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A Buck

Publications and source records attributed to A Buck.

At least 37 records · Page 2Linked to original sources
PubMed2001

Embryonic expression of the murine homologue of SALL1, the gene mutated in Townes--Brocks syndrome.

SALL1 is one of three human homologues of the Drosophila region-specific homeotic gene spalt (sal). Mutations of SALL1 on chromosome 16q12.1 cause Townes--Brocks syndrome (TBS) which is characterized by defects in multiple organ systems including limbs, ears, kidneys and anus. Here, we have analyzed the expression of the mouse homologue of SALL1 (Sall1) during early embryogenesis. Sall1 expression is very prominent in the developing brain and the limbs. Other sites of expression include the meso- and metanephros, lens, olfactory bulbs, heart, primitive streak and the genital tubercle. Hence, Sall1 expression to a large degree reflects the structures affected in human TBS.

Animals↗
PubMed2001

Synthesis and in vivo studies of the stereoisomers of N-[11C]methyl-homoepibatidine.

The carbon-11 labeled enantiomers of nicotinic acetylcholine receptor (nAChR) ligand N-[11C]methyl-homoepibatidine have been synthesized to study the neuronal nicotinic acetylcholine receptors (nAChRs). In vivo evaluations were performed in mice and pig using positron emission tomography (PET). The radioligands displayed a strong enantioselectivity. The (-)-enantiomer showed high uptake in the brain while the (+)-enantiomer was rapidly washed out. In metabolite studies in mice >65% unchanged ligand was found in the blood after 60 minutes. No metabolites were found in the brain. After intravenous application of N-[11C]methyl-(-)-homoepibatidine in the pig specific accumulation in the thalamus was seen. Blocking experiments with cytisine showed specific binding consistent with labeling of the alpha4beta2-nAChR-subtype in the brain. Quantitative kinetic modeling of radiotracers in the pig brain was performed using the arterial input function. The brain uptake of the (-)-isomer was best fitted by a three-compartment model. High distribution volumes were found in the thalamus (DV(TOT) = 66.617, DV(S) = 59.910) versus a low uptake in the cerebellum (DV(TOT) = 8.605m, DV(S) = 1.898). The binding characteristics suggest N-[11C]methyl-(-)-homoepibatidine to be suited for PET imaging studies, but high toxicity prevents routine use in humans.

Animals↗
PubMed2001

Proton magnetic resonance spectroscopy characteristics of a focal cortical dysgenesis during status epilepticus and in the interictal state.

We report the magnetic resonance imaging and proton magnetic resonance spectroscopic findings ((1)HMRS) in a patient with a focal cortical dysgenesis in the right superior frontal gyrus during intermittent frontal status epilepticus (IFSE) with simple partial seizures, and after she had become seizure free. During the status epilepticus, demonstrated by simultaneous behavioural and electroencephalographic telemetric long-term monitoring with scalp electrodes and ictal SPECT, we performed a single voxel spectroscopy of the dysgenic cortex. The(1)HMRS was repeated after 20 days when the patient's seizures were controlled. The N-acetyl-aspartate concentration in the focal dysgenic cortex was decreased in the interictal state but more during IFSE. The creatine/phosphocreatine concentration was normal in both instances. There was a clear lactate signal during IFSE, which was no longer visible in the interictal state. To our knowledge this is the first report of a(1)HMRS study of a focal cortical dysgenesis during an intermittent status epilepticus. We interpret the observed changes as signs of histopathological changes inherent to a cortical malformation and of an impaired energy metabolism due to the partial status epilepticus.

Adult↗
PubMed2001

Anatomical distribution and sclerotic activity of bone metastases from thyroid cancer assessed with F-18 sodium fluoride positron emission tomography.

Currently, bone scintigraphy (BS) is considered to lack sensitivity in detecting bone metastases (BM) from thyroid cancer. We evaluated the anatomical distribution and metabolic behavior of BM as well as the accuracy of BS with and without combination of whole-body iodine scintigraphy (WBI) in detecting metastatic bone disease in thyroid carcinoma. F-18 positron emission tomography (PET), x-ray, BS, and WBI were performed in 35 patients with known or suspected bone metastases from papillary (9 patients) or follicular (26 patients) thyroid carcinoma. Twenty-two metastases were previously known in 14 patients. The indication was staging in 21 patients with high risk for BM, elevated thyroglobulin (Tg)-levels or evaluation of exact extent of BM (14 patients). In addition, results of WBI (35 patients), X-ray (35 patients) F-18 PET (35 patients), MRI of the spine (13 patients), and FDG-PET (15 patients) as well as the clinical course (1.5-4 years) were correlated. BM were detected in 18 patients. Solitary, bifocal, or multiple lesions were present in 9, 2, and 7 patients, respectively. The anatomical distribution of BM (n = 43) was as follows: spine, 42%; skull, 2%; thorax, 16%; femur, 9%; pelvis, 26%; humerus and clavicle, 5%. Sensitivity of BS in interpreting patients as positive or negative for having BM was 64%-85% (specificity, 95%-81%). The combination of BS and WBI was 100% sensitive in detecting metastatic bone disease. One patient had a single BM that was positive at BS but negative on WBI. All metastases were osteolytic on x-ray and two-thirds presented a missing or very limited osteosclerotic bone reaction on F-18 PET. Our data confirm the limited sensitivity of planar BS in detecting BM from thyroid cancer. The combination of BS and WBI, however, was highly accurate. Compared to other malignancies, the distribution pattern of BM presented a lower percentage of vertebral metastases and more patients with single metastases. Those findings in combination with a missing or only slight osteosclerotic bone reaction explain the limited sensitivity of planar BS alone.

Adult↗
PubMed2001

No difference in brain activation during cognitive performance between ecstasy (3,4-methylenedioxymethamphetamine) users and control subjects: a [H2(15)O]-positron emission tomography study.

The long-term use of the serotonin-releaser and uptake-inhibitor 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") has been associated with memory impairments and increased liability to depressive mood and anxiety attacks. It is unclear, however, whether these psychologic deviations are reflected in alterations of the underlying neurophysiologic substrate. The authors compared mood and regional cerebral blood flow (rCBF) profiles between regular polytoxic Ecstasy users and Ecstasy-naive controls. Brain activity as indexed by rCBF was measured during cognitive activation by an attentional task using positron emission tomography and [H2(15)O]. Mood was assessed by means of the Hamilton Rating Scale for Depression (HAM-D) and the EWL Mood Rating Scale. Statistical parametric mapping revealed that brain activity did not differ between the two groups. Both groups also performed equally on the cognitive task requiring sustained attention. However, significantly higher levels of depressiveness as determined by the HAM-D and EWL scales were found in Ecstasy-using subjects. These data indicate that, despite differences in mood, polytoxic Ecstasy users do not differ from Ecstasy-naive controls in terms of local brain activity. Heightened depressiveness in the Ecstasy group was consistent with results from previous studies and could be related to serotonergic hypofunction resulting from repeated MDMA consumption. However, this study cannot exclude the possibility that the observed differences are preexisting rather than a result of Ecstasy use.

Adult↗
PubMed2000

Selection of currently relevant memories by the human posterior medial orbitofrontal cortex.

We have demonstrated previously that patients producing spontaneous confabulations fail to suppress currently irrelevant memory traces, so that they act and think on the basis of a false, temporally displaced (past) reality. All spontaneous confabulators had anterior limbic damage, in particular of the orbitofrontal cortex and basal forebrain. These findings indicated that these structures are essential for distinguishing between mental representations of ongoing reality and currently irrelevant memories. In the present study, we used a similar experimental paradigm as in our clinical studies and H(2)(15)O positron emission tomography to explore the selection of currently relevant memories by the healthy human brain. Subjects were repeatedly presented with the same set of pictures, arranged in different order each time, and were requested to indicate picture recurrences within the runs. Thus, performance in the first run depended on new learning, whereas subsequent runs required the distinction between picture repetitions within the current run ("now") and previous picture presentations in earlier runs. Whereas initial learning activated medial temporal structures, subsequent runs provoked circumscribed posterior medial orbitofrontal activation. We suggest that this area is essential for sorting out mental associations that pertain to ongoing reality.

Adult↗
PubMed2000

Magnetic resonance-based assessment of global coronary flow and flow reserve and its relation to left ventricular functional parameters: a comparison with positron emission tomography.

BACKGROUND: Measurement of coronary sinus blood flow (CSF) by phase-contrast magnetic resonance (PC-MR) imaging at rest and during hyperemia may allow noninvasive assessment of global coronary hemodynamics. METHODS AND RESULTS: Sixteen healthy volunteers (age, 22 to 32 years) were examined with MR and PET in random order within 1 to 2 days. At rest and during hyperemia (dipyridamole 0.56 mg/kg), CSF was measured by a cine PC-MR technique (temporal resolution, 40 ms; spatial resolution, 1.25x0.8 mm(2)), and myocardial blood flow (MBF) was measured by [(13)N]NH(3) PET. PET and MR agreed closely for coronary flow reserve (CFR; mean difference, 2.2+/-14.7%; Bland-Altman method). CSF divided by either total left ventricular mass or an estimate of drained myocardium (LVM(drain)) correlated highly with PET flow data (r=0.93 and 0.95, respectively) and with measures of oxygen demand, ie, heart rate, afterload-corrected fiber shortening, and peak systolic stress determined by MR (overall correlation coefficients, 0.81 and 0.87, respectively, multivariate analysis). CSF/LVM(drain) did not differ significantly from PET-derived MBF (difference, 3.6+/-16.6%). In orthotopic heart transplant recipients (n=9), CFR was reduced and blood supply-demand relationships at rest were shifted toward higher flows (P<0.0001). CONCLUSIONS: This integrated MR approach allows comprehensive assessment of autoregulated and hyperemic coronary flow and is suitable for serial measurements in patients. In transplanted hearts, elevated resting flow is the major cause of reduced CFR.

Adult↗
PubMed2000

Hierarchical visual processing is dependent on the oculomotor system.

Using functional MRI and eye movement recordings we studied the processing of hierarchical stimuli. In agreement with others, we found a minor left hemispheric dominance during local and right dominance during global processing. When attention was directed locally, well-known oculomotor cortical areas were activated, and saccades were elicited in 41% of the trials. Their latencies were similar to pro-saccades. During global processing virtually no saccades occurred. These results suggest two different operational modes of attention. Attending to local features induces a shift of attention, which simultaneously computes a saccade on any level above the brainstem with a computational burden equal to reflexive saccades. Conversely, attending to global features induces an expansion of the focus of attention, which reinforces fixation.

Attention↗
PubMed2000

Simplified quantitative determination of cerebral perfusion reserve with H2(15)O PET and acetazolamide.

The measurement of regional cerebral blood flow (rCBF) and perfusion reserve (PR) with H2(15)O positron emission tomography (PET) and acetazolamide challenge is of importance in evaluating patients with cerebrovascular disease and is thought to be useful in selecting patients for possible vascular surgery. Full quantitative assessment of rCBF with PET requires arterial blood sampling, which is inconvenient in a clinical setting. In this work, we present a simple non-invasive method with which to quantitatively evaluate PR in one PET session lasting no more than 30 min. In ten patients with cerebrovascular disease, rCBF was measured with H2(15)O PET under the baseline condition and after administration of 1 g acetazolamide using a standard technique involving arterial blood sampling. The activity accumulated over 60 s was normalized to injected activity per kilogram body weight (nAA) and compared with rCBF in eight different brain regions. A high linear correlation was found for PR based on nAA (PRnAA) and rCBF (PRrCBF) (PRnAA=0.843 PRrCBF + 0.092, r=-0.83, Pearson's correlation coefficient). Bland-Altman analyses further confirmed that PRnAA reflects PR in a quantitative manner. These results demonstrate that the method based on normalized counts allows the quantitative assessment of PR without blood sampling.

Acetazolamide↗
PubMed2000

3,4-Methylenedioxymethamphetamine (MDMA) modulates cortical and limbic brain activity as measured by [H(2)(15)O]-PET in healthy humans.

[H(2)(15)O]-Positron Emission Tomography (PET) was used to examine regional cerebral blood flow (rCBF) after administration of a single oral dose of the serotonin realeaser and uptake inhibitor MDMA (1.7 mg/kg) or placebo to 16 MDMA-naïve subjects. Psychological changes were assessed by psychometric rating scales. MDMA produced distributed changes in regional blood flow including increases in ventromedial frontal and occipital cortex, inferior temporal lobe and cerebellum; and decreases in the motor and somatosensory cortex, temporal lobe including left amygdala, cingulate cortex, insula and thalamus. Concomitant with these changes, subjects experienced heightened mood, increased extroversion, slight derealization and mild perceptual alterations. MDMA also produced increases in blood pressure and several side effects such as jaw clenching, lack of appetite and difficulty concentrating. These results indicate that a distributed cluster of brain areas underlie the various effects of MDMA in humans.

Adult↗
PubMed2000

Functional neuroanatomy of human sleep states after zolpidem and placebo: a H215O-PET study.

Changes in the functional organization of the brain during the course of sleep and waking are reflected by different patterns of regional cerebral blood flow (rCBF). To investigate the effect of the hypnotic zolpidem, a benzodiazepine receptor agonist, drug or placebo were administered to eight young, healthy men prior to bedtime. The subjects were sleep-deprived to promote sleep during the 4-h recording period in the positron emission tomography scanner. Intravenous injections of labelled water were administered during pre-drug wakefulness, and during Stage 2, Stage 4 and rapid eye movement (REM) sleep, each injection being followed by an emission scan. Statistical parametric mapping was used to investigate the effects of treatment and sleep states. During sleep (combined Stages 2 and 4, and REM sleep) relative rCBF was lower after zolpidem than after placebo in the basal ganglia and insula, and higher in the parietal cortex. A 'multiple study' analysis of REM sleep revealed that rCBF in the anterior cingulum was lower after zolpidem than after placebo, whereas rCBF in the occipital and parietal cortex, parahippocampal gyrus and cerebellum was higher. When the pooled data (drug and placebo) of Stages 2 and 4 were compared with wakefulness, rCBF was lower in prefrontal cortex and insula, and higher in the occipital and parietal cortex. The results indicate that some differences in rCBF from wakefulness to non-REM sleep are further augmented by zolpidem.

Adult↗
PubMed2000

Zolpidem and sleep deprivation: different effect on EEG power spectra.

To study the role of GABA-ergic mechanisms in sleep regulation, the combined action of 40 h sleep deprivation and either 20 mg zolpidem or placebo on the sleep electroencephalogram (EEG) were investigated by quantitative EEG analysis in eight young men who participated in a positron emission tomography study. Compared with baseline, sleep deprivation increased low-frequency (1.25-7.0 Hz) EEG power in non-rapid eye movement (NREM) sleep in the placebo night. After administration of zolpidem, power in the 3.75-10.0 Hz range and 14. 25-16.0 Hz band was reduced. The largest decrease was observed in the theta band. Comparison with placebo revealed that zolpidem attenuated power in the entire 1.75-11.0 Hz range. The plasma concentration of zolpidem at 4.5 h after intake showed a positive correlation with the drug-induced difference in power from placebo in the 14.25-16.0 Hz band. Regional EEG analysis based on bipolar derivations along the antero-posterior axis disclosed, for NREM sleep, a drug-induced posterior shift of power in the frequency range of 7.75-9.75 Hz. Zolpidem did not affect rapid eye movemnt sleep spectra. We conclude that sleep deprivation and agonistic modulation of GABAA receptors have separate and additive effects on power spectra and that their effects are mediated by different neurophysiological mechanisms.

Adult↗
PubMed2000

Evaluation of serotonergic transporters using PET and [11C](+)McN-5652: assessment of methods.

[11C](+)McN-5652 is an established positron emission tomography tracer used to assess serotonergic transporter density. Several methods have been used to analyze [11C](+)McN-5652 data; however, no evaluation of candidate methods has been published in detail yet. In this study, compartmental modeling using a one-tissue compartment model (K1, k2"), a two-tissue compartment model (K1 to k4), and a noncompartmental method that relies on a reference region devoid of specific binding sites were assessed. Because of its low density of serotonergic transporters, white matter was chosen as reference. Parameters related to transporter density were the total distribution volume DV" (= K1/k2", one tissue compartment), DVtot, (=K1/k1' (1 + k3/k4), two tissue compartments), and Rv (= k3'/k4, noncompartmental method). The DV", DVtot, and Rv values extended over a similar range and reflected the known pattern of serotonergic transporters. However, all parameters related to transporter density were markedly confounded by nonspecific binding. With regard to K1, the one-tissue compartment model yielded markedly lower values, which were, however, more stable. The minimal study duration needed to determine stable values for the distribution volume was approximately 60 minutes. The choice of the method to analyze [11C](+)McN-5652 data depends on the situation. Parametric maps of Rv are useful if no information on K1 is needed. If compartmental modeling is chosen, both the one- and the two-tissue compartment models have advantages. The one-tissue compartment model underestimates K1 but yields more robust values. The distribution volumes calculated with both models contain a similar amount of information. None of the parameters reflected serotonergic transporter density in a true quantitative manner, as all were confounded by nonspecific binding.

Adult↗
PubMed2000

Similarity and robustness of PET and SPECT binding parameters for benzodiazepine receptors.

The single photon emission computed tomography (SPECT) radiotracer [123I]iomazenil is used to assess benzodiazepine receptor binding parameters. These measurements are relative indices of benzodiazepine receptor concentration (B'max). To evaluate the ability of such indices in accurately accessing the B'max the authors compared them with absolute values of B'max, measured using positron emission tomography (PET). The authors performed SPECT, PET, and magnetic resonance imaging (MRI) studies on a group composed of seven subjects. For SPECT studies, the authors administered a single injection of [123I]iomazenil and estimated the total and specific distribution volumes (DV(T SPECT), DV(S SPECT)) and the binding potential (BP) using unconstrained (BP(SPECT)) and constrained (BP(C SPECT)) compartmental models. For PET studies, the authors used a multiinjection approach with [11C]flumazenil and unlabeled flumazenil to estimate absolute values of receptor concentration, B'max, and some other binding parameters. The authors studied the correlation of different binding parameters with B'max. To study the robustness of the binding parameter measurements at the pixel level, the authors applied a wavelet-based filter to improve signal-to-noise ratio of time-concentration curves, and the calculated kinetic parameters were used to build up parametric images. For PET data, the B'max and the DV(PET) were highly correlated (r = 0.988). This confirms that it is possible to use the DV(PET) to access benzodiazepine receptor density. For SPECT data, the correlation between DV(SPECT) estimated using a two- and three-compartment model was also high (r = 0.999). The DV(T SPECT) and BP(C SPECT) parameters estimated with a constrained three-compartment model or the DV(T''SPECT) parameter estimated with a two-compartment model were also highly correlated to the B'max parameter estimated with PET. Finally, the robustness of the binding parameters allowed the authors to build pixel-by-pixel parametric images using SPECT data.

Adult↗
PubMed2000

Molecular cloning, chromosomal localization, and expression of the murine SALL1 ortholog Sall1.

SALL1 has been identified as one of now three human homologs of the region specific homeotic gene spalt (sal) of Drosophila, which encodes a zinc finger protein of characteristic structure. Mutations of SALL1 on chromosome 16q12.1 cause Townes-Brocks syndrome (TBS, OMIM no. 107480). In order to facilitate functional studies of this gene in a model organism, we searched for the murine homolog of SALL1. Here we report the genomic cloning, chromosome mapping, and partial expression analysis of the gene Sall1. Sequence comparison, Northern blot hybridization as well as the conserved chromosome location on the homologous mouse chromosome indicate that we have indeed isolated the murine homolog of SALL1.

Amino Acid Sequence↗
PubMed2000

Radiation exposure to sonographers from fluorine-18-FDG PET patients.

OBJECTIVE: We estimated the amount of radiation exposure to sonographers from patients who were injected with 18F-fluorodeoxyglucose (FDG) at 2 and 3 h postinjection. METHODS: We studied 8 patients who were given between 380-420 MBq 18F-FDG. The patients were measured with a RADOS RDS-120 dosimeter between 2 and 3 h after FDG injection. The dosimetry measurement was taken at a distance of 0.5 m from the injected patient, a distance used by a sonographer to perform an abdominal ultrasound. Measurements were taken at the levels of the sonographer's shoulder, abdomen, and gonads. RESULTS: At the first measurement at 2 h, the mean exposures to the shoulder, abdomen, and gonads of the sonographer in pSv/h were 31.9+/-11.3, 37.1+/-9.5, and 32.8+/-11.8, respectively. At 3 h, the mean exposures to the shoulder, abdomen, and gonads were 21.5+/-4.2, 20.2+/-5.8, and 19.6+/-4.9, respectively. CONCLUSION: The amount of radiation exposure to a sonographer is minimal. Radiation exposure risks should be considered, however, if the sonographer comes into daily, repeated contact with patients who have been given 18F-FDG.

Abdomen↗