PubMed Health⌕ Search

Biomedical subjects

Peter König

Publications and source records attributed to Peter König.

13 recordsLinked to original sources
PubMed2002

Cellular localization of the endothelin receptor subtypes ET(A) and ET(B) in the rat heart and their differential expression in coronary arteries, veins, and capillaries.

In the heart, the endothelin (ET)/endothelin-receptor system is markedly involved in pathophysiological mechanisms underlying various cardiac diseases. Based upon pharmacological studies both ET-receptor subtypes take part in the regulation of coronary vascular tone, however, their detailed cellular distribution in the coronary vascular bed based upon direct mRNA and protein detection is unknown. This issue was addressed in the rat heart by means of non-radioactive in situ hybridization, RT-PCR, and immunohistochemistry. Expression of vascular ET(A)-receptors was detected in arterial smooth muscle and capillary endothelium while ET(B)-receptors were present in arterial, venous, and capillary endothelium, and in arterial and venous smooth muscle cells. This differential distribution of the ET-receptor subtypes supports the concept that ET(A)- as well as ET(B)-receptors mediate arterial vasoconstriction, while postcapillary vascular resistance is exclusively regulated by ET(B)-receptors. The observed capillary endothelial expression of the ET(A)-receptor correlates with the known ability of ET(A)-receptor antagonists to attenuate increases in cardiac microvascular permeability during endotoxin shock and ischemia/reperfusion injury.

Animals↗
PubMed2002

Apical, but not basolateral, endotoxin preincubation protects alveolar epithelial cells against hydrogen peroxide-induced loss of barrier function: the role of nitric oxide synthesis.

The influence of LPS preincubation on hydrogen peroxide (H(2)O(2))-induced loss of epithelial barrier function was investigated in rat alveolar epithelial type II cells (ATII). Both apical and basolateral H(2)O(2) administration caused a manyfold increase in transepithelial [(3)H]mannitol passage. Apical but not basolateral preincubation of ATII with LPS did not influence control barrier properties but fully abrogated the H(2)O(2)-induced leakage response. The effect of apical LPS was CD14 dependent and was accompanied by a strong up-regulation of NO synthase II mRNA and protein and NO release. Inhibition of NO by N(G)-monomethyl-L-arginine suppressed the LPS effect, whereas it was reproduced by exogenous application of gaseous NO or NO donor agents. Manipulation of the glutathione homeostasis (buthionine-(S,R)-sulfoximine) and the cGMP pathway (1H-(1,2,4)oxadiazolo[4,3-alpha]quinoxaline-1-one; zaprinast) did not interfere with the protective effect of LPS. Superoxide (O*(-)(2)) generation by ATII cells was reduced by exogenous NO and LPS preincubation. O*(-)(2) scavenging with exogenous superoxide dismutase, the intracellular superoxide dismutase analog Mn(III)tetrakis(4-benzoic acid) porphyrin, and the superoxide scavenger nitroblue tetrazolium and, in particular, hydroxyl radical scavenging with hydroxyl radical scavenger 1,3-dimethyl-thiourea inhibited the H(2)O(2)-induced epithelial leakage response. In conclusion, apical but not basolateral LPS preincubation of ATII cells provides strong protection against H(2)O(2)-induced transepithelial leakage, attributable to an up-regulation of epithelial NO synthesis. It is suggested that the LPS-induced NO formation is effective via interaction with reactive oxygen species, including superoxide and hydroxyl radicals. The polarized epithelial response to LPS may be part of the lung innate immune system, activated by inhaled endotoxin or under conditions of pneumonia.

Animals↗
PubMed2002

Combining high and low frequencies in rTMS antidepressive treatment: preliminary results.

The antidepressive potency of repetitive transcranial magnetic stimulation (rTMS) seems to depend on variables such as the stimulation placements, different frequencies, stimulus intensities, coil shape and interstimulus intervals. The aim of this pilot study was to investigate the augmentation properties of rTMS combining low and high frequencies. Thirty six depressed medicated in-patients were recruited and assigned to three different rTMS treatment modalities as an add-on strategy (each n = 12). In group 1 a stimulus intensity of 110% of the motor threshold (MT) was used with a frequency of 10 Hz over the left dorsolatero prefrontal cortex (DLPC). The right DLPC was stimulated in the same session with 110% MT at 1 Hz. In group 2 the patients were stimulated only over the left DLPC with alternating trains of 110% MT at 10 Hz and trains of 110% MT at 1 Hz in the same session. In group 3 the high frequency stimulation over the left DLPC was performed as an internal control group. None of the treatment modalities was superior but different side effects were observed. These preliminary findings suggest that rTMS, at varying frequencies and stimulation placements, evokes different psychoactive effects of clinical relevance.

Depressive Disorder↗
PubMed2002

Irreversible airway obstruction in childhood asthma? A clinician's viewpoint.

Even though childhood asthma is assumed to comprise reversible airway obstruction, some children develop irreversible airway obstruction (not reversed by a bronchodilator or corticosteroids); this may be due to inflammation that has caused remodeling. Lately, it has been claimed that in the absence of treatment with inhaled corticosteroids, most patients will develop progressive irreversible obstruction. Several studies culminating with the Childhood Asthma Management Program (CAMP) study, which was the first randomized placebo-controlled prospective long-term study designed to test for irreversible obstruction, did not show the development of such progressive irreversible obstruction. Nevertheless, deterioration in pulmonary function does occur in some patients, probably due to inadequate anti-inflammatory treatment, and possibly also due to maintenance adrenergic treatment. Most previous studies concentrated on forced expiratory volume in 1 sec (FEV(1)), a test assessing mostly large airway obstruction. More studies are needed to investigate the presence of small airway obstruction.

Airway Obstruction↗
PubMed2002

Sensory neurons respond to hypoxia with NO production associated with mitochondria.

Oxygen is pivotal for mammalian cell function, and recent studies suggest an involvement of NO in cellular adaptation to low oxygen supply. Here, we report that endothelial NO-synthase is ubiquitously expressed in rat and mice sensory neurons, and is targeted to juxtamitochondrial compartments of the ER. There it is activated in response to hypoxia while generation of reactive oxygen species remains unaltered. Developing a technique for ultrastructural localization of an NO-sensitive indicator allowed to identify the inner mitochondrial membrane as the target of NO under hypoxia. The demonstrated hypoxic stimulation of endothelial NOS in sensory neurons shall contribute to resistance against hypoxia, since NO promotes cellular survival by interfering with mitochondrial function.

Animals↗
PubMed2002

Learning the invariance properties of complex cells from their responses to natural stimuli.

Neurons in primary visual cortex are typically classified as either simple or complex. Whereas simple cells respond strongly to grating and bar stimuli displayed at a certain phase and visual field location, complex cell responses are insensitive to small translations of the stimulus within the receptive field [Hubel & Wiesel (1962) J. Physiol. (Lond.), 160, 106-154; Kjaer et al. (1997) J. Neurophysiol., 78, 3187-3197]. This constancy in the response to variations of the stimuli is commonly called invariance. Hubel and Wiesel's classical model of the primary visual cortex proposes a connectivity scheme which successfully describes simple and complex cell response properties. However, the question as to how this connectivity arises during normal development is left open. Based on their work and inspired by recent physiological findings we suggest a network model capable of learning from natural stimuli and developing receptive field properties which match those of cortical simple and complex cells. Stimuli are drawn from videos obtained by a camera mounted to a cat's head, so they should approximate the natural input to the cat's visual system. The network uses a competitive scheme to learn simple and complex cell response properties. Employing delayed signals to learn connections between simple and complex cells enables the model to utilize temporal properties of the input. We show that the temporal structure of the input gives rise to the emergence and refinement of complex cell receptive fields, whereas removing temporal continuity prevents this processes. This model lends a physiologically based explanation of the development of complex cell invariance response properties.

Animals↗
PubMed2002

Distribution of the novel eNOS-interacting protein NOSIP in the liver, pancreas, and gastrointestinal tract of the rat.

BACKGROUND & AIMS: Recently, a yeast 2-hybrid screen served to identify a new endothelial nitric oxide synthase (eNOS)-interacting protein (NOSIP), which causes redistribution of eNOS from the plasma membrane to intracellular compartments and reduces eNOS activity. Its in situ distribution is unknown and is reported here in comparison with that of eNOS and neuronal NOS for the rat gastrointestinal tract. METHODS: Immunofluorescence was performed on acetone-fixed cryosections by using a polyclonal antiserum raised against a NOSIP-glutathione S-transferase fusion protein; specificity was verified by Western blotting. RESULTS: Cytoplasmic NOSIP immunoreactivity was observed in endothelial cells of some locations, e.g., the hepatic central vein, but it was mainly observed in the striated esophageal muscle; vascular, gastric, and intestinal smooth muscle; and in interstitial cells of Cajal. Nuclear NOSIP immunoreactivity was more widespread, including some myenteric neurons and several epithelial cell types of esophagus, stomach, pancreas, liver, and gut. This cellular distribution matched with that of its potential binding partner eNOS, as determined by immunohistochemistry and reduced nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry, and eNOS, but not neuronal NOS, could be coimmunoprecipitated with NOSIP from small intestine. CONCLUSIONS: NOSIP coimmunoprecipitates and is widely codistributed with eNOS in nonvascular cells in the gastrointestinal tract, suggesting an involvement of eNOS/NOSIP in the regulation of gastrointestinal secretion and motility.

Animals↗
PubMed2002

Effect of chronic repetitive transcranial magnetic stimulation on regional cerebral blood flow and regional cerebral glucose uptake in drug treatment-resistant depressives. A brief report.

Brain imaging studies have shown that repetitive transcranial magnetic stimulation (rTMS) is biologically active. The aim of the present study was to investigate the patterns of the regional cerebral glucose uptake rate (rCMRGlu) and regional (99m)Tc HMPAO uptake rate (regional cerebral blood flow; rCBF) during a series of therapeutic rTMS sessions at low frequency. Four drug-resistant depressed patients underwent 10 rTMS sessions as an add-on measure over 14 days. One day before and 1 day after the TMS series, 511-keV SPECT with simultaneous (18)F-fluorodeoxyglucose and (99m)Tc HMPAO measurements were carried out. All patients showed a good clinical outcome. Statistically significant common changes in rCBF and rCMRGlu patterns were found in the upper frontal regions bilaterally in terms of increased uptake rates and in the left orbitofrontal cortex in terms of decreased uptake rates of both isotopes compared to controls. However, the lateralization patterns of rCBF and rCMRGlu after rTMS treatment revealed marked differences. Thus, although no relevant changes in lateralization of the glucose uptake were observed, a clear right-sided preponderance of rCBF also in areas remote from the stimulation site was described. Therapeutic rTMS seems to influence distinct cortical regions, affecting rCBF and rCMRGlu in a homogeneous manner as well as in different ways, which are probably region dependent and illness related. The role of the stimulation coil placement site should be taken into account.

Adult↗
PubMed2000

Clinical impacts of single transcranial magnetic stimulation (sTMS) as an add-on therapy in severely depressed patients under SSRI treatment.

Research on single and rapid transcranial magnetic stimulation (sTMS/rTMS) indicates an antidepressive efficacy of these methods. In our 4 week study of sTMS, 12 patients affected by severe non-psychotic major depression (DSM-III-R) were enrolled and put on standardized combined antidepressant medication with the serotonin re-uptake inhibitor citalopram, and the serotonin modulating drug, trazodone. They underwent sTMS in a specific method as an add-on therapy. Age, gender, illness and episode duration, episode number, Hamilton Rating Depression Scale-24 (HRDS), Mini-Mental State (MMS), drug levels assessed by HPLC, magnesium and thyroid stimulating hormone (TSH) were recorded. For each patient functional brain imaging was performed by (18)FDG and (99m)Tc HMPAO SPECT at the beginning of the study, as were EEG tracings which also were recorded at the end. Lorazepam was allowed as co-medication. Of the patients, 66.7 per cent (N=8) could be identified as sTMS responders. Possible predictors for sTMS response as add-on therapy may be duration, pattern of improvement in global and in specific single items of the HRDS, lorazepam dosage, functional involvement of basal ganglia and cortical temporal lobe and the initially lower mean frequency and lability of the alpha-activity of EEG. These variables possibly predict the clinical outcome of depressed patients treated by sTMS as an add-on therapy. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗
PubMed1990

Stimulus-Dependent Neuronal Oscillations in Cat Visual Cortex: Inter-Columnar Interaction as Determined by Cross-Correlation Analysis.

We have demonstrated previously that neurons in cat striate cortex, in response to their preferred stimuli, exhibit oscillatory responses in a frequency range of 40 - 60 Hz. Recently, we obtained evidence that such oscillatory responses can synchronize across columns. We have now performed an extensive analysis of this phenomenon for both unit and field potential responses. In addition, we studied the stimulus conditions leading to intercolumnar synchronization. We recorded both multi-unit activity and local field potentials from area 17 of adult cats with arrays of several electrodes. Interelectrode distances ranged from 0.4 to 12 mm. For all pairs of unit (n=200) and field potential (n=174) recordings, we computed auto- and cross-correlation functions. The modulation of the correlograms was quantified by fitting a damped sine wave (Gabor) function to the data. Cross-correlation analysis of the unit data revealed that in 90 out of 200 cases the recorded cells established a constant phase-relationship of their oscillatory responses. This occurred, on average, with no phase difference. If the receptive fields were nonoverlapping, we observed a synchronization primarily between cells with similar orientation preferences. Cells with overlapping receptive fields also showed a high incidence of synchronization if their orientation preferences were different. In this latter group, synchronization occurred even in cases where the stimulus was optimal for only one of the recording sites. Under conditions of monocular instead of binocular stimulation the oscillatory modulation of the responses was attenuated, but the cross-correlogram still indicated a significant interaction. Similar effects were seen with the application of stationary instead of moving stimuli. A synchronization of oscillatory field potential responses was observed in 136 out of 174 paired recordings. At all distances investigated, the probability of synchronization of field potential responses was independent of the orientation preferences of the cells. However, the strength of interaction decreased with increasing spatial separation. Control experiments showed that the synchronization of field potential responses was not due to volume conduction. The results demonstrate that oscillatory responses at separate cortical sites can transiently synchronize. The probability and strength of synchronization are dependent on the spatial separation of the recorded cells and their orientation preferences. In addition, the cross-columnar synchronization is influenced by features of the visual stimulus. It is suggested that this synchronization provides a mechanism for the formation of neuronal assemblies in the visual cortex.

Journal Article↗
PubMed1990

Stimulus-Dependent Neuronal Oscillations in Cat Visual Cortex: Receptive Field Properties and Feature Dependence.

Previously we have demonstrated that neurons in the striate cortex of lightly anaesthetized cats exhibit oscillatory responses at a frequency near 50 Hz in response to their preferred stimuli. Here we have used both single and multiple unit recording techniques to determine: (i) the receptive field properties and laminar distribution of cells exhibiting oscillatory responses; and (ii) the influence of changing stimulus properties on the temporal behaviour of the oscillatory responses. Oscillatory responses were detected and evaluated by computation of the autocorrelation function of the neuronal spike trains. We recorded oscillatory responses in 56% of the standard complex cells and in 12% and 11% of the simple and special complex cells. Cells exhibiting oscillatory responses were located primarily in supra- and infragranular layers. The oscillatory modulation amplitude of the autocorrelation function was enhanced by binocular stimulation (9 out of 16 cells) and reduced by combined stimulation with optimal and orthogonally orientated light bars (16 out of 21 cells). Changing stimulus orientation caused no change in the oscillation frequency of the sampled population of cells, while oscillation frequency increased monotonically with respect to stimulus velocity within the range of 1 - 12 degrees per second (10 out of 11 cells). The oscillatory modulation of the autocorrelation function increased as a function of stimulus length within the boundary of the cell's receptive field (11 out of 11 cells). In 6 out of these 11 cells, the responses did not show an oscillatory modulation if elicited by small moving spots of light. Moving stimuli were much more effective in evoking oscillatory responses than were stationary stimuli (19 out of 20 cells). In no instance, using either stationary or moving stimuli, was the phase of the oscillatory response synchronized with the stimulus. These results demonstrate functional heterogeneity among cells within striate cortex based on their temporal firing patterns and provide evidence that the temporal pattern of oscillatory cellular activity is influenced by changes in stimulus properties.

Journal Article↗