Placental and placental-like alkaline phosphatases in sera from healthy adults and cancer patients.
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Adolescent↗
Biomedical subjects
T Stigbrand
Publications and source records attributed to T Stigbrand.
Antigenic determinants of human placental and testicular placental-like alkaline phosphatases as mapped by monoclonal antibodies.
Placental alkaline phosphatase (PLAP) in humans shows a high degree of genetic polymorphism as disclosed by electrophoretic analysis. Human testes contain trace amounts of a PLAP-like enzyme, that although immunologically cross-reactive with PLAP, shows unique catalytic properties. As an alternative approach to study enzyme polymorphism we have developed monoclonal antibodies to purified allelic variants of PLAP. Five different monoclonal antibodies are described in this report. The antibodies react with different epitopes on the PLAP molecule. Both conformational dependent and independent determinants are detected. Two epitopes are modified when comparing the S and F allelic variants of PLAP. One epitope is common to PLAP and the intestinal isoenzyme of alkaline phosphatase. The five epitopes appear to be mapped on two rather distant antigenic domains. Combinations of any two antibodies binding to different domains give immunoprecipitates with PLAP on Ouchterlony tests and give good response in sandwich enzyme-linked immunosorbent assays. A study of PLAP-like enzyme in 32 individual testis samples indicates differences in four of the epitopes when compared with PLAP. Four types of testicular enzymes can be distinguished based on their reactivities. These results indicate structural differences between the testicular PLAP-like enzyme and PLAP. These differences are compatible with an underlying genetic mechanism.
Alkaline Phosphatase↗
Evaluation of carcinoembryonic antigen, tissue polypeptide antigen, placental alkaline phosphatase, and modified nucleosides as biological markers in malignant lymphomas.
We have evaluated CEA, TPA, PLAP in sera from patients with three different kinds of malignant lymphomas. Six modified nucleosides, psi, m1A, m1G, m1I, m2G, and m2(2)G were analyzed in the urine from the same group of patients. The histological diagnoses were histiocytic lymphoma (21 patients), lymphocytic lymphoma (19 patients) and Hodgkin's disease (23 patients). The patients were classified into four different clinical stages. Consecutive samples were analyzed before and during ongoing radiotherapy and chemotherapy and during the post-treatment period. Our results showed that TPA and PLAP had limited value as biological markers for patients with malignant lymphomas. For CEA a possible correlation with clinical stage was observed only in patients with Hodgkin's disease. The modified nucleosides, especially psi, showed a correlation with clinical stage for patients with all three diagnoses. Elevated levels of psi in urine were in healthy adults 4%, in patients in clinical stage 1 14%, and in patients with advanced disease 62%. Six cases showed a good correlation between the change in clinical stage upon treatment and the parallel change in the level of psi in the urine. Our results suggest that modified nucleosides, especially psi, are valuable as biological markers for patients with malignant lymphomas.
Adolescent↗
A clinical evaluation of serum placental alkaline phosphatase in seminoma patients.
Serum levels of placental alkaline phosphatase (PLAP) were measured in 100 patients with seminoma. A specific double antibody radioimmunoassay was used. PLAP was elevated for 9 out of 21 patients with primary tumours, to a mean of 53 micrograms/l. Of the 12 cases with recurrent or metastatic growth, nine had raised PLAP. The sensitivity of PLAP determinations for primary and advanced disease was 55%. After successful treatment of seminoma, the PLAP level decreased. In a group of 68 patients with no evidence of disease, nine had slightly elevated serum PLAP. In many, but not all patients, serum PLAP parallelled the changes in tumour burden. In such patients and for follow-up of treatment, PLAP might be used as a new marker for seminomatous disease.
Adult↗
Tumor markers in bronchogenic carcinoma. An evaluation of carcinoembryonic antigen, tissue polypeptide antigen, placental alkaline phosphatase and pseudouridine.
From 62 patients with bronchogenic carcinoma, carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), placental alkaline phosphatase (PLAP) in serum and pseudouridine, a modified nucleoside, were analysed in urine. About 60 per cent of the patients had squamous cell carcinoma, and 20 per cent had small cell carcinoma. The patients were allocated into 3 different clinical stages based upon tumor burden, and the markers were analysed before treatment and thereafter. TPA and PLAP had limited value as biologic markers. For both CEA and pseudouridine the frequency of elevated values increased parallel to clinical stage. Elevated levels of these 2 markers were also correlated to shorter survival.
Adult↗
A possible new locus of alkaline phosphatase expressed in human testis.
Human testes contain trace amounts of heat-stable placental-like alkaline phosphatase. Using a recently described allotype-specific monoclonal antibody (F11) toward placental alkaline phosphatase (PLAP), we show that the frequencies of reactivity of the testis enzymes differ greatly from those of the placental phenotypes. By means of the enzyme inhibitors L-Phe, L-Phe-gly-gly, L-Leu, and L-Leu-gly-gly, the testis enzyme can be clearly distinguished in all cases from the placental enzyme. These results argue that the testis enzyme is not a product of the placental gene and suggest the possible existence of a new locus of alkaline phosphatase.
Adult↗
Genetic variants of placental alkaline phosphatase as detected by a monoclonal antibody.
Human placental alkaline phosphatase (PLAP) is a highly polymorphic enzyme. Several common as well as rare allelic forms of PLAP are characterized in this paper in terms of their reactivity with a murine monoclonal antibody (F11). The common type 1 (S) and 3 (I) variants, and the rare type 4 (S2) and 18 (D) variants were found to react with the F11 antibody, so as did three new electrophoretically defined variants (19, 20, and 21). In contrast, the common type 2 (F1) variant and the rare type 8 (F3) and 9 (F2) variants do not react with the F11 antibody. This selective reactivity of F11 has also allowed the identification of two molecular variants of PLAP with identical electrophoretic mobility. These results establish monoclonal antibodies as invaluable adjuncts in the study of PLAP polymorphism.
Alkaline Phosphatase↗
Carbohydrate complexity of the mouse thymocyte Thy-1 glycoprotein as demonstrated by lectin affinity and isoelectric focusing.
The Thy-1 glycoprotein of mouse thymocytes was analysed with regard to the properties of its carbohydrate part. Of the different lectins tested, partial binding of Thy-1 from membrane extracts was found to Lens culinaris agglutinin (approximately 50%) and wheat germ agglutinin (approximately 25%). In contrast, concanavalin A bound all Thy-1. The results indicate that there is considerable microheterogeneity in the oligosaccaride chains within the Thy-1 population. Thy-1 was purified from thymocyte membrane extracts by concanavalin A affinity chromatography and gel filtration. The purified preparation revealed, on analysis by isoelectric focusing, at least six charge variants (isoelectric points ranging from approximately 5-9). These variants were isolated, treated with neuraminidase and tested for lectin binding and isoelectric point. It was shown that the charge heterogeneity was due to different amounts of sialic acid; even the most basic form contained at least one sialic acid residue. Furthermore, it was concluded that the degree of sialylation was not correlated to the lectin-binding properties. Analysis of Thy-1 from surface 125I-labelled thymocytes showed that the purified preparation was representative in its complexity of the Thy-1 glycoprotein exposed on the surface membrane. The possible biological implications of the findings are discussed.
Animals↗
Estrogenic potency of oral replacement therapy estimated by the induction of pregnancy zone protein.
The induction of a highly estrogen-inducible plasma protein, the pregnancy zone protein/pregnancy associated alpha 2-globulin (PZP/PA alpha 2 G), was used to design a sensitive method to quantify and compare the potency of various estrogens commonly used in clinical practice. Serum PZP levels were followed in 100 post-menopausal women during 6 months' estrogen replacement therapy. Ethinyl estradiol caused more marked changes than the natural estrogens. Conjugated estrogens were more potent than estrone sulphate and estradiol-17 beta which had similar values. Estriol, irrespective of daily dosage, exerted a negative effect. The following sequence of equipotency was calculated: ethinyl estradiol = 100 x conjugated estrogens = 450 x estrone sulphate = 500 x estradiol-17 beta = 650 x estradiol valerate. These data were compared with other estimates of estrogenic potency from the literature. Compared with other clinical methods, PZP induction offers several advantages. Factors such as intestinal absorption, protein binding and intracellular metabolism are included in the net result of an increased protein synthesis which is easily followed in patients' sera during therapy.
Climacteric↗
The genetic basis of alkaline phosphatase isozyme expression.
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Alkaline Phosphatase↗
Characterization and use of an allotype-specific monoclonal antibody to placental alkaline phosphatase in the study of cancer-related phosphatase polymorphism.
The hybridoma technique was used to produce an allotype-specific monoclonal antibody (F11) that reacts with the products of the S, I, and D alleles of PLAP but not of the F allele. Serum and ascites samples from patients with different cancers containing high levels of PLAP were tested for reactivity with F11. These tumor-derived PLAPs were of the Nagao type as shown by their sensitivity to inhibition by L-leucine. This type of inhibition is exhibited also by the rare D allelic variant of PLAP but not by the common forms. Thus, it has been proposed that the Nagao enzyme represents reexpression of the D allele of PLAP. F11 reactive and nonreactive samples as well as samples with intermediate reactivity were found among the cancer sera and ascites. Our results show tha tumor-derived Nagao enzyme does not represent the reexpression of the D allele but instead, in spite of its distinct inhibition pattern, expresses the same genetic polymorphism that is found in the placenta.
Alkaline Phosphatase↗
Placental alkaline phosphatase as a tumor marker for seminoma.
A sensitive and specific enzyme-linked immunoabsorbent assay was used in a retrospective study of serum levels of placental alkaline phosphatase (PLAP) in testicular cancer. Sixteen of 28 men with active seminoma had elevated PLAP levels, and 71% had elevated levels of either PLAP, human chorionic gonadotropin, or both. Only four of 22 men with active nonseminomatous cancer had elevated PLAP levels, and the levels were normal in all control patients, including 33 men apparently cured of testicular cancer. In six of ten serial studies, PLAP levels provided information not otherwise available that would have been useful clinically, and the levels never were elevated inappropriately. Our data suggest that PLAP is a clinically useful serum tumor marker for seminoma.
Alkaline Phosphatase↗
Effects of sex hormone binding globulin capacity and pregnancy zone protein of treatment with combinations of ethinyl-oestradiol and norethisterone.
Sex hormone binding globulin (SHBG) and pregnancy zone protein (PZP) are two highly oestrogen-inducible serum proteins. SHBG capacity and PZP level were measured in 49 women treated with three different combinations of ethinyloestradiol and norethisterone. SHBG capacity and PZP were measured before and after 6 mth of treatment and both serum factors significantly increased during treatment for all three groups. PZP induction was found to be more sensitive and mainly to reflect the oestrogen component of a combined preparation while SHBG capacity was more sensitive to the modulating effect of the progestogen.
Dose-Response Relationship, Drug↗
51cr-release assay for quantitation of membrane bound and solubilized Thy-1 antigen.
A method for quantitative determination of mouse Thy-1 antigen is presented. Antigen to be assayed is incubated with anti-Thy-1 serum and remaining antibody activity is measured by adding 51Cr-labelled thymocytes and complement. The detection limit corresponds to the amount of Thy-1 antigen exposed on the surface of 25,000 thymocytes, which can be calculated to correspond to approximately 0.5 ng. The assay was designed to be performed in the presence or absence of detergent, and is therefore a useful tool for quantitation of Thy-1 in purification procedures and studies on the biological significance of this membrane antigen.
Animals↗
Manifestation and growth of a transplantable osteosarcoma in mice: the effects of thymectomy and thymosin treatment.
Normal and thymectomized CBA mice treated with and without thymosin were injected with 2 x 10(6) viable osteosarcoma cells. The activity and weight of tumors, the cell-mediated and humoral-immune responses against the tumors, and the light microscopic characteristics suggested that thymectomy resulted in a significantly decreased tumor frequency. There were also significant increases in cell-mediated cytotoxic activity in vitro as measured by lysis of 51Cr-labeled tumor cells incubated with spleen cells, and in lymphocytic infiltration around the tumors. While thymosin treatment of thymectomized mice restored these parameters to those of intact animals, thymosin had no demonstrable effects on nonthymectomized animals.
Animals↗
Serum levels of the "pregnancy-zone protein" during short-term prenatal dexamethasone therapy.
The serum concentrations of the "Pregnancy Zone Protein" (PZP) was followed in 5 patients treated with dexamethasone (12 mg per day for 1 week) in the third trimester of pregnancy. The serum concentration of PZP was found to decrease significantly to an average of 58 per cent of the pretreatment levels. The simultaneous change in serum estriol levels during treatment and other factors of possible importance for the serum concentration of PZP are discussed.
Dexamethasone↗
"Sandwich" enzyme immunoassay for placental alkaline phosphatase.
Alkaline phosphatase of the placental type in serum has been suggested as a "marker" for malignancy and pregnancy. We describe a highly sensitive enzyme-linked immunosorbent assay (ELISA) for the measurement of this enzyme in serum and ascitic fluid. The assay will detect as little as 0.4 microgram/L, significantly less than with a radioimmunoassay performed with the same reagents. It is highly specific; it does not measure even above-normal concentrations of the intestinal and liver isoenzymes of alkaline phosphatase. The assay is technically simple and allows the processing of many samples in less than 10 h. We measured this isoenzyme in serum of an adult control population. The upper limit of normality is 1.85 microgram/L. Interference by rheumatoid factor was eliminated. Concentrations of the analyte were increased in all pregnancy sera tested. Concentration and activity as measured by two different catalytic assays correlated well. Samples from cancer patients also showed a good correlation, with some exceptions. Possible reasons for these exceptions are discussed. The high sensitivity, specificity, and simplicity of this assay should make it a useful adjunct in monitoring cancer and pregnancy.
Alkaline Phosphatase↗
Skeletin immunoreactivity in peripheral nerves.
By use of monospecific antibodies against the cow heart intermediate filament protein, skeletin, an antigenic relationship between skeletin and neurofilament protein of peripheral nerves is demonstrated. Crossreactivity is also demonstrated in the filament-containing Schwann cells. The results are consistent with the existence of several subclasses of related intermediate-sized filament proteins.
Animals↗