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Biomedical subjects

C Braun

Publications and source records attributed to C Braun.

At least 55 records · Page 3Linked to original sources
PubMed2000

Distribution of mislocalizations of tactile stimuli on the fingers of the human hand.

Sensitivity of the fingers of the two hands to faint tactile stimuli were tested in eight healthy subjects with a von Frey hair in a forced choice point localization test. Frequencies of correct responses were higher on the left than on the right hand, consistent with a right hemispheric advantage for spatial processing. Within the hands, stimulations of the ring fingers resulted in the highest percentage of correct localizations and stimulations of the thumbs in the fewest correct responses. This superiority of the ring fingers is probably related to a higher point pressure sensitivity and does not reflect the relative size of the representational area of the different fingers in the somatosensory cortex. Mislocalizations, i.e., stimuli that were not correctly attributed to the stimulation site, were located in the vicinity of the stimulation site within the finger as well as across fingers. The distribution of mislocalization across fingers deviates from a distribution expected by chance, showing a higher frequency of mislocalizations to the neighboring fingers than to more distant fingers. This observation in humans matches well with electrophysiological evidence from animal studies that some primary somatosensory cortex neurons have receptive fields that are not restricted to a single digit, but rather cover neighboring digits.

Adult↗
PubMed2000

Improvement of renal dysfunction in rats with chronic heart failure after myocardial infarction by treatment with the endothelin A receptor antagonist, LU 135252.

OBJECTIVE: To investigate the role of an activated endothelin system in the renal dysfunction observed in chronic heart failure after myocardial infarction. METHODS: In rats with heart failure after myocardial infarction and in sham-operated animals (Sham), we investigated the effect on renal function of long-term oral treatment with the selective endothelin A (ETA) receptor antagonist, LU 135252 (30 mg/kg per day; groups MI/LU and Sham/LU) or placebo (groups MI/P, Sham/P). Only animals with extensive myocardial infarction (at least 46% of the left ventricle) were included in the study. Infarct size was matched between groups MI/P and MI/LU. Endogenous creatinine clearance, fractional sodium excretion, and plasma and urinary concentrations of endothelin were determined 12 weeks after myocardial infarction. RESULTS: Endogenous creatinine clearance was significantly lower in group MI/P than in group Sham/P (MI/P: 0.64 +/- 0.05, Sham/P: 0.81 +/- 0.04 ml/min per 100 g body weight; P= 0.01 (means +/- SEM)). Treatment with LU 135252 completely prevented the decline in creatinine clearance in rats with chronic myocardial infarction (MI/LU: 0.98 +/- 0.21; Sham/LU: 0.83 +/- 0.10). Fractional sodium and protein excretion did not differ among the four groups. Group MI/P had a marked increase in plasma endothelin concentrations, which was not affected by treatment with LU 135252. Urinary endothelin excretion was significantly lower in group MI/P than in group Sham/P. In the treatment groups, no difference could be observed between animals that had suffered myocardial infarction and the sham-operated group, although LU 135252 markedly increased the urinary excretion of endothelin. CONCLUSION: Our data demonstrate a restoration of impaired renal function in chronic ischaemic heart failure by treatment with the selective ETA receptor antagonist, LU 135252. These results offer a promising therapeutic option for the treatment of renal insufficiency in patients with chronic heart failure.

Animals↗
PubMed2000

Treatment with a combined endothelin A/B-receptor antagonist does not prevent chronic renal allograft rejection in rats.

A markedly increased expression of endothelin (ET)-1 has been observed in renal allografts with chronic rejection, one of the most common causes of kidney graft loss. In this study we investigated the effect of treatment with a combined ET-A/B-receptor antagonist on the course of chronic renal allograft rejection. Experiments were performed in the Fisher-to-Lewis rat model of chronic rejection. Lewis-to-Lewis isografts and uninephrectomized Lewis rats served as controls. Animals were treated with either the oral combined ET-A/B-receptor antagonist LU224332 (20 mg/kg/day) or vehicle. Animal survival, blood pressure, creatinine clearance, proteinuria, and urinary ET excretion were investigated for 24 weeks. Kidneys were removed for light-microscopic evaluation and immunohistochemical assessment of cell-surface markers. Treatment with LU224332 did not improve survival after 24 weeks (0.47 vs. 0.38; p > 0.05 by log-rank test), nor did it have an influence on blood pressure, creatinine clearance, or proteinuria. Combined ET-A/B-receptor blockade was associated with a reduction of expression of cell-surface markers for macrophages (EDI), T-cells (R73), and major histocompatibility complex (MHC) II (F17-23-2), but did not lead to an improvement of histologic changes of chronic allograft rejection. Our data show that blocking both ET-A- and -B receptors, in opposition to a previously published beneficial effect of selective ET-A blockade, does not prevent the progression of chronic renal allograft rejection and does not prolong survival in this model. Functional integrity of the ET-B receptor therefore seems to play an important role in the nephroprotection provided by selective ET-A-receptor antagonists in chronic renal allograft nephropathy.

Animals↗
PubMed2000

Independent autonomic modulation of sinus node and ventricular myocardium in healthy young men during sleep.

INTRODUCTION: The aim of this study was to investigate whether autonomic modulation of ventricular repolarization may spontaneously differ from that of the sinoatrial node. METHODS AND RESULTS: Onset of P waves, QRS complexes, and the apex and end of T waves were detected beat to beat in high-resolution ECGs from nine healthy young men during the night. There were time-dependent fluctuations in the QT/RR slopes of consecutive 5-minute segments that could not be explained by the mean RR cycle length of the respective segment. Because the variability found in QT intervals could not be explained by either possible effects of rate dependence or hysteresis, autonomic effects were obvious. Power spectral analysis was performed for consecutive 5-minute segments of PP and QT tachograms. In a given subject, trends in the time course of low-frequency (LF) and high-frequency (HF) power in PP and QT often were similar, but they were quite different at other times. The mean LF/HF ratio for QTend (0.75 +/- 0.1) was different from that of PP (1.8 +/- 0.2; P = 0.002), indicating differences in sympathovagal balance at the different anatomic sites. Furthermore, at a given mean heart rate, averaged QT intervals were different on a time scale of several minutes to hours. The QT/RR slope of 5-minute segments correlated significantly with the HF power of QT variability but not with that of PP variability, indicating effects of the autonomic nervous system on ventricular action potential restitution. CONCLUSION: These differences demonstrate that changes in sinus node automaticity are not necessarily indicative of the autonomic control of ventricular myocardium.

Adult↗
PubMed2000

The renoprotective potential of endothelin receptor antagonists.

The endothelin system has been identified as having a substantial role in renal failure, both acute and chronic. Beside its well characterised haemodynamic effects, its mitogenic and pro-fibrotic properties have gained increased interest in the pathophysiology of chronic renal failure. This review outlines the role of endothelin in the pathogenesis of various renal diseases with a special focus on the potential of blocking this system with endothelin receptor antagonists. So far, most data were derived from animal models, but they provide strong evidence that endothelin receptor antagonists may represent a powerful therapeutic strategy in ameliorating the course of acute and chronic renal failure.

Animals↗
PubMed1999

Prevention of chronic renal allograft rejection in rats with an oral endothelin A receptor antagonist.

BACKGROUND: Chronic rejection is the most common cause of graft loss in renal transplantation. The pathomechanisms underlying chronic rejection are poorly understood, and no treatment has yet successfully been established. We hypothesized that, in analogy to models of reduced renal mass, the administration of a selective endothelin (ET) A receptor antagonist could improve the course of chronic rejection in renal allografts. METHODS: Experiments were performed in the Fisher-to-Lewis rat model of chronic rejection. Lewis-->Lewis isografts served as controls. Animals were treated with either the oral selective ET-A receptor antagonist LU135252 (50 mg/kg/day) or vehicle. Animal survival, blood pressure, creatinine clearance, proteinuria, and urinary ET excretion were investigated for 24 weeks. Kidneys were removed for light microscopical evaluation, determination of ET mRNA expression and tissue protein concentration, and immunohistochemical assessment of cell surface markers. RESULTS: Rats with chronic rejection showed an increase in renal ET mRNA synthesis and ET protein content. Treatment with LU135252 resulted in a significant improvement in survival after 24 weeks (0.92 vs. 0.38, P<0.01 by log-rank test). Creatinine clearance was higher in animals treated with the selective ET-A receptor antagonist (P<0.05). LU135252 had no influence on blood pressure and proteinuria. Selective ET-A blockade was associated with significantly less morphological changes and a significant reduction of expression of cell surface markers for macrophages (ED1), T cells (R73), and MHC II (F17-23-2). CONCLUSION: The renal ET-A system plays an important role in the pathomechanisms underlying chronic renal allograft rejection, because the treatment with a selective ET-A receptor antagonist dramatically improves the course of chronic renal failure after allograft transplantation. These results offer a novel therapeutical option for treatment of chronic renal allograft rejection, for which so far no therapy is known.

Administration, Oral↗
PubMed1999

CAPN 8: isolation of a new mouse calpain-isoenzyme.

Recent molecular biological approaches indicate that calpain, also named CANP for calcium-activated neutral protease and originally characterized as an intracellular cytoplasmatic nonlysosomal cysteine protease that requires calcium ions for activity, constitutes a large superfamily consisting of ubiquitous and tissue specific homologues, which are widely distributed in cells of various organisms from human to fungus. Due to the increasing number of substrates along with the involvement of calpain isoenzymes in mammalian diseases, especially in malignancies, members of the calpain superfamily seem to be important biomodulators in physiological as well as pathological cell function. Here we report the characterisation of a new calpain, named CAPN 8 with a different C-terminal domain, implicating a putative new regulatory mechanism. Northern blot analysis revealed an ubiquitous expression with different RNA levels in all tissues examined. Highest levels were found in brain, kidney, and digestive tract, suggesting a specific regulatory function of CAPN 8 in these tissues.

Amino Acid Sequence↗
PubMed1999

Gamma-band MEG activity to coherent motion depends on task-driven attention.

We examined gamma-band magnetoencephalographic (MEG) activity in humans manipulating attention to visual stimuli by auditory distractors. After exposure to both visual and auditory noise (a baseline), subjects attended to the first of two stimuli (either regular motion of bars or a tone sequence) presented asynchronously, and responded to its offset. A spectral power analysis revealed an increased, relative to baseline, 40 Hz MEG response to attended coherent motion. The enhancement occurred within the initial 50-250 ms from motion onset over modality-specific (occipital) cortices. The increase was not observed when attention was captured by auditory distractors. Our findings suggest that 40 Hz activity in the human visual cortex is related to integration of featural information that is supported by attention.

Acoustic Stimulation↗
PubMed1999

Expression of calpain I messenger RNA in human renal cell carcinoma: correlation with lymph node metastasis and histological type.

Calpain, also named CANP (for calcium-activated neutral protease), is an intracellular cytoplasmatic non-lysosomal cysteine endopeptidase that requires calcium ions for activity. Many substrates of the calpain isoenzymes, such as the transcription factors c-Fos and c-Jun, the tumor supressor protein p53, protein kinase C, pp60c-src and the adhesion molecule integrin, have been implicated in the pathogenesis of different human tumors, suggesting an important role of the calpains in malignant diseases. We now report differential expression of the calpain I gene (CL I) in a variety of tumors, extending our study to a larger series of renal cell carcinomas. Using Northern-blot analysis, we studied calpain I expression in 30 renal cell carcinomas as compared with matched healthy tissues. Tumor samples were classified according to their histological type: 21 clear cell carcinomas, 4 chromophobe carcinomas, 3 papillary carcinomas and 2 oncocytomas. In renal tumor samples, calpain I gene mRNA was expressed at highly variable levels, significantly depending on the different histological types. Moreover, there was a correlation of higher calpain I expression with increased malignancy: within the clear cell carcinoma subset, tumor samples with advanced nodal status (N1 and N2) showed a significantly higher calpain I expression than tumors without metastasis to regional lymph nodes. Our data suggest an important role of calpain isoenzymes in carcinogenesis and tumor progression.

Biomarkers, Tumor↗
PubMed1999

Coherence of gamma-band EEG activity as a basis for associative learning.

Different regions of the brain must communicate with each other to provide the basis for the integration of sensory information, sensory-motor coordination and many other functions that are critical for learning, memory, information processing, perception and the behaviour of organisms. Hebb suggested that this is accomplished by the formation of assemblies of cells whose synaptic linkages are strengthened whenever the cells are activated or 'ignited' synchronously. Hebb's seminal concept has intrigued investigators since its formulation, but the technology to demonstrate its existence had been lacking until the past decade. Previous studies have shown that very fast electroencephalographic activity in the gamma band (20-70 Hz) increases during, and may be involved in, the formation of percepts and memory, linguistic processing, and other behavioural and perceptual functions. We show here that increased gamma-band activity is also involved in associative learning. In addition, we find that another measure, gamma-band coherence, increases between regions of the brain that receive the two classes of stimuli involved in an associative-learning procedure in humans. An increase in coherence could fulfil the criteria required for the formation of hebbian cell assemblies, binding together parts of the brain that must communicate with one another in order for associative learning to take place. In this way, coherence may be a signature for this and other types of learning.

Adult↗
PubMed1999

Modeling extended sources of event-related potentials using anatomical and physiological constraints.

For the study of functional organization and reorganization of the human cortex by means of electromagnetic source imaging, a measure of the location and spatial extent of neural sources is of interest. This study evaluates the cortical patch method (CPM), an iterative procedure introduced by Lütkenhöner et al. [1995] that models EEG/MEG activity by means of extended cortical patches. Anatomical information is used to constrain estimates of location and extent of neural sources that generate the measured evoked potential. Whereas minimum norm approaches use mathematical constraints to solve the ambiguity of the inverse problem, the CPM introduces constraints based on anatomical and physiological knowledge about neural mass activity. In order to test the proposed method, the simulated activity in an artificial sulcus was subjected to the CPM. The results show that even activity on opposing walls of a sulcus can be well reconstructed. The simulations demonstrate the usefulness and limits of the CPM in estimating the spatial extent of neural sources in the cerebral cortex. As an example, an application of the method on experimental somatosensory evoked potentials is presented in the Appendix.

Brain↗
PubMed1999

[Technique of finger arthrodesis by dorsal thread tension band fixation. Comparing biomechanical investigations].

Dorsal tension band fixation is a wide-spread technique of finger arthrodesis. When using a resorbable PDS-suture as tension band fixation a costly implant removal is not needed. Aim of this study is the investigation of the primary stability of this technique in combination with the cup-in-cone-procedure. Freeze-preserved fingers with thread tension band fixation using the PDS-material (series 1), the same fixating method on formaldehyde preserved fingers (series 3), freeze-preserved fingers with a standard tension band fixating (wire loop, series 2) are load in a four-point-bending in the direction of palmarflexion. From 6 degrees onwards the wire-tension-system requires a higher torque for bending, but in case of higher torque frequently leads to fracture. The examination shows that the thread-tension-band method by PDS-loop for the stabilisation of finger joint arthrodesis has a sufficient initial stability against bending forces.

Adult↗
PubMed1999

The polar average reference effect: a bias in estimating the head surface integral in EEG recording.

A reference-independent measure of potential is helpful for studying the multichannel EEG. The potentials integrated over the surface of the body is a constant, i.e. inactive across time, regardless of the activity and distribution of brain electric sources. Therefore, the average reference, the mean of all recording channels at each time point, may be used to approximate an inactive reference. However, this approximation is valid only with accurate spatial sampling of the scalp fields. Accurate sampling requires a sufficient electrode density and full coverage of the head's surface. If electrodes are concentrated in one region of the surface, such as just on the scalp, then the average is biased toward that region. Differences from the average will then be smaller in the center of the region, e.g. the vertex, than at the periphery. In this paper, we illustrate how this polar average reference effect (PARE) may be created by both the inadequate density and the uneven distribution of EEG electrodes. The greater the coverage of the surface of the volume conductor, the more the average reference approaches the ideal inactive reference.

Brain↗
PubMed1999

Receiver operating characteristics of perceptrons: influence of sample size and prevalence.

In many practical classification problems it is important to distinguish false positive from false negative results when evaluating the performance of the classifier. This is of particular importance for medical diagnostic tests. In this context, receiver operating characteristic (ROC) curves have become a standard tool. Here we apply this concept to characterize the performance of a simple neural network. Investigating the binary classification of a perceptron we calculate analytically the shape of the corresponding ROC curves. The influence of the size of the training set and the prevalence of the quality considered are studied by means of a statistical-mechanics analysis.

Biophysical Phenomena↗
PubMed1999

Suppression of alcohol intake by chronic naloxone treatment in P rats: tolerance development and elevation of opiate receptor binding.

BACKGROUND: This study was planned to determine the feasibility of using a slow release naloxone preparation to treat alcoholism, because compliance with medication is a significant problem in alcoholics. METHODS: Experiments were performed in alcohol-preferring P rats maintained either on continuous access or on limited access (1 hr/day) to alcohol with water and food provided ad libitum. Naloxone (Nx) was administered either by twice daily subcutaneous injections or by slow release (1.1 mg/kg/hr) osmotic minipump. In limited access experiments, Nx was injected immediately before access to alcohol. RESULTS: An initial experiment estimated the dose-effect curve for Nx subcutaneous suppression on alcohol intake. Nx (2.5-20 mg/kg) had a stronger effect during the first 2 hr after injection (ED50 = 2.1 mg/kg); however, the effect was more modest on 24-hr consumption. Similar results were found with chronic Nx treatment. Low doses of Nx (0.5 and 2.0 mg/kg) injected immediately before limited access to alcohol produced almost complete suppression of alcohol intake for at least 14 consecutive days. However, 14 days of treatment with 26 mg/kg/day by minipump or injection produced an initial 50% suppression of 24-hr alcohol intake with the gradual development of tolerance. An acute challenge with Nx immediately after the pumps were scheduled to be empty provided additional evidence of tolerance development in chronically Nx-treated rats. Brain micro-opiate receptors, estimated autoradiographically by using the ligand [3H][D-Ala2,N-Me-Phe4, Gly-ol5][tyrosyl-3,5-3H]-enkephalin, showed that rats chronically exposed to Nx and showing tolerance to Nx suppression of drinking exhibited 17% to 250% increases in [3H][D-Ala2,N-Me-Phe4, Gly-ol5][tyrosyl-3,5-3H]-enkephalin binding. CONCLUSIONS: High doses of Nx are required to suppress continuous access alcohol consumption in P rats, and tolerance develops to the ethanol consumption-suppressing effect of Nx that may be related to increases in micro-opiate receptors.

Alcohol Drinking↗
PubMed1999

Detection and follow-up of homonymous visual field defects - perimetric essentials for evaluation of spontaneous recovery.

Clinical detection and follow-up of homonymous visual field defects require appropriate perimetric procedures: since postgeniculate lesions are usually characterised by absolute scotomata, time consuming threshold methods can be replaced by supraliminal strategies with comparatively high stimulus densities. Compared with equidistant rectangular grids, a centripetal stimulus condensation represents the physiological conditions more adequately and thus is more effective. It allows one to differentiate central changes of the visual field, like macular sparing or splitting, which also interfere with reading performance. This procedure requires test points to be located to either side of the vertical meridian, rather than directly on it. Multimodal assessment of visual subfunctions (using static, kinetic or colour test points, random dot patterns or optokinetic stimulation) specifies the effect of the lesion in different channels or regions of the visual pathways. Automation of perimetric procedures and continuous monitoring of fixation are important tools, enhancing the quality of examination and follow-up. The above mentioned psychophysical techniques for detection of functional defects and documentation of eventual recovery, as well as matching neuroimaging findings, are demonstrated by illustrative cases.

Journal Article↗
PubMed1998

Lesion location influences perception of homonymous scotomata during flickering random dot pattern stimulation.

An attempt was made to clarify whether the site of postchiasmal lesions affects subjective perception of homonymous visual field defects during stimulation with flickering random dot patterns (white noise-field). Out of 56 patients with homonymous hemianopia, 38 (68%) perceived scotomata in this situation, but 18 (32%) discerned none at all. Neuroradiologic superposition of cerebral lesions detected by computed tomography (CT) or magnetic resonance imaging (MRI) showed that nearly all patients who perceived their scotomata had lesions involving the primary visual cortex or the perigeniculate region, whereas those who received no scotoma had lesions centered within the optic radiation. Functional MRI of six normal subjects during stimulation with flickering random dot patterns indicated predominant activation of the primary visual cortex. Since noise-field defects were most frequently perceived by patients whose lesion involved the primary visual cortex, it appears that the sensitivity of noise-field campimetry depends on the site of damage in the visual pathway. The explanation for this may be that damage to long-range horizontal connections impairs filling-in processes.

Adolescent↗