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Biomedical subjects

R A Mulivor

Publications and source records attributed to R A Mulivor.

At least 19 recordsLinked to original sources
PubMed1991

Raised urinary excretion of inorganic pyrophosphate in asymptomatic members of a hypophosphatasia kindred.

We report the screening of an Anglo-Welsh kindred in which two children were affected by different clinical forms of hypophosphatasia. Among the clinically normal adult members of the kindred, a raised urinary concentration of pyrophosphate was the commonest biochemical abnormality. The concentration of phosphate in serum was elevated in only one adult member of the kindred, the mother of the propositus. Consanguinity in this kindred suggests probable recessive inheritance, and the obligate heterozygotes each exhibited a low serum AP activity plus one other biochemical abnormality indicative of a carrier state.

Adult↗
PubMed1991

Intrauterine cytomegalovirus infection presenting as fetal meconium peritonitis.

Recent reports have suggested that focal hyperechoic abdominal masses detected during the second trimester may represent a normal variation in fetal intestinal development that is transient in nature and not associated with pathologic conditions. The patient described here had second-trimester ultrasonic findings of fetal meconium peritonitis without ascites, polyhydramnios, or other anomalies. Subsequent ultrasound examinations at 22, 30, and 36 weeks demonstrated no change in the abdominal appearance. At birth, this preterm male infant had clinical symptoms of congenital cytomegalovirus infection confirmed by viral culture and serologic studies. Retrospective studies of maternal serum obtained early in the second trimester confirmed a primary cytomegalovirus infection 4 weeks before the initial ultrasound examination. Although fetal hydrops and ascites have occasionally been associated with intrauterine cytomegalovirus infection, fetal meconium peritonitis has not been previously recognized in patients with congenital cytomegalovirus.

Adult↗
PubMed1989

Benign familial hyperphosphatasemia.

Elevated alkaline phosphatase activity in serum suggests bone or liver disease or a neoplasm but can also indicate pregnancy or another benign condition. A family with benign hyperphosphatasemia was studied to elucidate the genetics and enzyme defect. Serum total alkaline phosphatase activity was greater than the population mean in all six family members, and more than 7 SDs above the mean in two of four offspring. Monoclonal antibodies to three alkaline phosphatase isoenzymes, intestinal, placental, and tissue nonspecific (liver/bone/kidney), demonstrated markedly increased intestinal alkaline phosphatase levels (29% to 44% of total) in all family members and significantly elevated liver/bone/kidney activity in the two offspring. Guanidine hydrochloride denaturation of the liver/bone/kidney component showed high alkaline phosphatase activity from liver in both siblings and from bone in one. The mode of inheritance in this family is obscure, but a complex regulation of the products of two different alkaline phosphatase genes seems likely. Steps toward diagnosis are suggested. Early recognition of this benign biochemical abnormality should help to avoid unnecessary diagnostic tests.

Adult↗
PubMed1989

Analysis of liver/bone/kidney alkaline phosphatase mRNA, DNA, and enzymatic activity in cultured skin fibroblasts from 14 unrelated patients with severe hypophosphatasia.

Hypophosphatasia is a heritable disorder characterized by defective bone mineralization and a deficiency of liver/bone/kidney alkaline phosphatase (L/B/K ALP) activity in serum and tissues. Severe forms of the disease, which are generally lethal in infancy, are inherited in an autosomal recessive fashion. The gene defects that produce hypophosphatasia are poorly understood, but many are likely to occur at the L/B/K ALP locus. To investigate these gene defects, we analyzed L/B/K ALP DNA, RNA, and enzyme activity in cultured dermal fibroblasts from 14 patients with perinatal or infantile hypophosphatasia and from 12 normal individuals. Southern blot analyses of the L/B/K ALP genes from patients and controls revealed identical restriction patterns. Control fibroblast ALP activity correlated with the corresponding L/B/K ALP mRNA levels estimated by blot hybridization analysis and densitometry (r = .94, P less than .0001). In contrast, fibroblasts from the hypophosphatasia patients were deficient in ALP enzyme activity but expressed apparently full-sized L/B/K ALP mRNA at normal levels. Bone specimens from one of the patients were examined and found to be deficient in histochemical ALP but contained immunologic cross-reactive material detected by anti-human liver ALP antiserum. Our results demonstrate that the deficiency of ALP activity in fibroblasts from 14 patients with severe hypophosphatasia is not due to decreased steady-state levels of the corresponding mRNA. The presence of enzymatically inactive L/B/K ALP protein in one of these patients is consistent with a point mutation or small in-frame deletion in the coding region of L/B/K ALP gene.

Alkaline Phosphatase↗
PubMed1988

A missense mutation in the human liver/bone/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia.

Hypophosphatasia is an inherited disorder characterized by defective bone mineralization and a deficiency of serum and tissue liver/bone/kidney alkaline phosphatase (L/B/K ALP) activity. Clinical severity is variable, ranging from death in utero (due to severe rickets) to pathologic fractures first presenting in adult life. Affected siblings, however, are phenotypically similar. Severe forms of the disease are inherited in an autosomal recessive fashion; heterozygotes often show reduced serum ALP activity. The specific gene defects in hypophosphatasia are unknown but are thought to occur either at the L/B/K ALP locus or within another gene that regulates L/B/K ALP expression. We used the polymerase chain reaction to examine L/B/K ALP cDNA from a patient with a perinatal (lethal) form of the disease. We observed a guanine-to-adenine transition in nucleotide 711 of the cDNA that converts alanine-162 of the mature enzyme to threonine. The affected individual, whose parents are second cousins, is homozygous for the mutant allele. Introduction of this mutation into an otherwise normal cDNA by site-directed mutagenesis abolishes the expression of active enzyme, demonstrating that a defect in the L/B/K ALP gene results in hypophosphatasia and that the enzyme is, therefore, essential for normal skeletal mineralization.

Alkaline Phosphatase↗
PubMed1987

Analysis of fetal intestinal enzymes in amniotic fluid for the prenatal diagnosis of cystic fibrosis.

Amniotic-fluid intestinal alkaline phosphatase activity, gamma-glutamyltranspeptidase activity, and leucine-aminopeptidase activity were quantitated to assess their reliability for the prenatal diagnosis of cystic fibrosis. The results indicate that for each of these enzymes an arbitrary cutoff point could be chosen that would enable one to correctly predict the outcome for the majority of at-risk pregnancies. However, some false positives and false negatives occurred with each enzyme. To obtain optimal diagnostic discrimination, the three enzyme values obtained for each sample were combined into a single linear discriminant function that proved to be a more accurate indicator of the outcome of the pregnancy. This was especially important for those cases in which the predicted outcome as based on the individual enzyme results was in disagreement. From the cases studied here, it appears that this method can be expected to give a correct prediction in approximately 96.5% of all 25%-at-risk pregnancies. False positives can be expected in approximately 1.4% of the pregnancies and false negatives in approximately 2.2%.

Alkaline Phosphatase↗
PubMed1985

Quantitative analysis of alkaline phosphatases in serum and amniotic fluid: comparison of biochemical and immunologic assays.

An immunoprecipitation method using monoclonal antibodies specific for the three categories of alkaline phosphatases, liver/bone/kidney, placental, and intestinal, is described and compared with the heat denaturation-chemical inhibition method for quantitating the contributions of the various isoenzymes to the total activity in biologic fluids. Activity values for the three categories of isoenzymes present in normal and pregnancy sera as well as in early gestation amniotic fluids were determined by both methods. There is very close correlation between the values obtained by both methods. Thus, two independent procedures are now available for quantitating the contributions of the various alkaline phosphatase isoenzymes in biologic fluids.

Alkaline Phosphatase↗
PubMed1979

Origin of the alkaline phosphatases in amniotic fluid.

The nature and origins of amniotic fluid ALP activity were investigated early (14 to 22 weeks) and late (25 to 44 weeks) in pregnancy. The total enzyme activities for both stages were significantly different and considerable changes in the activities of individual enzyme components occurred. Early activity consists of intestinal (81%), bone/liver/kidney (15%), and placental (4%) ALP. In late fluids, the values are 5%, 69% and 27%, respectively. The intestinal enzyme is shown to be of fetal origin, presumably arising from the direct entry of desquamated intestinal mucosal cells into the amniotic fluid. The bone/liver/kidney enzyme is mostly of maternal serum origin early with an increased fetal contribution toward term. Early in pregnancy, the placental ALP activity is probably derived both directly from the placenta and from the placental activity in maternal serum. The latter source contributes more toward term.

Alkaline Phosphatase↗