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Biomedical subjects

A Kok

Publications and source records attributed to A Kok.

At least 19 recordsLinked to original sources
PubMed2006

CSF biomarkers and medial temporal lobe atrophy predict dementia in mild cognitive impairment.

OBJECTIVE: To study CSF biomarkers, beta-amyloid(1-42) (Abeta(1-42)) and tau, and medial temporal lobe atrophy (MTA) on MRI in their ability to predict dementia in patients with mild cognitive impairment (MCI). METHODS: Fifty-nine MCI patients (49% male, mean age 69+/-8), follow-up 19 months, were included. Baseline CSF levels of Abeta(1-42), tau and MTA-score were dichotomized. RESULTS: Thirty-three (56%) of the MCI patients progressed to dementia, 30 of which had Alzheimer's disease. Lower CSF Abeta(1-42) level, higher CSF-tau and higher MTA-scores at baseline were found in progressed patients. Cox proportional hazards models revealed that abnormal CSF Abeta(1-42), CSF tau and MTA were significantly associated with dementia at follow-up (hazard ratio (95% confidence interval): 4.0 (1.3-12.1), 5.9 (1.6-21.7) and 2.1 (1.0-4.6)). A fourfold higher risk was found for patients with both abnormal CSF biomarkers and MTA compared to patients with either test abnormal. Ninety-four percent of patients with both abnormalities converted to dementia. CONCLUSIONS: These findings suggest an added value of CSF to MRI in the diagnostic work up of patients presenting at a memory clinic.

Aged↗
PubMed2005

Effects of stop-signal modality on the N2/P3 complex elicited in the stop-signal paradigm.

The principal aim of the present study was to clarify how stop-signal modality affected the speed and efficacy of stopping, using ERP components as converging measures of stop processes. Both performance and ERP latency findings suggested faster processing of stop signals in the auditory than visual version of the stop task. The effects of successful versus unsuccessful stopping on the amplitude and topography of N2/P3 components elicited by the stop signals appeared to be largely independent of the modality of the stop signals. Stop signals elicited a fronto-central N2 that was much larger on unsuccessful than successful stop trials in stimulus-locked waveforms. N2 was followed by a P3 component that showed a fronto-central distribution on successful stop trials. P3 elicited on unsuccessful stop trials showed a posterior-parietal focus, but this topography was manifested more clearly in response-locked than stimulus-locked waveforms. A dipole source analyses confirmed these topographical differences of P3, and further showed that the location of the corresponding dipoles remained largely identical across the visual and auditory versions of the stop-signal task. Taken together, the present findings support the suggestion that ERP components in the stop task reflect endogenous aspects of stop-signal processing, such as effective inhibition of responses on successful stop trials and detection of errors on failed inhibition trials.

Adult↗
PubMed2005

Decrease of CD4+CD25+ T cells in peripheral blood after liver transplantation: association with immunosuppression.

CD25 (IL-2 receptor alpha-chain) marks a population of CD4-positive T cells with a suppressor phenotype. These CD4+CD25+ regulatory T cells can suppress both effector T cells and antigen-presenting cells and have been identified as a principle regulator of tolerance in experimental transplantation models. In the setting of human liver transplantation, however, little is known about the dynamics of these cells in relation to rejection, tolerance, and immunosuppression. In the current study we determined CD4+CD25+ T cell in blood of liver transplant recipients using flow cytometry and investigated a possible link with immunosuppressive therapies. Peripheral blood mononuclear cells (PBMC) of 27 liver transplant patients (pretransplantation and 12 months posttransplantation) and 16 healthy controls were included. We found that the percentages of CD25+ cells within the CD4 T-cell population was significantly reduced in more than two-thirds of patients 1 year after transplantation. Also the total percentage of CD4-positive T cells declined significantly within this period, making the absolute reduction of regulatory T cells after transplantation even more profound. Comparing PBMC samples of patients and healthy controls revealed an increased percentage of CD4+ T cells in the patients before transplantation, probably related to the chronic liver illness. The reduction in CD4+CD25+ T cells after transplantation was similar for different immunosuppression regiments. All patients, however, received calcineurin inhibitors, suggesting a possible suppressive effect of this therapy on regulatory T-cell levels in peripheral blood. Currently, assays for regulatory T-cell activity are used to further support this hypothesis.

Adrenal Cortex Hormones↗
PubMed2004

Effects of stop-signal probability in the stop-signal paradigm: the N2/P3 complex further validated.

The aim of this study was to examine the effects of frequency of occurrence of stop signals in the stop-signal paradigm. Presenting stop signals less frequently resulted in faster reaction times to the go stimulus and a lower probability of inhibition. Also, go stimuli elicited larger and somewhat earlier P3 responses when stop signals occurred less frequently. Since the amplitude effect was more pronounced on trials when go signals were followed by fast than slow reactions, it probably reflected a stronger set to produce fast responses. N2 and P3 components to stop signals were observed to be larger and of longer latency when stop signals occurred less frequently. The amplitude enhancement of these N2 and P3 components were more pronounced for unsuccessful than for successful stop-signal trials. Moreover, the successfully inhibited stop trials elicited a frontocentral P3 whereas unsuccessfully inhibited stop trials elicited a more posterior P3 that resembled the classical P3b. P3 amplitude in the unsuccessfully inhibited condition also differed between waveforms synchronized with the stop signal and waveforms synchronized with response onset whereas N2 amplitude did not. Taken together these findings suggest that N2 reflected a greater significance of failed inhibitions after low probability stop signals while P3 reflected continued processing of the erroneous response after response execution.

Adolescent↗
PubMed2003

A flow cytometric method to detect apoptosis-related protein expression in minimal residual disease in acute myeloid leukemia.

Minimal residual disease (MRD) cells are thought to be responsible for the persistence and relapse of acute myeloid leukemia (AML). Flow cytometric MRD detection by the establishment of a leukemia-associated phenotype (LAP) at diagnosis can be used in 80% of AML patients, allowing detection and functional characterization of MRD in follow-up bone marrow. One of the mechanisms contributing to inefficient chemotherapy is apoptosis resistance. Measuring apoptosis parameters in MRD cells will help to unravel the importance of apoptosis resistance in AML. We therefore developed a four-color flow cytometry method that enables establishment of apoptosis-related protein expression such as Bcl-2, Bcl-x(L), Mcl-1 and Bax at diagnosis and in MRD. Firstly, validation of this assay using Western blot analysis in five leukemia cell lines showed a significant correlation (R=0.70: P<0.0001). Secondly, the influence of the permeabilization procedure on LAP expression was investigated in 38 AML samples at diagnosis and in 42 MRD samples. Quantification of the frequency of LAP+ cells with and without permeabilization showed no significant differences (diagnosis: P= 0.57, follow-up: P= 0.43). The flow cytometric protocol thus enables analysis of apoptosis-related proteins at different stages of the disease, which will lead to a better understanding of the role of apoptosis resistance in the emergence of MRD in AML.

Acute Disease↗
PubMed2001

Neuroelectrical signs of selective attention to color in boys with attention-deficit hyperactivity disorder.

In order to gain insight into the functional and macroanatomical loci of visual selective processing deficits that may be basic to attention-deficit hyperactivity disorder (ADHD), the present study examined multi-channel event-related potentials (ERPs) recorded from 7- to 11-year-old boys clinically diagnosed as having ADHD (n=24) and age-matched healthy control boys (n=24) while they performed a visual (color) selective attention task. The spatio-temporal dynamics of several ERP components related to attention to color were characterized using topographic profile analysis, topographic mapping of the ERP and associated scalp current density distributions, and spatio-temporal source potential modeling. Boys with ADHD showed a lower target hit rate, a higher false-alarm rate, and a lower perceptual sensitivity than controls. Also, whereas color attention induced in the ERPs from controls a characteristic early frontally maximal selection positivity (FSP), ADHD boys displayed little or no FSP. Similarly, ADHD boys manifested P3b amplitude decrements that were partially lateralized (i.e., maximal at left temporal scalp locations) as well as affected by maturation. These results indicate that ADHD boys suffer from deficits at both relatively early (sensory) and late (semantic) levels of visual selective information processing. The data also support the hypothesis that the visual selective processing deficits observed in the ADHD boys originate from deficits in the strength of activation of a neural network comprising prefrontal and occipito-temporal brain regions. This network seems to be actively engaged during attention to color and may contain the major intracerebral generating sources of the associated scalp-recorded ERP components.

Attention↗
PubMed2001

On the utility of P3 amplitude as a measure of processing capacity.

The present review focuses on the utility of the amplitude of P3 of as a measure of processing capacity and mental workload. The paper starts with a brief outline of the conceptual framework underlying the relationship between P3 amplitude and task demands, and the cognitive task manipulations that determine demands on capacity. P3 amplitude results are then discussed on the basis of an extensive review of the relevant literature. It is concluded that although it has often been assumed that P3 amplitude depends on the capacity for processing task relevant stimuli, the utility of P3 amplitude as a sensitive and diagnostic measure of processing capacity remains limited. The major factor that prompts this conclusion is that the two principal task variables that have been used to manipulate capacity allocation, namely task difficulty and task emphasis, have opposite effects on the amplitude of P3. I suggest that this is because, in many tasks, an increase in difficulty transforms the structure or actual content of the flow of information in the processing systems, thereby interfering with the very processes that underlie P3 generation. Finally, in an attempt to theoretically integrate the results of the reviewed studies, it is proposed that P3 amplitude reflects activation of elements in a event-categorization network that is controlled by the joint operation of attention and working memory.

Electroencephalography↗
PubMed2001

Nonspatial intermodal selective attention is mediated by sensory brain areas: evidence from event-related potentials.

The present study focuses on the question of whether inter- and intramodal forms of attention are reflected in activation of the same or different brain areas. ERPs were recorded while subjects were presented a random sequence of visual and auditory stimuli. They were instructed to attend to nonspatial attributes of either auditory or visual stimuli and to detect occasional target stimuli within the attended channel. An occipital selection negativity was found for intramodal attention to visual stimuli. Visual intermodal attention was also manifested in a similar negativity. A symmetrical dipole pair in the medial inferior occipital areas could account for the intramodal effects. Dipole pairs for the intermodal attention effect had a slightly more posterior location compared to the dipole pair for the intramodal effect. Auditory intermodal attention was manifested in an early enhanced negativity overlapping with the N1 and P2 components, which was localized using a symmetrical dipole pair in the lateral auditory cortex. The onset of the intramodal attention effect was somewhat later (around 200 ms), and was reflected in a frontal processing negativity. The present results indicate that intra- and intermodal forms of attention were indeed similar for visual stimuli. Auditory data suggest the involvement of multiple brain areas.

Adolescent↗
PubMed2001

Error-related brain potentials are differentially related to awareness of response errors: evidence from an antisaccade task.

The error negativity (Ne/ERN) and error positivity (Pe) are two components of the event-related brain potential (ERP) that are associated with action monitoring and error detection. To investigate the relation between error processing and conscious self-monitoring of behavior, the present experiment examined whether an Ne and Pe are observed after response errors of which participants are unaware. Ne and Pe measures, behavioral accuracy, and trial-to-trial subjective accuracy judgments were obtained from participants performing an antisaccade task, which elicits many unperceived, incorrect reflex-like saccades. Consistent with previous research, subjectively unperceived saccade errors were almost always immediately corrected, and were associated with faster correction times and smaller saccade sizes than perceived errors. Importantly, irrespective of whether the participant was aware of the error or not, erroneous saccades were followed by a sizable Ne. In contrast, the Pe was much more pronounced for perceived than for unperceived errors. Unperceived errors were characterized by the absence of posterror slowing. These and other results are consistent with the view that the Ne and Pe reflect the activity of two separate error monitoring processes, of which only the later process, reflected by the Pe, is associated with conscious error recognition and remedial action.

Adolescent↗
PubMed2000

Age-related changes in involuntary and voluntary attention as reflected in components of the event-related potential (ERP).

The present paper provides an overview of age-related changes in both involuntary and voluntary attention in adult subjects as manifested in scalp-recorded ERPs. A decline in orienting with old age was inferred from a substantial reduction with age in the magnitude of deviance-related ERP components like MMN, target as well as nontarget P3s, novelty P3 and N400. A review of focused attention studies further suggested that old and young subjects do not differ substantially in the quality of attentional operations. In old subjects early selection processes, as reflected in their selection potentials, have a somewhat slower onset than in young subjects, especially in conditions in which selection is based upon complex discrimination of stimulus features. Furthermore, the global pattern emerging from visual and memory search studies is that search-related negativities in the ERPs are smaller and of longer duration in old than in young subjects over the central and anterior scalp sites. These effects could indicate that controlled search is less intense or takes more time per search operation in old than in young subjects. At more posterior scalp sites there was tendency towards an enhanced search-related negativity that could reflect a specific difficulty (or compensatory increase in mental effort) of old subjects in spatially locating targets in complex visual fields.

Adult↗
PubMed2000

Age effects on response monitoring in a mental-rotation task.

A mental-rotation task was presented to young (18-28 years) and old (60-76 years) adults to simultaneously assess age-related changes in performance, response monitoring and adaptive behavior. Relative to young participants, older adults were less inclined to adjust their speed at the expense of accuracy. They displayed a larger number of slow errors, smaller error potentials (Ne and Pe), more immediate corrections of errors when detected, and a larger speed reduction on trials following an error. The data suggest that for older adults an increase of task complexity sometimes caused a radical failure in determining the correct response, rather than a gradual reduction of efficiency.

Adolescent↗
PubMed2000

The mismatch negativity during natural sleep: intensity deviants.

Auditory event-related potentials (ERPs) were recorded from 7 subjects who slept for a single night in the laboratory. An 'oddball' sequence of brief tone pips, differing in intensity, was used. Frequently occurring 70 dB 'standards' were presented with infrequent 80 dB intensity increment deviants and 60 dB intensity decrement deviants. The probability of each deviant was 0.1. Stimuli were presented in a random sequence every 600 ms while subjects were awake but inattentive and during stages 2 and REM of sleep. During wakefulness, the intensity increments elicited a broad fronto-central negativity with two discernable peaks. The first, peaking at approximately 120 ms, showed a polarity inversion at the mastoid and likely represented a summation of the N1 wave and the mismatch negativity (MMN). The second, peaking at approximately 330 ms, may have reflected an enhanced N2b component. In REM sleep, the increment deviants elicited a small amplitude 100-200 ms negativity but its amplitude was not significantly larger than the baseline level. It was followed by a larger and significant 300-450 ms negativity but this was considered too delayed to represent the MMN. The decrement deviants elicited a small amplitude, but statistically non-significant, MMN-like wave during both wakefulness and in REM sleep. A MMN-like wave was absent in stage 2 sleep.

Acoustic Stimulation↗
PubMed2000

Inhibitory inefficiency and failures of intention activation: age-related decline in the control of saccadic eye movements.

Young and older adults' control of saccadic eye movements was compared using an antisaccade task, which requires the inhibition of a reflexive saccade toward a peripheral onset cue followed by an intentional saccade in the opposite direction. In 2 experiments, an age-related decline was found in the suppression of reflexive eye movements, as indicated by an increased proportion of saccades toward the cue, and a longer time needed to initiate correct antisaccades. The results from Experiment 2 suggested that older adults' slower antisaccades may be explained partly in terms of increased failures to maintain the cue-action representation at a sufficient activation level. The results suggest that the notion of selective preservation with age of the ability to inhibit spatial responses does not apply to the active inhibition of prepotent spatial responses.

Adolescent↗
PubMed2000

Stroke and apolipoprotein E epsilon4 are independent risk factors for cognitive decline: A population-based study.

BACKGROUND AND PURPOSE: Stroke and apolipoprotein E epsilon4 (ApoE epsilon4) are individually important risk factors for cognitive decline, including Alzheimer disease. It has been suggested that ApoE epsilon4 multiplies the risk for cognitive decline following stroke. In a population-based sample, using well-defined sensitive cognitive measures, this study investigates whether cognitive decline following stroke is worse for patients who carry the ApoE epsilon4 allele. METHODS: Subjects were participants in the Longitudinal Aging Study Amsterdam (LASA). The sample consisted of 1224 subjects, aged 62 to 85 years, who participated in the 3-year follow-up examination and for whom ApoE and stroke data were complete. We assessed cognitive decline using the Mini-Mental State Examination, the Auditory Verbal Learning Test (memory: immediate and delayed recall), and the Coding Task (information processing speed). The effects of stroke and ApoE epsilon4 on cognitive decline were evaluated with ANOVA and multiple logistic regression analysis, adjusted for age, sex, education, and baseline cognition. RESULTS: A synergistic effect modification for stroke and ApoE epsilon4 on cognitive decline was not observed. Unexpectedly, instead, stroke patients carrying the epsilon4 allele demonstrated a nonsignificantly lowered risk for Mini-Mental State Examination decline (OR=0.3; 95% CI 0.1 to 1.1). ApoE epsilon4 was associated with declines in information processing speed (OR=1.5; 95% CI 1.1 to 2.1) and small declines for immediate and delayed recall. CONCLUSIONS: Stroke and ApoE epsilon4 may impair cognition through distinct nonsynergistic mechanisms. The slowing of information processing speed for ApoE epsilon4 carriers was more evident than impairment in memory.

Aged↗
PubMed2000

Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to polymorphic epithelial mucin.

PURPOSE: Polymorphic epithelial mucin (PEM or MUC1) is being studied as a vaccine substrate for the immunotherapy of patients with adenocarcinoma. The present study analyzes the incidence of naturally occurring MUC1 antibodies in early breast cancer patients and relates the presence of these antibodies in pretreatment serum to outcome of disease. MATERIALS AND METHODS: We measured immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to MUC1 with an enzyme-linked immunoassay (PEM.CIg), which uses a MUC1 triple-tandem repeat peptide conjugated to bovine serum albumin, in pretreatment serum samples obtained from 154 breast cancer patients (52 with stage I disease and 102 with stage II) and 302 controls. The median disease-specific survival time of breast cancer patients was 74 months (range, 15 to 118 months). A positive test result was defined as MUC1 IgG or IgM antibody levels equal to or greater than the corresponding rounded-up median results obtained in the total breast cancer population. RESULTS: A positive test result for both MUC1 IgG and IgM antibodies in pretreatment serum was associated with a significant benefit in disease-specific survival in stage I and II (P =.0116) breast cancer patients. Positive IgG and IgM MUC1 antibody levels had significant additional prognostic value to stage (P =.0437) in multivariate analysis. Disease-free survival probability did not differ significantly. However, stage II patients who tested positive for MUC1 IgG and IgM antibody and who relapsed had predominantly local recurrences or contralateral disease, as opposed to recurrences at distant sites in the patients with a negative humoral response (P =.026). CONCLUSION: Early breast cancer patients with a natural humoral response to MUC1 have a higher probability of freedom from distant failure and a better disease-specific survival. MUC1 antibodies may control hematogenic tumor dissemination and outgrowth by aiding the destruction of circulating or seeded MUC1-expressing tumor cells. Vaccination of breast cancer patients with MUC1-derived (glyco)peptides in an adjuvant setting may favorably influence the outcome of disease.

Adolescent↗
PubMed1999

Plasma concentration of C-reactive protein is increased in type I diabetic patients without clinical macroangiopathy and correlates with markers of endothelial dysfunction: evidence for chronic inflammation.

Moderately increased plasma concentrations of C-reactive protein are associated with an increased risk of cardiovascular disease. C-reactive protein, its relation to a low degree of inflammatory activation and its association with activation of the endothelium have not been systematically investigated in Type I (insulin-dependent) diabetes mellitus. C-reactive protein concentrations were measured in 40 non-smoking patients with Type I diabetes without symptoms of macrovascular disease and in healthy control subjects, and in a second group of Type I diabetic patients (n = 60) with normo- (n = 20), micro- (n = 20) or macroalbuminuria (n = 20). Differences in glycosylation of alpha1-acid glycoprotein were assayed by crossed affinity immunoelectrophoresis. Activation of the endothelium was measured with plasma concentrations of endothelial cell markers. The median plasma concentration of C-reactive protein was higher in Type I diabetic patients compared with healthy control subjects [1.20 (0.06-21.64) vs. 0.51 (0.04-9.44) mg/l; p<0.02]. The Type I diabetic subjects had a significantly increased relative amount of fucosylated alpha1-acid glycoprotein (79+/-12% vs. 69+/-14% in the healthy control subjects; p<0.005), indicating a chronic hepatic inflammatory response. In the Type I diabetic group, log(C-reactive protein) correlated significantly with von Willebrand factor (r = 0.439, p<0.005) and vascular cell adhesion molecule-1 (r = 0.384, p<0.02), but not with sE-selectin (r = 0.008, p = 0.96). In the second group of Type I diabetic patients, increased urinary albumin excretion was associated with a significant increase of von Willebrand factor (p<0.0005) and C-reactive protein (p = 0.003), which were strongly correlated (r = 0.53, p<0.0005). Plasma concentrations of C-reactive protein were higher in Type I diabetic patients without (clinical) macroangiopathy than in control subjects, probably due to a chronic hepatic inflammatory response. The correlation of C-reactive protein with markers of endothelial dysfunction suggests a relation between activation of the endothelium and chronic inflammation.

Adult↗