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

We have established reference ranges for three microvillar intestinal enzymes--alkaline phosphatase (EC 3.1.3.1), gamma-glutamyltransferase (EC 2.3.2.1), and leucine aminopeptidase (EC 3.4.1.1)--measured in amniotic fluid in a reference population of 1875 women presenting for routine amniocentesis. These data were derived for use in prenatal diagnostic studies in a population at risk (1:4) for cystic fibrosis. False-positive or indeterminate results were noted for fewer than 3.5% of all low-risk cases for each enzyme evaluated. Total alkaline phosphatase and its isoenzymes and leucine amino-peptidase and gamma-glutamyltransferase were measured in amniotic fluid sampled between the 15th and 19th weeks of gestation. Restriction fragment length polymorphism analysis of DNA was also performed when possible. In 52 cases examined for cystic fibrosis thus far, 46 were diagnosed on the basis of DNA analysis and (or) by sweat testing; for the other six cases, only abnormal enzyme results were obtained before termination of pregnancy. Predictions based on microvillar enzyme results were falsely negative in three cases. In only one case was there a discrepancy between enzyme results and DNA analysis. Diagnostic accuracy was highest during the 17th and 18th week of gestation. Preliminary results suggest the false-negative rate of this diagnostic strategy may be greater than or equal to 10%.
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PMID:Prenatal diagnosis of cystic fibrosis: microvillar enzymes and DNA analysis compared. 289 57

We determined the activity concentrations of alkaline phosphatase (ALP), ALP isoenzymes, gamma-glutamyltransferase (GGT), and alpha-glucosidase (AGL) in 1200 unselected amniotic fluids and in amniotic fluids from 40 pregnancies at high risk for cystic fibrosis (CF). From the results we established the normal range and CF-predictive cutoff values for these enzymes in the second trimester of pregnancy. In all predicted normal pregnancies that went to term, normal children were born. Among the predicted affected pregnancies, 14 were terminated and two went to term, one resulting in a CF-affected child and the other in a healthy child. Evidence for CF was found in all 13 aborted fetuses examined (the parents of one refused to allow autopsy). We noted no differences in the amniotic fluid enzyme activities for the Arab and various Jewish ethnic groups living in Israel. We conclude that prenatal diagnosis of CF among the Israeli population at risk for CF is feasible by means of a reliable, fast, and economic test in the second trimester of pregnancy.
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PMID:Enzyme analysis of amniotic fluid for prenatal diagnosis of cystic fibrosis in high-risk pregnancies. 290 7

This paper reports further study of the identity and function of a protein shown to be elevated in serum from cystic fibrosis (CF) patients and clinically normal heterozygotes. Monoclonal antibodies, specifically recognizing the tentatively named cystic fibrosis antigen (CFAg), were produced. Immunoaffinity purification of CFAg from several sources revealed two components: 11 x 10(3) and 14 x 10(3) Mr protein. cDNA clones corresponding to each protein have been isolated. Data-base comparisons of the deduced amino acid sequences suggest that both genes encode related but distinct calcium-binding proteins. We propose the name calgranulin A and B, for the 11 x 10(3) and 14 x 10(3) Mr components, respectively. It is clear from the assignment of the calgranulin genes to chromosome 1 that neither is the product of the mutant CF gene, which maps to chromosome 7. We have used the monoclonal antibodies to study the tissue distribution of the two proteins in a wide-ranging immunohistological survey. Where possible the pattern of expression was confirmed by RNA blot analysis. Strong calgranulin expression in granulocytes was confirmed. In addition to myeloid cells, a restricted subset of normal stratified squamous epithelia were found to be calgranulin-positive. These included tongue, oesophagus and buccal cells, the last of which has been shown to have altered calmodulin activity in CF patients. Using indirect alkaline phosphatase staining, tissue sections of lung, pancreas and skin (normally considered sites where the CF defect is expressed) were not calgranulin-positive. However, by indirect immunofluorescence, nasal polyp sections showed weak patchy calgranulin expression in some epithelial cells, and stronger, higher frequency expression when such cells were briefly cultured.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression pattern of two related cystic fibrosis-associated calcium-binding proteins in normal and abnormal tissues. 326 95

Prenatal diagnosis of cystic fibrosis by microvillar enzyme assay on amniotic fluid supernatant has been carried out on 258 sequential pregnancies with a 1 in 4 recurrence risk, all with known outcome. In general the three enzymes evaluated, gamma-glutamyltranspeptidase, aminopeptidase M and the intestinal isoenzyme of alkaline phosphatase, showed a high degree of concordance. However, there were two unusual patterns of microvillar enzyme activity; in seven cases a low gamma-glutamyltranspeptidase activity was associated with elevated values of intestinal alkaline phosphatase, and in ten cases there were isolated low values of intestinal alkaline phosphatase. The former pattern was found to be associated with cystic fibrosis in five cases, while the latter was associated with a normal outcome in all ten cases. A retrospective analysis of enzyme values suggested that the optimal system for minimizing false positives and false negatives was to define foetal cystic fibrosis as a sample where two of the three microvillar enzymes were below a cut-off of half the median value for the gestational week. If such scoring were applied to the cases where conventional microvillar enzyme patterns were observed, the false positive rate was 2.3% and the false negative rate 4.4% between 17 and 20 weeks of gestation.
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PMID:Prenatal diagnosis of cystic fibrosis by microvillar enzyme assay on a sequence of 258 pregnancies. 334 16

Amniotic fluid analysis of microvillar enzymes, including alkaline phosphatase (ALP) total activity and ALP isoenzymes, has been widely experimented with and used for the prenatal diagnosis of cystic fibrosis in the second trimester of gestation. Since the development of cystic fibrosis molecular analysis, interest in these biochemical tests has been maintained for those instances in which the pregnancy is not fully informative by restriction fragment length polymorphism analysis or DNA is not available from the index-affected child. However, recommended biochemical protocols do not provide clear-cut diagnostic results in a minority of cases. We have tested the reliability of cystic fibrosis biochemical prediction by ALP high-resolution electrophoresis and ALP kinetic studies after inactivation by urea. With this approach, all the amniotic fluid samples that had not been unambiguously classified as affected or unaffected by standard microvillar enzymes analysis were definitely categorized. The proposed method seems to improve the diagnostic accuracy in pregnancies with a one in four risk of resulting in a child with cystic fibrosis.
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PMID:Protocol for prenatal diagnosis of cystic fibrosis based on studies of alkaline phosphatase isoenzymes. 339 23

Immunoreactive trypsin (IRT) has been studied in amniotic fluid as a possible complementary test substance for the prenatal diagnosis of cystic fibrosis (CF). 219 normal amniotic fluids have been tested in order to establish the normal ranges from 14 to 40 gestational weeks (g.w.). The IRT level increases from g.w. 14 to 19, remains stable from g.w. 19 to 25 and then decreases rapidly to low levels. A retrospective study of 4 presumed CF fluids, as determined by abnormal alkaline phosphatase levels, showed decreased IRT values in 3 out of 4 fluids. The difference between the mean value and the normal mean was not significant. The prospective study allowed us to test 2 fluids from pregnancies affected by meconium ileus. IRT level was highly elevated, 530 times the normal mean value at g.w. 34 for a non-CF fetus and 18 times the normal mean value for a CF fetus at g.w. 31. In 4 out of 5 cases of fetal severe intra-uterine growth retardation, IRT levels appeared mildly elevated. Other abnormalities are reviewed.
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PMID:Amniotic immunoreactive trypsin in pregnancies with normal and pathological outcomes. 343 39

Prenatal diagnosis of cystic fibrosis was performed in 200 pregnancies with a 1-in-4 risk, and was based on significant modifications in amniotic fluid taken at 17, 18, 19 weeks of pregnancy, of six enzymatic assays: gamma-glutamyl-transpeptidase, aminopeptidase M, and alkaline phosphatase (total and isoenzymes). On the basis of normal values, normal outcome was predicted in 135 pregnancies reaching term, all the babies were normal. On the basis of significantly abnormal enzymatic values, an affected fetus was predicted in 56 pregnancies, 53 were terminated, and 3 went to term; the infants were affected. There were discrepancies in enzymatic values in nine cases, in eight cases normal outcome was predicted, six babies were normal and two were affected; in one case an affected baby was predicted, the pregnancy went to term and the baby is normal. Criteria giving evidence for cystic fibrosis in fetuses have been described: macroscopic observation of a typical meconium ileus, significant increase of albumin content in the meconium, and PAS-positive mucus-like material in some pancreatic acini. Using these criteria, diagnosis of cystic fibrosis has been confirmed in all the examined fetuses. The recurrence rate of cystic fibrosis was 22.5% in 147 diagnoses in which the index case had cystic fibrosis without a history of meconium ileus at birth, but was 47.5% when the index case had meconium ileus. The results of the study suggest that prenatal diagnosis of cystic fibrosis can be performed with an accuracy of 98%.
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PMID:Prenatal diagnosis in 200 pregnancies with a 1-in-4 risk of cystic fibrosis. 353 26

Adult cystic fibrosis (CF) patients are increasingly diagnosed with hepatic cirrhosis, cholecystitis, and cholelithiasis. A continuing diagnostic problem is the early detection of cirrhosis prior to diffuse liver involvement. Sonography has been used in evaluating the pancreas, gallbladder, liver, and spleen in cystic fibrosis patients. We used a real-time mechanical sector scanner to study the portal veins in adult CF patients randomly selected from our CF population and correlated the portal vein diameters with liver function studies. A measurement greater than 12 mm was interpreted as a probable sign of portal hypertension. Of 21 patients studied, 14 had portal veins that measured greater than 12 mm, and 12 patients had (although not necessarily at the time of the exam) elevated serum alkaline phosphatase levels. Three patients had associated splenomegaly and thrombocytopenia, and 10 patients also exhibited cholelithiasis and abnormal gallbladders on sonography. Initial results indicate that portal vein measurement may be a sensitive indicator of early portal hypertension. Sonography may, thus, isolate patients at high risk for possible future complications. Serial sonograms can be performed easily in evaluating the progress of liver disease.
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PMID:Portal vein measurement by ultrasonography in patients with long-standing cystic fibrosis: preliminary observations. 354 Feb 61

The potential value of microvillar enzymes in the prenatal diagnosis of cystic fibrosis (CF) has previously been demonstrated and is corroborated in the present comparative study. Maltase and alkaline phosphatase (ALP) activities were studied in the amniotic fluids of 57 pregnancies with a 1 in 4 risk for CF or with a known CF outcome and in 489 controls. A simple assay for maltase activity (MU-maltase) with the fluorogenic substate 4-methylumbelliferyl alpha-glucoside, offers great technical advantages and an at least equal detection rate of CF, when compared to the previously used test with maltose as substrate. Intestinal ALP was estimated either as phenylalanine inhibitable activity (PI-ALP) or as the proportions of residual activity in the presence of the inhibitors phenylalanine or homoarginine. MU-maltase and PI-ALP appeared the most successful methods: both tests were able to detect 14 of the 16 (88 per cent) pregnancies with fetal CF. Each of the two tests alone also allowed a correct prediction in 24 of the 25 pregnancies at risk but with normal outcome; however all 25 cases could be correctly predicted by a combined evaluation. It is suggested that more than one intestinal enzyme activity should be evaluated to allow optimal results in the prenatal monitoring of pregnancies at high risk for CF.
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PMID:Prenatal detection of cystic fibrosis; comparative study of maltase and alkaline phosphatase activities in amniotic fluid. 354 22

Utilizing their differential susceptibilities to inhibitors and heat, we determined the amounts of the placental, liver, and fetal-intestinal isoenzyme forms of alkaline phosphatase in 143 samples of normal amniotic fluid obtained at 14 to 18 weeks' gestation (1). For reliable results, it was necessary to standardize inhibition profiles for each pure isoenzyme in amniotic fluid. Total activity and the absolute amounts of placental and fetal-intestinal activities were significantly related to gestational age (p less than 0.05). These relationships that were absent when activities were expressed as percentages of the total. The mean isoenzyme composition of the 143 samples, expressed as a percentage of total alkaline phosphatase activity, was: placental, 3.4%; liver, 9.8% (maximum, 47%); and fetal intestinal, 87% (minimum, 53%). The presence of phosphate in the assay medium (13.5 mmol/L) profoundly and differentially inhibited the isoenzymes of alkaline phosphatase and changed the inhibition profiles of the tissue-specific enzymes; thus, it would not be feasible to use inhibitors to differentiate the forms. We therefore propose a phosphate-free technique for quantifying the isoenzymes of alkaline phosphatase in amniotic fluid obtained at 14 to 18 weeks' gestation, to achieve the highest predictive values in a prenatal diagnostic test for cystic fibrosis.
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PMID:Isoenzymes of alkaline phosphatase in amniotic fluid: implications in prenatal screening for cystic fibrosis. 369 Aug 26


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