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Biomedical subjects

P M Crofton

Publications and source records attributed to P M Crofton.

At least 37 records · Page 2Linked to original sources
PubMed1996

Biochemical markers of bone turnover.

Three studies to evaluate procollagen type I C-terminal propeptide, type I collagen cross-linked telopeptide and bone alkaline phosphatase (BALP) in the assessment of bone turnover and growth in children are presented. (1) In 50 short normal children treated with placebo or growth hormone, delta BALP after 3 months of treatment was highly correlated with height velocity response after 1 year (r = 0.67, p < 0.0001). (2) In 12 children with acute lymphoblastic leukaemia, marked changes in collagen peptides, BALP, and lower leg length velocity were seen during the first 6 months of chemotherapy. Suppression occurred during induction and the two intensification phases, with catch-up during the intervening phase (paired t-tests, p < 0.001). (3) Fourteen babies (birthweight < 1,500 g) treated with high-dose dexamethasone for bronchopulmonary dysplasia were compared with 25 non-steroid-treated babies < 1,500 g. Both collagen peptides decreased rapidly and dramatically (mean decreases 41-68%) after dexamethasone was started, accompanied by weight loss and lower leg shrinkage and followed by recovery during steroid weaning.

Alkaline Phosphatase↗
PubMed1995

Bone alkaline phosphatase and height velocity in short normal children undergoing growth-promoting treatments: longitudinal study.

We studied the temporal and quantitative relation between bone alkaline phosphatase (ALP) and height velocity in 62 short normal children as part of a prospective randomized study to compare placebo, growth hormone, oxandralone, and testosterone, singly and in combination, in promoting short-term growth acceleration and increased final height. The pretreatment cross-sectional correlation between bone ALP and height velocity was poor (P > or = 0.25), but was much higher (P = 0.0001) 3 months after treatment started. In each treatment group, there was a parallel relation between bone ALP and height velocity through time. Individual children showed a variety of growth responses over 12-42 months, but in almost all cases bone ALP paralleled height velocity. Within individual children, bone ALP was strongly correlated with 6-month height velocity (r > 0.9 in 30% of the children, r > 0.7 in 70%). We conclude that bone ALP is a useful short-term marker of growth in short normal children treated with growth hormone.

Adolescent↗
PubMed1992

Albuminuric growth failure. A case of Munchausen syndrome by proxy.

A five-year-old girl presented with profound growth failure, lethargy, vomiting and acidosis. A diagnosis of Munchausen syndrome by proxy was made after the demonstration of egg albumin, diphenhydramine and phenothiazine metabolites in her urine. Growth improved dramatically, but a subsequent child in the family died of sudden infant death syndrome.

Albuminuria↗
PubMed1992

Wheat-germ lectin affinity electrophoresis for alkaline phosphatase isoforms in children: age-dependent reference ranges and changes in liver and bone disease.

This modified lectin affinity electrophoresis method is suitable for simultaneous measurement of liver, bone, and high-molecular-mass (high-Mr) isoforms of alkaline phosphatase (ALP; EC 3.1.3.1) in children. Age-related isoform reference ranges were derived for 247 children, ages 0-13 years. Liver ALP did not appear in plasma until after six months of age, and remained constant after one year of age. Bone ALP was highest in the youngest age group, and declined to relatively constant activities thereafter. High-MrALP was not detected in normal children. In bone disease, the bone isoform was increased in all age groups. In liver disease, only 5 of 30 infants younger than six months had detectable liver ALP, although half had increased bone ALP. Among children older than six months, 5 patients with biliary atresia and 15 patients with hepatitis A all had increased liver isoform activity. Liver ALP was also a sensitive index of early hepatobiliary complications in 27 nonjaundiced children with cystic fibrosis. Measurement of ALP isoforms therefore yields useful clinical information in children older than six months but is of doubtful value in younger infants.

Aging↗
PubMed1988

What is the cause of benign transient hyperphosphatasemia? A study of 35 cases.

In a study of 35 children with benign transient hyperphosphatasemia, I found a marked seasonal clustering of cases after the summer months. Furthermore, plasma 25-hydroxyvitamin D concentrations were almost twice those of controls matched for age and time of year. Many children had evidence of weight loss and one had idiopathic hypercalcemia of infancy. Activities both of liver and bone isoenzymes of alkaline phosphatase (EC 3.1.3.1) in plasma were increased. The liver and (to a lesser extent) bone isoenzymes had enhanced electrophoretic mobility, and both showed increased binding to wheat-germ lectin by affinity electrophoresis. For the liver (and probably also the bone) isoenzyme, these changes were due to an increased content of sialic acid. A possible etiology for the condition is proposed involving (a) increased synthesis of alkaline phosphatase, mediated by vitamin D metabolites, and (b) decreased hepatic clearance caused by the high sialic acid content and exacerbated in some cases by the effects of some drugs on the liver.

Acetylglucosaminidase↗
PubMed1987

Properties of alkaline phosphatase isoenzymes in plasma of preterm and term neonates.

The isoenzymes of alkaline phosphatase (EC 3.1.3.1) in plasma of 37 preterm and 21 term neonates two weeks postpartum have been studied with regard to electrophoretic mobility, sialic acid content, inhibition properties, heat lability, molecular mass, and binding to lectins. Term infants generally had a single form of alkaline phosphatase present in significant amounts, identified by the above criteria as originating in bone. All the preterm neonates had two alkaline phosphatase isoenzymes in plasma, namely, bone- and fetal-type intestinal alkaline phosphatase. Liver-, placental-, and adult-type intestinal alkaline phosphatase were not detected in any of the plasma samples.

Alkaline Phosphatase↗
PubMed1987

Alkaline phosphatase isoenzymes in the plasma of preterm and term infants: serial measurements and clinical correlations.

Serial measurements of the bone and fetal intestinal isoenzymes of alkaline phosphatase (EC 3.1.3.1) in the plasma of 43 term and 43 preterm infants, from birth to six weeks later, indicate that the bone isoenzyme gradually increases over this period in both preterm and term infants fed with unsupplemented commercial formulas. Preterm babies given formula supplemented with calcium (with or without additional phosphate) had significantly lower bone isoenzyme activities for most of the study period. The concentrations of fetal intestinal isoenzyme increased, under the stimulation of milk feeding, from generally undetectable at birth to a peak during the first two weeks postpartum, and then declined. This increase was highly significantly negatively correlated with gestational age, the preterm infants having a much higher and more prolonged increase in this isoenzyme than did term infants. Unlike the adult isoenzyme, fetal intestinal alkaline phosphatase in plasma showed no relationship with blood group status.

Alkaline Phosphatase↗
PubMed1984

Alpha 1 antitrypsin and lung function in British coalminers.

Alpha 1 antitrypsin (alpha 1 AT) serum concentration was determined for a group of coalminers with particularly low levels of lung function, not thought to be explicable in terms of age and dust exposure, and compared with two other groups of coalminers who had average or above average lung function. There was no evidence for an alpha 1 AT deficiency in coalminers with poor lung function. On the contrary, a reactionary increase was evident, even in non-smokers, which may have resulted from the high frequency of chest disease in these men. Within the non-smoking group men with poor lung function had been exposed to higher mean levels of dust, and a greater proportion had early signs of bronchitis. There was no indication that the presence or degree of pneumoconiosis was affecting the results.

Coal Mining↗
PubMed1982

Biochemistry of alkaline phosphatase isoenzymes.

The review discusses the similarities and differences between the common isoenzymatic forms of ALP. Methods for separating, measuring, and purifying the isoenzymes on the basis of these differing properties are described. The evidence is reviewed for the existence of different genes coding for different isoenzymes, and the current state of knowledge is surveyed concerning the location, development, function, and regulation of the isoenzymes. Finally, some unusual forms of ALP which may appear in the circulation are described.

Alkaline Phosphatase↗
PubMed1981

Alkaline phosphatase from human thyroid.

Alkaline phosphatase activity was found in human thyroid homogenate at a specific activity of about 0.01 units/mg protein. The enzyme responsible appears to be a membrane-bound sialoglycoprotein. The properties of thyroid membrane alkaline phosphatase were examined after extraction with non-ionic detergent or butanol. It was detected mainly as a single electrophoretic form with a mobility similar to that of the liver form of the enzyme. It was readily inhibited by homoarginine, but not by phenylalanine. It reacted in Ouchterlony double diffusion with antiserum raised against liver alkaline phosphatase, but not with antiserum to placental alkaline phosphatase. Heat treatment at 56 degree C for 10 min at pH 7.5 resulted in an approx. 50% loss of enzyme activity. Its relative molecular mass was estimated to be 320000 by gel filtration, and 300000 by gradient gel electrophoresis. It required magnesium for full activity, and had a pH optimum of 10.5 in Tris-borate buffers. It was concluded that thyroid alkaline phosphatase belongs to the liver/bone/kidney isoenzyme group, but may exist in a molecular form distinct from others previously described.

Alkaline Phosphatase↗
PubMed1981

Site of alkaline phosphatase attachment in alkaline phosphatase-immunoglobulin G complexes.

Sera containing the rare alkaline phosphatase-immunoglobulin G complex were studied to try to determine the type of interaction involved. Pepsin and papain digestion of immunoglobulin G showed that alkaline phosphatase was attached to the F(ab')2 region of the immunoglobulin molecule and not to the Fc region. Sialic acid did not play a role in this attachment. Attempts to generate the complex in vitro using polyclonal immunoglobulin, and attempts to dissociate the complex is an immune complex in vitro, were both unsuccessful. It is concluded that the complex is an immune complex formed by antibody-antigen reaction in the circulation, and consists of two molecules of monovalent alkaline phosphatase associated with one molecule of divalent immunoglobulin G.

Alkaline Phosphatase↗
PubMed1981

Complexes in serum between alkaline phosphatase and immunoglobulin G: immunological and clinical aspects.

A retrospective study was performed on 31 patients in whose sera an immune complex between alkaline phosphatase and immunoglobulin G had been detected. The average age of these patients was 64 years and the sexes were equally represented. Twenty-three patients (74%) had a disease with either an autoimmune aetiology or associated with circulating immune complexes or autoantibodies. Sera from 16 patients were tested for the presence of circulating immune complexes in addition to the alkaline phosphatase immune complex, and these complexes were detected in 14 cases (88%). Sera from 17 patients were tested for the presence of specific autoantibodies and these were detected in 9 cases (53%). Twelve patients were followed up for a mean period of 11.6 months (range 0.5 to 39 month). At the end of the follow-up period, 10 patients (83%) showed persistence of the immunoglobulin-G-alkaline phosphatase complex.

Alkaline Phosphatase↗
PubMed1981

High-molecular-mass alkaline phosphatase in serum and bile: physical properties and relationship with other high-molecular-mass enzymes.

High-molecular-mass alkaline phosphatase has similar properties in serum and bile. It is of sufficiently large size to be excluded by Sepharose 6B and carries a high negative charge at alkaline pH, largely accounted for by the presence of sialic acid residues. It is slightly more heat labile than the lower-molecular-mass liver isoenzyme. Other enzymes originating from the hepatocyte plasma membrane are present as similar high-molecular-mass forms in normal bile, and in both bile and serum from patients with liver disease. The activities of these relatively large enzymic forms in serum were correlated with one another and we show they are converted similarly to lower-molecular-mass forms by solubilization with detergents. However, they carry slightly different net charges, thereby ruling out the possibility that they all consisted of a single homogeneous multi-enzyme complex. These findings are discussed in the light of two current hypotheses that the high-molecular-mass enzymes represent (a) membrane fragments released into the circulation in liver disease or (b) low-molecular-mass enzymes that aggregate, after release, with the lipid and protein in the circulation.

Alkaline Phosphatase↗
PubMed1981

High-molecular-mass alkaline phosphatase in serum and bile: nature and relationship with lipoprotein-X.

Using immunoelectrophoresis and other techniques, we have demonstrated an association between lipoprotein-X and (a) alkaline phosphatase and (b) other enzymes originating from the hepatocyte membrane, namely gamma-glutamyltransferase and leucine aminopeptidase. The high-molecular-mass forms of these enzymes, in both serum and bile, were precipitated by lipoprotein-X antiserum but not by antisera to other plasma proteins. The activity of high-molecular-mass alkaline phosphatase in serum was positively correlated with lipoprotein-X and with lipoprotein-X-associated alkaline phosphatase, both assessed semi-quantitatively. On the other hand, many sera possessed high activities of high-molecular-mass alkaline phosphatase but no detectable lipoprotein-X. Incubation of serum with conjugated bile salts and with synthetic detergents, at concentrations which did not dissociate the high-molecular-mass enzymes, caused parallel alterations in the electrophoretic mobility of serum lipoprotein-X and its associated enzyme activity. Incubation of normal dialyzed hepatic bile with normal, lipoprotein-X-negative serum produced an alteration in electrophoretic mobility of biliary lipoprotein and its associated enzyme activity from anodal to cathodal in agar gel. Digestion with papain had a variable effect on the different enzymes in the complex, without affecting the lipoprotein moiety. Leucine aminopeptidase was removed most readily from the complex to give the low-molecular-mass form present in normal serum; gamma-glutamyltransferase dissociated somewhat less readily, and alkaline phosphatase was completely resistant to dissociation from the complex. These results are discussed in the light of current knowledge, and a hypothesis is proposed for the nature of the high-molecular-mass enzymes in serum and bile.

Alkaline Phosphatase↗
PubMed1980

Alkaline phosphatase of high and low molecular mass in human serum and bile: a comparative study of kinetic properties.

We studied the kinetic properties of high- and low-molecular-mass forms of alkaline phosphatase purified from serum and bile, to clarify their interrelationships. They were found to share virtually identical kinetic properties, and to obey the same general kinetics as the liver-derived isoenzyme from serum and the low-molecular-mass isoenzyme from bile with regard to optimum conditions of assay, activation by magnesium ions, inhibition by L-homoarginine, inhibition by nickel and zinc ions, and inactivation by urea. Most of the characteristics such as Km (at low magnesium ion concentrations), Ki for L-homoarginine, and half-life for urea inactivation, were closely similar for low- and high-molecular-mass alkaline phosphatase. We conclude that these forms of alkaline phosphatase in plasma and bile are closely related. We discuss the possible nature of this relationship.

Alkaline Phosphatase↗
PubMed1979

An ion-exchange assay for high molecular weight alkaline phosphatase.

An ion-exchange method for the measurement of a high molecular weight form of alkaline phosphatase in serum is described. The method is simple, rapid, precise and suitable for processing small batches of samples. Other forms of alkaline phosphatase commonly encountered in serum do not interfere. The correlation between results obtained by this method and those obtained by Sephadex 6B chromatography is discussed. Electrophoretic methods of measurement were also investigated but were found to be both imprecise and inaccurate.

Alkaline Phosphatase↗