Biomedical subjects

B W van der Meer

Publications and source records attributed to B W van der Meer.

8 recordsLinked to original sources

PubMed2002

Kappa-squared: from nuisance to new sense.

The orientation factor, which is commonly called kappa-squared, is often considered to be a nuisance because it represents a significant uncertainty in the distance obtained with the FRET technique. It is shown that this uncertainty is rather small in almost all cases of practical interest if one takes the width of a 67% confidence interval (CI) for the distance distribution as a measure of uncertainty. Kappa-squared has the potential to open up new information on orientations and rotations from time-resolved studies of donor and acceptor anisotropies. One can make sense of such data by designing matrix models for the transitions between states describing various orientations and positions of donors and acceptors in the system.

Anisotropy↗

PubMed1993

Designing matrix models for fluorescence energy transfer between moving donors and acceptors.

A recipe is given for designing theoretical models for donor-acceptor systems in which fluorescence energy transfer and motion takes place simultaneously. This recipe is based on the idea that a system exhibiting both motion and fluorescence energy transfer can be modeled by specifying a number of "states" and the rates of transitions between them. A state in this context is a set of specific coordinates and conditions that describe the system at a certain moment in time. As time goes on, the coordinates and conditions for the system change, and this evolution can be described as a series of transitions from one state to the next. The recipe is applied to a number of example systems in which the donors and/or acceptors undergo either rotational or translational motion. In each example, fluorescence intensities and anisotropies for the donor and acceptor are calculated from solutions of eigensystems. The proposed method allows for analyzing time-resolved fluorescence energy transfer data without restrictive assumptions for motional averaging regimes and the orientation factor. It is shown that the fluorescence quantities depend on the size of the motional step (i.e., on the number of states), only if fluorescence energy transfer occurs. This finding indicates that fluorescence energy transfer studies may reveal whether the dynamics of a system (e.g., a protein) is better described in terms of transitions between a relatively small number of discrete states (jumping) or a large number of dense states (diffusion).

Biophysical Phenomena↗

PubMed1993

[The clinical significance of anti-gliadin antibodies determination in blood of children with suspected celiac diseases].

Screening tests for coeliac disease may be useful to select the patients who should undergo a small intestine biopsy. It has been reported that the determination of serum levels of anti-gliadin antibodies is a good screening method for small intestine damage in coeliac disease. We have retrospectively assessed the value of the anti-gliadin antibody test in detecting villous atrophy of the small bowel. Antigliadin antibodies were measured with an ELISA technique in sera of 44 children seen at the Department of Paediatrics, Leiden University Hospital, who underwent 53 small intestine biopsies because of suspected coeliac disease. The relation between the histopathological findings of the small intestine and the results of the anti-gliadin antibody quantifications in serum were studied. In 9 of the 10 children with villous atrophy high Ig total and IgG-titers were found. Five children with villous atrophy, 2 of them with a selective IgA-deficiency, had normal IgA-AGA titers in serum. 17 Children with normal biopsies had high Ig total and IgG-AGA titers, but no child with normal small intestine biopsy had high IgA-AGA titers in serum. We conclude that the determination of anti-gliadin antibodies as screening for mucosal damage must be based on the measurement of antibodies within the IgG as well as the IgA class.

Autoantibodies↗

PubMed1989

Role of BBM lipid composition and fluidity in impaired renal Pi transport in aged rat.

Renal tubular phosphate (Pi) transport is impaired in the aged rat. The decrement in Pi transport is manifested as a decrease in the Vmax of the luminal brush-border membrane (BBM) sodium-dependent Pi transport. In the present study we determined the potential role of alterations in cortical BBM lipid composition and fluidity in the age-related phosphaturia observed in rats. In the aged rat there are significant increases in the BBM cholesterol (Chol, 504 vs. 422 nmol/mg protein in adult, P less than 0.01) and sphingomyelin (Sph, 41.8 vs. 37.5 mol% in adult, P less than 0.01) and a decrease in the BBM fluidity [increase in fluorescence anisotropy of diphenylhexatriene (DPH), rDPH, 0.221 vs. 0.215 in adult, P less than 0.01]. The BBM lipid compositional and fluidity alterations may also play an important role in the impaired renal adaptation to a low-Pi diet in the aged rat. In the adult rat the renal adaptation to a low-Pi diet is associated with a decrease in BBM Chol (370 to 307 nmol/mg protein, P less than 0.01) and an increase in fluidity (decrease in rDPH 0.207 to 0.201, P less than 0.05). In the aged rat the renal adaptation to a low-Pi diet is incomplete and is associated with impaired ability to lower BBM Chol (441 to 429 nmol/mg protein, P = NS) and to increase fluidity (rDPH 0.211 to 0.211, P = NS). The results of this study therefore suggest that in the aged rat the increase in BBM Chol and Sph content, and the decrease in BBM fluidity play an important role in the impaired renal tubular Pi transport and adaptation to a low-Pi diet.

Aging↗

PubMed1987

Quantitative contributions of cholesterol and the individual classes of phospholipids and their degree of fatty acyl (un)saturation to membrane fluidity measured by fluorescence polarization.

Steady-state fluorescence polarization (P) measurements, using the probe 1,6-diphenyl-1,3,5-hexatriene, in a large variety of well-defined liposomes at 25 degrees C allowed a quantitative description of the contributions of cholesterol, sphingomyelin, and (un)saturation of fatty acyl groups in the various phospholipids to the structural order (or the mutual affinity) of membrane lipids. The P values for liposomes prepared from lipid extracts of natural (purified) membranes of various origins could be more or less predicted (calculated) from the relative contributions of the individual lipid components. In all cases, the polarization varied with the cholesterol/phospholipid molar ratio (C/PL) according to the equation P = Pplat -(Pplat -Pzero) exp(-alpha C/PL), in which Pzero refers to the polarization without cholesterol and Pplat is a maximal plateau value, reached at a high C/PL (greater than 1). The "cholesterol-ordering coefficient" alpha of the phospholipids was found to increase with the fraction of sphingomyelin or dipalmitoylphosphatidylcholine molecules, indicating that the susceptibility of phospholipids to be ordered by cholesterol is increased by these compounds. Pzero increases curvilinearly with the fraction of either of these molecules. Pplat increases linearly with the fraction of saturated acyl chains for most phospholipids. Highly unsaturated fatty acyl chains (e.g., 20:4 and 22:6) strongly depress Pplat but not Pzero. The results suggest that such phospholipids are unlikely to associate with cholesterol and may thus create extremely fluid membrane domains. The disproportionation of cholesterol in the cell can be understood by the differing composition of the phospholipids in plasma membranes and endomembranes and their ordering susceptibility (affinity) toward cholesterol.

Animals↗

PubMed1986

Steady-state fluorescence polarization data in membranes. Resolution into physical parameters by an extended Perrin equation for restricted rotation of fluorophores.

An extended Perrin equation is derived applicable to the restricted rotation of fluorophores. The equation results in a relation between time-resolved (r infinity) and steady-state fluorescence anisotropy (rs) data. This relation contains a parameter m, which expresses the difference between rotational diffusion in a lipid membrane and that in an isotropic reference oil having the same rs value. The relation is in agreement with rs, r infinity literature data for a variety of artificial and biological membranes labeled with various probes. Cholesterol and fatty acyl unsaturation affect the value of m, but temperature does not. The results indicate that, as far as fluorescence depolarization is concerned, either liposomes of saturated phospholipids without cholesterol or liposomes of unsaturated phospholipids containing cholesterol are good model systems for biological membranes. The accuracy of estimating order parameters or rotational diffusion constants from rs data is discussed. The formalism described here introduces a novel way of applying Arrhenius plots and allows for an unambiguous interpretation of rs data.

Cholesterol↗

PubMed1985

The effects of pressure and cholesterol on rotational motions of perylene in lipid bilayers.

Using steady-state fluorescence polarization measurements, an isothermal pressure-induced phase transition was observed in dimyristoyl-L-alpha-phosphatidylcholine multilamellar vesicles containing perylene. The temperature-to-pressure equivalence, dT/dP, estimated from the phase transition pressure, P1/2, is about 22 K X kbar-1, which is comparable to values determined from diphenylhexatriene polarization (Chong, P.L.-G. and Weber, G. (1983) Biochemistry 22, 5544-5550). In addition, we have employed a new method, introduced in this paper, to calculate the rate of in-plane rotation (Rip) and the rate of out-of-plane rotation (Rop) of perylene in lipid bilayers. The effects of pressure and cholesterol on the rotational rates of perylene in two lipid bilayer systems have been examined. They are 1-palmitoyl-2-oleoyl-L-alpha-phosphatidylcholine (POPC) multilamellar vesicles (MLV) and 50 mol% cholesterol in POPC (MLV). Rop is smaller than Rip due to the fact that the out-of-plane rotation requires a larger volume change than the in-plane rotation. Cholesterol seems not to affect Rop significantly, but pressure causes a decrease in Rop by about a factor of three. In contrast, the effects of pressure and cholesterol on Rip are less straightforward. At 1 atm cholesterol increases Rip by a factor of about two. Similarly, in the absence of cholesterol 1.5 kbar pressure essentially triples Rip. However, if both cholesterol is added and pressure is applied, Rip decreases sharply. The possible interactions between cholesterol and perylene are discussed.

Benz(a)Anthracenes↗

PubMed1984

An explanation of the low lecithin/sphingomyelin ratio of amniotic fluid in early pregnancy.

We have attempted to determine why the lecithin/sphingomyelin (L/S) ratio of amniotic fluid is lower than 2 during an early stage of pregnancy. We found that, at 16 wk of gestation, long before the fetal lung secretes lecithin into the amniotic fluid, the L/S ratio was about 1. High-density lipoprotein isolated from the amniotic fluid also had such a low L/S ratio. The L/S ratios of the high-density lipoprotein from umbilical cord blood and maternal blood, however, were much higher, viz. 3.7 (+/- 0.25) and 6.4 (+/- 0.33), respectively. The increase coincided with a decrease in their fluorescence polarization. We suggest that the low L/S ratio of 16 wk amniotic fluid is caused by lipolysis of its lecithin, which is derived from fetal or maternal high-density lipoproteins.

Amniotic Fluid↗