Tartrate-inhibitable Acid Phosphatase Research Articles

Biochemical parameters as prognostic factors in prostatic adenocarcinoma.

The serum levels of creatinine (CR), alkaline phosphatase (ALP), acid phosphatase (ACP) and tartrate inhibitable acid phosphatase (TIAP) were related to Gleason score, TM-category, disease progression and survival in 325 prostatic adenocarcinoma patients followed up for over 12 years. Elevated serum levels of CR, ALP, ACP and TIAP were related to invasive and metastatic disease as well as with a high Gleason score. Elevated serum levels of CR, ALP, ACP and TIAP, all significantly predicted prognosis in a univariate analysis. In the M0 tumours, ACP and TIAP and TIAP had prognostic value, as they did in the T1-2M0 tumours respectively. Cox's multivariate analysis showed that serum creatinine level at diagnosis had independent prognostic value additional to the TM-classification, Gleason score and patient age. In the M0 tumours, ALP had independent prognostic significance additional to the T-category, Gleason score and patient age. In the T1-2M0 tumours, TIAP had independent prognostic value supplementary to the Gleason score, T-category and patient age, whereas in the T1M0 tumours, the gleason score was an independent prognostic parameter. The results indicate that these simple laboratory tests give important prognostic information in prostatic adenocarcinoma.

Ratio of Serum Tartrate-Inhibitable Acid Phosphatase to Total Serum Protein in Benign Prostatic Hypertrophy and Prostatic Carcinoma

The activity concentration and the specific activity (the ratio of enzyme activity to total serum protein) of the tartrate-inhibitable fraction of acid phosphatase [orthophosphoric monoester phosphohydrolase (acid optimum), EC 3.1.3.2; TIAP] were related to benign prostatic hypertrophy and to prostatic carcinoma. As expected, the TIAP activity concentrations assayed in the sera of patients with benign prostatic hypertrophy were within the range of those assayed in normal human sera. In contrast, the specific activities of TIAP determined in the sera of patients with benign prostatic hypertrophy were significantly higher than those determined in the control group. In the sera of prostatic carcinoma patients, both the TIAP activity concentrations and the TIAP specific activities differed significantly (F = 730) from the normal values.

Effect of ultrasound guided core biopsy of prostate on serum concentration of prostate specific antigen and acid phosphatase activity.

Forty-three patients had their serum concentrations of prostate specific antigen and activity of tartrate inhibited acid phosphatase measured before and after digital rectal examination, transrectal ultrasonography and transrectal core biopsy. Transrectal core biopsy significantly increased the values for both tumor markers but rectal examination and ultrasonography without biopsy had no such effect. The measurements returned to normal within one week of biopsy in all but four patients who still had slightly increased concentrations of prostate specific antigen. We recommend that the concentration of prostate specific antigen and activity of tartrate inhibited acid phosphatase are checked before biopsy of the prostate is carried on.

Comparison of assays for prostatic and total acid phosphatase

Total and tartrate inhibited acid phosphatase was determined on the Technicon Chem 1 and evaluated against a Cobas-Bio centrifugal analysis procedure and an immunochemical method. Precision and reference range studies were performed for the Chem 1 acid phosphatase procedure and correlation was established with the other methods. The Chem 1 method for measuring total and prostatic acid phosphatase is a sensitive method with good correlation to the centrifugal analysis and the immunochemical method. The assay is fully automated and requires no manual off-line sample preparation.

Total, tartrate-resistant, and tartrate-inhibited acid phosphatases in serum: biological variations and reference limits.

We studied several factors affecting biological variation in serum acid phosphatases in a population of 1195 apparently healthy subjects four years old or older. We assayed total acid phosphatase activities in the presence of a transphosphorylating agent and using alpha-naphthyl phosphate as substrate. The main factors modifying total and tartrate-resistant acid phosphatases activities in serum are similar to those observed for total and bone alkaline phosphatases activities: age, sex, and hormonal state (puberty or menopause). The tartrate-inhibited acid phosphatase activity is, however, independent of biological variations. Finally, we propose reference limits for total, tartrate-resistant, and tartrate-inhibited acid phosphatases in serum.

Biosynthesis of prostatic acid phosphatase in a normal human cell line

The biosynthesis of the prostatic form of human acid phosphatase was studied in normal embryonic lung cells, WI-38, by metabolic labeling with tritiated leucine and [ 32P]phosphate, followed by specific immunoprecipitation, gel electrophoresis, and fluorography. Of the total tartrate-inhibitable acid phosphatase activity in WI-38 cells, 30% is due to the prostatic form. The primary translation product that leads eventually to the mature prostatic enzyme is a precursor polypeptide of 112 kDa. The precursor polypeptide is processed to mature polypeptides of 59, 55, and 49 kDa via an intermediate 91-kDa precursor. WI-38 cells also secrete a 113-kDa peptide into the medium. The precursor and mature polypeptides are glycosylated and phosphorylated. Upon treatment with endo-β-hexosaminidase H, the apparent molecular weights of the polypeptides are reduced by approximately 4 kDa and phosphate is lost.

Biosynthesis and processing of lysosomal acid phosphatase in cultured human cells

The biosynthesis of lysosomal acid phosphatase was studied in a normal human embryonic lung cell line, WI-38. Cells were labeled with radioactive leucine under a variety of conditions, the enzyme was immunoprecipitated using a monospecific antiserum raised against human liver lysosomal acid phosphatase, and the products were separated by electrophoresis and were visualized by fluorography. Lysosomal acid phosphatase constitutes 60% of the total tartrate-inhibitable acid phosphatase in WI-38. It is initially synthesized as a high-molecular-weight precursor polypeptide of 69 kDa. The precursor polypeptide is rapidly glycosylated and processed to a mature enzyme of 53-45 kDa via intermediates of 65 and 60 kDa in WI-38 cells. The 69-kDa precursor polypeptide is also converted to larger precursor polypeptides of 74 and 80 kDa. The multiplicity of precursor polypeptides is due at least in part to differences in the glycosylation and phosphorylation of the polypeptides. Sensitivity of phosphorylated oligosaccharide chains from precursor, mature and small polypeptides to endo-β-hexosaminidase H-catalyzed cleavage suggests the presence of high-mannose phosphorylated oligosaccharide chains similar to those present on many other lysosomal enzymes. The effects of tunicamycin and ammonium chloride were also studied. In contrast to the effect of ammonium chloride on arylsulfatase A secretion, the lysosomal acid phosphatase in WI-38 cells was not secreted in the presence of NH 4Cl. This is consistent with the existence of an alternate route for the transfer of lysosomal acid phosphatase into lysosomes. This alternate route may be the reason that I-cell fibroblasts contain a normal level of lysosomal acid phosphatase.

Isolation and characterization of a homogeneous acid phosphatase from catfish liver

1. 1. A homogeneous, tartrate-inhibitable acid phosphatase (AcPase) was obtained from the liver of channel catfish ( Ictalurus punctatus) by the use of Affi Gel-10-coupled aminohexyltartramic acid affinity chromatography. 2. 2. The enzyme has a molecular weight of 82,500 and is a dimer consisting of two apparently equivalent subunits with subunit weights of 35,000 ± 3000. Amino acid composition data are presented and compared with those of mammalian acid phosphatases. 3. 3. Data suggest that the enzyme is a metalloacid phosphatase. 4. 4. Catfish liver AcPase exhibits two molecular forms with pI 5.66 and 5.37 which were separated by chromatofocusing. 5. 5. A spontaneous conversion of the less acidic form to a more acidic form was observed and this conversion was accompanied by a decreased sensitivity towards tartrate inhibition.

On female ejaculation

Addiego et al. (1981) reported a case study in which a woman's urethral orgasmic expulsions differed from her urine in concentrations of urea, creatinine, and tartrate inhibitable acid phosphatase (a more appropriate term than prostatic acid phosphatase used by Addiego et al. [cf. Stolorow, Hanucher, & Stuver, 1976; Sensabaugh & Kahane, 1982]). Addiego et al. referred to, but did not report data from, pilot work with urine and orgasmic expulsion specimens by the subject in the absence of the research (p. 17). Because specimens were collected in the absence of the research team, the results were not submitted for publication. Addiego et al. believed that the analyses first reported concerning this issue should be based on specimens in as nearly a controlled condition as possible and that the team should be able to report that members had seen the source of the specimens and how they were collected. Sensabaugh and Kahane (1982), concerned about the implications of the work by Addiego et al. (1981) for adjudicating rape cases, obtained four specimens of female ejaculate in an unspecified manner. Their finding that acid phosphatase concentration was approximately one order of magnitude greater in the putative female ejaculate specimens than in urine (p. 2), tends to support the finding by Addiego et al. that not all female orgasmic expulsions differ from urine.

Tartrate-inhibitable acid phosphatase. Purification from placenta, characterization and subcellular distribution in fibroblasts.

Tartrate-inhibitable acid phosphatase was purified to apparent homogeneity from human placenta. The enzyme is composed of two subunits with an apparent molecular mass of 48 kDa. Each subunit carries one oligosaccharide of the high-mannose/hybride type. The purified enzyme has an isoelectric point of pH 6.2. It cleaves phosphomonoester bonds at acid pH, is competitively inhibited by L-tartrate, Ki = 0.51 microM, and phosphate, Ki = 0.8mM. A monospecific antiserum raised against the purified placental enzyme precipitated 62% and 85% of the tartrate-inhibitable acid phosphatase present in extracts of placenta and fibroblasts, respectively. By means of subcellular fractionation and immunoprecipitation it was shown that the majority of tartrate-inhibitable acid phosphatase is located in lysosomes in normal and mucolipidosis II fibroblasts. In the human Hep G-2 hepatoma cells a significant fraction of the enzyme appears to be associated with non-lysosomal organelles.

Saure Phosphatase im Serum (Substrat: α-Naphthylphosphat): Referenzwerte und diagnostische Aussage

We report the results obtained with a modification of Hillmann's method (1) for determination of the catalytic concentration of acid phosphatase in serum using alpha-naphthylphosphate as the substrate. In a group of 158 males aged 16-85 years, the upper limit of the reference range (95th percentile) for the total acid phosphatase was established as 4.7 U/l (37 degrees C) and 4.2 U/l (30 degrees C), respectively; the corresponding values for the tartrate-inhibited acid phosphatase were 1.6 U/l (37 degrees C) and 1.5 U/l (30 degrees C). The upper limit of the reference range (95th percentile) for the total acid phosphatase determined in 60 females aged 18-80 years was 3.7 U/l (37 degrees C) and 3.0 U/l (30 degrees C). The catalytic concentrations in men and women did not show any age-related differences. The catalytic concentration of the tartrate-inhibited acid phosphatase was determined with the substrates alpha-naphthylphosphate and p-nitrophenylphosphate in a group of 89 patients with prostatic carcinoma (stages C and D). In 74 of these patients, the concentration of the prostatic specific acid phosphatase was assayed by enzyme-immunoassay and radioimmunoassay. The sensitivity of the method with p-nitrophenylphosphate was found to be unsatisfactory (66%), while that obtained with the other methods was superior and intercomparable (approx. 90%). The results obtained with the two substrates (p-nitrophenylphosphate vs. alpha-naphthylphosphate) differed significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of androgens and estrogens on human prostatic cells in culture.

A ceil culture system has been developed in order to assess the response of human prostatic carcinoma cells to the presence of androgens and estrogens. A single cell suspension of these cells was incubated in minimum essential medium, in the absence of added sex steroids (standard culture), for 24 h. Equal aliquots of these cultured cells were incubated for a further 24–72 h in standard medium or in medium to which testosterone (T, 17.4 nM), dihydrotestosterone (DHT, 1.7 nM) or estradiol (E2, 0.36 nM) had been added. At the end of the incubations, the levels of tartrate-inhibitable acid phosphatase were compared in the standard cultures and the cultures to which sex steroids had been added.There were three patterns of response of patients' cells to the presence of androgens. From a total of 91 cell cultures, obtained from 85 patients, androgens were associated with an increased acid phosphatase production in 58. In 22 incubations, there was no androgenic effect on acid phosphatase production, and in II incubations, androgens were associated with lower enzyme levels than in the standard cultures. The qualitative effects of T and DHT were the same, but the quantitative effect of DHT was greater than that of T in those experiments in which there was a positive androgenic effect on acid phosphatase production. In 10 of 46 incubations with E2, acid phosphatase levels were lower than the standard incubations, while in 28 there was no difference in enzyme levels. In eight incubations, E2 was associated with a greater acid phosphatase production than that found in the standard cultures.In cultures of the cells from 180 men with benign prostatic hyperplasia and 5 men with normal prostatic tissue, androgens and estrogens had no effect on acid production by these cells, even at DHT concentrations of 1.7 × 10−7 M.It is concluded that prostatic carcinoma cells behave differently, in culture, in response to sex steroids, than do cells from benign hyperplastic or normal prostatic tissue.

The diagnostic significance of serum creatine kinase-BB isoenzyme in adenocarcinoma of prostate

The relative diagnostic usefulness of total serum acid phosphatase, tartrate-inhibited fraction of acid phosphatase, immunoreactive prostatic acid phosphatase, and creatine kinase-BB isoenzyme was evaluated in 30 patients with biopsy-proven adenocarcinoma of prostate. The total and tartrate-inhibited acid phosphatase, measured by standard chemical methods, were elevated in 8 patients with stage D disease. The radioimmunoassay (RIA) method confirmed these abnormal values and also indicated the presence of elevated prostatic serum acid phosphatase in 3 additional patients. The electrophoretic fractionation of total serum creatine kinase (CK) into its various isoenzyme components showed the presence of CK-BB isoenzyme in 8 patients. In 5 of these patients with detectable CK-BB isoenzyme, RIA values for prostatic acid phosphatase were also elevated. Histologic studies of the prostatic tissues revealed that the presence of serum CK-BB was invariably associated with poorly differentiated adenocarcinoma of prostate. The results of the present studies indicate that 1) with simultaneous measurements of serum CK-BB and immunoreactive prostatic acid phosphatase laboratory confirmation of prostatic cancer can be obtained in 50 per cent of patients; 2) determination of total and tartrate-inhibited acid phosphatase along with CK-BB and immunoreactive prostatic acid phosphatase does not increase the frequency of correct diagnosis; and 3) the presence of serum CL-BB isoenzyme is suggestive of poorly differentiated adenocarcinoma of prostate.

Tageszeitliche Änderungen erhöhter Aktivitäten der sauren Phosphatase beim Prostatacarcinom

The diurnal rhythm of total acid phosphatase and prostatic phosphatase activities was investigated in patients with prostate carcinoma. In these patients, the activities of total acid phosphatase, the tartrate-sensitive fraction of acid phosphatase, and lactate dehydrogenase decrease after therapy, whereas the activity of alkaline phosphatase increases. In all patients with prostate carcinoma, the total and tartrate-inhibited acid phosphatase, and the level of cortisol show a diurnal rhythm before therapy, with a minimum at night. In one patient, after orchiectomy, the cortisol rhythm remained unchanged, but the daily phosphatase variation was absent. Diurnal variations of lactate dehydrogenase and alkaline phosphatase were also observed in 2 patients without prostate carcinoma, but with elevated levels of these enzymes.

Common antigens found on fetal cells and viral transformed adult prostatic tissue.

In vivo and in vitro immunologic cross reactivity between SV40 virus transformed prostatic tissue and fetal antigens of LVG/LAK strain hamsters has been studied. The hamsters immunized with fetal antigens demonstrated significant resistance to tumor growth. Complement-dependent humoral cytotoxicity of target SV40 tumor cells in microtest plates was used to demonstrate the presence of significant antibody titer in fetal-immunized hamsters. When the immune sera were absorbed with SV40 transformed prostatic tissue, cytotoxicity indices were markedly lower than with the unabsorbed immune sera. The transformed prostatic tissue was found to have an elevated tartrate inhibited acid phosphatase indicative of the presence of epithelial components in the transformed tissue. These experiments demonstrate in vivo and in vitro cross reactviity between fetal antigens and tumor associated antigens of transformed prostatic tissue. This study suggests a similarity between fetal antigens and antigens of a specific organ tissue (prostate) transformed by a DNA oncogenic virus.

Cytochemical polymorphism of acid phosphatase in hairy cell leukemia

In four cases of hairy cell leukemia a cytochemical polymorphism concerning acid phosphatase (AP) is evident. Any AP is lacking in all hairy cells of one case; only tartrate inhibitable AP is occurring in two cases, in another case tartrate resistant AP is found in high activity. Thus, the lack of tartrate resistant AP seems not to be an argument against hairy cell leukemia.

Serum acid phosphatase. The influence of routine rectal examination with diagnostic palpation of the prostate.

In 61 patients (40 patients with benign hyperplasia of the prostate and 21 patients with normal prostate), the concentration of total acid phosphatase (t.a.p.) as well as the concentration of tartrate-inhibited acid phosphatase (tip.), was determined in serum by the method of Bessey-Lowry, and 1/4, 2, 24, 48, 72, and 96 hours after rectal examination with diagnostic palpation of the prostate. No significant difference was found in the mean values of the two patient groups, and no significant systematic change in the mean values after rectal examination. Taking each patient per se, no significant increase could be demonstrated following rectal examination with diagnostic palpation, either in t.a.p. or in tip. During the first 24 hours after rectal examination, the individual variations in concentration of both tap. and t.i.p. were of the same order of magnitude as in a control material of 10 patients who did not undergo rectal examination.It is concluded that rectal examination, with diagnostic palpation of the prostate, does not interfere with the determination of acid phosphatase in serum by the method of Bessey-Lowry.

Characteristics of murine prostatic acid phosphatase: Comparison with other tissues and species

The acid phosphatase of mouse prostate was compared with that of other tissues, tumors, and cultured cells. Inhibitors of human prostatic acid phosphatase, such as tartrate and molybdate, inhibited the mouse prostatic enzyme only partially. Acid phosphatase from other mouse tissues (kidney, liver, cardiac and skeletal muscle) and tumors (sarcoma-180, adenocarcinoma-755, and the subcutaneous tumors induced by in vitro transformed prostate cells) were partially inhibited by 0.02 M tartrate also. Although there is some correlation between the prostatic origin of cells and the percentage of tartrate-inhibitable acid phosphatase (T i), it is not possible to conclude that T i is prostate-specific in the mouse. Histochemical studies with mouse prostate showed that acid phosphatase is localized predominantly in the epithelial cells of the acini. Mouse prostate tissue as well as the transformed prostate cells contained acid phosphatase that was not inhibited by tartrate. Acrylamide gel electrophoresis of mouse prostatic and kidney acid phosphatase was done under various conditions. No differences, with respect to electrophoretic mobilities or tartrate inhibition of the enzyme band after the electrophoresis, were found. It is concluded that acid phosphatase is not a suitable marker enzyme for mouse prostate cells.

Viral neoplastic transformation of hamster prostate tissue in vitro.

Cultures of hamster prostatic tissues infected with simian virus 40 undergo transformation in vitro, and the transformed cells produce malignant tumors when injected into homologous hosts. Tartrate-inhibited acid phosphastase is found in the cultures of transformed cells and in the tumors they produce. Tartrate-inhibited acid phosphatase activity is elevated in the serum of tumor-bearing animals.