Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using a solid-phase monoclonal antibody enzyme immuno-assay, we evaluated in a multicenter study (18 laboratories) the utility of evaluating catalytic activity of human placental alkaline phosphatase (hPLAP, EC 3.1.3.1) in serum as a potential tumor marker. We determined hPLAP in serum samples from 130 patients with ovarian cancer, 79 patients with testicular cancer (53 seminoma testis, 26 nonseminoma testis), 537 patients with various other malignant diseases (95 lung, 39 gastrointestinal, 195 breast, 208 others), 291 patients with benign diseases, and 213 healthy controls. To assess the influence of smoking on hPLAP activity in serum, we evaluated 79 serum samples from patients with noncancerous diseases for whom smoking habits had been recorded. Our main findings are: (a) hPLAP activity is frequently increased (greater than 100 mU/L) in pre-operative serum samples from ovarian cancer patients (49%) and from testicular cancer patients (59% overall; 72% seminoma, 35% nonseminoma); (b) heavy smoking may increase hPLAP activity; (c) excluding heavy smokers, a 96% specificity for cancerous lesions was observed; (d) in patients with ovarian malignancies, CA 125 and hPLAP may behave as independent markers; and (e) in patients with seminoma, hPLAP is clearly more frequently increased than is beta-choriogonadotropin.
 ...
PMID:Multicenter evaluation of human placental alkaline phosphatase as a possible tumor-associated antigen in serum. 316 10

In 1930 the determination of serum alkaline phosphatase in patients with bone or liver disease ushered in the era of clinical enzymology. The association of elevated (bone) alkaline phosphatase in serum of patients with osteogenic sarcoma was the first evidence that tumor cells themselves produced the enzyme. It became clear, however, in the 1960s that the serum alkaline phosphatase was not a single enzyme but consisted of a family of isozymes originating from liver, bone, intestine, and placenta. This was a consequence of the introduction of a combination of electrophoretic separations, heat inactivation, and organ-specific amino acid inhibitors. This combination of measurements made possible the demonstration of a serum alkaline phosphatase of lung cancer origin, as confirmed by the histochemical visualization in lung cancer of the Regan Isozyme (placental alkaline phosphatase-PLAP). At present, the measurement of PLAP has its greatest utility as a tumor marker in seminoma and ovarian cancer. A PLAP-like isozyme in normal testis and ovary is expressed in these and other neoplasias and appears to be related to rare alleles of placental alkaline phosphatase. Current studies have utilized a panel of monoclonal antibodies to detect useful epitopes that suggest that PLAP and PLAP-like isozymes are coded by different genes. The PLAP gene has now been cloned and sequenced by Millan and others. This fundamental new information is providing a base line that will make it possible to explain the overlapping specificities of intestinal and placental isozymes, the degree of uniqueness of the PLAP-like isozyme, the precise mechanism of uncompetitive inhibition by L-phenylalanine and the evolutionary history of the alkaline phosphatases.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Clinical and biological significance of an isozyme tumor marker--PLAP. 332 92

In order to determine the subchromosomal location of the gene for human placental alkaline phosphatase (ALPP; EC 3.1.3.1.), a cDNA probe encompassing most of the ALPP translated sequences was hybridized in situ to metaphase chromosomes. Our results confirm previous assignment of the gene to chromosome 2 and allow its regional mapping to band q37.
 ...
PMID:Regional mapping of the human placental alkaline phosphatase gene (ALPP) to 2q37 by in situ hybridization. 335 75

Isoenzymes of alkaline phosphatase (EC 3.1.3.1) were separated by micro-scale two-dimensional electrophoresis, with isoelectric focusing in capillary gels in the first dimension and polyacrylamide gradient-gel electrophoresis in the second. The isoenzymes detected were identified by several treatments--e.g., incubation with sialidase, papain, Triton X-100, and wheat-germ agglutinin--and by comparison with alkaline phosphatase from liver microsomes. Liver and bone isoforms in normal sera showed overlapping isoelectric points but differed in molecular mass, estimated as 172 and 185 kDa, respectively. Sera of patients with liver disease showed several additional groups of alkaline phosphatase isoforms, two of which were found to consist of multi-molecular complexes. Others probably correspond to incompletely glycated enzyme proteins. A further isoform with a mass of about 250 kDa does not seem to correspond to any known isoform of alkaline phosphatase in serum. With this technique, we demonstrated intra- and interindividual variations of the placental alkaline phosphatase isoenzyme in pregnancy sera.
 ...
PMID:Micro-scale two-dimensional electrophoresis of alkaline phosphatase from serum. 335 9

Alkaline phosphatase in human milk was found to be heat stable and have a molecular size of placental alkaline phosphatase, a Mr of 160,000. However, the milk alkaline phosphatase is different from placental alkaline phosphatase. The alkaline phosphatase from milk was endowed with higher surface charge and not inhibited by L-phenylalanine (2.5 mmol/l) and L-homoarginine (10 mmol/1). Both enzymes are sialylated.
 ...
PMID:Alkaline phosphatase in human milk: a new heat-stable enzyme. 342 78

Amino-terminal amino acid sequences (42 residues) were determined for the products of the three common alleles at the human placental alkaline phosphatase [orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1] gene locus. The sequences differ at position 3, which is proline in types 1 and 2 but is leucine in type 3. cDNA libraries were constructed in phage lambda gt11 and used to isolate clones covering the coding regions of types 1 and 3 cDNAs. Comparison of the deduced amino acid sequences of the types 1 and 3 proteins showed 7 differences out of 513 amino acids, each due to a single base substitution. cDNA sequence comparisons showed three silent substitutions in the coding regions and three base differences in the greater than 1 kilobase pairs of 3' untranslated sequences.
 ...
PMID:Products of two common alleles at the locus for human placental alkaline phosphatase differ by seven amino acids. 346 52

Human placental alkaline phosphatase (HPLAP), carcinoembryonic antigen (CEA), and cancer antigen 125 (CA 125) were localized immunohistochemically in paraffin sections of normal lung tissue from 16 patients, using monoclonal antibodies and an indirect avidin-biotin-peroxidase staining procedure. HPLAP and CEA were present in epithelial cells of respiratory bronchioli and alveolar type I pneumocytes. CEA was also observed in the tracheal, bronchial, and bronchiolar epithelium. CA 125 was present in the tracheal, bronchial, bronchiolar, and terminal bronchiolar epithelium; in the tracheal and bronchial glands; and in the pleural mesothelium. Normal and hyperplastic type II pneumocytes were negative for HPLAP, CEA, and CA 125 but were histochemically positive for nonspecific alkaline phosphatase. Fetal lung tissue between 11 and 15 weeks of gestation was negative for HPLAP, CEA, and CA 125. The fetal tracheal and bronchial epithelium, tracheal glands, and pleural mesothelium were positive for CA 125. For ten malignant pulmonary tumors investigated, HPLAP staining was observed in five, CEA in nine, and CA 125 in seven. The localization of HPLAP, CEA, and CA 125 in apparently normal constituents of all pulmonary specimens is in disagreement with the concept that the expression of these substances in the lung is indicative of abnormal cellular activity.
 ...
PMID:Immunohistochemical localization of placental alkaline phosphatase, carcinoembryonic antigen, and cancer antigen 125 in normal and neoplastic human lung. 351 76

The complete amino acid sequence of the precursor and mature forms of human placental alkaline phosphatase have been inferred from analysis of a cDNA. A near full-length PLAP cDNA (2.8 kilobases) was identified upon screening a bacteriophage lambda gt11 placental cDNA library with antibodies against CNBr fragments of the enzyme. The precursor protein (535 amino acids) displays, after the start codon for translation, a hydrophobic signal peptide of 21 amino acids before the amino-terminal sequence of mature placental alkaline phosphatase. The mature protein is 513 amino acids long. The active site serine has been identified at position 92, as well as two putative glycosylation sites at Asn122 and Asn249 and a highly hydrophobic membrane anchoring domain at the carboxyl terminus of the protein. Significant homology exists between placental alkaline phosphatase and Escherichia coli alkaline phosphatase. Placental alkaline phosphatase is the first eukaryotic alkaline phosphatase to be cloned and sequenced.
 ...
PMID:Molecular cloning and sequence analysis of human placental alkaline phosphatase. 351 48

High-level synthesis of the periplasmic protein beta-lactamase in Escherichia coli caused the formation of insoluble protein precipitates called inclusion bodies. beta-Lactamase inclusion bodies differed from those reported previously in that they appeared to be localized in the periplasmic space, not in the cytoplasm. The inclusion bodies contained mature beta-lactamase and were solubilized more easily than has been reported for cytoplasmic inclusion bodies. In contrast, overproduction of the periplasmic protein alkaline phosphatase caused the formation of cytoplasmic inclusion bodies containing alkaline phosphatase precursor.
 ...
PMID:Localization of inclusion bodies in Escherichia coli overproducing beta-lactamase or alkaline phosphatase. 353 17

We have identified two mRNAs in rat intestinal mucosa by Northern blot analysis, using cloned cDNAs encoding human placental alkaline phosphatase (PLAP). Probes from both the NH2- and COOH-terminal ends of the human PLAP coding region identified, in rat intestine (especially duodenum), an mRNA of nearly identical size (3 kb) to that found in human placenta. A smaller mRNA (2.7 kb), detected only with the COOH-terminal probe, was more prevalent in jejunum. Following feeding of triacylglycerols, the prevalence of the 2.7 kb mRNA increased over 2-fold. The tissue distribution and response of the 2.7 kb mRNA to fat feeding corresponds exactly with the known behavior of the secreted alkaline phosphatase.
 ...
PMID:Fat feeding stimulates only one of the two mRNAs encoding rat intestinal membranous and secreted alkaline phosphatase. 359 43


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>