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Biomedical subjects

B de Graaf

Publications and source records attributed to B de Graaf.

At least 19 recordsLinked to original sources
PubMed2006

A novel susceptibility locus for Hirschsprung's disease maps to 4q31.3-q32.3.

We report on a multigenerational family with isolated Hirschsprung's disease (HSCR). Five patients were affected by either short segment or long segment HSCR. The family consists of two main branches: one with four patients (three siblings and one maternal uncle) and one with one patient. Analysis of the RET gene, the major gene involved in HSCR susceptibility, revealed neither linkage nor mutations. A genome wide linkage analysis was performed, revealing suggestive linkage to a region on 4q31-q32 with a maximum parametric multipoint LOD score of 2.7. Furthermore, non-parametric linkage (NPL) analysis of the genome wide scan data revealed a NPL score of 2.54 (p = 0.003) for the same region on chromosome 4q (D4S413-D4S3351). The minimum linkage interval spans a region of 11.7 cM (12.2 Mb). No genes within this chromosomal interval have previously been implicated in HSCR. Considering the low penetrance of disease in this family, the 4q locus may be necessary but not sufficient to cause HSCR in the absence of modifying loci elsewhere in the genome. Our results suggest the existence of a new susceptibility locus for HSCR at 4q31.3-q32.3.

Chromosome Mapping↗
PubMed2003

Familial multiple epiphyseal dysplasia due to a matrilin-3 mutation: further delineation of the phenotype including 40 years follow-up.

In this study, we followed-up the family with bilateral hereditary micro-epiphyseal dysplasia (BHMED) originally described by Elsbach [1959: J Bone Joint Surg [Br] 41-B:514-523]. Clinical re-examination of all available family members resulted in further delineation of the clinical and radiological phenotype, which is distinct from common multiple epiphyseal dysplasia (MED). Linkage analysis excluded EDM1, EDM2, and EDM3 as candidate genes. Linkage and mutation analysis of matrilin-3 (MATN-3) revealed a new pathogenic mutation confirming that BHMED is indeed a distinct disease entity among MED and MED-like disorders.

Adolescent↗
PubMed2002

Eye movements to yaw, pitch, and roll about vertical and horizontal axes: adaptation and motion sickness.

BACKGROUND: In the search for parameters to predict motion sickness that can be measured in the laboratory, we performed a longitudinal investigation in aviators. Since the vestibular system is involved in the generation of motion sickness as well as eye movements, vestibulo-ocular reflex (VOR) parameters seemed relevant. We investigated three topics: 1) the effect of axis orientation and its orientation to gravity on the VOR; 2) changes in VOR parameters depending on flight experience; and 3) differences in VOR parameters in aircrew with high and low susceptibility to motion sickness. HYPOTHESIS: Nystagmus decay after angular velocity steps would be faster for non-susceptible and trained aviators. METHODS: We recorded eye movements evoked by angular on-axis velocity steps (+/- 90 degrees x S(-2), to and from 90 degrees x S(-1)) in yaw, pitch, and roll, about both the Earth vertical and Earth horizontal axes in 14 subjects with a low susceptibility to motion sickness. These data were compared with those of 10 subjects with a high susceptibility. RESULTS: Horizontal axis rotations are nauseogenic. We found that during (per) and post-condition, left- and rightward rotation responses were equal, and the orientation with respect to gravity did not alter the basic nystagmus decay, apart from a sinusoidal modulation. Moreover, pitch and roll rotations show equal nystagmus decays, significantly faster than for yaw; yaw and pitch peak velocities were equal and were larger than for roll. With regard to changes in VOR parameters depending on flight experience, we found that repeated vestibular stimulation reduced nystagmus decay as well as the otolith modulation. With respect to the changes in VOR parameters and motion sickness susceptibility, we found that subjects highly susceptible to motion sickness showed a slower decay of nystagmus with a larger peak velocity than less susceptible subjects. CONCLUSIONS: Group averages indicate a difference in eye movement parameters, only in yaw, depending on flight experience; and between subjects with low and high susceptibility to motion sickness. The involvement of the velocity storage mechanism as realized by an internal model is given as a plausible explanation.

Adaptation, Physiological↗
PubMed2001

Hydroxyproline-rich glycoproteins in plant reproductive tissues: structure, functions and regulation.

The plant reproductive process of pollination involves a series of interactions between the male gametophyte (the pollen grain or pollen tube) and extracellular matrix (ECM) molecules secreted by different cell types along the pollen tube growth pathway in the female organ, the pistil. These interactions are believed to signal and regulate the pollen tube growth process to effect successful delivery of the sperm cells to the ovules where fertilization takes place. Hydroxyproline-rich glycoproteins secreted by plant cells are believed to play a broad range of functions, ranging from providing structural integrity to mediating cell-cell interactions and communication. The pistil and pollen tube ECM is enriched in these highly glycosylated proteins. Our discussions here will focus on a number of these proteins for which most information has been available, from Nicotiana tabacum, its self-incompatible relative N. alata, and Zea mays. In addition, the regulation of the synthesis and glyco-modification of one of these proteins, TTS (transmitting tissue-specific) protein from N. tabacum will be discussed in the light of how differential glycosylation may be used to regulate molecular interactions within the ECM.

Extracellular Matrix↗
PubMed2001

Familial frontotemporal dementia with ubiquitin-positive inclusions is linked to chromosome 17q21-22.

Hereditary frontotemporal dementia (FTD) is an autosomal dominant neurodegenerative disorder that is associated with mutations in the tau gene and with the pathological accumulation of hyperphosphorylated tau protein in affected brain cells in about a quarter of cases. However, most FTD families have no demonstrable tau mutations. Here we describe the clinical and neuropathological features of a large family with hereditary FTD. Genetic analysis showed strong evidence for linkage to chromosome 17q21-22 (maximum lod score 3.46, theta = 0 for marker D17S950), but mutations in the tau gene were not found. Clinical symptoms, neuropsychological deficits and neuroimaging findings of affected family members were similar to sporadic and tau-related FTD. The mean age at onset was 61.2 years, with loss of initiative and decreased spontaneous speech as the most prominent presenting symptoms. Pathological examination of the brains of two affected family members showed non-specific neuronal degeneration with dense cytoplasmic ubiquitin-positive inclusions in neurones of the second layer of the frontotemporal cortex and dentate gyrus of the hippocampus. In a number of neurones these inclusions appeared to be located inside the nucleus, although due to the small number of these inclusions this localization could not be confirmed by electron microscopy. The inclusions were not stained by tau, alpha-synuclein or polyglutamine antibodies. Biochemical analysis of soluble tau did not reveal abnormalities in tau isoform distribution and analysis of mRNA showed the presence of both three- and four-repeat transcripts. This is the first report of ubiquitin-positive, tau-negative inclusions in an FTD family with significant linkage to chromosome 17q21-22. Further characterization of the ubiquitin-positive inclusions may clarify the neurodegenerative pathways involved in this subtype of FTD.

Aged↗
PubMed1999

Contribution of the otoliths to the human torsional vestibulo-ocular reflex.

The dynamic contribution of the otolith organs to the human ocular torsion response was examined during passive sinusoidal body roll about an earth-horizontal axis (varying otolith inputs) and about an earth-vertical axis (invariant otolith inputs). Torsional eye movements were registered in 5 subjects by means of video-oculography. At a fixed amplitude of 25 degrees, the stimulus frequency was varied from 0.05 to 0.4 Hz. Additionally, at a fixed frequency of 0.2 Hz, the response was also measured at the amplitudes to 12.5 degrees and 50 degrees. The results showed that the gain and phase of the torsional slow component velocity (SCV) did not depend on stimulus amplitude, indicating a linear response. Contribution of the otoliths affected the ocular torsion response in three different ways. First, the gain of the SCV was slightly, but consistently, higher during rotation about an earth-horizontal axis than during rotation about an earth-vertical axis. With invariant otolith inputs the average gain increased from 0.10 at 0.05 Hz to 0.26 at 0.25 Hz. With varying otolith inputs, the average gain increased from 0.14 to 0.37. Second and more substantially, contribution of the otoliths improved the response dynamics by reducing the phase lead at frequencies up to 0.02 Hz. Third, the nystagmus showed considerably less anticompensatory saccades in upright conditions than in supine conditions, even though the SCV gain was lower in the latter. As a consequence, the average excursion of torsional eye position was highest during earth-horizontal rotation. This effect was observed in the entire frequency range. Thus, the otoliths controlled the human torsional VOR not only at low stimulus frequencies by keeping the slow component in phase with head motion, but also in a wider frequency range by modulating the saccadic behavior as to increase the amplitude of ocular torsion. We conclude that the primary concern of the otolith-oculomotor system during head tilt is to stabilize eye position in space, rather than to prevent retinal blur.

Adult↗
PubMed1998

Motion sickness: only one provocative conflict?

In reviewing the various forms of motion sickness, the classic sensory rearrangement theory has been redefined by demonstrating that only one type of conflict is necessary and sufficient to explain all different kinds of motion sickness. A mathematical description is provided from the summarizing statement that "All situations which provoke motion sickness are characterised by a condition in which the sensed vertical as determined on the basis of integrated information from the eyes, the vestibular system and the nonvestibular proprioceptors is at variance with the subjective vertical as expected from previous experience."

Computer Simulation↗
PubMed1998

Roll motion stimuli: sensory conflict, perceptual weighting and motion sickness.

In an experiment with 17 subjects, interactions of visual roll motion stimuli and vestibular body tilt stimuli were examined in determining the subjective vertical. Interindividual differences in weighting the visual information were observed, but in general, visual and vestibular responses added in setting the vertical. Despite the conflicting sensory information, motion sickness was not reported apart from one subject on one single occasion. This is in conflict with the sensory mismatch theory on motion sickness, but in agreement with the subjective vertical conflict theory.

Conflict, Psychological↗
PubMed1997

The retention of balance: an exploratory study into the limits of acceleration the human body can withstand without losing equilibrium.

The human limiting values for sudden accelerations we have determined can be used to evaluate specific physical conditions that cause problems in maintaining postural balance. A comparison between the data obtained in the laboratory and the situations occurring during public transport by tram, bus, and metro revealed that both the initial impetus ("jerk") and the level of acceleration found in practice were sufficient to ensure that none of the individuals measured in the laboratory would have been able to retain their balance without extra support. The study suggests that limiting the initial jerk component of the acceleration would help considerably in alleviating the problem.

Acceleration↗
PubMed1997

A sustained hyper-g load as a tool to simulate space sickness.

In April 1989 the three European scientist astronauts of the D1 Spacelab Mission were exposed to a 1.5 hours +3G centrifuge run in supine position, resulting in a linear acceleration along the subjects' x-axis. Afterwards, severe motion sickness symptoms were provoked by head movements (Sickness Induced by Centrifugation: SIC). The astronauts mentioned close similarities with what they experienced in space during the D1-Spacelab Mission in 1985, where head movements also provoked motion sickness symptoms (Space Adaptation Syndrome: SAS). Moreover, the astronauts agreed that the rank order of their susceptibility to SAS was the same as for SIC. It was therefore postulated that with this method SAS could be simulated on earth. Additionally, in otolith function tests following the centrifuge run, changes in visual-vestibular interaction were observed, which replicated objective findings obtained with the same astronauts immediately after the D1 Spacelab Mission. During the last couple of years a series of experiments has been carried out to determine the nature of the stimulus causing SIC, the incidence of SIC, and the underlying cardio-vascular and/or vestibular mechanisms. These experiments were carried out on several astronauts and some 50 'normal' healthy subjects. In the next sections the main findings of all these experiments and the implications are summarized.

Acceleration↗
PubMed1996

Determination of ocular torsion by means of automatic pattern recognition.

A new, automatic method for determination of human ocular torsion (OT) was developed based on the tracking of iris patterns in digitized video images. Instead of quantifying OT by means of cross-correlation of circular iris samples, a procedure commonly applied, this new method automatically selects and recovers a set of 36 significant patterns in the iris by the technique of template matching as described by In den Haak et al. Each relocated landmark results in a single estimate of the torsion angle. A robust algorithm estimates OT from this total set of individually determined torsion angles, thereby largely correcting for errors which may arise due to misjudgement of the rotation center. The new method reproduced OT in a prepared set of images of an artificial eye with an accuracy of 0.1 degree. In a sample of 256 images of human eyes, a practical reliability of 0.25 degrees was achieved. To illustrate the method's usefulness, an experiment is described in which ocular torsion was measured during two dynamic conditions of whole-body roll, namely during sinusoidally pendular motion about either an earth horizontal or earth vertical axis (that is "with" and "without" otolith stimulation, respectively).

Algorithms↗
PubMed1995

[With maintaining equilibrium: experimental study of the limits of acceleration which the human body can endure without losing postural balance].

OBJECTIVE: To explore the limits of acceleration to which a human organism can be exposed without loss of postural balance. DESIGN: Experimental study. SETTING: TNO Human Factors Research Institute, Soesterberg, and the public transport, Amsterdam. METHOD: Volunteers underwent accelerations of the underground in the laboratory. The acceleration that could be tolerated without extra support, was under investigation. In this way, conditions could be determined that cause loss of postural balance. RESULTS: A comparison of data obtained in the laboratory with measurements during public transportation proved that in tram, bus and tube, the 'jerk' and the level of acceleration are both in principle unmanageable without extra support. CONCLUSION: A built-in limitation of the jerk component in vehicles of the public transport could offer a substantial contribution to solving the problem of loss of postural balance by the passengers.

Acceleration↗
PubMed1995

Explanations for high rates of eradication with triple therapy using metronidazole in patients harboring metronidazole-resistant Helicobacter pylori strains.

In 4 of 17 Helicobacter pylori strains obtained from antral biopsy samples, the registered primary resistance (MIC, > 32 microgram/ml) appeared to be nonstable after prolonged microaerophilic incubation. In all resistant strains tested, susceptibility could be obtained when culture under normal microaerophilic conditions was preceded by a period of anaerobic incubation. Both of these findings may explain the observed discrepancy between the results of in vitro susceptibility tests and the eradication obtained in vivo.

Antacids↗
PubMed1994

Arthrokinetic and vestibular information enhance smooth ocular tracking during linear (self-)motion.

We studied the gain of smooth ocular tracking for visual, vestibular and arthrokinetic cues, in combination as well as separately, in order to examine how these multisensory cues influence tracking performance. By use of motion along a linear track (besides the self-evident visual influence) evidence was found for arthrokinetic and vestibular enhancement of smooth ocular tracking. These results were in close correspondence with the results of our former study about arthrokinetic influence on linear self-motion perception. Therefore, we conclude that information from the limbs about linear (self-)movement has analogous characteristics and generates analogous responses to the information about angular (self-)movement.

Analysis of Variance↗
PubMed1994

Ocular torsion quantification with video images.

The present paper describes a technique to quantify eye rotations about the visual axis (ocular torsion). Two digitized polar transformed images of the iris are displayed on a video monitor in order to facilitate a visual comparison and manual interaction. Emphasis is placed on error analysis and the method's simplicity when applied to static ocular torsion measurement. The implementation, applying averaging over ocular torsion determined in partitioned iris images, yields a theoretical resolution of 5' of arc. In a control experiment with an artificial eye, the accuracy showed to be better than 14' of arc. In practice, the measuring device was validated with the data from the literature by means of an experiment about ocular torsion in humans during tilt and hypergravity conditions (up to 3 g).

Bias↗
PubMed1993

Postural consequences of long duration centrifugation.

In the present paper a series of experiments will be described in which the postural consequences of long (up to 1.5 h) duration 3G-centrifugation have been subject to investigation. A vestibular model is presented in order to explain for the postural imbalance found in specific conditions after the centrifuge run, and for the often concomitant feelings of motion sickness (50% of the subjects suffer from Sickness Induced by long duration Centrifugation). Finally, the possible relation between SIC and the Space Adaptation Syndrome is discussed.

Adaptation, Physiological↗