Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1519176 (PSA)
 5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PSA is a 34-kDa 240-amino-acid glycoprotein produced exclusively by prostatic epithelial cells. PSA is a serine protease, is a member of the kallikrein gene family, and has a high sequence homology with human glandular kallikrein. It has chymotrypsin-, trypsin-, and esterase-like activities. In the serum it is present mainly in a complex form with alpha 1-antichymotrypsin. It is secreted in the seminal plasma and is responsible for liquefaction of the seminal coagulum. The production of PSA proteins appears to be under the control of circulating androgens acting through the androgen receptors. The PSA gene is up-regulated predominantly by androgens at both the protein and mRNA levels. DRE causes minimal changes in the PSA level, while prostate massage, ultrasonography, systoscopic examination, and prostate biopsy can all cause clinically significant elevations. Other conditions, such as prostatitis, prostate intraepithelial neoplasia, acute urinary retention, and renal failure can also elevate the PSA level. The value of PSA as a screening tool is questionable because of the great deal of overlap in PSA levels between BPH and prostate cancer. However, if used in men over 50, in conjunction with DRE and/or ultrasonography, it may become a vital part of the early detection program. PSA's role in determining the clinical and pathological stage is also limited, in spite of the direct correlation between the pathological stage and the PSA level, because of great overlap in the PSA levels in various stages. The most important clinical utility of PSA is in monitoring patients after definitive therapy. PSA is most sensitive and reliable in the detection of a residual tumor, possibly recurrence, or disease progression following treatment, irrespective of the treatment modality. PSA can accurately predict the tumor status and can detect recurrence several months before its detection by any other method. PSA is also a very sensitive and specific immunohistochemical marker for tumors of prostatic origin. Compared to PAP, PSA is a more precise and meaningful marker in all clinical situations. With the development of ultrasensitive assays and the adoption of an international standard PSA calibrator, so that results from multicenter studies can be compared, PSA could become one of the most useful tumor marker in cancer biology.
 ...
PMID:Prostatic specific antigen. 753 74

We have explored various chromatographic procedures with the intention of establishing an isolation procedure that would allow us to isolate a large quantity of PSA-ACT (prostate specific antigen-alpha 1-antichymotrypsin) complex either from patients' sera or from incubation mixtures of free PSA and protease inhibitors. We found that at pH 7.2, both free PSA and PSA-ACT molecules are negatively charged and bind to the DEAE-Sepharose column. However, they could be separated from each other using a linear gradient of NaCl at pH 7.2. Both free PSA and PSA-ACT molecules were also found to be retained by the Con A Sepharose column because of the carbohydrate moiety of the PSA molecule. These two molecules were not separable by Con A chromatography. These two molecules apparently differ in their isoelectric points and were well separated by chromatofocusing using a pH gradient from pH 9 to 6. It appears that chromatofocusing can also be used to identify the isoforms of free PSA because of its high resolving power. The large difference in molecular size between free PSA and PSA-ACT complex allowed their separation by gel filtration chromatography on a column containing either S-100, S-200, or S-300 gel. S-200 gel appeared to be the best for the separation of free PSA from PSA-ACT and for the removal of other contaminating serum proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Purification of PSA-ACT complex: characterization of PSA-ACT complex by various chromatographic procedures. 753 36

Human prostate specific antigen, PSA, is a product of the human glandular kallikrein gene locus on chromosome 19 that is almost selectively expressed by prostate tissue. PSA is one of the dominating prostate derived proteins in seminal fluid. The mature form of PSA, a single chain glycoprotein of 237 amino acids, is a serine protease manifesting restricted chymotrypsin-like activity. PSA is mainly responsible for gel dissolution in freshly ejaculated semen by proteolysis of the major gel forming proteins, semenogelin I and II, and fibronectin. In semen approximately two thirds of PSA is enzymatically active. The remaining 30-40% is inactive due to internal cleavage(s). A few per cent of PSA in semen is complexed to the protein C inhibitor. PSA complexed to alpha 1-antichymotrypsin (ACT) constitutes the predominant molecular form of serum PSA, although complex formation is slow between the purified proteins in vitro. PSA also forms stable complexes with alpha 2-macroglobulin in vitro but as this results in encapsulation of PSA and complete loss of the PSA-epitopes, the in vivo significance of this complex formation is presently unclear. A free, non-complexed form of PSA constitutes a minor fraction of the serum PSA despite the large molar excess of antiproteasees such as ACT. In patients with carcinoma of the prostate the serum PSA level increases. Analysis of the serum level of PSA is used both for diagnosing and monitoring patients with carcinoma of the prostate (CAP).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Biochemistry of prostate specific antigen, PSA. 754 81

PSA is a proteolytic enzyme produced in the prostatic epithelium and secreted into the seminal fluid. PSA can also be a constituent of the serum even under apparently normal conditions. In many cases of prostate cancer (PCa), increased serum concentrations are found. Elevated serum levels, however, are also observed in benign prostatic hypertrophy (BPH), thus limiting the specificity of serum PSA as a marker for prostate cancer. Recently, subfractions of PSA ("free PSA"; PSA-antichymotrypsin complex) were analyzed in order to gain a higher specificity of PSA as a tumor marker. The present paper describes biochemical features and clinical significance of the various PSA subfractions, pointing out an improved discrimination of PCa and BPH by evaluating the ratio "free PSA": total PSA.
 ...
PMID:[Molecular forms of prostate-specific antigen and their clinical significance]. 754 41

An ELISA on microplate was established for the total serum PSA. We selected the monoclonal antibody for the assay from commercial sources making certain that it reacted with both free PSA and PSA-alpha 1-antichymotrypsin (PSA-ACT) complex from human serum with similar affinity (so-called "equimolar"). We also chose a test format with polyclonal anti-PSA antibodies coated on the well and monoclonal anti-PSA antibodies for quantification to gain higher test sensitivity. Two different sample volumes from each specimen, 5 and 50 microliters, were used for the assay in order not only to further increase test sensitivity and improve precision at both low and highly elevated PSA concentrations, but also to widen the assay concentration range (0-500 ng total PSA per ml). Using two sample volumes also reduces any hook effect and shortens the turn-around time because repeated determinations are usually required when specimens contain highly elevated PSA concentrations. The use of pooled sera containing approximately 95% PSA-ACT complex and 5% free PSA as a calibrator allows for a close matching of the calibrator with serum specimens in immunoreactivity and PSA composition. Moreover, our assay shows no hook effect up to 15,000 ng/ml. The within-day precision (% CV) in the critical concentration range of 4-12 ng/mL is approximately 5%. The PSA values obtained from this assay correlate well with that of the Hybritech kit (gamma = 0.998, slope equals to 1.033), indicating that this kit can replace the Hybritech Tandem E PSA kit for serum PSA determination in clinical laboratories.
 ...
PMID:Development of a microplate ELISA for free PSA and PSA-ACT complex in serum. 756 43

A calibrator composed of 90% prostate-specific antigen-alpha 1-antichymotrypsin (PSA-ACT) and 10% free PSA reduces the variation in control serums with widely divergent amounts of free PSA, from a mean of 28% among nine different assays to 9% after recalibration. The lyophilized form of the Stanford 90:10 calibrator is stable and therefore an excellent candidate for international standardization of PSA assays.
 ...
PMID:Progress in standardization of immunoassays for prostate-specific antigen. 912 23

We have established a procedure for the production of milligrams of free PSA (fPSA) from LNCaP cells derived from a human carcinoma of the prostate. By growing LNCaP cells in a serum-free medium in the presence of a synthetic androgen (R1881) and taking advantage of the special design of the Micro-mouse Hollow Fiber Bioreactor, relatively pure fPSA could be obtained. We found that columns containing either Sephacryl S-100 or S-200 could be used to remove the small amount of bovine serum albumin (BSA) and PSA-alpha 1-antichymotrypsin complex (PSA-ACT) from the preparation. More than 90% of the PSA from LNCaP cell cultures are fPSA. Like fPSA from seminal plasma, two fractions of fPSA differing in protease activity can be separated by DEAE-Sepharose chromatography. Based on the band pattern exhibited on the Western blot following sodium dodecyl sulfate-polyacrylamide electrophoresis separation, fPSA from LNCaP contains more inactive PSA isoforms. This was confirmed by chromatofocusing: the isoelectric point (pl) of the major PSA isoforms from the LNCaP cell culture were higher (6.8 and 6.6) than that (6.4 and 6.1) of fPSA from seminal fluid. We conclude that the LNCaP cell culture is a reliable source for obtaining large quantities of pure fPSA both for the preparation of assay calibrators and controls and for studying the difference in fPSA between benign prostate disease and prostate cancer.
 ...
PMID:Production of milligram concentrations of free prostate specific antigen (fPSA) from LNCaP cell culture: difference between fPSA from LNCaP cell and seminal plasma. 948 63

We have developed an assay specific for the PSA-ACT (PSA-alpha 1-antichymotrypsin) complex that effectively diminishes the problem of high assay background commonly reported by other investigators. The assay follows a two-site ELISA format. Polyclonal anti-PSA antibodies were coated on the microplate to capture the PSA complex from the serum, whereas the biotinylated anti-ACT polyclonal antibodies and HRP-conjugated streptavidin were used for detection. The high background ordinarily associated with this assay was greatly reduced when milk casein was added in addition to albumin for blocking and when the Super Block was also included in the diluents for sample dilution and dilution of enzyme conjugated detecting antibodies. The assay has a sensitivity of 0.05 ng/mL. The within-run precision ranges from 4.2-7.2% and the between-run precision falls between 5.8-8.5%. Cross reactions with ACT and free PSA (fPSA) are 0.0001% and 0.02%, respectively. The highest concentration of PSA-ACT complex in the maternal sera was < 0.4 ng/mL by this assay, much less than reported in the literature. Using this improved assay, the sum of fPSA and PSA-ACT concentrations were less than that of their corresponding total PSA (tPSA) most of the time. We believe that this improved assay should be used to replace the current tPSA assay for screening, monitoring, and managing patients with prostate cancer.
 ...
PMID:Development of an immunoassay specific for the PSA-ACT complex without the problem of high background. 948 64

Several advantages become immediately apparent when the prostate specific antigen (PSA, or tPSA) assay is replaced by the assay specific for the serum PSA-alpha 1-antichymotrypsin (PSA-ACT) complex. For instance, random contributions to the tPSA value by various serum minor PSA isoforms can be avoided, making possible the determination of a more accurate relation of the PSA-ACT concentration to the tumor activity. Discrepancies in percent free PSA (% fPSA) values from the same specimens due to the use of different commercial kits also can be eliminated, mainly because the PSA-ACT assay does not have the problems in antibody selection and calibrator preparation usually associated with the tPSA assay. We found that at the present time different cutoffs of % fPSA for the differentiation of BPH from prostate cancer must be established for each individual tPSA assay. Cutoffs established using values from one tPSA assay should not be used for making clinical decisions when their tPSA values are determined by a different kit. Moreover, when we monitored the patients during treatment with serum tPSA, specific fPSA, and specific PSA-ACT complex assays simultaneously, it was clear that any interpretation of the patient's clinical status based on tPSA values alone could be misleading. Because there is less PSA-ACT complex in BPH specimens relative to that found in cancer serum samples, expressing fPSA as "fPSA/PSA-ACT x 100" and measuring PSA-ACT complex concentrations instead of tPSA during screening improve the measurable contrast between BPH and prostate cancer. Although individually modest, collectively these advantages can add up to considerable improvements.
 ...
PMID:Advantages of replacing the total PSA assay with the assay for PSA-alpha 1-antichymotrypsin complex for the screening and management of prostate cancer. 948 67

PSA exists in multiple molecular forms in serum, with the majority complexed to proteinase inhibitors such as alpha 1-antichymotrypsin and alpha 2-macroglobulin. The uncomplexed, or "free" forms of PSA represent a very heterogenous distribution of molecular isoforms. It has been suggested that these variations in uncomplexed PSA may cause differences in their immunologic characteristics which may lead to analytical differences between various PSA assays. We report that various isoforms of uncomplexed PSA purified from seminal fluid as previously described show no differences in relative immunoreactivity and demonstrate equimolar behavior as measured by the TOSOH AIA-600 assay, which is a PSA assay based upon monoclonal PSA and monoclonal detecting antibodies (mono-mono). Furthermore, we show that carbohydrate side-chain modification does not change the equimolar immunoreactivity of these isoforms.
 ...
PMID:Different molecular forms of uncomplexed prostate specific antigen (PSA) show similar immunoreactivities. 1033 91


1 2 3 Next >>