic rats both before and after in vitro desaturation with 4 M MgCI2. Hyperprolactinemia resulted in a 40% increase in the number of available prolactin receptors (P < 0.05). In vitro desaturation of receptors resulted in loss of 84% of protein and 36 ± 6% and 52 ± 6% of prolactin receptors from ventral prostate membranes of control and hyperprolactinemic rats respectively (P < 0.05). We have concluded that the rat ventral prostate membranes are not suited to in vitro desaturation of prolactin receptors with MgCI2. From the increase in the number of available prolactin receptors after hyperprolactinemia we have concluded that prolactin is involved in the regulation of the number of its own receptors in the rat ventral prostate.
Methods for monitoring canine prostate size: Internal and external caliper measurements
Authors: Berry Stephen J. , Sterner Raymond , Coffey Donald S. , Ewing Larry L.
Published: February 2007

A method has been developed that allows the generation of a three‐dimensional representation of the canine prostate from a pair of orthogonal radiographs. This information can be used to externally measure the length, width, and height of the prostate and from these results to calculate prostate weight. This externally estimated prostate weight is correlated closely (r = 0.90) with the actual prostate weight. The ability to generate an external caliper measurement of prostate weight will facilitate future studies of the effect of aging and hormonal manipulation on the canine prostate.
Reduction in prostatic concentration of endogenous dihydrotestosterone in rats by hyperprolactinemia
Authors: Lee Chung , Hopkins David , Holland James M.
Published: February 2007

Persistently high levels of circulating prolactin can be achieved in male rats when pituitaries from female donors are grafted under the renal capsule. Enhanced growth of the lateral prostate can be accomplished by an apparent synergistic effect of excess prolactin with subphysiologic doses of testosterone. To define this effect we measured the endogenous dihydrotestosterone (DHT) concentrations in rat prostate lobes. Twenty Sprague‐Dawley male rats (250 g) were castrated and given subcutaneous implants of silastic tubing filled with 1 cm of crystalline testosterone. Ten of these rats simultaneously received two pituitary grafts under the renal capsule. The remaining ten rats received intrarenal skeletal muscle grafts as controls. Four weeks later, the weight (mg ± SE) of the ventral and dorsal lobes were not significantly different between the two groups, while the lateral lobe was significantly (P < 0.01) heavier in rats with pituitary grafts (121.4 ± 7.5) than in controls (81.7 ± 10.4). Endogenous DHT in the tissue extracts was determined by radioimmunoassay following KMnO4 treatment to eliminate testosterone. The concentration of DHT (ng/g tissue ± SE) was significantly (P < 0.01) lower in the lateral prostate of graft‐bearing animals (4.40 ± 0.29) than in the controls (5.98 ± 0.34). These results indicate that, in the rat, hyperprolactinemia induced by pituitary grafts is associated with a heavier lateral prostate and a lower concentration of endogenous DHT in that tissue. These results also suggest that the action of prolactin in the rat prostate is not mediated through the action of androgen.
Epidemiological study of prostatic cancer by matched‐pair analysis
Authors: Mishina Teruo , Watanabe Hiroki , Araki Hirotaka , Nakao Masahiro
Published: February 2007

In 1976, we designed an original questionnaire, consisting of 111 questions, directed at the epidemiology of prostatic disease. A case‐control study by matched‐pair analysis was conducted on 100 controls matched for age within 1 year and for residence in the same prefecture. Patients with prostatic cancer were distinguished from the general population of men by the following characteristics: 1) belonging to middle or lower socioeconomical class, 2) marriage at a young age and a long married life, 3) precocity, 4) vigorous sexual life followed by a fall‐off of sexuality in later life, and 5) Western food habits. Based on analysis of results obtained in this case‐control study, a high‐risk group for prostatic cancer was outlined.
A search for differentiation markers in prostatic fluid components with two‐dimensional electrophoresis and multiple protein detectors
Authors: Johnson A. H. , Merchant D. J. , Norman J. , Bourgeois N. , Lee C.
Published: February 2007

Components of prostatic fluid resolved by two‐dimensional polyacrylamide gel electrophoresis were detected by dye, silver stain, and autoradiography. Five components identified by autoradiography were not recognized by the dye or silver stain. While labeled components were found in primary fractions of split ejaculates and seminal fluid in addition to prostatic fluid, they have not been found in tissue extracts of heterologous organs or human serum.
Selective osteoblast mitogens can be extracted from prostatic tissue
Authors: Koutsilieris M. , Rabbani S. A. , Goltzman D.
Published: February 2007

Extracts of human prostatic carcinoma and of human benign prostatic hyperplasia were found to exhibit mitogenic activity in freshly isolated rat osteoblasts, rat fibroblasts, and osteoblast‐derived osteosarcoma cells. This activity was markedly reduced by tryptic digestion of extracts, indicating its protein nature. Results of bioassay studies suggested that the prostatic material was different from a number of known growth factors. Analysis by reversed‐phase high performance liquid chromatography revealed that extracts contained mitogenic activity for osteoblasts that was distinct from fibroblast‐stimulating activity. Such osteoblast growth factors could form the basis of the skeletal osteogenic response to metastatic prostatic adenocarcinoma.
Concentrations of androgens in human benign prostatic hypertrophic tissues incubated for up to three days
Authors: Bolton Nicholas J. , Vihko Reijo , Lukkarinen Olavi
Published: February 2007

Twenty‐one samples of surgically removed benign prostatic hypertrophy (BPH) were brought to the laboratory either in an insulated container (ambient temperature) or on ice. They were cleaned and roughly minced at room temperature. In 18 cases, samples of up to 1 g were kept at various temperatures (4°C, c. 20°C, and 37°C) for up to 77 h; some were taken for storage (— 70°C) at the beginning and others at various times within this period. In three cases, portions of tissue were incubated in liquid medium in the absence and presence of testosterone. The concentrations of six androgens (testosterone, 5α‐dihydrostestosterone (5α‐DHT), 5α‐androstane‐3α,17β‐diol, androstenedione, 5α‐androstanedione, and androsterone) were measured by radioimmunoassays.

The results indicated that in conditions resembling those after death, the BPH tissue content of 5α‐DHT falls to a variable degree, while concentrations of 5α‐androstane‐3α,17β‐diol, 5α‐androstanedione, and androsterone increase. After 2 to 3 days, the 5α‐DHT concentrations remained greater than those reported previously from this laboratory (and others) in normal prostate tissue removed at autopsy.
Effects of androgen blockade with ketoconazole and megestrol acetate on human prostatic protein patterns
Authors: Liu Junda , Albert Jerry , Geller Jack
Published: February 2007

We studied the effects of megestrol acetate (MA) and ketoconazole (KC) on protein synthesis of epithelial and stromal cells of human prostate. Patients with benign prostatic hypertrophy (BPH) were treated with MA (160 mg/day) plus KC (1,200 mg/day) for 7 days. Prostate tissues obtained from transurethral resection (TURP) were separated into epithelial and stromal cells with 0.5% collagenase. The separated cells were incubated with L‐35S‐methionine in methionine‐free MEM at 37°C for 3 hr. The protein synthesis in both epithelial and stromal cells was significantly inhibited in the group treated with MA and KC when compared to a control group (p < 0.05). The proteins incorporated with L‐35S‐methionine were analyzed by SDS‐PAGE and autoradiography. The molecular weights of the epithelial and stromal proteins inhibited ranged between 35–55K.
Heterotransplantation of human prostatic tissue
Authors: Hymer W. C. , Chapman R. , Chu M. , Croghan G. , Dekker A. , Gardner W. , Kelsey R. C. , Killian C. , Kish R. , Papsidero L. , Rohrbaugh J. , Waisman J.
Published: February 2007

Pieces of human prostatic tissue (˜ 1 mm3) were encapsulated in XM‐50 Amicon hollow fibers and either implanted into the testis of an adult male rat or placed in culture. The protein synthetic capacity of such tissue pieces removed 1‐42 days later was monitored by TCA precipitation, SDS‐PAGE, and autoradiography. The results showed that tissue pieces retained their functional protein synthetic elements after this procedure. A newly developed solid‐phase enzyme immunoassay for human prostatic antigen (PA), described in this report, was used to monitor PA levels in the serum of the receipient host or culture media. In some instances PA was detected 1‐2 weeks postimplantation, a result that implies maintenance of functional secretory elements in vivo. Finally, morphology of tissue pieces 1‐2 weeks postimplantation sometimes showed the presence of ductal epithelia and stromal elements in distribution patterns typical of those seen in fresh biopsy samples. We conclude that the function and structure of prostatic tissue implanted intratesticularly compares favorably with that manintained in conventional explant culture. As such, the hollow fiber method offers promise for a new way of monitoring hormonal and/or chemotherapy testing of human prostatic tissue.
Combination therapy using polyamine synthesis inhibitor alpha‐difluoromethylornithine and adriamycin in treatment of rats carrying the dunning R3327 MAT‐LyLu prostatic adenocarcinoma
Authors: Shaw Michael W. , Guinan Patrick D. , McKiel Charles F. , Dubin Alvin , Rubenstein Marvin
Published: February 2007

Prostate cells of human and rat origin produce polyamines in high content, whose apparent functions relate to cellular proliferation and secretory activities. Formation is dependent on the enzyme ornithine decarboxylase (ODC) which is irreversibly inhibited by alpha‐difluoromethylomithine (DFMO). It has been postulated that pretreatment with DFMO may render cells more susceptible to subsequent chemotherapy. Copenhagen X Fischer F1 rats bearing the Dunning R3327 MAT‐LyLu prostatic adenocarcinoma were given DFMO or adriamycin (ADR), alone or in combination. Those receiving DFMO were continuously provided the drug ad libitum, in water (2.5 %), for the duration of the experiment, beginning 2 days prior to ADR administration. At intervals, tumor sizes were measured, animal survivals noted and comparisons made to nontreated, tumor‐bearing controls. The results indicate that ADR alone or in combination with DFMO significantly reduced tumor progression, but that only combination therapy significantly prolonged survivals. Decreased tumor progression produced by DFMO alone was not statistically significant. Differences produced with combined use were additive and suggest that DFMO may augment ADR chemotherapy.
Pretreatment plasma levels of testosterone and sex hormone binding globulin binding capacity in relation to clinical staging and survival in prostatic cancer patients
Authors: Haapiainen R. , Rannikko S. , Alfthan O. , Adlercreutz H.
Published: February 2007

Pretreatment plasma concentrations of total testosterone (T), sex hormone binding globulin binding capacity (SHBG), T/SHBG ratio, and free testosterone (fT) were measured in 123 patients with prostatic cancer categorized into groups according to the UICC classification. The patients were randomized to orchiectomy or estrogen therapy and the mean follow‐up time was 48 months. The mean plasma levels of T were higher in patients without metastases and with intracapsular cancer, but the differences were not statistically significant. The calculated ratio of T/SHBG was noticed to be significantly higher (p < 0.05) in the M0 category. The prognostic significance of pretreatment T and, more impressively, T/SHBG ratio and fT was confirmed. Low pretreatment values indicated poorer prognosis. This study supports the view that there are differences in the pretreatment T and fT levels in prostatic cancer patients in relation to the stage of tumor and that these hormone assays could be used as prognostic factors.
An immunohistochemical technique for localization and semiquantitation of estramustine‐binding protein (EMBP) in rat and human prostate
Authors: Bichler Karl‐H. , Flüchter Stephan H. , Nelde Hans J. , Björk Per , Müntzing Jonas
Published: February 2007

An immunohistochemical technique for determination of “estramustine‐binding protein” (EMBP) in rat prostate is described. The localization and staining intensity of this protein were correlated to prostatic morphological structures in intact animals and at different time intervals after androgen deprivation by castration. EMBP was found almost exclusively in epithelial cells, while the fibromuscular stroma seemed to be negative. Intracellularly, immunostaining was confined to the cytoplasm, but was absent in nuclei. In intact rats, acinar lumina demonstrated heavy immunostaining, indicating secretion of EMBP. Orchiectomy caused a diminution of EMBP expression as well as secretion, suggesting that EMBP synthesis is under androgenic regulation.

Human benign hyperplastic and cancerous prostatic specimens were also examined. All human specimens examined so far exhibited positive epithelial staining although of varying intensity. Therefore, this immunohistochemical technique may be used for studying the correlation of EMBP with tumor malignancy grade and for clinical investigations of how various treatments affect EMBP expression in prostatic carcinomas.
Single‐drug parenteral estrogen treatment in prostatic cancer: A study of two maintenance‐dose regimens
Authors: Stege Reinhard , Carlström Kjell , Collste Lars , Eriksson Ambjörn , Henriksson Peter , Pousette Åke , von Schoultz Bo
Published: February 2007

Treatment of 17 patients with prostatic cancer with 320 mg polyestradiol phosphate (PEP) as intramuscular injections every fourth week suppressed serum testosterone (T) values to orchidectomy levels within 1 month, and serum estradiol‐17β (E2) rose to a mean level of 2,456 pmol/liter after 6 months. Following 6 months of treatment, the PEP dose was reduced to 80 mg/4 weeks in 9 and 160 mg/4 weeks in eight patients. Mean T levels increased significantly after dose reduction in both groups and were above the upper orchidectomy limit at 1 month after dose reduction in the 80 mg group. Mean T levels, however, remained below this level at 5 months in the 160 mg group. Dose reduction caused a rise in gonadotropin levels in the 80 mg but not in the 160 mg group. While 320 mg/4 weeks may be a suitable initial dosage, doses ≪ 160 mg/4 weeks are insufficient as maintenance dosages if orchidectomy values of T are required.
Effect of DMSO and DFMO on rat prostate tumor growth
Authors: Carvalho Luciano , Foulkes Kathleen , Mickey Don D.
Published: February 2007

An anaplastic, metastatic subline of the Dunning rat tumor was exposed to non‐cytodestructive doses of the cellular differentiation agents dimethylsulfoxide and difluoromethylornithine. Copenhagen rats hosting prostate tumors were evaluated by comparing solid tumor growth resulting from injection of treated cells with solid tumor growth of untreated control cells. Results showed significantly slower solid tumor growth after a 15 day in vitro exposure of cells to either agent, after oral treatment of host animals for 20 days with either agent before injection of untreated tumor cells, and after oral treatment of host animals with either agent initiated on the day of untreated tumor cell injection. Treatment of animals with established tumors with either agent also had an inhibitory effect on tumor growth, and the effect was related to the length of treatment.

Thus, exposure of these highly malignant rat prostate carcinoma cells to non‐cytotoxic doses of either agent induced slower tumor growth rates. Treatment with either agent could have selected for a slower growing population of tumor cells. Since a slowing of cell cycle transit times is an early indicator of cellular differentiation, these results could reflect an increase in the capacity of the malignant cells to differentiate.
Morphodynamic and biochemical assessment of seminal plasma in patients who underwent local prostatic hyperthermia
Authors: Rigatti Patrizio , Buonaguidi Arturo , Grasso Marco , Lania Caterina , Montorsi Francesco , Colombo Renzo , Galli Laura , Guazzoni Giorgio
Published: February 2007

Fourteen young and sexually active patients with chronic abacterial prostatitis who failed to respond to conventional medical therapy underwent four 60 minute sessions of local prostatic hyperthermia. Calculated prostatic temperature was 42 ± 0.5°C. Analysis of seminal plasma was performed pre‐ and postoperatively and included: number, motility, and morphology of spermatozoa; zinc, citric acid, D‐fructose, and free testosterone content. Pre‐operative semen analysis was normal in five patients and abnormal in nine. Morphodynamic and biochemical patterns of seminal plasma were not significantly altered by thermotherapy. Local prostatic hyperthermia can be safely used in patients with chronic abacterial prostatitis not responding to conventional medical therapy and desiring to preserve their reproductive potential.
Flow cytometric analysis of localized adenocarcinoma of the prostate: The use of archival DNA analysis in conjunction with pathological grading to predict clinical outcome following radical retropubic prostatectomy
Authors: Ring Kenneth S. , Karp Frieda S. , Olsson Carl A. , O'Toole Kathleen , Bixon Ronda , Benson Mitchell C.
Published: February 2007

Fifty‐four specimens from patients undergoing radical prostatectomy for clinically confined prostate cancer between 1983 and 1987 were reviewed to determine the potential for flow cytometric (FCM) analysis of DNA ploidy and replication rate to predict disease recurrence. Each specimen was deparaffinized for FCM analysis and the pathology slides were reviewed by a single pathologist. FCM characteristics were correlated with pathological grade and stage, and both were correlated with disease status. In this series of patients, routine FCM analysis of DNA ploidy and replication rate failed to significantly enhance the ability of standard histopathological grading to predict disease recurrence in patients having clinically localized prostate cancer. Aneuploid tumors pathologically confined to the prostate did not appear to negatively affect prognosis.
Morphologic and biochemical alterations in rat prostatic tumors induced by fetal urogenital sinus mesenchyme
Authors: Chung Leland W. K. , Zhau Haiyen E. , Ro Jae Y.
Published: February 2007

Because fetal urogenital sinus mesenchyme (UGM) has been found to be highly inductive when recombined with normal adult prostate tissues or normal and neoplastic bladder epithelium, we investigated whether fetal UGM also interacts with established hormone‐responsive and unresponsive rat Dunning and Nb prostate tumors. Our results indicate that: 1) fetal UGM acts directly on selected rat prostatic tumors by inducing histomorphologic changes (e.g., inducing acinar ductal structures and secretory activity) in the tumors toward more differentiated forms resembling that of the adult prostate gland; 2) fetal UGM either increased the growth rate of or maintained the sizes of three of the four interacting rat prostatic tumors; and 3) fetal UGM markedly reduced the lactate dehydrogenase activity of Nb‐autonomous tumor toward a level comparable to that of the normal rat prostate gland. Our data suggest that fetal UGM can directly affect the growth and differentiative functions of selected rat prostatic tumors.
Involvement of vitronectin and of a natural extracellular matrix in prostatic cell to cell contact and interaction with the substratum in culture
Authors: Chevalier Simone , Chapdelain Alcide
Published: February 2007

The kinetics and regulation of attachment, the spreading and initial growth of canine prostatic epithelial cells in primary monolayers, as well as the ability of the cells to produce a natural extracellular matrix (nECM) have been studied. Within 1 day of culture, attachment without spreading occurred in uncoated dishes while spreading was observed in nECM‐coated dishes. The attachment was stimulated by dialyzed fetal bovine serum (dFBS) and/or by the nECM and was not affected by the presence of cycloheximide at 10−6 M. This effect of dFBS on attachment was maximal at a concentration of 10% and increased with cell density and was mainly attributed to vitronectin as demonstrated by gel filtration, selective adsorption of serum proteins to the substratum, and indirect immunofluorescence of prostatic epithelial cells incubated with a rabbit antiserum against bovine vitronectin. Dog serum reduced attachment while bovine serum albumin, phenol red, and steroids were inactive. The maximal effect of the nECM on attachment was observed with matrices produced by canine prostatic epithelial cells cultured in the presence of dog serum for more than 10 days. As revealed by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis, several proteins of relative mass (Mr) of 210, 113, 61, 56, 52, 49, 45, and 42 kDa remained in the dish following nECM denudation and could be responsible for its effect on attachment. Their deposition as well as intercell adhesion and cell‐to‐substratum interactions required an active protein synthesis plus non‐steroidal serum components. Once attached and spread in primary monolayers, prostatic epithelial cells divided by the 3rd to 4th day; their growth, stimulated by dFBS at an optimal concentration of 20%, was inhibited by cycloheximide while the nECM was inactive. Thus, vitronectin in serum and the nECM synthesized by canine prostatic epithelial cells are responsible for the attachment and spreading of homologous cells to an in vitro substratum; nECM proteins also contribute to cell‐to‐cell contact and cell‐to‐substratum interaction in the monolayers.