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| 2. |
- Agardh, Carl-David, et al.
(författare)
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Influence of treatment with diethylstilbestrol for carcinoma of prostate on platelet aggregation and plasma lipoproteins
- 1986
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Ingår i: Urology. - : Elsevier BV. - 1527-9995 .- 0090-4295. ; 28:6, s. 469-471
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of prostatic carcinoma with estrogens is accompanied by an increased risk for thromboembolic and cardiovascular complications. The underlying mechanisms are still unknown. Patients treated with diethylstilbestrol (DES) were compared with patients given no estrogen treatment regarding factors (platelet aggregation in vitro and plasma lipoproteins) that have been suggested to contribute to increased thrombogenesis and cardiovascular risk. The results do not show any increase in in vitro platelet aggregation in patients treated with DES compared with those given no treatment. This indicates that hyperaggregability does not contribute to the increased incidence in thromboembolic events seen in DES-treated patients. This is in contrast to the increased platelet aggregation previously described in patients treated with polyestradiolphosphate + etinylestradiol. The changes in plasma lipoproteins observed during DES-treatment are generally considered beneficial from an atherogenic point of view and do not appear to cause the elevated incidence of cardiovascular disease in these patients.
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| 3. |
- Andersson, Karl-Erik, et al.
(författare)
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Pharmacologic perspective on the physiology of the lower urinary tract
- 2002
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Ingår i: Urology. - : Elsevier. - 0090-4295 .- 1527-9995. ; 60:5 Suppl 1, s. 13-20
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Tidskriftsartikel (refereegranskat)abstract
- Myogenic activity, distention of the detrusor, and signals from the urothelium may initiate voiding. In the bladder, afferent nerves have been identified not only in the detrusor, but also suburothelially, where they form a plexus that lies immediately beneath the epithelial lining. Extracellular adenosine triphosphate (ATP) has been found to mediate excitation of small-diameter sensory neurons via P2X3 receptors, and it has been shown that bladder distention causes release of ATP from the urothelium. In turn, ATP can activate P2X3 receptors on suburothelial afferent nerve terminals to evoke a neural discharge. However, most probably, not only ATP but also a cascade of inhibitory and stimulatory transmitters and mediators are involved in the transduction mechanisms underlying the activation of afferent fibers during bladder filling. These mechanisms may be targets for future drugs. The central nervous control of micturition involves many transmitter systems, which may be suitable targets for pharmacologic intervention. gamma-Aminobutyric acid, dopamine, enkephalin, serotonin, and noradrenaline receptors and mechanisms are known to influence micturition, and potentially, drugs that affect these systems could be developed for clinical use. However, a selective action on the lower urinary tract may be difficult to obtain. Most drugs currently used for treatment of detrusor overactivity have a peripheral site of action, mainly the efferent (cholinergic) neurotransmission and/or the detrusor muscle itself. In the normal bladder, muscarinic receptor stimulation produces the main part of detrusor contraction, but evidence is accumulating that in disease states, such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, and interstitial cystitis, as well as in the aging bladder, a noncholinergic activation via purinergic receptors may occur. If this component of activation is responsible not only for part of the bladder contractions, but also for the symptoms of the overactive bladder, it should be considered an important target for therapeutic interventions.
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| 4. |
- Angelopoulou, Katerina, et al.
(författare)
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Characterization of the BRCA1-like immunoreactivity of human seminal plasma
- 1999
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Ingår i: Urology. - 0090-4295. ; 54:4, s. 753-762
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. The subcellular localization of the breast cancer susceptibility gene product BRCA1 has been controversial. Discrepant results have been reported during the past 3 years, partially because of the unavailability of highly specific reagents for BRCA1 protein. Our objective was to characterize the BRCA1-like immunoreactivity that is detected in human seminal plasma by using monoclonal and polyclonal antibodies that are supposedly specific for BRCA1 protein. Methods. We used immunologic, chromatographic, and protein sequencing techniques to detect the immunoreactivity of BRCA1 in seminal plasma and to purify and partially identify the immunoreactive species. Results. We present data indicating that two BRCA1 antibodies, SG-11 and D-20, which were thought to be free of cross- reactivities, strongly interact with proteins present in human seminal plasma. This crossreactivity is detectable even at seminal plasma dilutions as high as 106-fold, and it is effectively blocked by peptides that capture the binding site of either SG-11 or D-20 antibodies. Purification and characterization of the immunoreactive compound revealed that this consists of a macromolecular complex that contains semenogelins. The D-20 polyclonal antibody was found to cross-react with purified semenogelins I and II; the SG-11 monoclonal antibody appeared to recognize a component of the macromolecular complex that was not semenogelin. Conclusions. Our data demonstrate that the BRCA1 antibodies SG-11 and D-20 strongly interact with seminal plasma proteins and are not highly specific for BRCA1 protein. It is thus suggested that BRCA1 antibodies should be used with caution until reagents free of interference are developed and evaluated. In light of the very high cross-reactivity of the two antibodies with seminal plasma proteins, we recommend that new BRCA1 antibodies should be examined for cross-reactivity with seminal plasma proteins to verify specificity.
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| 5. |
- Baert, L, et al.
(författare)
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Clinical Fluorescence Diagnosis of Human Bladder-carcinoma Following Low-dose Photofrin Injection
- 1993
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Ingår i: Urology. - : Elsevier BV. - 1527-9995 .- 0090-4295. ; 41:4, s. 322-330
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Tidskriftsartikel (refereegranskat)abstract
- A point-monitoring fluorescence diagnostic system based on a low-energy pulsed laser, fiber transmission optics, and an optical multichannel analyzer was used for diagnosis of patients with bladder malignancies. Twenty-four patients with bladder carcinoma, carcinoma in situ, and/or dysplasia were injected with hematoporphyrin derivative, Photofrin, 0.35 or 0.5 mg/kg body weight, forty-eight hours prior to the investigation. The ratio between the red sensitizer emission and the bluish tissue autofluorescence provided excellent demarcation between papillary tumors and normal bladder wall. Certain cases of dysplasia also could be differentiated from normal mucosa. Benign exophytic lesions such as malakoplakia appeared different from malignant tumors in fluorescence. Flat suspicious bladder mucosa such as seen in infectious diseases or after radiation therapy appeared normal on fluorescence.
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| 6. |
- Björk, Thomas, et al.
(författare)
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Alpha 1-antichymotrypsin production in PSA-producing cells is common in prostate cancer but rare in benign prostatic hyperplasia
- 1994
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Ingår i: Urology. - : Elsevier BV. - 1527-9995 .- 0090-4295. ; 43:4, s. 427-434
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE. To investigate the distribution and production of alpha 1-antichymotrypsin (ACT) and prostate-specific antigen (PSA) in benign hyperplastic and malignant prostatic tissue, respectively. METHODS. Using monoclonal anti-ACT and anti-PSA IgGs for immunocytochemistry and alkaline phosphatase conjugated 30-mer oligodeoxynucleotide probes for nonradioactive in situ hybridization, tissue specimens were studied from 15 patients with benign prostatic hyperplasia after transurethral resection of the prostate (TURP) and from 9 patients with bladder cancer who underwent cystoprostatectomy. Cancer specimens were from 23 TURP patients and from ultrasound guided core biopsies in 14 patients. Prostate tumors were graded according to the Gleason system. RESULTS. We found no or only occasional small foci of immunostaining for ACT, and no ACT transcripts in the PSA-producing epithelium in areas with benign nodular hyperplasia. By contrast, a high proportion of cells expressed both ACT and PSA in prostate cancers with low Gleason score, as detected by immunocytochemistry and in situ hybridization. Poorly differentiated tumor cells manifested greater variation in immunostaining for both ACT and PSA. As compared to tumors of low Gleason score, high-score tumors less frequently manifested immunostaining for ACT than for PSA, and less frequently generated hybridization signals for both PSA and ACT transcripts. CONCLUSIONS. A significantly higher proportion of serum PSA has been reported to be complexed to ACT in patients with prostate cancer than in patients with benign prostatic hyperplasia. The presently reported lack of ACT production in PSA-containing BPH nodules may contribute to this by making conditions less optimal for complex formation between PSA and ACT. As opposed to this, production of both ACT and PSA in prostate cancers may enhance the complex formation between PSA and ACT.
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| 7. |
- Bratt, O, et al.
(författare)
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Sons of men with prostate cancer : their attitudes regarding possible inheritance of prostate cancer, screening, and genetic testing
- 1997
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Ingår i: Urology. - 0090-4295. ; 50:3, s. 5-360
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study attitudes regarding possible inheritance of prostate cancer among sons of men with prostate cancer.METHODS: A questionnaire was sent to 69 men with prostate cancer and their 101 unaffected sons. All participants were also interviewed by telephone. Sociodemographic data were collected, as were data about the fathers' disease.RESULTS: The response rate was high; 100 sons (99%) and 65 fathers (94%) answered all questions. Sixty of the sons claimed they had worries about having an increased risk of prostate cancer due to possible inheritance. About 90% of the sons wanted to know whether prostate cancer was inheritable (66 definitely and 24 probably), were positively inclined to undergo screening (65 definitely and 27 probably), and to undergo genetic testing (50 definitely and 41 probably), provided there had been multiple cases of prostate cancer in their family. An interest to know whether prostate cancer could be inherited was more frequent among sons with less than 12 years of education, worries about inheritance, younger age, a father treated with curative intent, and with children of their own, especially if sons. Interest in genetic testing was associated with less than 12 years of education and with worries about inheritance.CONCLUSIONS: A large majority of healthy men with a family history of prostate cancer were interested in knowing whether the disease could be inherited and were positively inclined to undergo screening and genetic testing. Our findings indicate that genetic counseling and a screening program could have beneficial psychological effects in families with multiple cases of prostate cancer.
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| 8. |
- Iwamura, Masatsugu, et al.
(författare)
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Alteration of the hormonal bioactivity of parathyroid hormone-related protein (PTHrP) as a result of limited proteolysis by prostate-specific antigen
- 1996
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Ingår i: Urology. - 0090-4295. ; 48:2, s. 317-325
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To discover whether the proteolytic activity of prostate- specific antigen (PSA) affects the structure and function of parathyroid hormone-related protein (PTHrP), as both are abundant components of human seminal plasma. Methods. The ability of PTHrP to act as a substrate was studied by incubating a synthetic polypeptide, consisting of 34 amino acid residues of the amino-terminal domain of PTHrP, with purified PSA. The incubate was then analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, high-pressure liquid chromatography separation, amino- terminal peptide sequencing, and mass spectrometry. The physiologic effect of the proteolytic activity of PSA on PTHrP was studied by measuring any alteration in PTHrP (1-34)-induced elevation of cyclic adenosine monophosphate (cAMP) production by UMR-106 rat osteosarcoma cells in culture. All cell culture experiments were performed with PSA and PTHrP (1-34) at physiologic concentrations. Results. Our data show that PSA proteolytically cleaves PTHrP (1-34) after either residue 22 or 23, generating three peptide fragments. Both cleavages occur carboxy terminally of a phenylalanine residue. The cAMP production in rat osteosarcoma cells, induced by the amino- terminal portion of PTHrP (1-34), as a result of its structural similarity with parathyroid hormone (PTH), was abated by PSA in a dose- and time- dependent fashion. In contrast, heat-inactivated PSA had no effect on cAMP production. Conclusions. Our study demonstrates that PTHrP is a substrate for PSA. The cleavage of the amino-terminal portion of PTHrP completely disrupts its ability to interact with the PTH/PTHrP receptor and thus inhibits its PTH-like activity. The proteolytic processing of PTHrP by PSA may play an important role in the post-translational/post-secretional regulation of prostatic PTHrP activities, which are believed to include regulation of prostate growth and differentiation.
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| 9. |
- Jacobsen, Steven J., et al.
(författare)
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Comparability of the tandem-R andIMx assays for the measurement of serum prostate-specific antigen
- 1994
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Ingår i: Urology. - 0090-4295. ; 44:4, s. 512-518
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Tidskriftsartikel (refereegranskat)abstract
- Objectives.: To assess the comparability of the Tandem-R and IMx serumprostate-specific antigen (PSA) assays across levels of the ratio of free-to-total serum PSA found in a community-based population of healthy men. Methods.: Banked serum samples from the baseline component of the Olmsted CountyStudy of Urinary Symptoms and Health Status Among Men were thawed and analyzed using the Tandem-R and IMx PSA assays. Serum levels also were determined for the free, noncomplexed form of PSA, PSA complexed to alpha-1 antichymotrypsin, and total PSA with a research-based immunofluorometric assay. Results.: The results of the Tandem-R and IMx assays were strongly correlated at alllevels of the ratio of free-to-total serum PSA. The Spearman correlation coefficients ranged from 0.87 to 0.98 (all p < 0.001). The relationship between the Tandem-R and IMx assays, however, differed at low levels of free-to-total serum PSA compared with high levels. In the lowest 10th percentile of the ratio of free-to-total serum PSA (0.04 to 0.18), the IMx assay read lower than the Tandem-R (slope ± standard error = 0.92±0.04, intercept ± standard error = 0.21 ± 0.14); whereas in the upper 10th percentile of free-to-total ratio (0.46 to 0.65) the IMx assay yielded values higher than the Tandem-R assay (slope = 1.21 ± 0.07, intercept = 0.14 ± 0.05). In the middle 90%, the slope did not statistically differ from 1.0. Conclusions.: For the majority of men, results of the Tandem-R and IMx PSA assays were virtually identical. The small differences found would not be of clinical significance for most men but should be considered when comparing results of different assays in sequential determinations for a specific man.
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| 10. |
- Jacobsen, Steven J., et al.
(författare)
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Stability of serum prostate-specific antigen determination across laboratory, assay, and storage time
- 1995
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Ingår i: Urology. - 0090-4295. ; 45:3, s. 447-453
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To understand the comparability of serum prostate-specific antigen (PSA) determinations across assays and storage time. Methods: Serum PSA levels were determined for men aged 40 to 79 years from the clinical subset of the Olmsted County Study of Urinary Symptoms and Health Status Among Men on fresh samples and after a median of 32 months on banked samples, frozen at -70 °C. Baseline serum PSA levels were determined by Tandem-R PSA assay. Follow-up levels on the banked samples were determined by the IMx PSA assay and a repeat Tandem-R PSA assay in a different laboratory and by an immunofluorometric PSA assay at another site. Results: The median serum PSA level determined by Tandem-R assay at baseline was 1.0 ng/mL (25th percentile, 0.6; 75th percentile, 1.7). The distributions of determination made by follow-up Tandem-R, IMx, and immunofluorometric analyses were essentially identical. Overall, the assays were highly correlated. The correlations between the baseline serum PSA determination and repeated Tandem-R, IMx, and immunofluorometric determinations were 0.96, 0.96, and 0.97, respectively (all P < 0.001). The median duration of frozen storage was 32 months (range, 26 to 39 months), and the correlations between baseline and follow-up determinations did not change when stratified by duration of storage. Conclusions: These data provide important reassurance about the use of serum PSA determinations obtained by different assays, in different laboratories, and in properly tored samples across time.
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| 11. |
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| 12. |
- Piironen, Timo, et al.
(författare)
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In vitro stability of free prostate-specific antigen (PSA) and prostate- specific antigen (PSA) complexed to α1-antichymotrypsin in blood samples
- 1996
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Ingår i: Urology. - 0090-4295. ; 48:6 SUPPL., s. 81-87
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To study the in vitro stability of free and complexed forms of prostate specific antigen (PSA) in blood samples in order to establish guidelines for specimen handling, in particular for the clinical utility of the analysis of percentage free PSA. Methods. Blood samples were collected and processed to generate serum, heparin plasma, and EDTA plasma. Three different two-site immunoassays were used to measure the concentrations of total PSA (PSA-T), free form of PSA (PSA-F), and PSA-α1-antichymotrypsin complex (PSA-ACT) in order to determine the effect of repeated freezing and thawing, delayed separation of serum from blood cells, and stability during storage at 4°C and 30°C. Results. Five cycles of freezing and thawing introduced no statistically significant changes in the measured concentrations of PSA-T, PSA-F, or PSA-ACT. The effect of storing blood samples at room temperature for 1-6 h before separation of serum revealed a statistically significant decrease only for PSA-F after 5.5 h of storage (mean decrease 3.5%). PSA-T and PSA-ACT showed good stability in both serum and plasma samples, whereas PSA-F, after 1 week of storage at 4°C, decreased on average by 28.8%, 7.8%, and 5.6%, respectively, in serum, heparin plasma, and EDTA plasma. The decreases of PSA-F at 4°C were statistically significant (P < 0.05) relative to the controls (samples stored at -20°C) after storage for 23 h in serum, 86 h in heparin plasma, and 71 h in EDTA plasma. When the same samples were stored at 30°C for 24 h, only the mean decrease of PSA-F (4.8%) in serum was statistically significant. Conclusions. PSA-F in blood samples is less stable than PSA-ACT. It is not advisable to store samples on the clot, especially if time and temperature cannot be controlled. Serum samples should be stored frozen if not analyzed during the same day. After thawing, samples can be stored up to 23 h at 4°C prior to analysis. The use of plasma samples improves the stability of free PSA.
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| 13. |
- Siivola, Pirjo, et al.
(författare)
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Time-resolved fluorescence imaging for specific and quantitative immunodetection of human kallikrein 2 and prostate-specific antigen in prostatic tissue sections
- 2000
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Ingår i: Urology. - 0090-4295. ; 56:4, s. 682-688
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To design protocols for specific and quantitative immunohistochemical detection of human kallikrein 2 (hK2) using lanthanide chelate-labeled monoclonal antibodies (Mabs) and time-resolved fluorescence imaging. Methods. Anti-prostate-specific antigen (PSA) Mabs were tested in microtiterplate assays for their ability to prevent PSA from cross-reacting with the anti-hK2 Mab 6H10. Europium-labeled 6H10 and terbium-labeled anti-PSA Mab 2E9, selected as the best blocker antibody, were used for dual-label immunodetection in routinely fixed benign (n = 7) and malignant (n = 5) prostate specimens. The amounts of IgG bound in tissue were calculated from drops containing known Mab concentrations. Results. The use of anti-PSA Mab 2E9 for blocking diminished the cross-reaction from 5% to 0.3%. In the analyzed tissues, there was considerable variation in staining intensity for both proteins; PSA signals varied from 0.1 to 36.6 times that of hK2, with on average 10-fold more bound anti-PSA Mab than anti-hK2 Mab. In malignant tissue, the amounts of bound IgGs were lower and more variable than in benign tissue using both the anti-PSA Mab and the anti-hK2 Mab. The variation in signal intensities for PSA and hK2 correlated significantly in benign tissue (P >0.05), but not in benign hyperplastic and malignant specimens (P <0.05). Conclusions. Quantification of two lanthanide chelate-labeled antibodies bound in the same tissue section enabled comparison of PSA and hK2 content in individual cells. The average cellular content of hK2 relative to that of PSA was consistent with previous mRNA studies. The time-resolved fluorescence imaging-based quantification method has universal applicability in fixed tissue specimens. Copyright (C) 2000 Elsevier Science Inc.
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| 14. |
- Tornblom, M, et al.
(författare)
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Diagnostic value of percent free prostate-specific antigen: retrospective analysis of a population-based screening study with emphasis on men with PSA levels less than 3.0 ng/mL
- 1999
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Ingår i: Urology. - 1527-9995 .- 0090-4295. ; 53:5, s. 945-950
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To retrospectively investigate the use of percent free prostate-specific antigen (PSA) compared with total PSA in serum as predictor of prostate cancer in men selected randomly from the general population who underwent biopsy on the basis of abnormal findings on digital rectal examination (DRE) or transrectal ultrasound (TRUS) and/or serum PSA levels greater than 10 ng/mL. METHODS: A single intervention, population-based screening study was undertaken in 1988 and 1989. Of the 2400 men aged 55 to 70 years invited to participate, 1782 men responded and were examined with DRE, TRUS, and PSA testing (Tandem-Hybritech). In 1995, frozen serum samples from 1748 men were analyzed for percent free PSA (Prostatus, Wallac OY). Five-year follow-up data on new cancers in the screened population were obtained from the Swedish Cancer Registry (SCR). RESULTS: Of the 1748 men, 367 underwent TRUS-guided biopsies because of abnormal findings on either DRE or TRUS or serum PSA levels of greater than 10 ng/mL. This resulted in the diagnosis of 64 cases of prostate cancer (3.7%). PSA levels of 3.0 ng/mL or greater were found in 55 (86%) of 64 cancer cases and in 399 (24%) of the 1684 benign cases. Among the 1294 men with PSA less than 3.0 ng/mL, 9 prostate cancers were diagnosed (14% of all prostate cancers). All 9 patients with cancer and with PSA less than 3.0 ng/mL had a percent free PSA of 18% or less. In the group of 1109 patients with PSA less than 3.0 ng/mL and a percent free PSA greater than 18%, 159 biopsies were performed because of abnormal DRE or TRUS. However, no prostate cancer was diagnosed in this category of patients. Five years after the screening intervention, 7 more cases of prostate cancer were clinically diagnosed in the screened population according to the SCR. CONCLUSIONS: The combination of PSA levels less than 3.0 ng/mL and percent free PSA greater than 18% defines a large part of the population at a very low risk of cancer of the prostate both at the time of screening and during the following 5 years. Men in this group may be spared DRE, and longer screening intervals may be considered. However, the risk of having prostate cancer is not negligible in men with PSA less than 3.0 ng/mL and percent free PSA of 18% or less. The results of this study indicate that biopsy should be recommended to men fulfilling these criteria, although these results should be confirmed in larger prospective studies because of the limited number of patients with prostate cancer in the present series.
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