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Biomedical subjects

A Thiele

Publications and source records attributed to A Thiele.

At least 19 recordsLinked to original sources
PubMed2006

A novel electrode-pipette design for simultaneous recording of extracellular spikes and iontophoretic drug application in awake behaving monkeys.

We developed a novel design of an electrode-pipette combination (EPC) which allows access to brain structures in awake behaving primates without the need for guide tubes or to mechanically open the dura prior to electrode insertion. The EPC consists of an etched tungsten in glass electrode flanked by two pipettes which allow for local and highly controlled iontophoretic administration of neuroactive substances. These EPCs have excellent single cell isolation properties and are sturdy enough to penetrate the primate dura for up to 8 weeks following either a craniotomy or a dura scrape (i.e. even after substantial built up of fibrous scar tissue). We show that the EPCs can be used to selectively manipulate the cholinergic system in primate V1 during passive fixation and while animals perform an attentionally demanding task.

Acetylcholine↗
PubMed2006

[A questionnaire study of the relationship between gender and chronic pain].

INTRODUCTION: The aim of this study was to assess the relationship between gender role orientation and the prevalence of chronic pain. METHOD: The individual gender role orientation in a sample of 45 chronic pain patients (ICD 10 diagnosis, F 45.4) was compared to gender role orientation in a matched, pain-free control group. Gender role orientation was assessed by questionnaires on the self-attribution of stereotypic gender traits (GEPAQ) and on the extent of agreement with traditional feminine and masculine role norms (MRNS, FRNS). Group differences were compared by multivariate analysis. RESULTS: In accordance with the hypothesis, results confirmed that pain patients showed stronger feminine and weaker masculine role orientations than healthy controls. Pain patients additionally ascribed to themselves more 'feminine' (e.g. worried, nervous) and less 'masculine' (e.g. aggressive, cynical) traits. CONCLUSION: Sociopsychological variables of gender role orientation were related to chronic pain in the groups observed. An integrated model consisting of psychodynamic, sociological, and sociopsychological factors is proposed.

Aggression↗
PubMed2006

Cholinergic modulation of response properties and orientation tuning of neurons in primary visual cortex of anaesthetized Marmoset monkeys.

Cortical processing is strongly influenced by the actions of neuromodulators such as acetylcholine (ACh). Early studies in anaesthetized cats argued that acetylcholine can cause a sharpening of orientation tuning functions and an improvement of the signal-to-noise ratio (SNR) of neuronal responses in primary visual cortex (V1). Recent in vitro studies have demonstrated that acetylcholine reduces the efficacy of feedback and intracortical connections via the activation of muscarinic receptors, and increases the efficacy of feed-forward connections via the activation of nicotinic receptors. If orientation tuning is mediated or enhanced by intracortical connections, high levels of acetylcholine should diminish orientation tuning. Here we investigate the effects of acetylcholine on orientation tuning and neuronal responsiveness in anaesthetized marmoset monkeys. We found that acetylcholine caused a broadening of the orientation tuning in the majority of cells, while tuning functions became sharper in only a minority of cells. Moreover, acetylcholine generally facilitated neuronal responses, but neither improved signal-to-noise ratio, nor reduced trial-to-trial firing rate variance systematically. Acetylcholine did however, reduce variability of spike occurrences within spike trains. We discuss these findings in the context of dynamic control of feed-forward and lateral/feedback connectivity by acetylcholine.

Acetylcholine↗
PubMed2005

Data-robust tight lower bounds to the information carried by spike times of a neuronal population.

We develop new data-robust lower-bound methods to quantify the information carried by the timing of spikes emitted by neuronal populations. These methods have better sampling properties and are tighter than previous bounds based on neglecting correlation in the noise entropy. Our new lower bounds are precise also in the presence of strongly correlated firing. They are not precise only if correlations are strongly stimulus modulated over a long time range. Under conditions typical of many neurophysiological experiments, these techniques permit precise information estimates to be made even with data samples that are three orders of magnitude smaller than the size of the response space.

Action Potentials↗
PubMed2004

Acetylcholine dynamically controls spatial integration in marmoset primary visual cortex.

Recent in vitro studies have shown that acetylcholine (ACh) selectively reduces the efficacy of lateral cortical connections via a muscarinic mechanism, while boosting the efficacy of thalamocortical/feed-forward connections via a nicotinic mechanism. This suggests that high levels of ACh should reduce center-surround interactions of neurons in primary visual cortex, making cells more reliant on feed-forward information. In line with this hypothesis, we show that local iontophoretic application of ACh in primate primary visual cortex reduced the extent of spatial integration, assessed by recording a neurons' length tuning. When ACh was externally applied, neurons' preferred length shifted toward shorter bars, showing reduced impact of the extra-classical receptive field. We fitted a difference and a ratio of Gaussian model to these data to determine the underlying mechanisms of this dynamic change of spatial integration. These models assume overlapping summation and suppression areas with different widths and gains to be responsible for spatial integration and size tuning. ACh significantly reduced the extent of the summation area, but had no significant effect on the extent of the suppression area. In line with previous studies, we also show that applying ACh enhanced the response in the majority of cells, especially in the later (sustained) part of the response. These findings are similar to effects of attention on neuronal activity. The natural release of ACh is strongly linked with states of arousal and attention. Our results may therefore be relevant to the neurobiological mechanism of attention.

Acetylcholine↗
PubMed2004

Contribution of inhibitory mechanisms to direction selectivity and response normalization in macaque middle temporal area.

Inhibitory mechanisms contribute to directional tuning in primary visual cortex, and it has been suggested that, in the primate brain, the middle temporal area (MT) inherits most of its directional information from primary visual cortex (V1). To test the validity of this hierarchical scheme, we investigated whether directional tuning in MT was present upon blockade of local gamma-aminobutyratergic (GABAergic) inhibitory mechanisms. Direction selectivity during the initial 50 ms after response onset was abolished in many MT cells when the local inhibitory network was inactivated whereas direction selectivity in later response periods was largely unaffected. Thus, direction selectivity during early response periods is often generated autonomously within MT whereas direction selectivity during later response periods is either inherited from other visual areas or locally mediated by mechanisms other than gamma-aminobutyric acid type A receptor (GABA(A)) inhibition. GABAergic inhibition may also mediate contrast normalization. Our data suggest that GABA(A) inhibition implements a local direction-selective static nonlinearity, rather than a full normalization in MT. These findings put constraints on strict hierarchical models according to which MT performs more complex computations based on local motion measurements provided by earlier areas, arguing for more distributed and independent information processing.

Animals↗
PubMed2003

Membrane differential filtration is safe and effective for the long-term treatment of Refsum syndrome--an update of treatment modalities and pathophysiological cognition.

Refsum's disease is a complex and difficult to diagnose storage disease caused by complex autosomal recessive peroxisomal disorder in which mutations of phytanolyl/pristanoyl-CoA-hydroxilase are the main cause. Poorly metabolised phytanic acid (PA), pristanic acid (PrA) and picolenic acid (PiA) accumulates in fatty tissues, myelin sheaths, heart, kidneys and retina, leading to retinitis pigmentosa, peripheral dissociative polyneuropathy, cerebellar ataxia ("sailors" walk), renal, cardiac and liver impairment. 65% of plasma PA and PrA is localized within VLDL, LDL and HDL lipoprotein particles. Dietary restriction of PA is mostly not sufficient to prevent acute attacks and stabilize the progressive course. LDL and VLDL bound PA/PrA can be effectively eliminated from plasma with extracorporal LDL-apheresis using membrane differential filtration. Mostly additive malnutrition will become worse the clinical picture. Latest experience with black cumin oil (nigella sativa) in a dose of 3 g/day shows a support and a regression of some malnutrition effects in PA restricted dietary and a supportive effect to MDF.

Blood Component Removal↗
PubMed2003

An exact method to quantify the information transmitted by different mechanisms of correlational coding.

We derive a new method to quantify the impact of correlated firing on the information transmitted by neuronal populations. This new method considers, in an exact way, the effects of high order spike train statistics, with no approximation involved, and it generalizes our previous work that was valid for short time windows and small populations. The new technique permits one to quantify the information transmitted if each cell were to convey fully independent information separately from the information available in the presence of synergy-redundancy effects. Synergy-redundancy effects are shown to arise from three possible contributions: a redundant contribution due to similarities in the mean response profiles of different cells; a synergistic stimulus-dependent correlational contribution quantifying the information content of changes of correlations with stimulus, and a stimulus-independent correlational contribution term that reflects interactions between the distribution of rates of individual cells and the average level of cross-correlation. We apply the new method to simultaneously recorded data from somatosensory and visual cortices. We demonstrate that it constitutes a reliable tool to determine the role of cross-correlated activity in stimulus coding even when high firing rate data (such as multi-unit recordings) are considered.

Action Potentials↗
PubMed2002

Spontaneous human herpes virus type 1 infection in a chinchilla (Chinchilla lanigera f. dom.).

A 1-year-old male chinchilla with a 2-week history of conjunctivitis suffered subsequently from neurological signs comprising seizures, disorientation, recumbency and apathy. After 3 weeks of progressive central nervous disease the animal was killed in view of the poor prognosis. A non-suppurative meningitis and polioencephalitis with neuronal necrosis and intranuclear inclusion bodies were observed at necropsy and by light microscopy. The brain stem and cerebral cortices were most severely affected. Both eyes displayed ulcerative keratitis, uveitis, retinitis and retinal degeneration, and optical neuritis. Additionally, a purulent rhinitis with focal erosions, epithelial degeneration and intranuclear inclusion bodies was present. Ultrastructurally, herpes virus particles were detected in neurons of the brain. Immunohistochemistry with antisera specific for human herpes virus types 1 and 2 resulted in viral antigen labeling in neurons, glial cells and in neuronal processes. Viral antigen was found in the rhinencephalon, cerebral cortices, hippocampus, numerous nuclei of the brain stem, single foci in the cerebellum, and in a solitary erosive lesion of the right nasal vestibulum. Viral antigen was not detected in the eyes. The virus was isolated from the CNS, and nucleic acid sequence analysis of the glycoprotein B and the DNA polymerase revealed a sequence homology with human herpes virus type 1 of 99% and 100%, respectively. The clinical signs, the distribution of the lesions and the viral antigen suggest a primary ocular infection with subsequent spread to the CNS. Chinchillas are susceptible to human herpes virus 1 and may play a role as a temporary reservoir for human infections.

Animals↗
PubMed2002

Neural mechanisms of saccadic suppression.

In normal vision our gaze leaps from detail to detail, resulting in rapid image motion across the retina. Yet we are unaware of such motion, a phenomenon known as saccadic suppression. We recorded neural activity in the middle temporal and middle superior temporal cortical areas during saccades and identical image motion under passive viewing conditions. Some neurons were selectively silenced during saccadic image motion, but responded well to identical external image motion. In addition, a subpopulation of neurons reversed their preferred direction of motion during saccades. Consequently, oppositely directed motion signals annul one another, and motion percepts are suppressed.

Animals↗
PubMed2002

Directional asymmetry of neurons in cortical areas MT and MST projecting to the NOT-DTN in macaques.

The cortical projection to the subcortical pathway underlying the optokinetic reflex was studied using antidromic electrical stimulation in the midbrain structures nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system (NOT-DTN) while simultaneously recording from cortical neurons in the superior temporal sulcus (STS) of macaque monkeys. Projection neurons were found in all subregions of the middle temporal area (MT) as well as in the medial superior temporal area (MST). Antidromic latencies ranged from 0.9 to 6 ms with a median of 1.8 ms. There was a strong bias in the population of cortical neurons projecting to the NOT-DTN for ipsiversive stimulus movement (towards the recording side), whereas in the population of cortical neurons not projecting to the NOT-DTN a more or less equal distribution of stimulus directions was evident. Our data indicate that there is no special area in the posterior STS coding for ipsiversive horizontal stimulus movement. Instead, a specific selection of cortical neurons from areas MT and MST forms the projection to the NOT-DTN and as a subpopulation has the same directional bias as their subcortical target neurons. These findings are discussed in relation to the functional grouping of cortical output as an organizational principle for specific motor responses.

Animals↗
PubMed2001

Regulation and possible function of beta-catenin in human monocytes.

In this study, we demonstrate that adherence factors, serum constituents, LPS, and zymosan are capable of inducing a cellular accumulation of beta-catenin in human monocytes. Whereas adherence-dependent accumulation of beta-catenin can be blocked by wortmannin, an inhibitor of phosphatidylinositol 3-kinase, accumulation induced by the remaining stimuli cannot be prevented by inhibition of phosphatidylinositol 3-kinase, implying the involvement of beta-catenin in other not yet described signal transduction pathways. A role of beta-catenin in adherence-dependent processes by interacting with classical cadherins can be excluded as we could not detect cadherins in monocytes. To test whether it is possible that beta-catenin interacts with LEF/TCF (lymphoid enhancer factor/T cell factor) transcription factors, we studied the expression of this protein family. TCF-4 was identified as the LEF/TCF transcription factor present in human monocytes. However, neither cellular induction of beta-catenin nor cotransfection experiments with beta-catenin conducted in the monocytic cell line THP-1 resulted in the activation of a LEF/TCF-dependent promoter, suggesting the requirement of additional signals. Concurrent with this suggestion, we found that LPS and zymosan, two physiological inducers of beta-catenin, caused an increase in the expression of genes that are positively regulated by beta-catenin.

Androstadienes↗
PubMed2001

Neural correlates of chromatic motion perception.

A variety of psychophysical and neurophysiological studies suggest that chromatic motion perception in the primate brain may be performed outside the classical motion processing pathway. We addressed this provocative proposal directly by assessing the sensitivity of neurons in motion area MT to moving colored stimuli while simultaneously determining perceptual sensitivity in nonhuman primate observers. The results of these studies demonstrate a strong correspondence between neuronal and perceptual measures. Our findings testify that area MT is indeed a principal component of the neuronal substrate for color-based motion processing.

Animals↗
PubMed2001

beta(1)-Adrenoceptor antibodies induce positive inotropic response in isolated cardiomyocytes.

beta(1)-Adrenoceptor autoantibodies are present in approximately 30% of patients suffering from dilated cardiomyopathy. The inotropic effects mediated by these antibodies remain to be studied. Monoclonal antibodies were raised against a peptide corresponding to the second extracellular loop of the human beta(1)-adrenoceptor in balb/C mouse (n=6), and were characterized by enzyme immunoassay after purification by protein A. Purified immunoglobulin G from non-immunized animals (controls) did not influence Ca(2+) transient and cell shortening of rat cardiomyocytes measured by confocal-laser-scanning-microscopy. beta(1)-adrenoceptor antibodies caused a dose-related increase in Ca(2+) transient (dilution 1:2: +35.3+/-5.1%), and in cell shortening (dilution 1:2: +40.5+/-6.3%) (P<0.01 vs. controls). The effect of the beta(1)-adrenoceptor antibodies was blocked by the antigenic peptide and by the antagonist metoprolol. In addition, beta(1)-adrenoceptor antibodies induced a dose-dependent increase of the cyclic adenosine monophosphate. The inotropic response induced by isoproterenol was attenuated by the beta(1)-adrenoceptor antibody. beta(1)-adrenoceptor antibodies as partial agonists induce a specific positive inotropic effect via the protein-kinase-A-cascade.

Adrenergic beta-Agonists↗
PubMed2001

Aza analogues of thalidomide: synthesis and evaluation as inhibitors of tumor necrosis factor-alpha production in vitro.

A synthetic entry to derivatives of the new classes of 5-phthalimidouracils and 5-phthalimidobarbituric acids is reported. These 5-phthalimidopyrimidines as well as phthalimido-2,4-difluorobenzenes were designed as analogues of thalidomide, a well known inhibitor of TNF-alpha production. A preliminary in vitro investigation of the compounds as inhibitors of the TNF-alpha production was performed. Among the compounds of the present series, 5-ethyl-1-phenyl-5-(tetrafluorophthalimido)barbituric acid and 2-(2,4-difluorophenyl)-4,5,6,7-tetrafluoro-1H-isoindole-1,3(2H)-dione were proved to be potent inhibitors. Both compounds showed inhibitory activity in the lower micromolar range on the LPS-induced TNF-alpha production in human monocytes.

Aza Compounds↗
PubMed2001

Speed skills: measuring the visual speed analyzing properties of primate MT neurons.

Knowing the direction and speed of moving objects is often critical for survival. However, it is poorly understood how cortical neurons process the speed of image movement. Here we tested MT neurons using moving sine-wave gratings of different spatial and temporal frequencies, and mapped out the neurons' spatiotemporal frequency response profiles. The maps typically had oriented ridges of peak sensitivity as expected for speed-tuned neurons. The preferred speed estimate, derived from the orientation of the maps, corresponded well to the preferred speed when moving bars were presented. Thus, our data demonstrate that MT neurons are truly sensitive to the object speed. These findings indicate that MT is not only a key structure in the analysis of direction of motion and depth perception, but also in the analysis of object speed.

Action Potentials↗
PubMed2000

A possible role of N-cadherin in thalidomide teratogenicity.

Several experimental findings indicate that the adhesion molecule N-cadherin participates in distinct processes of embryogenesis that spatiotemporarily correlate with high sensitivity to thalidomide. Therefore, we suppose that thalidomide might interfere with N-cadherin-mediated interactions. This hypothesis is supported by protein-ligand docking studies simulating and characterizing the binding of thalidomide to N-cadherin molecules. Thalidomide was found to bind at the N-terminal domain of N-cadherin mimicking a tryptophan residue which is critical for the homodimerization of the adhesion molecule. Based on these results, we suggest that thalidomide might disturb cellular recognition and migration processes in morphogenesis by interaction with N-cadherin.

Abnormalities, Drug-Induced↗