Showing papers by "Peter C. M. Molenaar published in 1999"

Monoclonal antibodies raised against Guillain-Barré syndrome–associated Campylobacter jejuni lipopolysaccharides react with neuronal gangliosides and paralyze muscle-nerve preparations

Abstract: Guillain-Barre syndrome and its variant, Miller-Fisher syndrome, are acute, postinfectious, autoimmune neuropathies that frequently follow Campylobacter jejuni enteritis. The pathogenesis is believed to involve molecular mimicry between sialylated epitopes on C. jejuni LPSs and neural gangliosides. More than 90% of Miller-Fisher syndrome cases have serum anti-GQ1b and anti-GT1a ganglioside antibodies that may also react with other disialylated gangliosides including GD3 and GD1b. Structural studies on LPS from neuropathy-associated C. jejuni strains have revealed GT1a-like and GD3-like core oligosaccharides. To determine whether this structural mimicry results in pathogenic autoantibodies, we immunized mice with GT1a/GD3-like C. jejuni LPS and then cloned mAb’s that reacted with both the immunizing LPS and GQ1b/GT1a/GD3 gangliosides. Immunohistology demonstrated antibody binding to ganglioside-rich sites including motor nerve terminals. In ex vivo electrophysiological studies of nerve terminal function, application of antibodies either ex vivo or in vivo via passive immunization induced massive quantal release of acetylcholine, followed by neurotransmission block. This effect was complement-dependent and associated with extensive deposits of IgM and C3c at nerve terminals. These data provide strong support for the molecular mimicry hypothesis as a mechanism for the induction of cross-reactive pathogenic anti-ganglioside/LPS antibodies in postinfectious neuropathies.

Miller Fisher anti-GQ1b antibodies: alpha-latrotoxin-like effects on motor end plates.

Abstract: In the Miller Fisher syndrome (MFS) variant of the Guillain-Barre syndrome, weakness is restricted to extraocular muscles and occasionally other craniobulbar muscles. Most MFS patients have serum antibodies against ganglioside type GQ1b of which the pathophysiological relevance is unclear. We examined the in vitro effects of MFS sera, MFS IgG, and a human monoclonal anti-GQ1b IgM antibody on mouse neuromuscular junctions (NMJs). It was found that anti-GQ1b antibodies bind at NMJs where they induce massive quantal release of acetylcholine from nerve terminals and eventually block neuromuscular transmission. This effect closely resembled the effect of the paralytic neurotoxin alpha-latrotoxin at the mouse NMJs, implying possible involvement of alpha-latrotoxin receptors or associated downstream pathways. By using complement-deficient sera, the effect of anti-GQ1b antibodies on NMJs was shown to be entirely dependent on activation of complement components. However, neither classical pathway activation nor the formation of membrane attack complex was required, indicating the effects could be due to involvement of the alternative pathway and intermediate complement cascade products. Our findings strongly suggest that anti-GQ1b antibodies in conjunction with activated complement components are the principal pathophysiological mediators of motor symptoms in MFS and that the NMJ is an important site of their action.

Activation of beta2-adrenergic receptors hastens relaxation and mediates phosphorylation of phospholamban, troponin I, and C-protein in ventricular myocardium from patients with terminal heart failure.

Abstract: Background—Catecholamines hasten cardiac relaxation through β-adrenergic receptors, presumably by phosphorylation of several proteins, but it is unknown which receptor subtypes are involved in human ventricle We assessed the role of β1- and β2-adrenergic receptors in phosphorylating proteins implicated in ventricular relaxation Methods and Results—Right ventricular trabeculae, obtained from freshly explanted hearts of patients with dilated cardiomyopathy (n=5) or ischemic cardiomyopathy (n=5), were paced at 60 bpm After measurement of the contractile and relaxant effects of epinephrine (10 μmol/L) or zinterol (10 μmol/L), mediated through β2-adrenergic receptors, and of norepinephrine (10 μmol/L), mediated through β1-adrenergic receptors, tissues were freeze clamped We assessed phosphorylation of phospholamban, troponin I, and C-protein, as well as specific phosphorylation of phospholamban at serine 16 and threonine 17 Data did not differ between the 2 disease groups and were therefore pooled Epinep

Putative β4-adrenoceptors in rat ventricle mediate increases in contractile force and cell Ca2+: comparison with atrial receptors and relationship to (−)-[3H]-CGP 12177 binding

Abstract: 1 We identified putative beta(4)-adrenoceptors by radioligand binding, measured increases in ventricular contractile force by (-)-CGP 12177 and (+/-)-cyanopindolol and demonstrated increased Ca2+ transients by (-)-CGP 12177 in rat cardiomyocytes. 2 (-)-[H-3]-CGP 12177 labelled 13-22 fmol mg(-1) protein ventricular beta(1), beta(2)-adrenoceptors (pK(D) similar to 9.0) and 50-90 fmol mg(-1) protein putative beta(4)-adrenoceptors (pK(D) similar to 7.3). The affinity values (PKi) for (beta(1),beta(2)-) and putative beta(4)-adrenoceptors, estimated from binding inhibition, were (-)-propranolol 8.4, 5.7; (-)-bupranolol 9.7, 5.8; (+/-)-cyanopindolol 10.0,7.4. 3 In left ventricular papillary muscle, in the presence of 30 mu M 3-isobutyl-1-methylxanthine, (-)CGP 12177 and (+/-)-cyanopindolol caused positive inotropic effects, (pEC(50) (-)-CGP 12177, 7.6; (+/-)-cyanopindolol, 7.0) which were antagonized by (-)-bupranolol (pK(B) 6.7-7.0) and (-)-CGP 20712A (pK(B) 6.3-6.6). The cardiostimulant effects of(-)-CGP 12177 in papillary muscle, left and right atrium were antagonized by (+/-)-cyanopindolol (pK(i), 7.0-7.4). 4 (-)-CGP 12177 (1 mu M) in the presence of 200 nM (-)-propranolol increased Ca2+ transient amplitude by 56% in atrial myocytes, but only caused a marginal increase in ventricular myocytes. In the presence of 1 mu M 3-isobutyl-1-methylxanthine and 200 nM (-)-propranolol, 1 mu M (-)-CGP 12177 caused a 73% increase in Ca2+ transient amplitude in ventricular myocytes. (-)-CGP 12177 elicited arrhythmic transients in some atrial and ventricular myocytes. 5 Probably by preventing cyclic AMP hydrolysis, 3-isobutyl-1-methylxanthine facilitates the inotropic function of ventricular putative beta(4)-adrenoceptors. suggesting coupling to G(s) protein-adenylyl cyclase. The receptor-mediated increases in contractile force are related to increases of Ca2+ in atrial and ventricular myocytes. The agreement of binding affinities of agonists with cardiostimulant potencies is consistent with mediation through putative beta(4)-adrenoceptors labelled with (-)-[H-3]-CGP 12177.

Additional aspects of third source variation for the genetic analysis of human development and behaviour: a commentary on Eaves et al.

Abstract: showing some effects of chaotic processes on MZ and DZ twin correlations. More specifically, they use the logistic equation, x(t +1 ) =kx(t)[1 ‐ x(t)], where k is a parameter and t denotes discrete time, as a simple developmental model and simulate MZ and DZ twin phenotypic time series under various assumptions concerning the starting value x(0) and using a number of distinct values for the parameter k. In discussing the results thus obtained, Eaves et al 1 draw some conclusions with respect to, for example, the possible forms and prevalence of chaotic variation in developmental processes as proposed by Molenaar et al. 2 In the following we present the results of alternative simulation studies that show additional aspects of chaotic variation in the genetic analysis of human development. Finally, we discuss some of the implications of our own results with respect to the interpretations given by Eaves et al 1 of their simulation results.

Using structural equation modeling to fit models incorporating principal components

Abstract: The aim of this article is to consider models incorporating principal components from the perspective of structural equation modeling. These models include the principal component analysis of patterned matrices, multiple analysis of variance based on principal components, and multigroup principal component analysis. We demonstrate that these models can be fit readily using the programs LISREL 8 and Mx. The models and certain extensions are discussed, and several illustrations are given.

Brain activity and cognitive transition during childhood: A longitudinal event-related brain potential study.

Abstract: This study examined the relation between brain activation and cognitive development using event-related brain potentials (ERPs) and a longitudinal design. Five-year-old girls performed a visual recognition (‘oddball’) task and an experimental analogue of the Piagetian conservation of liquid quantity task at three experimental sessions, with one year between consecutive sessions. The data revealed age-related changes in neurocognitive mechanisms common to both tasks. In comparing children before and after a Piagetian transition on a traditional clinical conservation test the data revealed a major shift in performance and ERPs to the experimental analogue of the liquid quantity task. These findings are consistent with a previously performed cross-sectional study and provide strong support for the hypothesis that cognitive transition is related to new neurocognitive mechanisms emerging during childhood. Possible implications of these findings for child neuropsychology are discussed.

Comment on fitting MA time series by structural equation models

Abstract: In a recent paper by van Buuren (1997) it is concluded that parameter estimates in pure moving-average (MA) models, obtained by software for fitting structural equation models (SEMs), are biased and inefficient. In this comment it is shown that this negative finding may be due to a particular feature of van Buuren's simulation experiment. A modified procedure for fitting MA models by means of SEM software is proposed, and some of its implications are discussed.

Acetylcholinesterase activity of skeletal muscle in a non-immunogenic model for myasthenia gravis in rats.

Abstract: Myasthenia gravis is caused by an autoimmune attack to acetylcholine receptors of skeletal muscle. Acetylcholine release from motor nerve terminals is upregulated in patients with myasthenia gravis and also in rat "myasthenic" models, dependent on the reduction of the number of acetylcholine receptors. This study addresses the question as to whether at "myasthenic" endplates there are changes in the activity of acetylcholinesterase. To this end we studied acetylcholinesterase activity in junctional and extrajunctional regions of dilator naris, extensor digitorum longus, and hemidiaphragm muscles from rats with alpha-bungarotoxin-induced myasthenia gravis. In all studied muscles from "myasthenic" rats there was no significant change of junctional acetylcholinesterase activity. In contrast, in dilator naris and extensor digitorum longus muscles, there was a 60% and 30% increase of extrajunctional acetylcholinesterase activity. There was no significant change in the extrajunctional activity in hemidiaphragm muscles. Velocity sedimentation analysis revealed that the increase in extrajunctional activity in extensor digitorum longus muscles could be attributed to an increase of the activity of the G4 form of acetylcholinesterase. Treatment of rats with 6.4 microgh(-1) neostigmine bromide for 29 days had no influence on junctional and extrajunctional acetylcholinesterase activity of extensor digitorum longus muscles from rats with alpha-bungarotoxin-induced myasthenia gravis.

Reaction time as recovery time after pertubation

Abstract: This paper introduces a preliminary model of reaction time that is derived from dynamic system theory. This alternative for the random walk model of reaction time applies another definition of information change and, as a consequence, another stop-criterion. Where the random walk in random walk models stops when a bound is reached, the walk in the dynamical model stops when it converges, or, in other words, when the system recovers stability. The mathematical formulation of the dynamical model is not yet complete. However, by computer simulation it can be shown that the model yields correct predictions about the reaction time distribution. First we will explain the background of this new model of reaction time, then the model is explained and compared with the

A Biological Plausible Maturation of an ART Network

Abstract: We present a numerical bifurcation analysis of a shunting neural network (SNN). Fold bifurcations appear to occur in the plane of parameters that are subject to post-natal maturation: the range and strength of lateral connections. The SNN is implemented as a content addressable memory (CAM) in Exact ART, a complete implementation of Adaptive Resonance Theory. The stability and functionality of Exact ART with the CAM in different dynamic regimes is maintained. Moreover, through a bifurcation, the learning behavior of Exact ART changes from forming local representations to forming distributed representations. Presently, we extend Exact ART by adding biologically plausible evolution equations for activation dependent maturation of lateral connections in a SNN (Van Ooyen et al., 1995). The resulting model is an epigenetic model of both morphological development and cognitive behavioral development.