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Showing papers by "Radboud University Nijmegen published in 1994"


Journal ArticleDOI
15 Jul 1994-Cell
TL;DR: In this article, the authors designed a knockout model for the fragile X syndrome in mice and found that the knockout mice lack normal Fmr1 protein and show macroorchidism, learning deficits, and hyperactivity.

981 citations


Journal ArticleDOI
TL;DR: An updated version of the Nijmegen soft-core potential is presented, which gives a much better description of the np data than the older version, and three new NN potential models are presented that have a nearly optimal chi^2 per datum and can therefore be considered as alternative partial-wave analyses.
Abstract: We present an updated version (Nijm93) of the Nijmegen soft-core potential, which gives a much better description of the np data than the older version (Nijm78). The ${\mathrm{\ensuremath{\chi}}}^{2}$ per datum is 1.87. The configuration-space and momentum-space versions of this potential are exactly equivalent, a unique feature among meson-theoretical potentials. We also present three new NN potential models: a nonlocal Reid-like Nijmegen potential (Nijm I), a local version (Nijm II), and an updated regularized version (Reid 93) of the Reid soft-core potential. These three potentials all have a nearly optimal ${\mathrm{\ensuremath{\chi}}}^{2}$ per datum and can therefore be considered as alternative partial-wave analyses. All potentials contain the proper charge-dependent one-pion-exchange tail.

977 citations


Journal ArticleDOI
01 Apr 1994-Science
TL;DR: A male patient with an autosomal recessive form of NDI was found to be a compound heterozygote for two mutations in the gene encoding aquaporin-2, a water channel, which is essential for vasopressin-dependent concentration of urine.
Abstract: Concentration of urine in mammals is regulated by the antidiuretic hormone vasopressin. Binding of vasopressin to its V2 receptor leads to the insertion of water channels in apical membranes of principal cells in collecting ducts. In nephrogenic diabetes insipidus (NDI), the kidney fails to concentrate urine in response to vasopressin. A male patient with an autosomal recessive form of NDI was found to be a compound heterozygote for two mutations in the gene encoding aquaporin-2, a water channel. Functional expression studies in Xenopus oocytes revealed that each mutation resulted in nonfunctional water channel proteins. Thus, aquaporin-2 is essential for vasopressin-dependent concentration of urine.

845 citations


Journal ArticleDOI
TL;DR: The authors investigated the extent to which this kind of rebound effect extends to unwanted stereotypic thoughs about others and found that stereotype suppressors responded more pejoratively to a stereotyped target on a range of dependent measures.
Abstract: For a variety of reasons, social perceivers may often attempt to actively inhibit stereotypic thoughts before their effects impinge on judgment and behavior. However, research on the psychology of mental control raises doubts about the efficacy of this strategy. Indeed, this work suggests that when people attempt to suppress unwanted thoughts, these thoughts are likely to subsequently reappear with even greater insistence than if they had never been suppressed (i.e., a ''rebound'' effect). The present research comprised an investigation of the extent to which this kind of rebound effect extends to unwanted stereotypic thoughs about others. The results provided strong support for the existence of this effect. Relative to control subjects (i.e., stereotype users), stereotype suppressors responded more pejoratively to a stereotyped target on a range of dependent measures. We discuss our findings in the wider context of models of mind, thought suppression, and social stereotyping.

792 citations


Journal ArticleDOI
TL;DR: Measurement of the combined local synthesis of antibodies against measles, rubella, and/or varicella zoster could represent a significant advance if it offers higher specificity (not sensitivity) for identifying chronic rather than acute inflammation.
Abstract: The Committee of the European Concerted Action for Multiple Sclerosis (Charcot Foundation) organised five workshops to discuss CSF analytical standards in the diagnosis of multiple sclerosis. This consensus report from 12 European countries summarises the results of those workshops. It is hoped that neurologists will confer with their colleagues in clinical chemistry to arrange the best possible local practice. The most sensitive method for the detection of oligoclonal immunoglobulin bands is isoelectric focusing. The same amounts of IgG in parallel CSF and serum samples are used and oligoclonal bands are revealed with IgG specific antibody staining. All laboratories performing isoelectric focusing should check their technique at least annually using "blind" standards for the five different CSF and serum patterns. Quantitative measurements of IgG production in the CNS are less sensitive than isoelectric focusing. The preferred method for detection of blood-CSF barrier dysfunction is the albumin quotient. The CSF albumin or total protein concentrations are less satisfactory. These results must be interpreted with reference to the age of the patient and the local method of determination. Cells should be counted. The normal value is no more than 4 cells/microliters. Among evolving optional tests, measurement of the combined local synthesis of antibodies against measles, rubella, and/or varicella zoster could represent a significant advance if it offers higher specificity (not sensitivity) for identifying chronic rather than acute inflammation. Other tests that may have useful correlations with clinical indices include those for oligoclonal free light chains, IgM, IgA, or myelin basic protein concentrations.

617 citations


Journal ArticleDOI
TL;DR: In this paper, a model of travel mode choice is tested by means of a survey among 199 inhabitants of a village, where the attitude toward choosing the car and the attitude towards choosing an alternative mode (i.e., train) was predicted from the attitude of a particular journey and from general car habit.
Abstract: A model of travel mode choice is tested by means of a survey among 199 inhabitants of a village. Car choice behavior for a particular journey is predicted from the attitude toward choosing the car and the attitude toward choosing an alternative mode (i.e., train), on the one hand, and from general car habit, on the other hand. Unlike traditional measures of habit, a script-based measure was used. General habit was measured by travel mode choices in response to very global descriptions of imaginary journeys. In the model, habit is predicted from the degree of involvement with the decision-making about travel mode choice for the particular journey (decisional involvement) and from the degree of competition in a household with respect to car use. The model proves satisfactory. Moreover, as suggested by Triandis (1977), there is a tradeoff between attitude and habit in the prediction of behavior: When habit is strong the attitude-behavior relation is weak, whereas when habit is weak, the attitude-behavior link is strong.

564 citations


Journal Article
TL;DR: These two criteria, cytonuclear differentiation and architectural differentiation, have been found to be more consistent throughout a DCIS lesion than previously employed criteria of architectural pattern or the presence or absence of necrosis.

550 citations


Journal ArticleDOI
TL;DR: In this article, an overview of the X-ray absorption spectra of 3D transition metals and their compounds is presented, focusing on the description of the absorption process and the various routes to interpret the results within the framework of their electronic structure.

528 citations


Journal ArticleDOI
TL;DR: In this paper, the authors relate les resultats d'une etude menee pour fournir des donnees pertinentes sur le developpement du modele de production de la parole chez des bilingues.
Abstract: Cet article relate les resultats d'une etude menee pour fournir des donnees pertinentes sur le developpement du modele de production de la parole chez des bilingues

440 citations


Journal ArticleDOI
01 Dec 1994-Futures
TL;DR: A quasi-evolutionary model is proposed which underpins the analysis of suggested strategies that could turn electric vehicles from an elusive legend, a plaything, into a marketable product.

414 citations


Journal ArticleDOI
TL;DR: The study clearly demonstrated that climacteric complaints occur in south-east Asia, and suggested that vasomotor-complaint-related distress might be 'translated' into psychological complaints, which are more frequently considered to warrant consulting a physician.

Journal Article
TL;DR: It is indicated that TGF-beta 1 injection into a normal joint induces inflammation, synovial hyperplasia, osteophyte formation, and prolonged elevation of proteoglycan synthesis and content in articular cartilage.

Journal ArticleDOI
TL;DR: Structural aspects, post-translational modifications, the occurrence outside of the eye lens, the heat-shock relation and the chaperone activity of alpha-crystallin are reviewed.
Abstract: α-Crystallin is a high-molecular-mass protein that for many decades was thought to be one of the rare real organ-specific proteins. This protein exists as an aggregate of about 800 kDa, but its composition is simple. Only two closely related subunits termed αA- and αB-crystallin, with molecular masses of approximately 20 kDa, form the building blocks of the aggregate.

Journal ArticleDOI
TL;DR: The widely held notion that the pyramidal neurons constitute the relatively constant basic framework of the cortex, whereas the local circuit neurons are variable and increase during phylogenetic development in number as well as in diversity is untenable.
Abstract: By way of introduction, an outline is presented of the origin and evolutionary development of the neocortex. A cortical formation is lacking in amphibians, but a simple three-layered cortex is present throughout the pallium of reptiles. In mammals, two three-layered cortical structures, i.e. the prepiriform cortex and the hippocampus, are separated from each other by a six-layered neocortex. Still small in marsupials and insectivores, this "new" structure attains amazing dimensions in anthropoids and cetaceans. Neocortical neurons can be allocated to one of two basic categories: pyramidal and nonpyramidal cells. The pyramidal neurons form the principal elements in neocortical circuitry, accounting for at least 70% of the total neocortical population. The evolutionary development of the pyramidal neurons can be traced from simple, "extraverted" neurons in the amphibian pallium, via pyramid-like neurons in the reptilian cortex to the fully developed neocortical elements designated by Cajal as "psychic cells". Typical mammalian pyramidal neurons have the following eight features in common: (1) spiny dendrites, (2) a stout radially oriented apical dendrite, forming (3) a terminal bouquet in the most superficial cortical layer, (4) a set of basal dendrites, (5) an axon descending to the subcortical white matter, (6) a number of intracortical axon collaterals, (7) terminals establishing synaptic contacts of the round vesicle/asymmetric variety, and (8) the use of the excitatory aminoacids glutamate and/or aspartate as their neurotransmitter. The pyramidal neurons constitute the sole output and the largest input system of the neocortex. They form the principal targets of the axon collaterals of other pyramidal neurons, as well as of the endings of the main axons of cortico-cortical neurons. Indeed, the pyramidal neurons constitute together a continuous network extending over the entire neocortex, justifying the generalization: the neocortex communicates first and foremost within itself. The typical pyramidal neurons represent the end stage of a progressive evolutionary process. During further development many of these elements have become transformed by reduction into various kinds of atypical or aberrant pyramidal neurons. Interestingly, none of the six morphological characteristics, mentioned above under 1-6, has appeared to be unassailable; pyramidal neurons lacking spines, apical dendrites, long axons and intracortical axon collaterals etc. have all been described. From an evolutionary point of view the typical pyramidal neurons represent not only the principal neocortical elements, but also the source of various excitatory local circuit neurons. The spiny stellate cells, which are abundant in highly specialized primary sensory areas, form a remarkable case in point.(ABSTRACT TRUNCATED AT 400 WORDS)

Journal ArticleDOI
TL;DR: A simulation model is developed which maintains the self-organizational characteristics but does not produce discontinuities and can also explain adaptation of morphology, in the sense of 'Wolff's law'.

Journal Article
TL;DR: Using an original stereoscopic technique, the present study of 60 mastectomy specimens shows that continuous and multifocal growth patterns are usual and should encourage the use of conserving treatment for eradicable DCIS.

Journal ArticleDOI
TL;DR: A genome-wide linkage analysis in a large Dutch kindred with autosomal dominant Noonan syndrome is performed, and data imply that a gene for Noonan Syndrome is located on chromosome 12q, between D12S84 and D 12S366.
Abstract: Noonan syndrome is characterized by typical facies, short stature and congenital cardiac defects. Approximately half of all cases are sporadic, but autosomal dominant inheritance with variable expression is well established. We have performed a genome-wide linkage analysis in a large Dutch kindred with autosomal dominant Noonan syndrome, and localized the Noonan syndrome gene to chromosome 12 (Zmax=4.04 at θ=0.0). Linkage analysis using chromosome 12 markers in 20 smaller, two-generation families gave Zmax=2.89 at θ=0.07, but haplotype analysis showed non-linkage in one family. These data imply that a gene for Noonan syndrome is located on chromosome 12q, between D12S84 and D12S366.

Journal ArticleDOI
TL;DR: The large size of this family enabled the possible involvement of candidate regions by multipoint linkage analysis to be tested and the region surrounding the NF1 locus on chromosome 17 and the proximal part of chromosome 22 could be excluded.
Abstract: We describe the largest Noonan syndrome (NS) family reported to date. The manifestations of the affected relatives are discussed. In the absence of a biochemical marker NS is still a clinical diagnosis. The diagnostic criteria that were used are presented compared with other published criteria for diagnosing NS. The large size of this family enabled us to test the possible involvement of candidate regions by multipoint linkage analysis. Both the region surrounding the NF1 locus on chromosome 17 and the proximal part of chromosome 22 could be excluded. Since NS may well be heterogeneous, the use of such a large family in linkage studies of NS should prove indispensable.

Journal ArticleDOI
TL;DR: This paper proposes a new convention for unambiguous and easily interpretable, 3-D joint angles, based on the concept of the attitude 'vector' as derived from Euler's theorem, which has better metrical properties and is less sensitive to measurement errors and to coordinate system uncertainties than Cardanic/Eulerian angles.

Journal Article
TL;DR: Based on the extent of microcalcifications, mammography usually underestimates the size of DCIS; although this discrepancy is less than 2 cm in 80% to 85% of the cases if state-of-the-art mammography, including magnification views, is used.

Journal ArticleDOI
TL;DR: Radiofrequency magnetron sputtering was used as an alternative method to deposit thin films of hydroxylapatite on titanium substrates and it was demonstrated that the sputtered layer was crystalline with a preferred (001) crystallographic orientation with the C-axis perpendicular to the substrate surface.
Abstract: Plasma-sprayed hydroxylapatite coatings on metals such as titanium have been investigated for many years and have shown a good biocompatibility when implanted in bony tissues. Radiofrequency magnetron sputtering was used as an alternative method to deposit thin films of hydroxylapatite on titanium substrates. X-ray diffraction demonstrated that the sputtered layer was crystalline with a preferred (001) crystallographic orientation with the C-axis perpendicular to the substrate surface. Scanning electron microscopy showed that the deposited films had a uniform and dense structure. The calcium phosphate ratio varied between 1.5 and 2.0, as determined by energy-dispersive X-ray analysis. The in vitro dissolution appeared to be determined by the degree of the coating's crystallinity. © 1994 John Wiley & Sons, Inc.

Journal ArticleDOI
TL;DR: It is concluded that a modifiable timing within the stride cycle takes place with a coupling between ipsilateral support and contralateral swing phase, obviously based on ipsilaterally modulation of leg extensor EMG by proprioceptive feedback and an appropriate central (e.g. spinal) modulation ofcontralateral tibialis anterior EMG activity.
Abstract: Human interlimb coordination and the adaptations in leg muscle activity were studied during walking on a treadmill with split belts. Four different belt speeds (0.5, 1.0, 1.5, 2.0 m/s) were offered in all possible combinations for the left and right leg. Subjects adapted automatically to a difference in belt speed within 10–20 stride cycles.This adaptation was achieved by a reorganization of the stride cycle with a relative shortening of the duration of the support and lengthening of the swing phase of the “fast” leg and, vice versa, in support and swing duration on the “slow” leg. The electromyogram EMG patterns were characterized by two basic observations: (1) onset and timing of EMG activity were influenced by biomechanical constraints. A shortening of the support phase on the faster side was related to an earlier onset and increase in gastrocnemius activity, while a coactivation pattern in the antagonistic leg muscles was predominant during a prolonged support phase on the slower side. (2) A differential modulation of the antagonistic leg muscles took place. An increase in ipsilateral belt speed in combination with a constant contralateral belt speed was associated with an almost linear increase in ipsilateral gastrocnemius and contralateral tibialis anterior EMG activity, while the contralateral gastrocnemius and ipsilateral tibialis anterior EMG activity were little affected. It is concluded that a modifiable timing within the stride cycle takes place with a coupling between ipsilateral support and contralateral swing phase. The neuronal control of this coupling is obviously based on ipsilateral modulation of leg extensor EMG by proprioceptive feedback and an appropriate central (e.g. spinal) modulation of contralateral tibialis anterior EMG activity.

Journal ArticleDOI
TL;DR: A meta-analysis was performed on the dental literature since 1970, presenting clinical data of conventional bridges, and the calculated overall survival rate was 74.0 +/- 2.1% after 15 yr.
Abstract: A meta-analysis was performed on the dental literature since 1970, presenting clinical data of conventional bridges. 42 publications were found that contained durability data of conventional fixed bridges. These publications dealt with 33 different samples. According to the exclusion criteria 26 studies were excluded for the meta-analysis. The data of 4118 conventional bridges were analyzed. The calculated overall survival rate was 74.0 +/- 2.1% after 15 yr.

Journal ArticleDOI
TL;DR: Investigation of αB-crystallin in the brains of Alzheimer's disease patients and nondemented controls found no evidence that this protein, in addition to glial fibrillary acidic protein (GFAP), can be a marker for gliosis in neurodegenerative diseases.
Abstract: αB-crystallin is a member of the small heatshock protein family. Under pathological conditions, the expression of αB-crystallin increases in proliferating astrocytes, which suggests that this protein, in addition to glial fibrillary acidic protein (GFAP), can be a marker for gliosis in neurodegenerative diseases. Immunoblotting and immunohistochemical methods were used for the detection of αB-crystallin in the brains of Alzheimer's disease (AD) patients and nondemented controls. An increase in αB-cyrstallin expression was found in the brains of AD patients. Immunoreaction was present in reactive astrocytes, microglia, and oligodendrocytes, indicating that all types of glia respond to the stress associated with AD pathology. Colocalization of GFAP and αB-crystallin was found in fibrous astrocytes. However, the intensity and range of αB-crystallin expression appeared to be limited as compared with the large increase in the number of GFAP-positive astrocytes. This indicates that expression of αB-crystallin is not a marker for gliosis in AD. Immunoreactivity to αB-crystallin in both astrocytes and microglia was found mainly restricted to areas with senile plaques and neurofibrillary tangles, suggesting the association of αB-crystallin with amyloid deposition in AD.

Journal ArticleDOI
TL;DR: Postural control in a moving visual environment cannot be understood simply in terms of minimization of retinal slip, and that dynamic coupling of vision into the postural control system must be taken into account.
Abstract: When standing human subjects are exposed to a moving visual environment, the induced postural sway forms a stable temporal relationship with the visual information. We have investigated this relationship experimentally with a new set-up in which a computer generates video images which correspond to the motion of a 3D environment. The suggested mean distance to a sinusoidally moving wall is varied and the temporal relationship to induced sway is analysed (1) in terms of the fluctuations of relative phase between visual and sway motion and (2) in terms of the relaxation time of relative phase as determined from the rate of recovery of the stable relative phase pattern following abrupt changes in the visual motion pattern. The two measures are found to converge to a well-defined temporal stability of the action-perception cycle. Furthermore, we show that this temporal stability is a sensitive measure of the strength of the action-perception coupling. It decreases as the distance of the visual scene from the observer increases. This fact and the increase of mean relative phase are consistent with predictions of a linear second-order system driven by the visual expansion rate. However, the amplitude of visual sway decreases little as visual distance increases, in contradiction to the predictions, and is suggestive of a process that actively generates sway. The visual expansion rate on the optic array is found to decrease strongly with visual distance. This leads to the conclusion that postural control in a moving visual environment cannot be understood simply in terms of minimization of retinal slip, and that dynamic coupling of vision into the postural control system must be taken into account.

Journal ArticleDOI
TL;DR: It is concluded that COL4A3 is a major gene in the genetically and clinically heterogeneous Alport syndrome, and Autosomal recessive inheritance due to pathogenic COL 4A3 mutations accounts for at least 13% of Alport Syndrome cases.
Abstract: A group of 22 unrelated patients with sporadic or non-X-linked Alport syndrome were screened for mutations in the non-collagenous domain of the type IV collagen alpha 3 (COL4A3) chain gene. The five 3'-exons of this gene, located on chromosome 2qter, were tested by single strand conformation polymorphism analysis and direct sequencing. One patient was heterozygous and another homozygous (Mochizuki et al., Nature Genetics, in press) for a deletion of five nucleotides. A third patient appeared to be a compound heterozygote for two different nonsense mutations. In two patients and the father of a deceased patient we found a heterozygous substitution of an evolutionary conserved leucine by proline. However, segregation data of the mutation and a COL4A3/COL4A4 CA-repeat marker in their families argued against a causative role of the missense mutation. Even drastic changes of strongly conserved amino acids, as in the Leu36Pro case, may not be significant. Autosomal recessive inheritance due to pathogenic COL4A3 mutations accounts for at least 13% of Alport syndrome cases in this sample. It is concluded that COL4A3 is a major gene in the genetically and clinically heterogeneous Alport syndrome.

Journal ArticleDOI
29 Jul 1994-Cell
TL;DR: The results suggest that 7B2 is a novel type of molecular chaperone preventing premature activation of proPC2 in the regulated secretory pathway.

Journal Article
TL;DR: In this paper, a single nucleotide deletion in the aquaporin 2 gene of three NDI patients from consanguineous matings was reported, which proved that mutations in the AQP2 gene cause autosomal recessive NDI.
Abstract: Mutations in the X-chromosomal V2 receptor gene are known to cause nephrogenic diabetes insipidus (NDI). Besides the X-linked form, an autosomal mode of inheritance has been described. Recently, mutations in the autosomal gene coding for water-channel aquaporin 2 (AQP2) of the renal collecting duct were reported in an NDI patient. In the present study, missense mutations and a single nucleotide deletion in the aquaporin 2 gene of three NDI patients from consanguineous matings are described. Expression studies in Xenopus oocytes showed that the missense AQP2 proteins are nonfunctional. These results prove that mutations in the AQP2 gene cause autosomal recessive NDI.

Journal ArticleDOI
TL;DR: It is concluded that when urinary 1-OH-pyrene excretion is used in the assessment of PAH exposure, one should particularly be aware of the interindividual variability of the baseline excretion ofPAH metabolites due to tobacco smoking and dietary PAH intake.
Abstract: Seventy-six male volunteers, who were not occupationally exposed to polycyclic aromatic hydrocarbons (PAHs), participated in a study on the effect of tobacco smoking, alcohol consumption, dietary PAH intake, age, and body fat content on the baseline excretion of 1-hydroxypyrene in urine. Major determinants of urinary 1-hydroxypyrene excretion were smoking, dietary PAH intake, and age. The mean 1-hydroxypyrene concentrations in the urine of the volunteers in this study ranged between 0.05 and 0.79 μmol/mol creatinine. Smokers excreted on average 0.25 μmol/mol creatinine (range: 0.10–0.79 μmol/mol creatinine), and nonsmokers on average 0.12 μmol/mol creatinine (range: 0.04–0.29 μmol/mol creatinine). The average number of cigarettes smoked per day correlated well with urinary 1-hydroxypyrene concentrations (r s = 0.67, P < 0.001). The consumption of PAH-containing food products and active smoking account for 99% of total pyrene intake. The effect of age on 1-hydroxypyrene excretion is probably caused by a lower creatinine excretion in the elderly. Passive smoking and fat content had a statistically significant, but negligible effect on urinary 1-hydroxypyrene excretion. Passive smoking and the inhalation of ambient air are relatively inimportant for total pyrene intake (both account for less than 1%). Neither the consumption of alcohol nor the inhalation of ambient air significantly affected urinary 1-hydroxypyrene excretion. It is concluded that when urinary 1-OH-pyrene excretion is used in the assessment of PAH exposure, one should particularly be aware of the interindividual variability of the baseline excretion of PAH metabolites due to tobacco smoking and dietary PAH intake.

Journal ArticleDOI
TL;DR: The results strongly suggest that inhalation is of minor importance for internal exposure, compared with other, presumably dermal, routes.
Abstract: In the Netherlands, special guidelines and safety precautions were introduced about 10 y ago for preparation and administration of antineoplastic agents. However, little is known about the effectiveness of these measures. In this study, occupational exposure to antineoplastic agents of nine pharmacy technicians who were involved in drug preparation was investigated. Cyclophosphamide, 5-fluorouracil, and methotrexate accounted for 95% of the antineoplastic agents prepared; therefore, the presence of these compounds was monitored. During preparation, cyclophosphamide was detected in the air of the work environment (< 0.04-10.1 micrograms/m3). Contamination of and permeation through latex gloves were found for each of the three compounds. The uptake of cyclophosphamide was assessed by the determination of cyclophosphamide in urine. The drug was found in urine samples of six pharmacy technicians, including three persons who were not directly involved in the preparation of cyclophosphamide. The amounts excreted ranged from 0.2 to 19.4 micrograms/24 h. The results strongly suggest that inhalation is of minor importance for internal exposure, compared with other, presumably dermal, routes.