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Biomedical subjects

K Barth

Publications and source records attributed to K Barth.

At least 19 recordsLinked to original sources
PubMed2006

Lack of evidence for caveolin-1 and CD147 interaction before and after bleomycin-induced lung injury.

Immunohistochemical and in vitro studies indicate that caveolin-1, which occurs abundantly in alveolar epithelial type I cells and microvascular endothelial cells of the lung, is selectively downregulated in the alveolar epithelium following exposure to bleomycin. Bleomycin is also known to enhance the expression levels of metalloproteinases and of the metalloproteinase inducer CD147/EMMPRIN in lung cells. Experimental in vitro data has showed that MMP-inducing activity of CD147 is under the control of caveolin-1. We studied the effects of bleomycin on the expression of caveolin-1, CD147 and metalloproteinases using an alveolar epithelial rat cell line R3/1 with properties of both alveolar type I and type II cells and explanted rat lung slices. In parallel, retrospective samples of bleomycin-induced fibrosis in rats and mice as well as samples of wild type and caveolin-1 knockout animals were included for immunohistochemical comparison with in vitro data. Here we report that treatment with bleomycin downregulates caveolin-1 and increases CD147 and MMP-2 and -9 expression/activity in R3/1 cells using RT-PCR, Western blot analysis, MMP-2 activity assay and immunocytochemistry. Immunofluorescence double labeling revealed that caveolin-1 and CD147 were not colocalized in vitro. The in vitro findings were confirmed through immunohistochemical studies of the proteins in paraffin embedded precision-cut rat lung slices and in fibrotic rat lung tissues. The caveolin-1-negative hyperplastic ATII cells exhibited enhanced immunoreactivity for CD147 and MMP-2. Caveolin-1-negative ATI cells of fibrotic samples were mostly CD147 negative. There were no differences in the pulmonary expression of CD147 between the normal and caveolin-1 deficient animals. The results demonstrate that bleomycin-induced lung injury is associated with an increase in CD147 expression and MMP activity, particularly in alveolar epithelial cells. In addition, our data exclude any functional interaction between CD147 and alveolar epithelial caveolin-1.

Animals↗
PubMed2005

Epithelial vs myofibroblast differentiation in immortal rat lung cell lines--modulating effects of bleomycin.

Two alveolar epithelial cell lines R3/1 and L2 were screened by immunocytochemical and RT-PCR analysis of epithelial and mesenchymal/contractile marker proteins. R3/1 and L2 cells were tested for their sensitivity to bleomycin (BLM), an anticancer drug, which is proposed to induce changes in lung cell differentiation. Both epithelial cell lines exhibited a mixed phenotype consisting of epithelial (E-cadherin, aquaporin-5 and cytokeratin 8) and myofibroblast-like (vimentin, alpha-SMA and caveolin-3) properties suggesting that the cell lines are arrested in vitro at a certain developmental stage during epithelial-mesenchymal transition (EMT). BLM treatment of R3/1 cells resulted in a partial reversal of this process modifying the cells in an epithelial direction, e.g., upregulation of E-cadherin, aquaporin-5 and other lung epithelial antigens at the mRNA and protein level. L2 cells showed similar alterations following BLM exposure.Immunohistochemical investigation of lung tissue from two different animal models of BLM-induced fibrosis (mouse and rat), revealed no signs of EMT, e.g., myofibroblastic differentiation of alveolar epithelial cells in situ. Immunohistological analysis of tissue samples of the rat model showed a heterogeneous population of myofibroblasts (alpha-SMA+/caveolin-3+, alpha-SMA-/caveolin-3+, and alpha-SMA+/caveolin-3-). These results suggest that BLM, on one hand, induces fibrosis and on the other hand possibly suppresses EMT during fibrogenesis.

Animals↗
PubMed2005

Apoptosis and release of CD44s in bleomycin-treated L132 cells.

The anti-cancer drug bleomycin (BLM) induces lung injury and triggers apoptosis of alveolar epithelial cells. In epithelia, among other functions, the adhesion protein CD44 promotes the contact to components of the extracellular matrix like hyaluronate. A functional link between apoptosis and the loss of CD44 has been observed in colon carcinoma cells and involvement of CD44 in apoptosis of lung cells has been reported in several studies. The present in vitro study examined the expression of CD44s (CD44 standard) in two human epithelial lung cell lines, L132 and A549, during BLM-induced apoptosis. A loss of CD44s by lung epithelial cells and an increase of the soluble form of this adhesion protein in culture supernatants upon exposure to BLM were observed. Apoptosis was characterized by an activation of caspase-3 as well as by release of cytochrome C into the cytosol as shown for L132 cells. Inhibition of apoptosis by the broad-range caspase inhibitor Z-VAD-fmk reduced CD44 release by both cell lines demonstrating that CD44 release is a result of apoptotic processes. Kinetic experiments failed to discriminate between the initiation of apoptosis and CD44 release. Blocking experiments using antagonistic anti-CD95 receptor antibodies revealed that BLM may cause apoptosis and CD44 release in a CD95-independent manner.

Apoptosis↗
PubMed2005

First results from the CERN axion solar telescope.

Hypothetical axionlike particles with a two-photon interaction would be produced in the sun by the Primakoff process. In a laboratory magnetic field ("axion helioscope"), they would be transformed into x-rays with energies of a few keV. Using a decommissioned Large Hadron Collider test magnet, the CERN Axion Solar Telescope ran for about 6 months during 2003. The first results from the analysis of these data are presented here. No signal above background was observed, implying an upper limit to the axion-photon coupling g(agamma)<1.16x10(-10) GeV-1 at 95% C.L. for m(a) less, similar 0.02 eV. This limit, assumption-free, is comparable to the limit from stellar energy-loss arguments and considerably more restrictive than any previous experiment over a broad range of axion masses.

Journal Article↗
PubMed2005

Effects of different titanium alloys and nanosize surface patterning on adhesion, differentiation, and orientation of osteoblast-like cells.

To test nanosize surface patterning for application as implant material, a suitable titanium composition has to be found first. Therefore we investigated the effect of surface chemistry on attachment and differentiation of osteoblast-like cells on pure titanium prepared by pulsed laser deposition (TiPLD) and different Ti alloys (Ti6Al4V, TiNb30 and TiNb13Zr13). Early attachment (30 min) and alkaline phosphatase (ALP) activity (day 5) was found to be fastest and highest, respectively, in cells grown on TiPLD and Ti6Al4V. Osteoblasts seeded on TiPLD produced most osteopontin (day 10), whereas expression of this extracellular matrix protein was an order of magnitude lower on the TiNb30 surface. In contrast, expression of the corresponding receptor, CD44, was not influenced by surface chemistry. Thus, TiPLD was used for further experiments to explore the influence of surface nanostructures on osteoblast adhesion, differentiation and orientation. By laser-induced oxidation, we produced patterns of parallel Ti oxide lines with different widths (0.2-10 microm) and distances (2-20 and 1,000 microm), but a common height of only 12 nm. These structures did not influence ALP activity (days 5-9), but had a positive effect on cell alignment. Two days after plating, the majority of the focal contacts were placed on the oxide lines. The portion of larger focal adhesions bridging two lines was inversely related to the line distance (2-20 microm). In contrast, the portion of aligned cells did not depend on the line distance. On average, 43% of the cells orientated parallel towards the lines, whereas 34% orientated vertically. In the control pattern (1,000 microm line distance), cell distribution was completely at random. Because a significant surplus of the cells preferred a parallel alignment, the nanosize difference in height between Ti surface and oxide lines may be sufficient to orientate the cells by contact guiding. However, gradients in electrostatic potential and surface charge density at the Ti/Ti oxide interface may additionally influence focal contact formation and cell guidance.

Alkaline Phosphatase↗
PubMed2004

Distribution of caveolin-1 and connexin43 in normal and injured alveolar epithelial R3/1 cells.

Using the new alveolar epithelial type I-like cell line R3/1 derived from fetal rat lung, we studied the distribution of connexin43 and caveolin-1 under conditions of bleomycin-induced injury in vitro. We show that under normal as well as under conditions of injury, endogenous connexin43 does not directly interact with endogenous caveolin-1 as revealed by immunofluorescence, glutathione S-transferase/caveolin-1 "pull down" assay, and co-immunoprecipitation experiments. The assessment of Triton X-100 solubility revealed that caveolin-1 was abundant in detergent-resistant membrane fractions. This is consistent with the localization of caveolin-1 in the lipid rafts/caveolae. Similarly, phosphorylated connexin43 was preferably detected in the Triton-insoluble fraction. Using a sucrose gradient we demonstrated that the majority of phosphorylated connexin43 colocalizes with caveolin-1 in lipid rafts, whereas all other forms of connexin43 remain in the bulk of cellular membranes and cytosolic proteins. Triton solubility assessment of bleomycin-treated cells revealed no differences in the caveolin-1 and connexin43 distribution. A further interesting outcome of our study is the shift of caveolin-1 from the lipid raft/caveolae fractions to the non-caveolar fractions after bleomycin treatment indicating an intracellular retention of caveolin-1. This result suggests the possibility that the translocation of caveolin-1 could be an important event regulating the metabolism of alveolar epithelial lung cells after injury.

Animals↗
PubMed2002

Establishment of the telencephalon during gastrulation by local antagonism of Wnt signaling.

Cells at the anterior boundary of the neural plate (ANB) can induce telencephalic gene expression when transplanted to more posterior regions. Here, we identify a secreted Frizzled-related Wnt antagonist, Tlc, that is expressed in ANB cells and can cell nonautonomously promote telencephalic gene expression in a concentration-dependent manner. Moreover, abrogation of Tlc function compromises telencephalic development. We also identify Wnt8b as a locally acting modulator of regional fate in the anterior neural plate and a likely target for antagonism by Tlc. Finally, we show that tlc expression is regulated by signals that establish early antero-posterior and dorso-ventral ectodermal pattern. From these studies, we propose that local antagonism of Wnt activity within the anterior ectoderm is required to establish the telencephalon.

Animals↗
PubMed2002

Focused ion beam sectioning and lift-out method for copper and resist vias in organic low-k dielectrics.

The focused ion beam lift-out technique for scanning electron microscope (SEM) and transmission electron microscope (TEM) sample preparation was shown to be applicable to copper/low-k dielectric semiconductor technology. High resolution SEM, TEM, and scanning transmission electron microscope analyses were performed on metal contacts and resist vias with no evidence of the interface damage or metal smearing commonly observed with mechanical polishing. Ion milling of the sample ex situ to the substrate provided decoration and adjustment of the exposed plane of the section when necessary for SEM analysis.

Copper↗
PubMed2000

Enhanced 3-D-reconstruction algorithm for C-arm systems suitable for interventional procedures.

Increasingly, three-dimensional (3-D) imaging technologies are used in medical diagnosis, for therapy planning, and during interventional procedures. We describe the possibilities of fast 3-D-reconstruction of high-contrast objects with high spatial resolution from only a small series of two-dimensional (2-D) planar radiographs. The special problems arising from the intended use of an open, mechanically unstable C-arm system are discussed. For the description of the irregular sampling geometry, homogeneous coordinates are used thoroughly. The well-known Feldkamp algorithm is modified to incorporate corresponding projection matrices without any decomposition into intrinsic and extrinsic parameters. Some approximations to speed up the whole reconstruction procedure and the tradeoff between image quality and computation time are also considered. Using standard hardware the reconstruction of a 256(3) cube is now possible within a few minutes, a time that is acceptable during interventions. Examples for cranial vessel imaging from some clinical test installations will be shown as well as promising results for bone imaging with a laboratory C-arm system.

Algorithms↗
PubMed1996

On-line evaluation of systolic performance by densitometry in digital left ventriculography.

The angiocardiographic evaluation of left ventricular end-diastolic (LVEDV) and end-systolic (LVESV) volumes and ejection fraction (EF) is routinely performed by the area-length method (ALM) but may lead to erroneous results. Digital imaging in real time allows densitometric procedures of determining left ventricular (LV) performance to be applied alternatively. In this study, we present densitometric algorithms for the analysis of LVEDV, LVESV, and EF from digital image data, establish accuracy and reproducibility, and determine value and limitations in comparison with ALM in single-plane 30 degrees right anterior oblique (RAO) projection. A linear relationship between iodine depth and measured densities is mainly burdened with scatter radiation and beam hardening which reduce primary radiation and suppress iodine depth. However, facilities such as deconvolution and correction algorithms are capable of reducing these sources of error. In the present study, computer-analyzed contrast images of iodine-filled wedges and spheres showed a near-linear relationship between iodine depth between 50-100 mg/cm2 and measured densities. Contrast images of heart casts and LV angio-grams of 54 patients were obtained with a digital image acquisition and processing system, and evaluated by two independent observers. The phantom study resulted in significantly (p < or = 0.01) better densitometric standard errors of estimate for volumes [3.3 ml densitometry (DENS) vs. 8.9 ml (ALM)] and simulated EF [4.3% (DENS) vs. 7.8% (ALM)] than ALM. The standard error of estimate for the comparison between both methods was 8.4 ml for volumes and 7.5% for EF. Densitometric volumes tended to underestimate volumes calculated by ALM. The angiographic study of patients demonstrated significant correlations between both methods (LVEDV r = 0.78, LVESV r = 0.83, total volumes: r = 0.89; EF r = 0.88). The standard errors of estimate can be ascribed to systematic, method-related errors of both DENS and ALM (LVEDV +/- 28.9 ml, LVESV +/- 23.4 ml, total volumes (EDV and ESV) +/- 27.1 ml; EF +/- 8.1%). The intra- and interobserver variability, respectively, exhibited significantly smaller (p < or = 0.01 and p < or = 0.05, respectively) standard errors of estimate for densitometric EF [4.6% (DENS) vs. 8.5% (ALM) and 7.1% (DENS) vs. 10.3% (ALM), respectively]. Inclined but not significant differences were found for LVEDV and LVESV. In conclusion, the data presented indicate that the calculation of LV volumes and EF in digital left ventriculography may be performed accurately by densitometric calculation in single-plane 30 degrees RAO projection. Minor underestimations in densitometric volume determination may be anticipated in the evaluation of LV geometry.

Adult↗
PubMed1996

Digital ventriculography: valid on-line calculation of cardiac volumes by corrected computer densitometry in coronary artery disease.

Cardiac catheterization facilitates the assessment of left ventricular function in coronary artery disease (CAD). Digital left ventriculography offers the potential for an on-line quantitative determination of left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV). These are routinely evaluated by the area-length method (ALM), which is considered as a standard. Densitometry (DENS) is an alternative method but may lead to calculated underestimations. The purpose of this study was to investigate the accuracy of corrected DENS for LVEDV and LVESV in comparison with ALM in single-plane 30 degrees right anterior oblique (RAO) projection. The computer densitometric correction equation was adapted from the linear regression analysis (y = 0.86x + 2.73) in cardiac models and applied to the analysis of digital left ventriculograms in patients suffering from CAD. The study of cardiac models yielded highly significant correlations (r > or = 0.9; P < or = 0.001) between true volumes and both DENS and ALM. DENS and ALM correlated highly significantly (r > or = 0.9; P < or = 0.001) with a low standard error of estimate (SEE) of +/-9.5 mL. The comparison of DENS and ALM in 44 patients' digital ventriculograms exhibited highly significant (r = 0.74; P < or = 0.001) correlations for noncorrected and corrected LVEDV. Systematic underestimation by DENS of LVEDV disappeared after correction and SEE decreased from +/-23.7 to +/-19.2 mL. DENS and ALM correlated highly significantly for LVESV (r = 0.78; P < or = 0.001; SEE +/- 15.6 mL +/- 13.5 mL, respectively) after correction. Following correction, mean values for DENS increased from 116 +/- 32 to 132 +/- 37 mL (LVEDV) and 50 +/- 22 to 55 +/- 25 mL (LVESV). For ALM, mean values decreased from 159 +/- 35 to 127 +/- 28 mL (LVEDV) and 55 +/- 25 to 46 +/- 21 mL (LVESV). This study shows that LVEDV and LVESV can be reliably analyzed on-line by corrected computer densitometry. Method-related errors of both DENS and ALM are present and account for minor volume deviations.

Aged↗
PubMed1996

Improved densitometric analysis of ventricular volumes in on-line digital cardiac imaging.

In digital angiocardiography left ventricular volumes are routinely calculated by the area-length-method (ALM) which is considered to be a standard and with which other techniques are compared. Densitometric analysis (DENS) is an alternative method and can be performed on-line but may lead to erroneous results. A novel technique of densitometric calculation of left ventricular enddiastolic and endsystolic volume (LVEDV resp. LVESV) is presented. Digital images were analyzed by measuring densities of iodine signals and transforming these into calculated volumes by applying appropriate computer algorithms. The evaluation of volumes in cardiac models demonstrated significant correlations between true volumes and both DENS and ALM. An algorithmic approach to volume correction in patient evaluation of left ventricular volumes was drawn from the linear regression analysis of DENS and true volumes in the cardiac models. LVEDV and LVESV calculated by DENS correlated significantly with volumes determined by ALM in patients (r=0.78 resp. r=0.83) but showed a systematic underestimation for volumes > or =45 ml without densitometric correction. Following correction for DENS, an improvement in calculation was observed for volumes < or =200 ml without systematic deviations. In conclusion, our study demonstrates that corrected densitometric volumetry offers the potential for a reliable on-line analysis of enddiastolic and endsystolic volumes. Modest, but no systematic deviations for densitometric analysis may be anticipated in myogene dilatation with volumes larger than 200 ml. However, when comparing both DENS and ALM, method-related errors of both techniques are present and account for volume deviations.

Absorptiometry, Photon↗
PubMed1993

[Digital subtraction angiocardiography: reliability of densitometric determination of left ventricular volume and ejection fraction].

The angiographic assessment of left ventricular volume (LV) and ejection fraction (EF) by means of the area-length method (ALM) is based upon geometric assumptions, which might lead to erroneous results. With the development of digital subtraction angiocardiography in real-time, densitometric procedures of calculating left ventricular parameters can be used on-line. This study examines both reliability and accuracy of a densitometric technique for evaluating LV and EF in comparison to the single-plane ALM. Contrast images of heart casts and left ventricular angiograms of 54 patients suffering from different cardiac diseases were obtained by the image acquisition and processing system Polytron 1000 VR (Siemens AG, Erlangen, FRG). Digital images of both heart casts and patients were evaluated densitometrically and geometrically by two independent observers. In the phantom study the densitometric method exhibited a significantly (p < 0.01) better agreement with the true values than the ALM. The evaluation of left ventricular angiograms in patients comparing densitometry with the ALM demonstrated a relatively high residual deviation (enddiastolic volume Syx = +/- 27 ml, endsystolic volume Syx = +/- 19.4 ml). This is mainly due to systematic, method-related errors of densitometry and the morphometric technique. The intra- and interobserver variability in calculating EF showed a significantly (p < 0.05) smaller residual deviation for densitometry than for ALM; no significant differences were found for the calculation of LV. In conclusion, we demonstrated that the presented densitometric technique offers an objective and simple means of determining LV and EF with comparable reliability and validity to the area-length method.

Absorptiometry, Photon↗
PubMed1991

Dieting and pain sensitivity: a validation of clinical findings.

To validate findings of a reduced pain sensitivity in anorexia and bulimia nervosa, the effects of dieting on somatosensation (especially pain sensitivity) were investigated in healthy young women. One group of subjects (n = 11) received a calorically reduced balanced diet for 21 days, while the other group (n = 14) continued to eat normally. The fasting state induced in the dieting subjects was comparable to that of eating disorder patients, since the dieters showed a reduction of the body mass index, a decrease in triiodothyronine and an increase in beta-hydroxybutyric acid plasma levels. However, neither the thresholds of pain, warmth, cold and vibration sensitivity nor the peripheral skin temperature changed systematically under the diet. Therefore, the reduced pain sensitivity in eating disorder patients is apparently not a mere effect of fasting, but a true pathological feature.

3-Hydroxybutyric Acid↗
PubMed1988

Factor analysis of the evaluation form for selecting patients for short-term anxiety-provoking psychotherapy. The Bergen project on brief dynamic psychotherapy.

The selection criteria of Sifneos' short-term anxiety-provoking psychotherapy has been assumed to consist of two separate dimensions, resources and motivation. A factor analysis revealed three factors: ego-resources, motivation for psychotherapy and motivation or desire to change. The resource items on the evaluation form constitute one factor as assumed, it is the items on the motivation section that are split into two independent factors. The evaluation form might become more useful if the motivation items are reorganized according to the two different dimensions of the concept.

Adult↗