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Biomedical subjects

J P Van Biervliet

Publications and source records attributed to J P Van Biervliet.

At least 19 recordsLinked to original sources
PubMed2006

An absence of cutaneous neurofibromas associated with a 3-bp inframe deletion in exon 17 of the NF1 gene (c.2970-2972 delAAT): evidence of a clinically significant NF1 genotype-phenotype correlation.

Neurofibromatosis type 1 (NF1) is characterized by cafe-au-lait spots, skinfold freckling, and cutaneous neurofibromas. No obvious relationships between small mutations (<20 bp) of the NF1 gene and a specific phenotype have previously been demonstrated, which suggests that interaction with either unlinked modifying genes and/or the normal NF1 allele may be involved in the development of the particular clinical features associated with NF1. We identified 21 unrelated probands with NF1 (14 familial and 7 sporadic cases) who were all found to have the same c.2970-2972 delAAT (p.990delM) mutation but no cutaneous neurofibromas or clinically obvious plexiform neurofibromas. Molecular analysis identified the same 3-bp inframe deletion (c.2970-2972 delAAT) in exon 17 of the NF1 gene in all affected subjects. The Delta AAT mutation is predicted to result in the loss of one of two adjacent methionines (codon 991 or 992) ( Delta Met991), in conjunction with silent ACA-->ACG change of codon 990. These two methionine residues are located in a highly conserved region of neurofibromin and are expected, therefore, to have a functional role in the protein. Our data represent results from the first study to correlate a specific small mutation of the NF1 gene to the expression of a particular clinical phenotype. The biological mechanism that relates this specific mutation to the suppression of cutaneous neurofibroma development is unknown.

Adolescent↗
PubMed2001

Serum alpha-tocopherol and selenium in Belgian infants and children.

Previous studies showed low selenium (Se) concentrations in Belgian children. Serum alpha-tocopherol, retinol, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, selenium (Se), and thiobarbituric acid-reactive substances were examined. In order to obtain further information on the Se status in Belgian children, Se, alpha-tocopherol, retinol, and lipid concentrations were examined and signs of peroxidative lipid damage were evaluated in a subgroup. The study was performed in 524 children (0-14 yr old) during vaccination campaigns. Three age groups were analyzed: 0-1, 1-4, and 4-14 yr. In 87 of them, where sufficient amounts of serum were available, analysis of thiobarbituric acid-reactive substances was done. Infants have high serum alpha-tocopherol concentrations: (23.2 micromol/L [median and interquartile range: 18.6-30.2]) and low Se concentrations (0.37 mol/L [0.27-0.47]). Se concentrations rise significantly during the first 4 yr (p < 0.0001) (Mann-Whitney U-test, tied p-values): 0.70 micromol/L (0.59-0.82); in the 4-14 yr olds, it was 0.75 micromol/L (0.67-0.86). These values remain low compared to results coming from other parts of the world. Alpha-tocopherol concentrations decrease significantly after infancy (p < 0.0001). The ratio alpha-tocopherol/total cholesterol is higher in infants. This is induced by the high vitamin E content of infant formulas. Signs of serum lipid peroxidation could not be detected by analysis of serum malondialdehyde concentrations. High alpha-tocopherol concentrations, as those observed in infant serum lipids, could be one of the protective mechanisms from the peroxidative lipid damages, sometimes observed in a low-Se status.

Adolescent↗
PubMed1995

Helix-helix interactions in reconstituted high-density lipoproteins.

In this work we calculated the ionic interactions between adjacent amphipathic helices of apo A-I and apo A-IV. The calculation of the electrostatic potential around the helices helps identify the charged residues susceptible to form salt bridges between adjacent helices. An estimation of the stability of the different pairs of helices is derived from the calculation of the energy of interaction between contiguous helices at a water/lipid interface after energy minimization. The most stable energetic conformation corresponds to the 17-residue helices oriented anti-parallel and separated by a stretch of 5 residues in an extended beta-strand conformation, as calculated through the 'stereo alphabet' calculation procedure. In a pair of helices, the hydrophobic faces are directed towards the lipid core of the discoidal phospholipid-apolipoprotein complex and the hydrophobic lipid-protein interactions are major determinants for the stability of the complex. Interactions between polar residues located on the opposite face of the helix and water molecules can also contribute to the overall energy of the system. Finally, salt bridge formation between residues of opposite charge along the edge of the helical segments contribute to the cooperativity of the phospholipid-apolipoprotein complex formation. The mode of assembly of the amphipathic helical repeats of the apolipoproteins around the edge of a discoidal complex is therefore determined both by the hydrophobic character of the residues and by the charge complementarity along the edge of the helices which increases the structural stability and determines the relative orientation of the helices.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Serum cholesterol, cholesteryl ester, and high-density lipoprotein development in newborn infants: response to formulas supplemented with cholesterol and gamma-linolenic acid.

Healthy newborn infants were either breast-fed or randomly designated to receive a standard formula, formula plus cholesterol, or formula plus gamma-linolenic acid at birth. At 0, 7, and 30 days of life, the following variables were measured: cholesteryl esters (cholesteryl arachidonate, cholesteryl oleate, cholesteryl palmitate, and cholesteryl linoleate), high-density lipoprotein (HDL) cholesterol, apoproteins (A-I, A-II, B, C-II, C-III, and E), and the cholesterol and apoprotein A-I content of the HDL subfractions HDL-2b, HDL-(2a + 3a), and HDL-(3b + 3c). Breast-fed infants had higher serum levels of cholesterol, cholesteryl oleate, cholesteryl palmitate, cholesteryl arachidonate, and HDL-2b than had formula-fed infants. Addition of gamma-linolenic acid to formula raised cholesteryl-arachidonate levels, and cholesterol and gamma-linolenic acid raised serum HDL-2b levels compared with those produced by unsupplemented formula. Our data suggest that both exogenous cholesterol and gamma-linolenic acid contribute to the maturation of HDL particles associated with human milk consumption in newborn infants. They may also promote adequate delivery of cholesterol and arachidonic acid to the developing brain.

Breast Feeding↗
PubMed1991

Catalytic triad residue mutation (Asp156----Gly) causing familial lipoprotein lipase deficiency. Co-inheritance with a nonsense mutation (Ser447----Ter) in a Turkish family.

We studied the molecular basis of familial Type I hyperlipoproteinemia in two brothers of Turkish descent who had normal plasma apolipoprotein C-II levels and undetectable plasma post-heparin lipoprotein lipase (LPL) activity. We cloned the cDNAs of LPL mRNA from adipose tissue biopsies obtained from these individuals by the polymerase chain reaction and directional cloning into M13 vectors. Direct sequencing of pools of greater than 2000 cDNA clones indicates that their LPL mRNA contains two mutations: a missense mutation changing codon 156 from GAU to GGU predicting an Asp156----Gly substitution and a nonsense mutation changing the codon for Ser447 from UCA to UGA, a stop codon, predicting a truncated LPL protein that contains 446 instead of 448 amino acid residues. Both patients were homozygous for both mutations. Analysis of genomic DNAs of the patients and their family members by the polymerase chain reaction, restriction enzyme digestion (the GAT----GGT mutation abolishes a TaqI restriction site), and allele-specific oligonucleotide hybridization confirms that the patients were homozygous for these mutations at the chromosomal level, and the clinically unaffected parents and sibling were true obligate heterozygotes for both mutations. In order to examine the functional significance of the mutations in this family, we expressed wild type and mutant LPLs in vitro using a eukaryotic expression vector. Five types of LPL proteins were produced in COS cells by transient transfection: (i) wild type LPL, (ii) Asp156----Gly mutant, (iii) Ser447----Ter mutant, (iv) Gly448----Ter mutant, and (v) Asp156----Gly/Ser447----Ter double mutant. Both LPL immunoreactive mass and enzyme activity were determined in the culture media and intracellularly. Immunoreactive LPLs were produced in all cases. The mutant LPLs, Asp156----Gly and Asp156----Gly/Ser447----Ter, were devoid of enzyme activity, indicating that the Asp156----Gly mutation is the underlying defect for the LPL deficiency in the two patients. The two mutant LPLs missing a single residue (Gly448) or a dipeptide (Ser447-Gly448) from its carboxyl terminus had normal enzyme activity. Thus, despite its conservation among all mammalian LPLs examined to date, the carboxyl terminus of LPL is not essential for enzyme activity. We further screened 224 unrelated normal Caucasians for the Ser447----Ter mutation and found 36 individuals who were heterozygous and one individual who was homozygous for this mutation, indicating that it is a sequence polymorphism of no functional significance. Human LPL shows high homology to hepatic triglyceride lipase and pancreatic lipase.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗
PubMed1991

Lipoprotein(a) profiles and evolution in newborns.

Plasma Lp(a) concentrations in newborns were quantified by a specific and sensitive ELISA assay and their evolution was followed between birth and 6 months. The influence of the diet on Lp(a) levels was also investigated. Moreover, the high sensitivity of the assay enabled the localisation of the Lp(a) fraction in the lipoprotein profile obtained after plasma separation by gel chromatography. Lp(a) levels are low at birth and rise significantly between 0 and 7 days post partum; in this newborn population, a continuous rise of the mean Lp(a) levels was observed until 180 days, in contrast with the apo B concentration that plateaus after 7 days. An early screening enabled the detection of newborns with elevated Lp(a) levels compared to the mean value of their age group. A further follow-up of some cases at 16 months confirmed the high Lp(a) levels measured in the infants and at least one of the parents. The investigation of the lipoprotein profiles as a function of the age of the newborn enabled an estimation of the size and distribution of the Lp(a) lipoprotein in four infants. At birth, Lp(a) particles were larger than LDL and tend to become more heterogeneous with increasing age of the newborn. We could not observe any statistically significant influence of the nutritional factors on the plasma Lp(a) concentrations at any age.

Age Factors↗
PubMed1991

Quantification of lipoprotein(a) in dried blood spots and screening for above-normal lipoprotein(a) concentrations in newborns.

Lipoprotein(a) [Lp(a)] is considered an additional, independent, and largely genetically determined risk factor for the development of premature coronary heart disease. Analogous with increased Lp(a) concentrations that represent an additional risk factor in adults, above-normal concentrations of Lp(a) can be detected in five- to seven-day-old newborns. We describe a simple enzyme-linked immunosorbent assay for measuring Lp(a) in dried blood spots collected by heel-prick in five- to seven-day-old infants. Lp(a) could be quantitatively recovered from blood spots. We chose a cutoff value of 100 mg/L for identifying the newborns at risk, based on the Lp(a) distribution in 180 such infants.

Apolipoproteins A↗
PubMed1986

Influence of dietary factors on the plasma lipoprotein composition and content in neonates.

Previous studies have shown that the cholesterol and apoprotein concentrations in newborn plasma are dependent on the degree of saturation (polyunsaturated/saturated fatty acids ratio) of the dietary fats. In the present study we compare the influence on the lipoprotein patterns of breast-feeding and of two adapted formulae with a similar P/S ratio in 30 infants. The lipoprotein distribution and composition were investigated by density-gradient ultracentrifugation at days 0, 7 and 30. The lipoprotein patterns were quite comparable at 0 and 7 days in the three groups. We found low VLDL and LDL and relatively elevated HDL concentrations with a high percentage of HDL2. A significant increase of both VLDL and LDL was observed between 0 and 7 days. The VLDL concentration in the breast-fed infants subsequently decreased between 7 and 30 days to a value close to that measured at birth. The infants receiving an adapted formula had significantly higher VLDL and lower LDL at 30 days compared to breast-fed children. HDL concentrations were not significantly different whereas the HDL2 percentage was significantly lower in the infants receiving the adapted formulae. These data further support the hypothesis that the lipoprotein patterns in infants are sensitive to the type of nutrition and that breast-feeding induces specific lipoprotein patterns compared to adapted milk formulae.

Apolipoproteins↗
PubMed1985

Hydrolysis of very-low-density lipoproteins labeled with a fluorescent triacylglycerol: 1,3-dioleoyl-2-(4-pyrenylbutanoyl)glycerol.

The fluorescent triacylglycerol (DPBG) 1,3-dioleoyl-2-(4-pyrenylbutanoyl)glycerol was incorporated into plasma very-low-density lipoproteins (VLDL) to form DPBG-VLDL. In the presence of albumin, the addition of milk lipoprotein lipase to DPBG-VLDL hydrolyses DPBG together with the VLDL triacylglycerol and pyrenyl fatty acids are transferred to albumin. As a consequence the monomer fluorescence increases while that of the excimer decreases [Mantulin, W. W., Massey, J. B., Gotto, A. M., Jr & Pownall, H. J. (1981) J. Biol. Chem. 256, 10815-10819]. The relationship of the intensity of the excimer at 475 nm to that of the monomer at 396 nm was measured before and after lipolysis of VLDL by milk lipoprotein lipase. These fluorescent changes parallel the release of free fatty acids from VLDL and their uptake by albumin. The rate of increase of monomer to excimer fluorescence was dependent upon the enzyme, substrate and albumin concentration. The lipolysis reaction, as monitored by fluorescence changes, followed Michaelis-Menten kinetics with a Km of 1.7 M for milk lipoprotein lipase. The use of the fluorescent triacylglycerol probe increases the sensitivity of the technique by a factor 50-80 compared to a technique previously reported using a fluorescent phospholipid. The present method is applicable to 2-10 micrograms triacylglycerol corresponding to about 50-100 microliters of newborn plasma or 30-50 microliters normal adult plasma. The use of an Airfuge ultracentrifuge for VLDL isolation, in conjunction with that of DPBG as a fluorescent probe enables a rapid study of VLDL lipolysis on minimal sample amounts. It can therefore be easily applied to normal and dyslipoproteinemic samples and to the newborns.

Albumins↗
PubMed1983

Isolation and characterization of lipoprotein profiles in newborns by density gradient ultracentrifugation.

Lipoproteins in newborn plasma were isolated from a minimal sample amount (0.3 ml) by a single-step ultracentrifugation in a density gradient, spanning the density range 1.02-1.20 g/ml. After 66 h ultracentrifugation in a swinging-bucket rotor, the content of the tube was eluted and collected in 0.4 ml fractions. Cholesterol and apoproteins AI, AII, and B were assayed in each fraction yielding both the distribution and composition of the very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL2, HDL3). Newborn plasma was characterized by a low amount of triglyceride-poor and cholesterol ester-rich VLDL and high content of HDL2 and HDL3. The VLDL and LDL concentrations increased drastically between 0 and 7 days together with the triglyceride content of the VLDL. At 30 days the lipid composition of VLDL was similar to that of adults, whereas the lipid/protein content remained low both in VLDL and LDL. The composition of HDL2 and HDL3 remained constant during this period, the percentage of HDL2 being higher in newborns than in adults. These compositional changes were reflected in the microviscosity of the lipoproteins, specially in the VLDL fraction.

Apoproteins↗
PubMed1982

A screening procedure for dyslipoproteinemia in the newborn. Apoprotein quantitation on dried blood spots.

A new screening procedure for the detection of dyslipoproteinemia in the newborn is proposed, based on apoprotein quantitation. Blood is collected by heel-prick in infants 5--7 days after birth--when apoprotein and lipids have reached stable values--and adsorbed on filter paper. Blood spots are eluted with a detergent and apoprotein A-I and B are assayed by immunonephelometry. The apo A-I/B ratio is used as a screening parameter, given its high discriminative power between normals and individuals with cardiovascular disease. The quantitation of the apo A-I/B ratio in blood spots is independent of the volume of the blood spot and of the newborn hematocrit. In a follow-up study, plasma lipid and apoprotein concentrations were assayed in the infants with an apo A-I/B ratio lower than 1.0 at 5 days, and a family study was carried out. On screening 1500, 30 infants gave positive results at birth, and were controlled between 2 and 8 months. In eight families studied, six children had abnormally high cholesterol and apo B values and five children had abnormally low HDL cholesterol and apo A-I concentrations. This screening procedure is a new approach to the detection of familial dyslipoproteinemia in the newborn, as it is based on the quantitation of the apo A-I/B protein ratio, instead of cholesterol, LDL cholesterol or beta-lipoprotein quantitation. It enables a differentiation to be made between various forms of dyslipoproteinemia, leads to a better characterization of various diseases, and decreases the percentage of false positive cases.

Adult↗