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J Aerts

Publications and source records attributed to J Aerts.

At least 19 recordsLinked to original sources
PubMed2002

Epimerization study on [18f]FDG produced by an alkaline hydrolysis on solid support under stringent conditions.

Since 1998, routine [18F]FDG syntheses are being carried out by alkaline hydrolysis on a solid support, i.e. the labeled intermediate is trapped on a tC18 solid phase extraction cartridge, purified and finally hydrolyzed within the cartridge, at room temperature, using sodium hydroxide. The present study demonstrated that no epimerization of [18F]FDG to [18F]FDM occurs even when 12 N NaOH is used and when the hydrolysis time is extended up to 1 h. The alkaline hydrolysis on solid support appears to be a simple method leading to [18F]FDG with high purity.

Fluorodeoxyglucose F18↗
PubMed2002

Cortical processing of noxious somatosensory stimuli in the persistent vegetative state.

The persistent vegetative state (PVS) is a devastating medical condition characterized by preserved wakefulness contrasting with absent voluntary interaction with the environment. We used positron emission tomography to assess the central processing of noxious somatosensory stimuli in the PVS. Changes in regional cerebral blood flow were measured during high-intensity electrical stimulation of the median nerve compared with rest in 15 nonsedated patients and in 15 healthy controls. Evoked potentials were recorded simultaneously. The stimuli were experienced as highly unpleasant to painful in controls. Brain glucose metabolism was also studied with [(18)F]fluorodeoxyglucose in resting conditions. In PVS patients, overall cerebral metabolism was 40% of normal values. Nevertheless, noxious somatosensory stimulation-activated midbrain, contralateral thalamus, and primary somatosensory cortex in each and every PVS patient, even in the absence of detectable cortical evoked potentials. Secondary somatosensory, bilateral insular, posterior parietal, and anterior cingulate cortices did not show activation in any patient. Moreover, in PVS patients, the activated primary somatosensory cortex was functionally disconnected from secondary somatosensory, bilateral posterior parietal, premotor, polysensory superior temporal, and prefrontal cortices. In conclusion, somatosensory stimulation of PVS patients, at intensities that elicited pain in controls, resulted in increased neuronal activity in primary somatosensory cortex, even if resting brain metabolism was severely impaired. However, this activation of primary cortex seems to be isolated and dissociated from higher-order associative cortices.

Adult↗
PubMed2001

The facile detection of 1505G-->A in Gaucher patients with different phenotypes.

In Gaucher disease patients, over 100 disease-causing mutations have been identified. For identification of the 1504C-->T (R463C) mutation it is common to use PCR-restriction fragmentation analysis using the restriction enzyme MspI. In the present study we investigated the reliability of this approach because accurate determination of genotypes is important in genotype-phenotype correlations. A simple modification, i.e. using the restriction enzyme HphI instead of MspI, revealed that type I and II Gaucher disease patients who had previously been identified as carrying the 1504C-->T mutation in fact carried the 1505G-->A (IVS10(-1)G-->A) mutation. Sequencing of the appropriate fragment confirmed this. The PCR method easily differentiates between these two mutations in Gaucher disease patients, thus circumventing the need for sequencing procedures. The phenotypes of the patients found to be carrying the 1505G-->A mutation are also described.

Adolescent↗
PubMed2001

Generation of rapid eye movements during paradoxical sleep in humans.

Although rapid eye movements (REMs) are a prominent feature of paradoxical sleep (PS), their origin and functional significance remain poorly understood in humans. In animals, including nonhuman primates, REMs during PS are closely related to the occurrence of the so-called PGO waves, i.e., prominent phasic activities recorded throughout the brain but predominantly and most easily in the pons (P), the lateral geniculate bodies (G), and the occipital cortex (O). Therefore, and because the evolution of species is parsimonious, a plausible hypothesis would be that during PS in humans, REMs are generated by mechanisms similar to PGO waves. Using positron emission tomography and iterative cerebral blood flow measurements by H(2)(15)O infusions, we predicted that the brain regions where the PGO waves are the most easily recorded in animals would be differentially more active in PS than in wakefulness, in relation with the density of the REM production [i.e., we looked for the condition (PS versus wakefulness) by performance (REM density) interaction]. Accordingly, we found a significant interaction effect in the right geniculate body and in the primary occipital cortex. The result supports the hypothesis of the existence of processes similar to PGO waves in humans, responsible for REM generation. The interest in the presence of PGO waves in humans is outstanding because the cellular processes involved in, or triggered by, PGO waves might favor brain plasticity during PS.

Adult↗
PubMed2001

Experience-dependent changes in cerebral functional connectivity during human rapid eye movement sleep.

One function of sleep is hypothesized to be the reprocessing and consolidation of memory traces (Smith, 1995; Gais et al., 2000; McGaugh, 2000; Stickgold et al., 2000). At the cellular level, neuronal reactivations during post-training sleep in animals have been observed in hippocampal (Wilson and McNaughton, 1994) and cortical (Amzica et al., 1997) neuronal populations. At the systems level, using positron emission tomography, we have recently shown that some brain areas reactivated during rapid-eye-movement sleep in human subjects previously trained on an implicit learning task (a serial reaction time task) (Maquet et al., 2000). These cortical reactivations, located in the left premotor area and bilateral cuneus, were thought to reflect the reprocessing--possibly the consolidation--of memory traces during post-training rapid-eye-movement sleep. Here, the experience-dependent functional connectivity of these brain regions is examined. It is shown that the left premotor cortex is functionally more correlated with the left posterior parietal cortex and bilateral pre-supplementary motor area during rapid-eye-movement sleep of subjects previously trained to the reaction time task compared to rapid-eye-movement sleep of untrained subjects. The increase in functional connectivity during post-training rapid-eye-movement sleep suggests that the brain areas reactivated during post-training rapid-eye-movement sleep participate in the optimization of the network that subtends subject's visuo-motor response. The optimization of this visuo-motor network during sleep could explain the gain in performance observed during the following day.

Brain Mapping↗
PubMed2001

A real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to detect breast carcinoma cells in peripheral blood.

BACKGROUND: The detection of occult carcinoma cells in patients with breast cancer has been shown to predict disease recurrence and metastasis. MATERIALS AND METHODS: To improve on molecular detection of breast carcinoma cells in blood, we have developed a sensitive and quantitative assay using real-time quantitative RT-PCR identifying transcripts of the cytokeratin-19 (CK19) gene. RESULTS: This real-time quantitative RT-PCR is sensitive, accurate and has a high reproducibility within a wide dynamic range, which permits simultaneous quantitative analysis of samples with varying input concentrations. Furthermore, the procedure offers several technical advantages over classic quantitative PCR methods (competitive RT-PCR, Northern blotting) such as decreased likelihood of contamination due to absence of post-PCR manipulations, high sample throughput because of absence of post-PCR processing time (no agarose gel electrophoresis). In this pilot study, we detected significantly elevated CK19 transcript levels in < 10% of the volunteers, in +/- 30% of stage I-IIIa patients preoperatively and in > 70% of the and stage IV breast cancer patients. CONCLUSIONS: Analyses using this real time quantitative RT-PCR for CK19 mRNA may prove to have clinical implications in the assessment of circulating tumour cells in peripheral blood, micrometastases in bone marrow or lymph nodes in breast cancer patients. Application of this technique in a clinical population may improve diagnosis and monitoring of metastatic breast cancer and its validation is currently ongoing.

Adult↗
PubMed2000

Novel oral treatment of Gaucher's disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis.

BACKGROUND: Current treatment for Gaucher's disease involves administration of intravenous glucocerebrosidase to degrade glucocerebroside stored in lysosomes. Lowering the rate of biosynthesis of glucocerebroside should decrease accumulation of this substrate. We investigated the safety and efficacy of OGT 918 (N-butyldeoxynojirimycin), an inhibitor of glucosyltransferase, as a novel oral treatment for non-neuronopathic Gaucher's disease. METHODS: We recruited, into a 1-year open-label study, 28 adults (seven with previous splenectomies) from four national Gaucher's referral clinics, who were unable or unwilling to receive enzyme treatment. We measured liver and spleen volume by computed tomography or magnetic resonance imaging at baseline and at months 6 and 12, and biochemical and haematological variables monthly, including chitotriosidase activity (a sensitive marker of Gaucher's disease activity). Patients were started on 100 mg oral OGT 918 three times daily. FINDINGS: Baseline liver volumes were 1.1-2.7 times normal and spleen volumes 5.1-24.8 times normal. At 12 months, mean liver and spleen volumes were significantly lowered by 12% (95% CI 7.8-16.4) and 19% (14.3-23.7), respectively (each p<0.001). Haematological variables improved slightly. Mean organ volume and blood counts improved continually between 6 months and 12 months of treatment. Mean chitotriosidase concentrations fell by 16.4% over 12 months (p<.0001). Six patients withdrew because of gastrointestinal complaints (two), personal reasons (two), or severe pre-existing disease (two). The most frequent adverse effect was diarrhoea, which occurred in 79% of patients shortly after the start of treatment. INTERPRETATION: Decrease of substrate formation by OGT 918 improves key clinical features of non-neuronopathic Gaucher's disease. The strategy justifies further trials in this and other glycosphingolipid storage disorders.

1-Deoxynojirimycin↗
PubMed2000

Striatum forever, despite sequence learning variability: a random effect analysis of PET data.

This PET study is concerned with the what, where, and how of implicit sequence learning. In contrast with previous studies imaging the serial reaction time (SRT) task, the sequence of successive locations was determined by a probabilistic finite-state grammar. The implicit acquisition of statistical relationships between serially ordered elements (i.e., what) was studied scan by scan, aiming to evidence the brain areas (i.e., where) specifically involved in the implicit processing of this core component of sequential higher-order knowledge. As behavioural results demonstrate between- and within-subjects variability in the implicit acquisition of sequential knowledge through practice, functional PET data were modelled using a random-effect model analysis (i.e., how) to account for both sources of behavioural variability. First, two mean condition images were created per subject depending on the presence or not of implicit sequential knowledge at the time of each of the 12 scans. Next, direct comparison of these mean condition images provided the brain areas involved in sequential knowledge processing. Using this approach, we have shown that the striatum is involved in more than simple pairwise associations and that it has the capacity to process higher-order knowledge. We suggest that the striatum is not only involved in the implicit automatization of serial information through prefrontal cortex-caudate nucleus networks, but also that it plays a significant role for the selection of the most appropriate responses in the context created by both the current and previous stimuli, thus contributing to better efficiency and faster response preparation in the SRT task.

Adult↗
PubMed2000

The role of lateral occipitotemporal junction and area MT/V5 in the visual analysis of upper-limb postures.

Humans, like numerous other species, strongly rely on the observation of gestures of other individuals in their everyday life. It is hypothesized that the visual processing of human gestures is sustained by a specific functional architecture, even at an early prelexical cognitive stage, different from that required for the processing of other visual entities. In the present PET study, the neural basis of visual gesture analysis was investigated with functional neuroimaging of brain activity during naming and orientation tasks performed on pictures of either static gestures (upper-limb postures) or tridimensional objects. To prevent automatic object-related cerebral activation during the visual processing of postures, only intransitive postures were selected, i. e., symbolic or meaningless postures which do not imply the handling of objects. Conversely, only intransitive objects which cannot be handled were selected to prevent gesture-related activation during their visual processing. Results clearly demonstrate a significant functional segregation between the processing of static intransitive postures and the processing of intransitive tridimensional objects. Visual processing of objects elicited mainly occipital and fusiform gyrus activity, while visual processing of postures strongly activated the lateral occipitotemporal junction, encroaching upon area MT/V5, involved in motion analysis. These findings suggest that the lateral occipitotemporal junction, working in association with area MT/V5, plays a prominent role in the high-level perceptual analysis of gesture, namely the construction of its visual representation, available for subsequent recognition or imitation.

Adult↗
PubMed2000

[(18)F]p-MPPF: aA radiolabeled antagonist for the study of 5-HT(1A) receptors with PET.

This paper summarizes the present status of the researches conducted with [(18)F]4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-fluorobenzamido ]ethyl]-piperazine known as [(18)F]p-MPPF, a new 5-HT(1A) antagonist for the study of the serotonergic neurotransmission with positron emission tomography (PET). This includes chemistry, radiochemistry, animal data (rats, cats, and monkeys) with autoradiography and PET, human data with PET, toxicity, and metabolism.

Aminopyridines↗
PubMed2000

Experience-dependent changes in cerebral activation during human REM sleep.

The function of rapid-eye-movement (REM) sleep is still unknown. One prevailing hypothesis suggests that REM sleep is important in processing memory traces. Here, using positron emission tomography (PET) and regional cerebral blood flow measurements, we show that waking experience influences regional brain activity during subsequent sleep. Several brain areas activated during the execution of a serial reaction time task during wakefulness were significantly more active during REM sleep in subjects previously trained on the task than in non-trained subjects. These results support the hypothesis that memory traces are processed during REM sleep in humans.

Adult↗
PubMed2000

Tissue distribution, autoradiography, and metabolism of 4-(2'-methoxyphenyl)-1-[2' -[N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethyl]piperazine (p-[(18)F]MPPF), a new serotonin 5-HT(1A) antagonist for positron emission tomography: An In vivo study in rats.

The in vivo behavior of 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-[(18)F]fluorobenzamido ]ethyl]-piperazine (p-[(18)F]MPPF), a new serotonin 5-HT(1A) antagonist, was studied in awake, freely moving rats. Biodistribution studies showed that the carbon-fluorine bond was stable in vivo, that this compound was able to cross the blood-brain barrier, and that a general diffusion equilibrium could account for the availability of the tracer. The great quantity of highly polar metabolites found in plasma did not contribute to the small amounts of metabolites found in hippocampus, frontal cortex, and cerebellum. Exvivo p-[(18)F]MPPF and in vitro 8-hydroxy-2-(di-n-[(3)H]propylamino)tetralin autoradiography were compared both qualitatively and quantitatively. Qualitative evaluation proved that the same brain regions were labeled and that the p-[(18)F]MPPF labeling is (a) in total agreement with the known distribution of 5-HT(1A) receptors in rats and (b) characterized by very low nonspecific binding. Quantitative comparison demonstrated that the in vivo labeling pattern obtained with p-[(18)F]MPPF cannot be explained by differences in regional blood flow, capillary density, or permeability. The 5-HT(1A) specificity of p-[(18)F]MPPF and binding reversibility were confirmed in vivo with displacement experiments. Thus, this compound can be used to evaluate parameters characterizing 5-HT(1A) binding sites in the brain.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Auditory processing in the vegetative state.

H(2)(15)O-PET was used to investigate changes in regional cerebral blood flow in response to auditory stimulation in patients in the vegetative state. Five patients in a vegetative state of hypoxic origin were compared with 18 age-matched controls. In addition, the cerebral metabolism of these patients and 53 age-matched controls was studied using [(18)F]fluorodeoxyglucose. In control subjects, auditory click stimuli activated bilateral auditory cortices [Brodmann areas (BA) 41 and 42] and the contralateral auditory association cortices (BA 22). In the patients, although resting metabolism was decreased to 61% of normal values, bilateral auditory areas 41 and 42 showed activation as seen in the controls, but the temporoparietal junction cortex (BA 22) failed to be activated. Moreover, the auditory association cortex was functionally disconnected from the posterior parietal association area (BA 40), the anterior cingulate cortex (BA 24) and the hippocampus, as revealed by psychophysiological interaction analysis. Thus, despite altered resting metabolism, the auditory primary cortices were still activated during external stimulation, whereas hierarchically higher-order multi- modal association areas were not. Such a cascade of functional disconnections along the auditory cortical pathways, from the primary auditory areas to multimodal and limbic areas, suggests that the residual cortical processing observed in the vegetative state cannot lead to the integrative processes that are thought to be necessary for the attainment of the normal level of awareness.

Acoustic Stimulation↗
PubMed1999

Impaired effective cortical connectivity in vegetative state: preliminary investigation using PET.

Vegetative state (VS) is a condition of abolished awareness with persistence of arousal. Awareness is part of consciousness, which itself is thought to represent an emergent property of cerebral neural networks. Our hypothesis was that part of the neural correlate underlying VS is an altered connectivity, especially between the associative cortices. We assessed regional cerebral glucose metabolism (rCMRGlu) and effective cortical connectivity in four patients in VS by means of statistical parametric mapping and [18F]fluorodeoxyglucose-positron emission tomography. Our data showed a common pattern of impaired rCMRGlu in the prefrontal, premotor, and parietotemporal association areas and posterior cingulate cortex/precuneus in VS. In a next step, we demonstrated that in VS patients various prefrontal and premotor areas have in common that they are less tightly connected with the posterior cingulate cortex than in normal controls. These results provide a strong argument for an alteration of cortical connectivity in VS patients.

Adult↗
PubMed1999

Hepatosplenomegalic lipidosis: what unless Gaucher? Adult cholesteryl ester storage disease (CESD) with anemia, mesenteric lipodystrophy, increased plasma chitotriosidase activity and a homozygous lysosomal acid lipase -1 exon 8 splice junction mutation.

A 36-year-old woman was admitted for hepatosplenomegaly and anemia. Bone marrow cytology showed "sea-blue histiocytes", vacuolated macrophages and plasma cells. As primary liver disease, malignancy or hematologic disorders were excluded, and plasma chitotriosidase activity was increased 27-fold over control, the presence of a lysosomal storage disease was suspected. Biochemical analysis of skin fibroblasts revealed normal glucocerebrosidase and sphingomyelinase activity, but lipid analysis showed a more than 15-fold accumulation of cholesterol esters within the cells. The activity of lysosomal acid lipase (LAL) in fibroblast homogenates was decreased to 12% of control subjects. Mutational analysis of the patient's blood showed the homozygous G-->A mutation at position -1 of the exon 8 splice donor site (E8SJM-allele) known for adult cholesteryl ester storage disease (CESD); the polymorphic background was that of the complex haplotype -6Thr, 2Gly, 894 G-->A. Based on clinical, laboratory, cytological and and biochemical findings, CESD can clearly be separated from other more frequent inherited lysosomal storage diseases, e.g. atypical forms of Gaucher disease.

Adult↗
PubMed1999

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