Biomedical subjects

C Braun

Publications and source records attributed to C Braun.

At least 19 recordsLinked to original sources

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

[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↗

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↗

PubMed1998

PROMM: the expanding phenotype. A family with proximal myopathy, myotonia and deafness.

We describe a family with a proximal myopathy, subclinical EMG myotonia, cataracts and deafness. Transmission through two generations and down the male line confirms autosomal dominant inheritance. There was no abnormal expansion of the CTG triplet repeat in the last exon of the dystrophia myotonica protein kinase (DMPK) gene associated with myotonic dystrophy. Heteroduplex analysis of all but the promoter region of the DMPK gene has excluded point mutations in this gene as an underlying cause for this myotonic disorder. The family was not sufficiently informative to exclude linkage to the sodium channel gene SCN4A or the chloride channel gene CLC1. This family clearly fulfils the recently established diagnostic criteria for PROMM (proximal myotonic myopathy) and in addition shows consistent severe deafness as a hitherto undescribed feature of PROMM. We discuss the diagnostic criteria of PROMM in relation to this family and other recent papers, all of which would now fulfil the aforementioned diagnostic criteria for PROMM.

Adult↗

PubMed1998

The cortical somatotopic map and phantom phenomena in subjects with congenital limb atrophy and traumatic amputees with phantom limb pain.

The extent of the cortical somatotopic map and its relationship to phantom phenomena was tested in five subjects with congenital absence of an upper limb, four traumatic amputees with phantom limb pain and five healthy controls. Cortical maps of the first and fifth digit of the intact hand, the lower lip and the first toe (bilaterally) were obtained using neuroelectric source imaging. The subjects with congenital upper limb atrophy showed symmetric positions of the left and right side of the lower lip and the first toe, whereas the traumatic amputees with pain showed a significant shift (about 2.4 cm) of the cortical representation of the lower lip towards the hand region contralateral to the amputation side but no shift for the toe representation. In healthy controls, no significant hemispheric differences between the cortical representation of the digits, lower lip or first toe were found. Phantom phenomena were absent in the congenital but extensive in the traumatic amputees. These data confirm the assumption that congenital absence of a limb does not lead to cortical reorganization or phantom limbs whereas traumatic amputations that are accompanied by phantom limb pain show shifts of the cortical areas adjacent to the amputation zone towards the representation of the deafferented body part.

Adult↗

PubMed1998

Influence of the renal endothelin A system on the autoregulation of renal hemodynamics in SHRs and WKY rats.

In this study, we investigated the influence of a short-term blockade of the renal endothelin A system on the autoregulation of total renal blood flow, cortical renal blood flow, and pressure-dependent plasma renin activity in spontaneously hypertensive rats (SHRs) and normotensive controls [Wistar-Kyoto (WKY) rats]. In anesthetized rats, renal blood flow was measured by a transit-time flow probe and cortical blood flow by a laser flow probe. Blood samples were taken for measurement of plasma renin activity. Renal perfusion pressure was reduced in 5-mm Hg steps by means of a servocontrolled electropneumatic device by an inflatable suprarenal cuff. During the experiments, the rats (n = 6, each group) received an intrarenal infusion of either the selective endothelin A-receptor antagonist BQ123 (3 mg/kg/h) or vehicle. We observed an improvement of total and cortical blood flow autoregulation as indicated by a shift of lower limits of autoregulation to lower threshold pressures [103 +/- 2 vs. 132 +/- 4 mm Hg compared with 98 +/- 3 vs. 120 +/- 4 mm Hg (mean +/- SEM); p < 0.01 resp. p < 0.05] in BQ123-treated SHRs, whereas BQ123 had no influence on breakpoints of autoregulation in WKY rats (p > 0.05). Pressure-dependent plasma renin activity in SHRs was not influenced by BQ123. Renal blood flow autoregulation is improved in SHRs after short-term blockade of the renal endothelin A system. This effect is independent of the renin-angiotensin system. The endothelin A system does not seem to play an important role in the autoregulation of renal blood flow in normotensive WKY rats.

Animals↗

PubMed1998

Improvement of postischemic acute renal failure with the novel orally active endothelin-A receptor antagonist LU 135252 in the rat.

The endothelin (ET) system may play an important role in the pathogenesis of acute renal failure (ARF). We hypothesize that the course of ARF in an ischemia-reperfusion model will be markedly attenuated by the orally active ET(A)-receptor antagonist LU 135252 (LU) because of an improvement of renal perfusion. ARF was induced in rats by clamping both renal arteries for 60 min. The study was divided into two parts. In part 1, Rats received LU orally (100 mg/kg/day) starting 1 h after induction of ARF for 14 days. Cr(s), Cl(cr) and FE(na) were measured on days 1, 6, 9, and 14 after ARF. Cr(s) was lower in the treatment group on days 1 [1.3 +/- 0.31 mg/dl (n = 9) vs. 2.7 +/- 0.46 mg/dl (n = 10); p < 0.05] and 6 [0.5 +/- 0.1 mg/dl (n = 9) vs. 1.0 +/- 0.2 mg/dl (n = 9); p < 0.05], and Cl(cr) was higher on day 1 [0.9 +/- 0.17 ml/min (n = 9) vs. 0.2 +/- 0.1 ml/min (n = 8); p < 0.05] and 6 [1.8 +/- 0.29 ml/min (n = 9) vs. 1.0 +/- 0.21 ml/min (n = 9); p < 0.05] compared with vehicle. Additionally, FE(na) was lower in treated rats on day 1 [1 +/- 0.4% (n = 9) vs. 8 +/- 3% (n = 8); p < 0.051 compared with vehicle. In part 2, ARF was induced as described. Treated animals received 10 mg/kg LU on days 0, 1, 3, 6, 9, and 14 after ARF as an i.v. bolus injection. RBF, cortex blood flow (CBF), and medulla blood flow (MBF) were measured after application of LU on the same days: LU induced an increase in RBF (day 1: 14 +/- 5.3%, n = 6, p = 0.04; day 3: 15 +/- 2.8%, n = 8; p = 0.0008; day 6: 21 +/- 5.8%, n = 6, p = 0.02; day 9: 13 +/- 4%, n = 6; p = 0.03) and CBF (day 1: 8 +/- 2.2%, n = 7, p = 0.03; day 3: 7 +/- 2.5%, n = 7; p = 0.05; day 6: 18 +/- 4.8%, n = 6, p = 0.04; day 9: 10 +/- 2.5%, n = 6; p = 0.008) up to the first 9 days. MBF did increase on days 1 (9 +/- 3.1%, n = 6; p = 0.04) and 6 (13 +/- 3.6%, n = 6; p = 0.03). Our data confirm the hypothesis that ET plays a major role in the genesis of ARF associated with ischemia-reperfusion.

Acute Kidney Injury↗

PubMed1998

Adaptive AR modeling of nonstationary time series by means of Kalman filtering.

An adaptive on-line procedure is presented for autoregressive (AR) modeling of nonstationary multivariate time series by means of Kalman filtering. The parameters of the estimated time-varying model can be used to calculate instantaneous measures of linear dependence. The usefulness of the procedures in the analysis of physiological signals is discussed in two examples: First, in the analysis of respiratory movement, heart rate fluctuation, and blood pressure, and second, in the analysis of multichannel electroencephalogram (EEG) signals. It was shown for the first time that in intact animals the transition from a normoxic to a hypoxic state requires tremendous short-term readjustment of the autonomic cardiac-respiratory control. An application with experimental EEG data supported observations that the development of coherences among cell assemblies of the brain is a basic element of associative learning or conditioning.

Adaptation, Physiological↗

PubMed1998

Comparative studies of diagnostic bacteriological methods for the recovery of Salmonella from faecal samples from flocks of layers.

Several conventional culture procedures were compared for the recovery of Salmonella from faecal samples of layer flocks. The cultural media employed consisted of Rappaport-Vassiliadis and tetrathionate broth for selective enrichment and three different plating media (Brilliant Green, Xylose-Lysine-Desoxycholate and modified semisolid Rappaport-Vassiliadis medium). The initial enrichment and plating procedures were repeated in a four-stage secondary enrichment. Selective enrichment in Rappaport-Vassiliadis or tetrathionate broth followed by plating on modified semisolid Rappaport-Vassiliadis medium (selective motility enrichment) resulted in a significantly higher isolation rate for Salmonella from faecal samples of layers compared to Brilliant Green and Xylose-Lysine-Desoxycholate medium. The selective enrichment yielded additional Salmonella isolates up to the second stage. Further enrichment did not increase the isolation rate.

Animals↗

PubMed1998

Preserved autonomic modulation of the sinus and atrioventricular nodes following posteroseptal ablation for treatment of atrioventricular nodal reentrant tachycardia.

INTRODUCTION: Following radiofrequency catheter ablation of AV nodal reentrant tachycardia (AVNRT), inappropriate sinus tachycardia may occur, possibly due to damage to autonomic cardiac nerve fibers. Furthermore, inducibility of AVNRT is often critically dependent on the autonomic balance. We investigated whether successful ablation of AVNRT is associated with an alteration of autonomic input to the sinus and AV nodes. METHODS AND RESULTS: To estimate changes in the autonomic modulation of the sinus and AV nodes, power spectra of beat-to-beat PP and PR intervals were analyzed from high-quality nighttime ECG recordings of 11 patients before and after radiofrequency application. Normalized HF power (nHF) of PP and PR intervals was used as an index of efferent vagal modulation and the LF/HF ratio as an index of sympathovagal balance of the sinus node (PP) and AV node (PR). Before ablation, LF/HF(PP) was 3.2 and nHF(PP) was 0.3 in the sinus node. For the AV node, LF/HF(PR) was 1.2 and nHF(PR) was 0.5. Following ablation, LF/HF(PP) (3.5) and nHF(PP) (0.3) of the PP intervals did not change. Similarly to the sinus node, there were no changes in the autonomic modulation of the AV node, as both LF/HF(PR) (1.2) and nHF(PR) (0.5) remained unchanged. CONCLUSION: Our results indicate that autonomic control of the sinus and AV nodes is preserved following successful radiofrequency ablation of AVNRT. The effects of posteroseptal radiofrequency current application are not necessarily mediated by changes in the autonomic input to the AV node.

Adult↗

PubMed1998

Demonstration of nonlinear components in heart rate variability of healthy persons.

We present a systematic approach for detecting nonlinear components in heart rate variability (HRV). The analysis is based on twenty-three 48-h Holter recordings in healthy persons during sinus rhythm. Although many segments of 1,024 R-R intervals are stationary, only few stationary segments of 8,192-32,768 R-R intervals can be found using a test of Isliker and Kurths (Int. J. Bifurcation Chaos 3:1573-1579, 1993.). By comparing the correlation integrals from these segments and corresponding surrogate data sets, we reject the null hypothesis that these time series are realization of linear processes. On the basis of a test statistic exploring the differences of consecutive R-R intervals, we reject the hypothesis that the R-R intervals represent a static transformation of a linear process using optimized surrogate data. Furthermore, time irreversibility of the heartbeat data is demonstrated. We interpret these results as a strong evidence for nonlinear components in HRV. Thus R-R intervals from healthy persons contain more information than can be extracted by linear analysis in the time and frequency domain.

Adult↗

PubMed1998

Renal endothelin system in polycystic kidney disease.

Polycystic kidney disease (PKD) is characterized by interstitial fibrosis and formation of renal cysts. Interestingly, interstitial fibrosis and renal cyst formation were also seen in human endothelin-1 (ET-1) transgenic mice. This study, therefore, analyzes the tissue distribution of ET-1, the tissue concentrations of ET-1, as well as the expression of ET receptor subtypes in the kidneys of a rat model of PKD: Han:SPRD rats. Six-week-old heterozygous (cy/+) and homozygous (cy/cy), as well as 6-mo-old heterozygous (cy/+) Han:SPRD rats and the corresponding age-matched Sprague Dawley littermates (SD) (+/+) were analyzed. Furthermore, the acute effects of the mixed (A/B) endothelin receptor antagonist bosentan on hemodynamic and renal function were investigated in 6-mo-old, conscious, chronically instrumented (cy/+) rats. The kidneys of affected rats showed significantly elevated tissue levels of ET-1 compared with age-matched controls (3.5 +/- 0.3-fold in young cy/cy rats, P < 0.01; 1.4 +/- 0.2-fold in young cy/+ rats, P < 0.01; 6.2 +/- 0.4-fold in old cy/+ rats, P < 0.001) due to a highly increased ET-1 synthesis within the epithelial cells of the cysts. Analyzing tissue sections from patients with typical autosomal dominant PKD demonstrated a high ET-1 expression within the epithelial cells of the cysts as well. Scatchard analysis revealed a markedly decreased ETA and ETB receptor density in all groups of affected rats. The acute blockade of both endothelin receptor subtypes using bosentan in 6-mo-old heterozygous PKD rats led to a significant decrease in mean arterial BP (MAP) (-19.7 +/- 2.1 mmHg, P < 0.05) and GFR (-41 +/- 5%, P < 0.005). Renal blood flow (RBF) was significantly increased (+2.1 +/- 0.5 ml/min, P < 0.05) after bosentan, whereas bosentan had no effect on MAP, GFR, and RBF in age-matched controls. These data show that the paracrine renal endothelin system is activated in PKD and participates in the regulation of MAP, GFR, RBF, and possibly contributes to renal cyst formation and fibrosis.

Analysis of Variance↗

PubMed1998

[Comparative stability studies with the modified Stellbrink external fixator].

We replaced original Stellbrink-fixator clamps with adjustable horizontal and vertical clamps. Thus, smaller bone fragments can be fixed and there is a possibility to correct their position after application of the fixator. This study compared the primary stability of different constructions by defined flexibility loadings in four-point bending. Statistical evaluation was done by the student-t-test. When used as compression osteosynthesis, the original Stellbrink fixator is the most stable (100%), whereas the modified fixator reaches only 90% of the stability of the original. The better stability of the original Stellbrink fixator only becomes significant when the flexion becomes greater than 13 degrees. Used for distance osteosynthesis, the original Stellbrink fixator is significantly more stable. Clinical examples are presented.

Biomechanical Phenomena↗