Biomedical subjects

C van Leeuwen

Publications and source records attributed to C van Leeuwen.

At least 19 recordsLinked to original sources

PubMed2006

Neural correlates of priming on occluded figure interpretation in human fusiform cortex.

The visual system rapidly completes a partially occluded figure. We probed the completion process by using priming in combination with neuroimaging techniques. Priming leads to more efficient visual processing and thus a reduction in neural activity in relevant brain areas. These areas were studied with high spatial resolution and temporal accuracy with focus on early perceptual processing. We recorded magnetoencephalographic responses from 10 human volunteers in a primed same-different task for test figures. The test figures were preceded by a sequence of two figures, a prime or control figure followed by an occluded figure. The prime figures were one of three possible interpretations of the occluded figures: global and local completions and mosaic interpretation. A significant priming effect was evident: in primed trials as compared with control trials, subjects responded faster and the latency was shorter in the magnetoencephalographic signal for the largest peak between 50 and 300 ms after the occluded figure onset. Tomographic and statistical parametric mapping analyses revealed stages of activation in occipitotemporal areas during occluded figure processing. Notably, we found significantly reduced activation in the right fusiform cortex between 120 and 200 ms after occluded figure onset for primed trials as compared with control trials. We also found significant spatiotemporal differences of local, global and mosaic interpretations for individual subjects but not across subjects. We conclude that modulation of activity in the right fusiform cortex may be a neural correlate of priming in the interpretation of an occluded figure, and that this area acts as a hub for different occluded figure interpretations in this early stage of perception.

Adult↗

PubMed2004

Effects of natural and synthetic estrogens and various environmental contaminants on vitellogenesis in fish primary hepatocytes: comparison of bream (Abramis brama) and carp (Cyprinus carpio).

Interaction of environmental estrogens with the estrogen receptor (ER) has been shown in various fish species. Our objective was to compare the sensitivity of bream (Abramis brama) to (xeno-)estrogens with that of the carp (Cyprinus carpio), by measuring the effects of 17beta-estradiol (E2), estrone (E1), ethynylestradiol (EE2), bisphenol A (BPA), nonylphenol (NP), methoxychlor (MXCL), and halogenated aromatic hydrocarbons (HAHs) such as polychlorinated biphenyls (PCB126, PCB118), 2,3,7,8-tetrachlorodibenzo-dioxin (TCDD), and 2,3,4,7,8-pentachlorodibenzofuran (PCDF) on vitellogenesis in primary hepatocytes. Comparing the EC50 values in bream hepatocytes: EE2 (0.1-0.2 microM) < E1 (0.6-0.2 microM) < E2 (1.9 microM) with those of carp hepatocytes EE2 (0.03-0.06 microM) < E2 (0.3 microM) approximately E1 (0.2-0.3 microM) we found differences in sensitivity and ranking of the estrogenic potency of E2 and E1, indicating interspecies differences. Exposure to BPA, NP, MXCL, and HAHs did not or only weakly induce vitellogenesis. Bream hepatocytes coexposed to E2 and TCDD, PCB126 or PCDF showed a concentration-dependent inhibition of E2-induced vitellogenesis. IC50 (concentration of a compound that elicits 50% inhibition of E2-induced vitellogenesis) values determined in bream were: TCDD (0.02-0.09 nM) < PCB126 (0.35-0.1 nM) < PCDF (2.0-0.1) and in carp were: TCDD (0.01 nM) < PCB126 (0.4 nM). PCB118 showed no (anti-)estrogenic response. IC50 values and benchmark-concentration for TCDD and PCB126 in bream and carp hepatocytes were in the same range, indicating similar sensitivity to these compounds. Due to their anti-estrogenic capacity with benchmark-concentrations in the pM range TCDD, PCDF, and PCB126 may form a potential hazard for the reproductive success of fish species by inhibition of vitellogenesis.

Animals↗

PubMed1998

Creative discovery in imagery and perception: combining is relatively easy, restructuring takes a sketch.

A figure combination task, in which three components are combined into an object, was administered under imagery-alone and externalization conditions to subjects with different levels of sketching expertise. In externalization conditions the imaged combinations were sketched. In accordance with earlier studies, the combinations were rated equally creative across conditions. The combinations were scored with regard to the novelty of their spatial configurations of the components (combining score), and with regard to the novelty of the structure of the components (restructuring score). For expert sketchers the latter score was found to be increased by sketching. Creativity ratings correlated with both combining and restructuring scores in the sketching condition, but only with combining scores in the imagery condition. The results are interpreted in terms of a model in which creative processes use combining and restructuring strategies in a flexible way. Whereas restructuring draws heavily on both externalization and expertise in externalization, combining can be used independently of externalization and expertise.

Adult↗

PubMed1998

Venlafaxine's effects on healthy volunteers' driving, psychomotor, and vigilance performance during 15-day fixed and incremental dosing regimens.

Effects of venlafaxine, an antidepressant acting by selective serotonin and norepinephrine reuptake inhibition with a potency ratio of 5:1, were assessed in a standardized, actual driving test, a battery of psychomotor tests (Critical Flicker/Fusion Frequency, Critical Tracking, Divided Attention), and a 45-minute vigilance test (Mackworth Clock). Thirty-seven healthy volunteers, 22 of whom completed the study, received venlafaxine in fixed (37.5 mg twice a day) and incremental (37.5-75 mg twice a day) doses as well as mianserin (10-20 mg three times a day) and placebo according to a 4-period (15 days each), double-blind, crossover design. Testing occurred on days 1 and 7 and after dose increments, on days 8 and 15. Plasma concentrations of venlafaxine and its active metabolite were measured on test days for confirming compliance. Venlafaxine had no significant effect on the primary driving parameter (standard deviation of lateral position) and failed to impair psychomotor performance. Mianserin profoundly and consistently impaired driving and psychomotor performance. However, both drugs significantly impaired vigilance performance. Maximal effects occurred on day 1 with mianserin and similarly on day 7 with venlafaxine in both series. The increment in venlafaxine's dose on day 8 did not increase this effect. The drug's selectively impairing effect on vigilance is shared by other "serotonergic" anxiolytics and antidepressants, suggesting that interference with 5-HT transmission reduces arousal in particularly monotonous tasks or environments. This study concludes that venlafaxine does not generally affect driving ability and should be safe for use by patients who drive.

Adult↗

PubMed1997

Visual search strategy and perceptual organization covary with individual preference and structural complexity.

The pattern of interactions between visual search profile (serial versus nonserial) and perceptual organization type (functionally local versus global) was investigated in three experiments. The task was a matching judgment performed on two separate figures that fit in a jigsaw-puzzle fashion. Reaction times and errors showed that serial search preferably goes together with local organization and nonserial search with global organization. Choice of search profile and organization type depend on task and individual preference. Structural complexity in the target area reinforces the combination of local organization and serial search. This combination was also chosen by subjects preferring accuracy. The combination of global organization and nonserial search was chosen with simpler targets or by subjects preferring speed. The results support an interactive notion of perceptual organization and search. Perceptual organization type is determined by individual preferences in combination with visual search task demands; visual search is guided by the specific organization of the stimulus pattern.

Humans↗

PubMed1995

Seven new mutations in hMSH2, an HNPCC gene, identified by denaturing gradient-gel electrophoresis.

Hereditary nonpolyposis colorectal cancer (HNPCC) is a relatively common autosomal dominant cancer-susceptibility condition. The recent isolation of the DNA mismatch repair genes (hMSH2, hMLH1, hPMS1, and hPMS2) responsible for HNPCC has allowed the search for germ-line mutations in affected individuals. In this study we used denaturing gradient-gel electrophoresis to screen for mutations in the hMSH2 gene. Analysis of all the 16 exons of hMSH2, in 34 unrelated HNPCC kindreds, has revealed seven novel pathogenic germ-line mutations resulting in stop codons either directly or through frameshifts. Additionally, nucleotide substitutions giving rise to one missense, two silent, and one useful polymorphism have been identified. The proportion of families in which hMSH2 mutations were found is 21%. Although the spectrum of mutations spread at the hMSH2 gene among HNPCC patients appears extremely heterogeneous, we were not able to establish any correlation between the site of the individual mutations and the corresponding tumor spectrum. Our results indicate that, given the genomic size and organization of the hMSH2 gene and the heterogeneity of its mutation spectrum, a rapid and efficient mutation detection procedure is necessary for routine molecular diagnosis and presymptomatic detection of the disease in a clinical setup.

Base Sequence↗

PubMed1994

A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors.

Germ-line mutations in the human adenomatous polyposis coli (APC) gene result in familial adenomatous polyposis, an autosomal dominant disorder characterized by the early onset of multiple adenomatous polyps in the large bowel with a high likelihood of developing colorectal carcinomas. To understand the role of APC in intestinal tumor formation, we have introduced a chain-termination mutation in the 15th exon of the mouse Apc gene and employed it to modify the endogenous gene by homologous recombination in embryonic stem cells. Mice which are heterozygous for the Apc gene modification progressively develop intestinal tumors in a manner that is similar to that observed in patients with familial adenomatous polyposis and in mice which carry a mutation called multiple intestinal neoplasia (Min). Our results indicate that the Apc gene modification is a critical event in the initiation of intestinal tumor formation and results in an autosomal dominant predisposition toward development of spontaneous colonic and intestinal tumors in mice.

Adenomatous Polyposis Coli↗

PubMed1994

Rapid detection of translation-terminating mutations at the adenomatous polyposis coli (APC) gene by direct protein truncation test.

Familial adenomatous polyposis (FAP) is usually associated with protein truncating mutations in the adenomatous polyposis coli (APC) gene. The APC mutations are known to play a major role in colorectal carcinogenesis. For the identification of protein truncating mutations of the APC gene, we developed a rapid, sensitive, and direct screening procedure. The technique is based on the in vitro transcription and translation of the genomic PCR products and is called the protein truncation test. Samples of DNA from individual FAP patients, members of a FAP family, colorectal tumors, and colorectal tumor-derived cell lines were used to show the effectiveness of this method.

Adenomatous Polyposis Coli↗

PubMed1994

Affordances, perceptual complexity, and the development of tool use.

Perceiving the affordance of a tool requires the integration of several complementary relationships among actor, tool, and target. Highers order affordance structures are introduced to deal with these forms of complex action from an ecological-realist point of view. The complexity of the higher order affordance structure was used to predict the difficulty of perceiving the tool function. Predictions were tested in 3 experiments involving children between 9 months and 4 years old. In a classical tool use task dating back to W. Köhler, a desirable target was obtained by using a hook as a tool. The relative positions of the hook and the target were systematically varied to obtain structures differing in complexity. The observed difficulty of the task was found essentially in accordance with the theoretical complexity of the higher order affordance structures involved in perceiving the tool function.

Child, Preschool↗

PubMed1993

Context influence on the perception of figures as conditional upon perceptual organization strategies.

Two experiments tested the effect of context on figure perception. Subjects were shown rapid sequences of three figures: a prime, a whole, and a part. They were asked to decide if the third figure was a part of the second (Experiment 1) or if the second and third figures were the same or different with respect to a particular angle (Experiment 2). The prime served to establish a context for stimuli that followed to be compared. Priming had influence on the part-whole comparison in Experiment 1, but not on the local comparison in Experiment 2. The results of Experiment 1 were interpreted as evidence for a role of prior information in perceptual organization. Experiment 2 showed that the task must require an integrative perceptual organization strategy for the priming effects to occur.

Adult↗

PubMed1991