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V O Van Hoof

Publications and source records attributed to V O Van Hoof.

14 recordsLinked to original sources
PubMed1998

Gly341Arg mutation indicating malignant hyperthermia susceptibility: specific cause of chronically elevated serum creatine kinase activity.

We report on three families with the Gly341Arg ryanodine receptor gene (RYR1) mutation. Thirteen individuals were heterozygote carriers of the Gly341Arg mutation and had clearly positive in vitro contracture tests, indicating malignant hyperthermia susceptibility. Nine Gly341Arg mutation positive individuals from two families had elevated serum creatine kinase (CK) activity at rest (up to six times the normal upper limit). Their clinical and neurological examinations as well as detailed muscle histology were normal. The third family did not show increased CK activity. These findings indicate that the Gly341Arg mutation can be a specific cause of chronically elevated serum CK activity in asymptomatic individuals.

Adult↗
PubMed1997

How do plasma membranes reach the circulation?

Diagnostic enzymology measures the serum or plasma levels of enzymes that were originally located within the cell, or were attached to its plasma membrane with their active sites exposed to the external milieu. The process by which they are released varies under different physiological and pathological conditions. In this way, shedding of hepatocyte plasma membranes is thought to be responsible for the release of liver plasma membrane fragments (LiPMF) into the circulation in metastatic, infiltrative and cholestatic liver diseases. Several membrane-bound enzymes, such as gamma-glutamyltransferase (gamma-GT), alkaline phosphatase (ALP), leucine aminopeptidase (LAP) and 5'-nucleotidase (5'-Nu) are expressed at the surface of the shedded LiPMF. These enzymes are attached to the cell membrane by means of hydrophobic interactions between the anchoring domain of the enzyme and lipid components of the cell membrane, e.g. through a specific glycan phosphatidylinositol (GPI) anchor. There is a striking homology between these LiPMF and the membrane fragments shedded or actively formed by other cells, such as bone matrix vesicles-rich in bone ALP-, membrane fragments of the syncitiotrophoblast-rich in placental ALP-, and membrane fragments present in duodenal fluid-rich in intestinal ALP. With the exception of LiPMF, membrane-bound (Mem-) forms of ALP are only very exceptionally found in human serum. Normally, the soluble (Sol-ALP) dimeric fractions of the enzyme predominate in serum, but liver, bone, placental and intestinal ALP can also be present as GPI-anchor bearing (Anch-) hydrophobic isoforms. Models for the release in the circulation of Mem-, Anch- and Sol-liver and intestinal ALP, involving both plasma membrane-associated GPI-phospholipase-D (GPI-PLD) and liver bile salts are proposed.

5'-Nucleotidase↗
PubMed1997

High prevalence of adynamic bone disease diagnosed by biochemical markers in a wide sample of the European CAPD population.

BACKGROUND: Adynamic bone disease (ABD) has been described in the current dialysis population to have an unexpectedly high prevalence. Moreover, it is clearly more prevalent in CAPD patients, compared to haemodialysis patients. Recently we demonstrated that both a low (< or = 27 U/1) level of bone alkaline phosphatase (BAP) as determined by an optimized agarose gel electrophoretic technique and a low (< or = 150 pg/ml ) level of iPTH are good markers of ABD with sensitivities of 78.1% and 80.6% and specificities of 86.4% and 76.2% respectively. METHODS: In this study (n = 212), the prevalence of ABD in the European CAPD population was evaluated by means of these biochemical markers. Clinical data on the patients included were recorded at the moment of blood sampling. In patients under CAPD treatment for longer than 9 months, we calculated an index of calcium exposure through PD fluid. RESULTS: In this population with a low exposure to aluminium, the prevalence of ABD as indicated by either a low level of BAP or PTH was 43%. The following risk factors could be identified: advanced age, shorter time on renal replacement therapy, male gender, and high calcium content of PD fluid. The index of calcium exposure was significantly higher in the patients with low BAP and low iPTH levels compared to those with either BAP > or = 27 U/1 or iPTH > 150 pg/ml. The latter finding gives further support to the hypothesis that a high calcium load administered to renal failure patients may lead to 'oversuppressed' parathyroids in ABD. In a subgroup of patients with a high level of BAP associated with a low iPTH level a profile previously shown to be associated in the presence of aluminium overload, significantly higher serum aluminium levels were noted. suggesting that even in patients with low exposure to aluminium, this element still can affect bone metabolism. CONCLUSION: A high prevalence of ABD--as diagnosed by biochemical markers--was observed in the European CAPD population. A number of risk factors could be put forward. The aetiology and pathogenesis of this type of renal osteodystrophy remain to be elucidated, but appear, however, to be multifactorial.

Adult↗
PubMed1996

Purification of circulating liver plasma membrane fragments using a monoclonal antileucine aminopeptidase antibody.

Membrane-bound liver alkaline phosphatase (Mem-LiALP, EC 3.1.3.1) is a high-molecular-mass liver alkaline phosphatase (ALP) present in metastatic, infiltrative and cholestatic liver disease. Shedding of hepatocyte plasma membrane fragments (LiPMF) is thought to be responsible for the appearance of Mem-LiALP in the circulation. Several other membrane-bound enzymes, such as gamma-glutamyltransferase (gamma-GT), leucine aminopeptidase (LAP), and 5'-nucleotidase (5'-Nu) are present in the membrane of the shedded LiPMF. By means of immunohistochemical and immunoassay procedures, we presently show that AD-1, a specific monoclonal antibody originally produced against Mem-LiALP, reacts with LAP, a constituent of the human liver plasma membrane. Using AD-1 as an immunosorbant, we isolated circulating LiPMF from cholestatic sera to a high level of purity and separated it from other high-molecular-mass material, such as liver ALP or similar lipoprotein-X complexes. These purified membrane fragments retained their biochemical characteristics. Glycosyl-phosphatidylinositol anchor bearing liver ALP (Anch-LiALP) could be released from the LiPMF by Triton X-100. Whereas ALP was released upon treatment of AD-1 purified LiPMF with phospholipase C, phospholipase D only cleaved the glycosyl-phosphatidylinositol anchor following detergent solubilization of the enzyme. Serum LiPMF from patients with different kinds of cholestatic liver disease were bound onto AD-1 coated nitrocellulose disks and the activity of four membrane-bound enzymes (LAP, ALP, 5'Nu, gamma-GT) was analyzed. A considerable interindividual variation of enzyme activities was observed, suggesting some heterogeneity in the membrane composition of these fragments.

5'-Nucleotidase↗
PubMed1996

Low serum levels of alkaline phosphatase of bone origin: a good marker of adynamic bone disease in haemodialysis patients.

BACKGROUND: Adynamic bone disease was recently described to be increasingly prevalent in the dialysis population. At present the diagnosis of this type of renal osteodystrophy can only be made by bone histomorphometry. We assessed the value of different biochemical serum markers in the diagnosis of adynamic bone disease. METHODS: In 103 haemodialysis patients a bone biopsy was performed after double tetracycline labelling, and the serum levels of intact PTH, osteocalcin, and the bone isoenzyme of alkaline phosphatase were determined. Bone alkaline phosphatase was measured by an optimized agarose gel electrophoretic method, recently shown to have a high accuracy, precision and reproducibility, also in the lower range. RESULTS: In 38 (37%) of the patients the diagnosis of adynamic bone disease was histologically established. Constructing receiver operator curves optimal cut-off levels for the diagnosis of adynamic bone disease were determined, being <=27 U/litre for the bone isoenzyme of alkaline phosphatase, <=14 microg/litre for osteocalcin and <=150 pg/ml for intact PTH. Concentrations of bone alkaline phosphatase or intact PTH below these cut-off levels, were shown to be the best performing tests in the detection of adynamic bone disease as indicated by a sensitivity of 78.1 and 80.6% and a specificity of 86.4 and 76.2% respectively. Applying Bayes' theorema, it was calculated that in the current haemodialysis population in which a prevalence of adynamic bone disease up to 35% has been described, the positive predictive values for the proposed cut-off values are 75% for bone alkaline phosphatase, 65% for intact PTH and 55% for osteocalcin. Moreover, in this population, levels of bone alkaline phosphatase and intact PTH below the optimal cut-off excluded hyperparathyroid bone disease. CONCLUSION: In view of the relative easy and accurate methodology for bone alkaline phosphatase determination, the closer physiological link with osteoblast function and the lesser expense for its determination we suggest that this marker is a useful tool in the non-invasive diagnosis of the adynamic type of bone disease in the individual patient.

Alkaline Phosphatase↗
PubMed1995

Immunoradiometric method and electrophoretic system compared for quantifying bone alkaline phosphatase in serum.

Agarose electrophoresis (Isopal, Beckman) and an immunoradiometric assay (IRMA) involving specific monoclonal antibodies (Ostase, Hybritech), two methods for the quantification of serum bone alkaline phosphatase (ALP, EC 3.1.3.1), a marker of osteoblastic activity, were compared in 293 patients: 79 with end-stage renal failure treated with hemodialysis and 214 with malignant disease. Overall correlation between the two methods was good (r = 0.92), except (a) for low values of bone ALP and (b) in some samples with high total liver ALP activity--both due to considerable cross-reactivity of the anti-bone ALP antibodies of the Ostase kit with liver ALP. This interference was not constant and was not evenly distributed across all concentrations of bone ALP. Low bone ALP determined with the IRMA (< or = 5 micrograms/L) was confirmed by electrophoresis (< or = 21 U/L), but bone ALP activity determined by electrophoresis to be low (< or = 21 U/L) was not correlated with the IRMA results. After standardizing our results by computing z-values for bone ALP, delta z (= zOstase - zIsopal) was significantly correlated with liver ALP activity (r = 0.73, P < 0.0001). We conclude that the IRMA for quantifying bone ALP is acceptable as a screening method. However, when high values for bone ALP are found with the Ostase method, confirmation by electrophoresis remains mandatory to rule out cross-reactivity with high amounts of liver ALP. For detecting low bone ALP activities, electrophoresis remains the method of choice.

Alkaline Phosphatase↗
PubMed1994

Interpretation and clinical significance of alkaline phosphatase isoenzyme patterns.

Alkaline phosphatase (ALP, EC 3.1.3.1) is a membrane-bound metalloenzyme that consists of a group of true isoenzymes, all glycoproteins, encoded for by at least four different gene loci: tissue-nonspecific, intestinal, placental, and germ-cell ALP. Through posttranslational modifications of the tissue-nonspecific gene, for example, through differences in carbohydrate composition, bone and liver ALP are formed. Nowadays, most commercially available methods for separating or measuring ALP isoenzymes are easy to perform and sensitive and allow for reproducible and quantitative results. As more isoenzymes and isoforms have been characterized, confusion has arisen due to the many different names they were given. For the sake of simplicity and because of structural analogies, we propose an alternative nomenclature for the ALP isoenzymes and isoforms based on their structural characteristics: soluble, dimeric (Sol), anchor-bearing (Anch), and membrane-bound (Mem) liver, bone, intestinal, and placental ALP. Together with lipoprotein-bound liver ALP and immunoglobulin-bound ALP, these names largely fit the many forms of ALP one can encounter in human serum and tissues. The clinically relevant isoenzymes are sol-liver, Mem-liver, lipoprotein-bound liver, and Sol-intestinal ALP in liver diseases, and Sol-bone and Anch-bone ALP in bone diseases. Many different isoenzyme patterns can be found in malignancies and renal diseases. This test provides the clinician with valuable information for diagnostic purposes as well as for follow-up of patients and monitoring of treatment. However, ALP isoenzyme determination will only provide clinically useful information if the patterns are correctly interpreted. In this respect, care should be taken to use the proper reference ranges, taking into account the age and sex of the patient. A normal total ALP activity does not rule out the presence of an abnormal isoenzyme pattern, particularly in children. Separating ALP into its isoenzymes adds considerable value to the mere assay of total ALP activity.

Aging↗
PubMed1992

Differential release of human intestinal alkaline phosphatase in duodenal fluid and serum.

Human intestinal alkaline phosphatase (IAP) can be released by the enterocyte into duodenal fluid as a mixture of three isoforms. A proportion of the enzyme is associated with triple-layered membrane vesicles (vesicular IAP). Although, occasionally, free hydrophilic IAP dimers are present, the remaining enzyme usually consists of a mixture of hydrophobic IAP dimers and more complex hydrophobic IAP structures of larger size, both entities being identified as "intestinal variant" alkaline phosphatase (VAR IAP). The hydrophobicity of VAR IAP stems exclusively from its attached glycosyl-phosphatidylinositol (GPI) anchor. Both vesicular IAP and VAR IAP are converted to hydrophilic enzyme upon removal of the GPI tail by phospholipase D (PLD) present in duodenal fluid. The IAP released into the vascular bed consists mainly of VAR IAP; vesicular IAP is absent. The enzyme characteristics of VAR IAP partially purified from duodenal fluid and from serum are identical. In plasma, VAR IAP appears to associate with (lipo)protein complexes and is thus protected from further degradation by plasma PLD. Such complex formation may explain why, in the serum of a healthy reference population, VAR IAP was more abundant than hydrophilic dimeric IAP.

Alkaline Phosphatase↗
PubMed1992

Alkaline phosphatase isoenzyme patterns in malignant disease.

Early treatment of patients with malignant disease and liver or bone metastasis may increase their survival time. We have used the activity patterns of liver and bone isoenzymes of alkaline phosphatase (ALP), separated by agarose gel electrophoresis, to detect early metastasis. We studied ALP isoenzyme patterns in a background population of 101 patients with no evidence of any disease that might influence this pattern; a healthy reference population (n = 330); and the following three groups of patients: 143 with malignant disease, 47 with nonmalignant liver disease, and 22 with nonmalignant bone disease. Cutoff and predictive values of liver ALP, high-molecular-mass (high-M(r)) ALP, and bone ALP were established for detecting liver and bone metastasis. The positive predictive value of liver and high-M(r) ALP was higher than that of total ALP in detecting liver metastasis, but liver and high-M(r) ALP did not enable us to differentiate between malignant and nonmalignant liver disease. Total ALP activity was of slightly more value than liver and high-M(r) ALP in enabling us to rule out liver metastasis. From bone ALP activity we could not distinguish between nonmalignant bone disease and bone metastasis. The negative predictive value of bone ALP in the diagnosis of bone metastasis was low, but its positive predictive value was high and superior to that of total ALP.

Adult↗
PubMed1990

Age and sex distribution of alkaline phosphatase isoenzymes by agarose electrophoresis.

We separated isoenzymes of alkaline phosphatase (ALP; EC 3.1.3.1) in 1383 sera of normal individuals (ages 4-65 years) by agarose electrophoresis with the Isopal system (Analis). As expected, the predominant isoenzyme in children was of bone origin, and almost all (99%) of the children had low activities of a second bone fraction, "bone variant" ALP. The "bone variant" disappeared after age 17 in girls and after age 20 in boys. The highest (median) bone ALP activity was reached at age 9 to 10 in girls and at age 13 to 14 in boys, followed by a gradual decline in girls and a steep decline in boys. During adulthood, activity of the bone fraction was constant and no significant differences were observed between sexes, neither for bone nor for liver ALP activity. The latter remained almost unchanged throughout life. We observed no high-Mr ALP activity in children, whereas sera from 60% of the adults contained low activities of high-Mr ALP. Intestinal ALP (soluble form) and "intestinal variant" ALP (hydrophobic form) were frequently present, in 21% and 37% of all samples, respectively. No significant differences were observed between age groups and sexes for the intestinal isoenzymes.

Adolescent↗
PubMed1988

Improved agarose electrophoretic method for separating alkaline phosphatase isoenzymes in serum.

A modified agarose electrophoretic system for the separation of alkaline phosphatase (ALP, EC 3.1.3.1) isoenzymes is described. Bone, liver, high-molecular-mass, and intestinal ALP are separated with high reproducibility. The sensitivity of the agarose system is superior to cellulose acetate in detecting high-Mr ALP. Correlation is good between bone ALP fractions scanned before and after treatment with neuraminidase. Immunoglobulin-bound ALPs, the ALP-lipoprotein-X complex, and the additional ALP fraction observed in transient hyperphosphatasemia in children are detected by their peculiar electrophoretic mobility in the proposed system. Approximately 25% of the samples contained an additional fraction of intestinal-type ALP, as evidenced by neuraminidase treatment and use of polyclonal and monoclonal antibodies. Because the electrophoretic mobilities of this "intestinal variant" and of some immunoglobulin-bound ALP fractions are identical to those of bone and intestinal ALP, respectively, treatment of the samples with a polyclonal antibody that reacts with intestinal ALP is advised.

Alkaline Phosphatase↗