| 1. |
- Abrahamsson, Per-Anders, et al.
(författare)
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Radioimmunoassay of beta-microseminoprotein, a prostatic-secreted protein present in sera of both men and women
- 1989
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Ingår i: Clinical Chemistry. - 0009-9147. ; 35:7, s. 1497-1503
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Tidskriftsartikel (refereegranskat)abstract
- We describe a simple radioimmunoassay of beta-microseminoprotein, one of the three most abundant secretory proteins of the prostate gland. The detection limit of the assay is 1 microgram/L, and its precision, expressed as the total coefficient of variation, is less than 10% for values between 10 and 150 micrograms/L. Using this assay, we found that beta-microseminoprotein immunoreactivity was present in sera from both sexes at about the same concentration. The protein detected had the same molecular size on gel chromatography as the protein isolated from seminal plasma, and dilution curves for the sera paralleled that for the pure protein. The findings suggest that beta-microseminoprotein is present in serum of healthy subjects of both sexes and that it originates in tissue other than the prostate gland. The range of the serum concentration was 0-10.6 micrograms/L (median 4.1) for 51 healthy adult women and 1.1-14.7 micrograms/L (median 6.2) for 35 healthy adult men not older than 40 years. In males with prostatic cancer the concentration in serum was highly variable and often greatly increased. The concentration of beta-microseminoprotein was correlated with that of creatinine in serum, suggesting that the protein is eliminated--at least partly--from the circulation by glomerular filtration. Little of the protein was present in the urine of women. In urine from men the concentration was high and variable, probably because of local contribution from the prostate gland to the urethral urine.
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| 2. |
- Bjartell, Anders, et al.
(författare)
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Production of alpha-1-antichymotrypsin by PSA-containing cells of human prostate epithelium
- 1993
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Ingår i: Urology. - 1527-9995. ; 42:5, s. 502-510
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Tidskriftsartikel (refereegranskat)abstract
- Prostate-specific antigen (PSA) is a chymotrypsin-like serine protease exclusively produced by the prostate epithelium, and abundant in seminal fluid. In serum, PSA is predominantly complexed to a liver-derived serine protease inhibitor, alpha-1-antichymotrypsin (ACT). A higher proportion of serum PSA is complexed to ACT in prostate cancer than in benign prostate hyperplasia. Since the molecular basis for this is unclear, we have investigated whether or not ACT may be produced in the prostate gland. Immunocytochemistry, using either monoclonal or polyclonal IgGs, demonstrated specific immunostaining for ACT in normal PSA-containing prostate epithelium. Production of ACT in the normal PSA-producing prostate epithelium was demonstrated by means of nonradioactive in situ hybridization using 30-mer anti-sense DNA probes for ACT and for PSA. The ACT and PSA coding transcripts, as detected by in situ hybridization, were distributed perinuclearly, in contrast to the specific immunostaining for ACT and PSA which was most intense in the apical portion of the secretory cells. The results strongly suggest local production and release of ACT by the normal prostate epithelium that may be important for interaction between PSA and ACT in extracellular compartments.
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| 3. |
- 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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| 4. |
- Björk, Thomas, et al.
(författare)
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Comparison of analysis of the different prostate-specific antigen forms in serum for detection of clinically localized prostate cancer
- 1996
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Ingår i: Urology. - 1527-9995. ; 48:6, s. 882-888
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To compare different forms and ratios of serum prostate-specific antigen (PSA) to determine which form or ratio provides optimal diagnostic specificity and sensitivity in distinguishing between benign prostatic hyperplasia (BPH) and clinically localized prostate cancer. METHODS: Serum samples were obtained from 47 patients with BPH and 39 with clinically localized prostate cancer. Patients with BPH underwent either transurethral resection of the prostate or transurethral microwave thermotherapy. Patients with prostate cancer, all of whom had no metastases on radionucleotide bone scans and no pelvic lymph node involvement, underwent either radical external beam radiation therapy or radical retropubic prostatectomy. All patients had pretreatment serum PSA levels between 1 and 20 ng/mL. The different forms of serum PSA (free PSA [PSA-F], PSA complexed to alpha 1-antichymotrypsin [PSA-ACT], and total PSA [PSA-T]) were measured using different monoclonal antibodies against PSA and ACT and immunofluorometric assay techniques. Furthermore, three ratios (PSA-F/PSA-T, PSA-ACT/PSA-T, and PSA-F/PSA-ACT) were calculated. RESULTS: By receiver operating characteristic curve analysis, the performance of the different forms and ratios were compared. The PSA-F/PSA-T ratio had the greatest area under the curve (AUC, 0.776), significantly larger than that for PSA-T (0.612; P = 0.024). For PSA-ACT/PSA-T, the AUC was 0.695 (P = 0.283 versus PSA-T) and 0.773 for PSA-F/PSA-ACT (P = 0.051 versus PSA-T). At a cutoff level < 0.17, PSA-F/PSA-T had a sensitivity of 79%, a specificity of 66%, and a positive predictive value of 66% compared with 74%, 38%, and 50%, respectively, for PSA-T at a cutoff level > 4.0 ng/mL. CONCLUSIONS: The PSA-F/PSA-T ratio gives the best diagnostic performance compared with that for other forms and ratios of PSA and will reduce the number of prostatic biopsies in patients with BPH.
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| 5. |
- Björk, Thomas, et al.
(författare)
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Rapid exponential elimination of free prostate-specific antigen contrasts the slow, capacity-limited elimination of PSA complexed to alpha 1-antichymotrypsin from serum
- 1998
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Ingår i: Urology. - 1527-9995. ; 51:1, s. 57-62
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study the rates of elimination of total prostate-specific antigen (PSA-T), free PSA (PSA-F), and PSA complexed to alpha 1-antichymotrypsin (PSA-ACT) from blood after radical retropubic prostatectomy (RRP). METHODS: We obtained venous blood from 10 patients with prostate cancer who were undergoing RRP. We analyzed PSA-F and PSA-ACT and equimolar detection of both of these forms together (PSA-T) by using immunofluorometric assays. An attempt was made to fit the serum concentrations of PSA-F, PSA-ACT, and PSA-T for each patient to exponential curves by applying one- and two-compartment models for pharmacokinetic analysis. RESULTS: Manipulation of the prostate during RRP resulted in a 3- to 28-fold increase in PSA-F concentrations in serum. Removal of the prostate resulted in a rapid, biexponential elimination of PSA-F from serum, corresponding to a mean initial (alpha) half-life of 0.81 hours and a mean terminal (beta) half-life of 13.9 hours. Serum PSA-ACT concentrations decreased by 20% to 40% immediately after removal of the gland; the elimination after surgery was slow and nonexponential, corresponding to a mean rate of 0.8 ng/mL/day. The elimination of PSA-T reflects a combination of the elimination patterns for PSA-F and PSA-ACT. CONCLUSIONS: The main proportion of PSA-F is rapidly eliminated from serum, possibly by glomerular filtration. PSA-F released during surgery did not form complexes with ACT, as suggested by the lack of PSA-ACT elevation in serum. The size (approximately 90 kDa) and the extensive in vitro stability of the PSA-ACT complex prevents renal clearance. The nonexponential elimination of the PSA-ACT complex is evidence of a capacity-limited process (e.g., metabolic transformation).
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| 8. |
- Lilja, Hans, et al.
(författare)
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Long-term prediction of prostate cancer up to 25 years before diagnosis of prostate cancer using prostate kallikreins measured at age 44 to 50 years.
- 2007
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 25:4, s. 431-436
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Tidskriftsartikel (refereegranskat)abstract
- Purpose We examined whether prostate-specific antigen (PSA) forms and human kallikrein 2 (hK2) measured at age 44 to 50 years predict long-term risk of incident prostate cancer. Methods From 1974 to 1986, 21,277 men age <= 50 years in Malmo, Sweden, enrolled onto a cardiovascular study (74% participation). The rate of PSA screening in this population is low. According to the Swedish Cancer Registry, 498 were later diagnosed with prostate cancer. We measured hK2, free PSA, and total PSA (tPSA) in archived blood plasma from 462 participants later diagnosed with prostate cancer and from 1,222 matched controls. Conditional logistic regression was used to test for association of prostate cancer with hK2 and PSA forms measured at baseline. Results Median delay between venipuncture and prostate cancer diagnosis was 18 years. hK2 and all PSA forms were strongly associated with prostate cancer (all P < .0005). None of the 90 anthropometric, lifestyle, biochemical, and medical history variables measured at baseline was importantly predictive. A tPSA increase of 1 ng/mL was associated with an increase in odds of cancer of 3.69 (95% CI, 2.99 to 4.56); addition of other PSA forms or hK2 did not add to the predictive value of tPSA. tPSA remained predictive for men diagnosed >= 20 years after venipuncture, and the predictive value remained unchanged in an analysis restricted to palpable disease. Conclusion A single PSA test at age 44 to 50 years predicts subsequent clinically diagnosed prostate cancer. This raises the possibility of risk stratification for prostate cancer screening programs.
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| 9. |
- Lilja, Hans, et al.
(författare)
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Semenogelin, the predominant protein in human semen. Primary structure and identification of closely related proteins in the male accessory sex glands and on the spermatozoa
- 1989
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Ingår i: Journal of Biological Chemistry. - 0021-9258. ; 264:3, s. 900-1894
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Tidskriftsartikel (refereegranskat)abstract
- The predominant protein in human semen, semenogelin, was characterized by lambda gt11 clones isolated from a seminal vesicular cDNA library. One clone, carrying a cDNA insert of 1606 nucleotides and a polyadenylated tail, coded for the entire semenogelin precursor. An open reading frame of 1386 nucleotides encodes a signal peptide and the mature protein of 439 amino acid residues, in which residues 85-136 are identical with a previously characterized semenogelin fragment. The polypeptide chain displays a most conspicuous region of internal sequence homology where 46 of the 58 amino acid residues at positions 259-316 are repeated at positions 319-376. An abundant seminal vesicular transcript of 1.8 kilobases (kb) codes for semenogelin. Two additional transcripts, one seminal vesicular 2.2-kb species and one epididymal 2.0-kb species, code for related proteins that have a close structural relationship as well as antigenic epitopes in common with semenogelin. Semenogelin and the semenogelin-related proteins are the major proteins involved in the gelatinous entrapment of ejaculated spermatozoa. Antigenic epitopes common to these proteins are localized to the parts of the spermatozoa involved in locomotion. The spermatozoa become progressively motile as the gel-forming proteins are fragmented by the kallikrein-like protease, prostate-specific antigen, and the gel dissolves.
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| 10. |
- Oesterling, Joseph E., et al.
(författare)
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Free, Complexed and Total Serum Prostate Specific Antigen : The Establishment of Appropriate Reference Ranges for their Concentrations and Ratios
- 1995
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Ingår i: The Journal of urology. - 0022-5347. ; 154:3, s. 1090-1095
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Prostate specific antigen (PSA) exists in the serum in several molecular forms that can be measured by immunodetectable assays: free PSA, PSA complexed to alpha 1-antichymotrypsin (complexed PSA) and total PSA, which represents the sum of the free and complexed forms. We determined the normal distribution of values and established the appropriate reference ranges for these 3 molecular forms of PSA and their ratios (free-to-total, complexed-to-total and free-to-complexed PSA). Knowing the amount and ratio of these molecular forms appears to be useful in enhancing the ability of PSA to distinguish potentially curable prostate cancer from benign prostatic hyperplasia and in decreasing the number of unnecessary prostate biopsies. Materials and Methods: A total of 422 healthy men 40 to 79 years old was randomly chosen from the male population of Olmsted County Minnesota and underwent a detailed clinical examination that included digital rectal examination, serum PSA determination and transrectal ultrasound to exclude the presence of prostate cancer. Using newly developed, monoclonal-monoclonal immunofluorometric assays for each molecular form, the free, complexed and total PSA, and the ratios of these 3 forms were determined for each study participant. Results: All 3 molecular forms correlated directly with patient age (r = 0.45, r = 0.43 and r = 0.45, respectively). Using the 95th percentile, the recommended age-specific reference ranges for the free, complexed and total PSA forms, respectively, are 0.5, 1.0 and 2.0 ng./ml. for men 40 to 49 years old; 0.7, 1.5 and 3.0 ng./ml. for men 50 to 59 years old; 1.0, 2.0 and 4.0 ng./ml. for men 60 to 69 years old, and 1.2, 3.0 and 5.5 ng./ml. for men 70 to 79 years old. With regard to each of the ratios (free-to-total, complexed-to-total and free-to-complexed PSA) none correlated with patient age. As a result, the appropriate upper limit of normal (95th percentile) for all 3 ratios is constant for men of all ages. These reference ranges are greater than 0.15 for free-to-total PSA ratio, less than 0.70 for complexed-to-total PSA ratio and greater than 0.25 for free-to-complexed PSA ratio. The free-to-total PSA ratio will have its greatest value for men with a serum PSA value between 2 and 10 ng./ml. Conclusions: The establishment of appropriate reference ranges for free, complexed and total PSA as well as the ratios will allow the practicing urologist to incorporate these new parameters into the diagnostic evaluation of men at risk for early, potentially curable prostate cancer.
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