Biomedical subjects

C Eder

Publications and source records attributed to C Eder.

At least 19 recordsLinked to original sources

PubMed2006

A tissue engineering approach to meniscus regeneration in a sheep model.

OBJECTIVE: Regeneration of the meniscal tissue occurs to a limited extent, and the loss of meniscal tissue leads to osteoarthritis. A new biomaterial consisting of hyaluronic acid and polycaprolactone was used as a meniscus substitute in sheep to evaluate the properties of the implant material with regard to size, biomechanical stability, tissue ingrowth, and integration. METHODS: Eight sheep (right stifle joints) were treated with three total and three partial meniscus replacements while two meniscectomies served as empty controls. The animals were euthanized after 6 weeks. The specimens were assessed by gross inspection and histology, and compared with the nonoperated left joints. RESULTS: The surgical technique was found to be feasible. The implants remained in position, did not tear, and showed excellent tissue ingrowth to the capsule. Tissue integration was also observed between the original meniscus and the implant. However, graft compression and extrusion occurred. The histological investigation revealed tissue formation, cellular infiltration and vascularization. Cartilage degeneration was more severe in the operated joints. CONCLUSION: The present study shows promising results concerning the qualities of this biomaterial with regard to implantation technique, stability and tissue ingrowth.

Adjuvants, Immunologic↗

PubMed2005

Serum free cell culture: the free access online database.

The cultivation of cells in vitro is an important tool for biomedical research and production purposes. The supplementation of animal/human cell culture media with sera (components) of animal origin remains still standard, providing for e.g. necessary nutrition, shear protection, growth factors and cytokines. Because of undefined composition, risk of contaminations, the cost factor and also animal welfare considerations concerning the production of sera, the conversion to serum free alternatives is promoted by regulatory authorities, industry and the research community in general. To support this trend and to help save one of the scientists most valuable resources -- time -- a data bank was compiled of commercially available formulations, searchable for products, applications, cell lines and manufacturers. The database is accessible free of charge in HTML format and as PDF download, the informations are checked and updated twice a year. Problems concerning serum free cell culture are discussed at and comments are welcome.

Animals↗

PubMed2005

SKY and FISH analysis of radiation-induced chromosome aberrations: a comparison of whole and partial genome analysis.

For a retrospective dose estimation of human exposure to ionising radiation, a partial genome analysis is routinely used to quantify radiation-induced chromosome aberrations. For this purpose, fluorescence in situ hybridisation (FISH) with whole chromosome painting probes for selected chromosomes is usually applied covering about 20% of the whole genome. Since genome-wide screening techniques like spectral karyotyping (SKY) and multiplex FISH (mFISH) have been developed the detection of radiation-induced aberrations within the whole genome has now become feasible. To determine the correspondence between partial and whole genome analysis of radiation-induced chromosome aberrations, they were measured comprehensively in this study using in vitro irradiated blood samples from three donors. We were able to demonstrate that comparable results can be detected with both approaches. However, complex aberrations might be misinterpreted by partial genome analysis. We therefore conclude that whole genome analysis by SKY is useful especially in the high dose range to correct aberration data for complex exchange aberrations.

Adult↗

PubMed2004

[Laser microdissection and molecular typing of dysplastic cells from Pap smears: a new approach to early detection of cervical cancer].

The Papanicolaou smear (Pap) is a worldwide screening tool for early detection of cervical cancer and its precursor lesions. The transition from dysplasia to cancer is a highly complex genetic process and cannot be predicted based solely on cell morphology. Molecular characterization of precursor lesions could yield a better definition of lesions at high risk for progression. We developed an analytical concept comprising not only morphological characterization but also molecular analysis with multiple parameters of dysplastic cells from cervical smears. We isolated dysplastic cells from 52 fixed Pap-stained smears of various grades by laser microdissection and analyzed them for genetic lesions typical for cervical carcinoma. The loss of heterozygosity (LOH) as published for cervical carcinoma tissue was detected. Markers for early stages showed a LOH in 43% and 22%, and those for late stages in 26% of the cases. Combining morphological characterization with molecular analysis by multiple molecular markers could open up new opportunities for early detection of cervical carcinoma.

Female↗

PubMed2004

Decrease of plasma apolipoprotein A-IV during weight reduction in obese adolescents on a low fat diet.

OBJECTIVE: Apolipoprotein (apo) A-IV is an antiatherogenic apolipoprotein, which may be involved in the regulation of food intake. Plasma apoA-IV is elevated in human obesity and apoA-IV polymorphisms have been associated with the extent of obesity. Our aim was to determine the effects of weight loss on plasma apo-IV in obese adolescents and to examine the relation of apoA-IV with the degree of obesity. DESIGN: Longitudinal intervention study of a low fat hypocaloric diet conducted in a dietary camp. SUBJECTS: Two groups of obese adolescents (n=47 and n=29), age: 12.7+/-1.7 and 11.7+/-2.6 y, relative body mass index (RBMI): 168+/-24 and 175+/-34%, respectively. MEASUREMENTS: Plasma total apoA-IV, apoA-I, apoB, plasma distribution of apoA-IV, leptin, lipids, and lipoproteins before and after 3 weeks of weight reduction. RESULTS: Plasma apoA-IV decreased from 11.5+/-4.1 mg/dl before to 6.7+/-2.2 mg/dl after weight reduction in the first group (P<0.001) and to a similar extent in the second group. The relative amount of lipid-free apoA-IV and apoA-IV associated with apoA-I increased slightly, whereas apoA-IV associated with lipoproteins devoid of apoA-I decreased. ApoA-IV levels before and after weight reduction and the changes in plasma apoA-IV did not independently correlate with RBMI, weight loss, or plasma leptin. CONCLUSION: Plasma apoA-IV decreases markedly in overweight adolescents undergoing short-term weight reduction. The decrease is not directly related to the degree of weight loss and the mechanisms underlying this reduction remain to be clarified.

Adolescent↗

PubMed2002

Allergic pulmonary and ocular tissue responses in the absence of serum IgE antibodies (IgE) in an allergic dog model.

Allergen-specific serum IgE may be insensitive as a marker for IgE-mediated reactions at the mucosal level. Five of six atopic beagle dogs developed high ovalbumin (OVA)-specific serum IgE levels after sensitization. This study aimed to show that these dogs still express allergen-specific IgE at the pulmonary and ocular mucosal levels and in the skin even when corresponding serum IgE was below the detection limit. When serum IgE levels were negative, all dogs exhibited allergic reactions at the tissue level. Specifically, they displayed positive ocular reactions after an ocular OVA challenge. After airway challenge with aerosolized OVA, five out of six animals reacted with decreased compliance and increased resistance of the lungs. Furthermore, an eosinophilia in the bronchoalveolar lavage fluid (BALF) was observed. Four weeks after the last exposure to OVA, IgE-positive BALF cells were seen in all animals. Six weeks on, all dogs still displayed positive skin reactions to OVA. This indicates that not only skin testing but also detection of ocular and pulmonary allergic tissue reactions including cell-bound IgE in BALF can serve as more sensitive and lasting surrogate markers of hypersensitivity in the allergic dog model than detection of allergen-specific serum IgE levels.

Animals↗

PubMed2002

Child pedestrian injuries at tram and bus stops.

In order to analyse these injuries and to create guidelines for prevention, injuries at bus or tram stops were analysed retrospectively. Medical records were analysed and questionnaires were sent to the parents in order to obtain detailed information about the mode and physical sequelae or post-traumatic behavioural disturbances of the injury.Thirty children of a median age of 9.5 years (2.7-15.3 years) were treated within a 6-year period. Sixteen out of 30 children (53.3%) were injured on their way to school and 3 (10.0%) on their way to kindergarten. Nine out of 30 children (30%) were injured when crossing the street from behind the bus or the tram. Five children (16.7%) were injured by buses, 6 (20.0%) by trams and 19 (63.3%) by passing motorised vehicles. Twelve (40.0%) were injured in the presence of accompanying adults. In 17 of 30 cases (56.7%) the visibility of the vehicle and/or the child was obstructed. The median Injury Severity Score (ISS) was 4.5 (1-75) and the mortality rate 2 out of 30 (6.7%), both children had been killed at bus stops alongside country roads. Nine out of 28 surviving children (32.1%) suffer from minor physical sequelae and 6 (21.4%) from post-traumatic behavioural disturbances. Crossing the road from behind a bus in the area of a stop alongside a country road is extremely dangerous. It is mandatory to increase the safety at bus stops along country roads.

Accidents, Traffic↗

PubMed2002

Lysophospholipids induce membrane hyperpolarization in microglia by activation of IKCa1 Ca(2+)-dependent K(+) channels.

Effects of the lysophospholipids sphingosine-1-phosphate and lysophosphatidic acid were studied in cultured murine microglia using the patch-clamp and video imaging techniques. Both lysophospholipids induced transient membrane hyperpolarization and K(+) current activation. The lysophospholipid-induced K(+) current was blocked by charybdotoxin or iberiotoxin, but was unaffected by apamin. In recordings with 1 microM intracellular free Ca(2+), Ca(2+)-dependent K(+) currents of microglia showed a similar pharmacological profile to lysophospholipid-induced currents. The Ca(2+)-dependent K(+) channels activated in microglia by lysophospholipids are most likely encoded by the IKCa1 channel gene. The presence of IKCa1 mRNA in microglia was demonstrated by reverse transcriptase-polymerase chain reaction studies. Ca(2+) imaging experiments revealed increases in the intracellular free Ca(2+) concentration of microglia to a mean value of about 400 nM after application of 1 microM sphingosine-1-phosphate or 1 microM lysophosphatidic acid. We suggest that the transient membrane hyperpolarization seen in microglia following exposure to sphingosine-1-phosphate or lysophosphatidic acid is caused by activation of IKCa1 Ca(2+)-dependent K(+) channels. Increases in the concentration of intracellular free Ca(2+) evoked by the lysophospholipids are sufficient to activate microglial Ca(2+)-dependent K(+) channels.

Animals↗

PubMed2001

Voltage-gated proton channels in microglia.

Microglia, macrophages that reside in the brain, can express at least 12 different ion channels, including voltage-gated proton channels. The properties of H+ currents in microglia are similar to those in other phagocytes. Proton currents are elicited by depolarizing the membrane potential, but activation also depends strongly on both intracellular pH (pH(i)) and extracellular pH (pH(o)). Increasing pH(o) or lowering pH(i) promotes H+ channel opening by shifting the activation threshold to more negative potentials. H+ channels in microglia open only when the pH gradient is outward, so they carry only outward current in the steady state. Time-dependent activation of H+ currents is slow, with a time constant roughly 1 s at room temperature. Microglial H+ currents are inhibited by inorganic polyvalent cations, which reduce H+ current amplitude and shift the voltage dependence of activation to more positive potentials. Cytoskeletal disruptive agents modulate H+ currents in microglia. Cytochalasin D and colchicine decrease the current density and slow the activation of H+ currents. Similar changes of H+ currents, possibly due to cytoskeletal reorganization, occur in microglia during the transformation from ameboid to ramified morphology. Phagocytes, including microglia, undergo a respiratory burst, in which NADPH oxidase releases bactericidal superoxide anions into the phagosome and stoichiometrically releases protons into the cell, tending to depolarize and acidify the cell. H+ currents may help regulate both the membrane potential and pH(i) during the respiratory burst. By compensating for the efflux of electrons and counteracting intracellular acidification, H+ channels help maintain superoxide anion production.

Animals↗

PubMed2001

Astrocyte-released cytokines induce ramification and outward K+ channel expression in microglia via distinct signalling pathways.

Differentiation of microglial cells is characterized by transformation from ameboid into ramified cell shape and up-regulation of K+ channels. The processes of microglial differentiation are controlled by astrocytic factors. The mechanisms by which astrocytes cause developmental changes in morphological and electrophysiological properties of microglia have remained unclear. We show here that the cytokines transforming growth factor-beta (TGF-beta), macrophage colony-stimulating factor (M-CSF) and granulocyte/macrophage colony-stimulating factor (GM-CSF) are released by astrocytes at concentrations sufficient to induce ramification and up-regulation of delayed rectifier (DR) K+ channels in microglia. Transformation from ameboid into ramified morphology induced in microglia by exposure to astrocyte-conditioned medium (ACM) was inhibited by neutralizing antibodies against TGF-beta, M-CSF or GM-CSF, whilst ACM-induced DR channel expression was exclusively inhibited by antibodies against TGF-beta. Although both ramification and DR channel up-regulation occurred simultaneously, DR channel blockade by charybdotoxin failed to inhibit microglial ramification. The ACM-induced ramification of microglia was inhibited by the tyrosine kinase inhibitor genistein, whereas DR channel up-regulation did not occur in the presence of the serine/threonine kinase inhibitor H7. Our data suggest that astrocytes modulate processes of microglial differentiation in parallel but via distinct signalling pathways.

Animals↗

PubMed2001

Vehicles reversing or rolling backwards: an underestimated hazard.

OBJECTIVES: A retrospective analysis of injuries caused by vehicles that were reversing or rolling backwards to establish guidelines for prevention was performed. PATIENTS AND METHODS: Medical records and questionnaires completed by parents for 32 children admitted to the Department of Pediatric Surgery, Graz, within the past eight years, were analysed. RESULTS: The median age was 2.1 years (1.0-14.0 years). Fourteen of 32 of the cars were driven by family members (43.8%); three were rolling backwards without a driver (9.4%). The median injury severity score was 3 (1-27) and the most common injuries were contusions (40.6%), fractures (31.3%), and lacerations/burns (21.9%). Most incidents occurred in driveways (37.5%) or farmyards (21.9%). Altogether 70.3% of children sustained "run-over" injuries, 29.6% were hit by the rear bumper or injured by a breaking window. CONCLUSIONS: Toddlers playing in driveways or farmyards are at risk of a injury caused by reversing vehicles/vehicles rolling backwards.

Accidents, Home↗

PubMed2001

Influence of environmental and genetic factors on allergen-specific immunoglobulin-E levels in sera from Lipizzan horses.

To investigate whether allergen-specific IgE production is influenced by environmental and genetic factors, IgE levels against 2 mould extracts (Alternaria alternata [Alt a] and Aspergillus fumigatus [Asp f]) and against recombinant (r) rAlt a 1, rAsp f 7 and rAsp f 8 were determined by ELISA in sera from 448 Lipizzan horses living in 6 studfarms. Statistical evaluation showed a significant effect of studfarm-specific environment on IgE levels against the different allergens, but genetic factors also influenced allergen-specific IgE production: an heritability of 0.33 was found for IgE levels against the 2 mould extracts and of 0.21 for rAsp f 8-specific IgE. Heritability estimates for rAlt a 1- and rAsp f 7-specific IgE were negligible. Investigations for a possible association between Major Histocompatibility Complex (MHC) class I antigens and specific IgE levels were carried out. The most consistent significant association was found between the equine leucocyte antigen (ELA) A8 and undetectable IgE titres against rAsp f 7 and rAsp f 8. Significant ELA associations were also demonstrated between ELA A1 and higher specific IgE levels, between ELA A14 and lower IgE levels against the mould extracts and in one studfarm between ELA Be27 and lower Aspergillus-specific IgE levels.

Age Factors↗

PubMed2000

Detection of mammaglobin expressing cells in blood of breast cancer patients.

Expression of human mammaglobin (hMAM) was published to be exclusively expressed in mammary tissue, in solid tumors, axillary lymph nodes and disseminated cancer cells in blood of breast cancer patients. A quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) test was applied to investigate hMAM expression in blood of breast cancer patients. Mammaglobin mRNA expression was found not only in breast cancer cell lines but also in cell lines of other cancer origin. In our patient cohort hMAM expression in 11/98 (11%) samples of breast cancer and 3/12 (25%) ovarian cancer patients could be detected. hMAM mRNA expression as a candidate marker for the detection of disseminated cancer cells in blood of breast cancer patients showed low sensitivity and reduced tissue specificity. A prognostic significance of hMAM expression could not be demonstrated.

Adult↗

PubMed2000

Allergen-specific IgE levels against crude mould and storage mite extracts and recombinant mould allergens in sera from horses affected with chronic bronchitis.

Immunoglobulin E antibody (IgE) levels against four recombinant (r) mould allergens (r-Aspergillus fumigatus [rAsp f] 7, 8 and 9; r-Alternaria alternata 1 [rAlta1]) and crude mould (Aspergillus fumigatus, Alternaria alternata, Penicillium notatum) and storage mite extracts were determined by ELISA in sera from 24 pulmonary sound control horses and 26 horses suffering from chronic bronchitis/bronchiolitis (CB), also called chronic obstructive pulmonary disease (COPD). Serum IgG and IgA titres were also determined against Aspergillus fumigatus extract and rAsp f 8.IgE against the crude extracts could be measured in all sera, but there was no significant difference between CB-affected and control horses. In contrast, only 8-30% of the horses, depending on the r-allergen tested, had detectable IgE levels in serum against the r-allergens. Horses with CB had significantly more often detectable IgE levels than controls against rAlt a 1 (10/26 and 3/24, respectively, p=0. 054), rAsp f 7 (13/26 and 2/24, respectively, p<0.01) and rAsp f 8 (11/26 and 1/24, respectively, p<0.01). Only four horses (three CB-affected and one healthy, p0.05) had detectable IgE levels against rAsp f 9. Furthermore, CB-affected horses were often sensitised against two or more r-allergens (13/26 of the CB-affected horses) while only one of the 24 healthy horses had positive IgE levels against more than one r-allergens. Similarly to IgE levels, no significant differences between CB-affected and healthy horses were found for IgG titres against the Aspergillus fumigatus extract. However, horses with CB had significantly higher serum IgG titres against rAsp f 8 than healthy controls (median=28 versus 10 relative ELISA units [REU], p<0.01). Additionally, horses with detectable IgE titres against rAsp f 8 had significantly higher IgG titres against this r-allergen than horses with undetectable IgE titres (median IgG titres=46 and 13 REU, respectively; p<0.01). For serum IgA titres, neither differences between healthy and CB-affected animals nor correlations between IgA and IgG or IgE titres could be found. These results show that horses suffering from CB are more often sensitised to some Aspergillus fumigatus and Alternaria alternata allergens than control horses and that they are partly sensitised to the same fungal proteins as mould-allergic human patients. Furthermore, this study shows that r-allergens allow a much more sensitive determination of specific serum antibody levels by ELISA than crude mould extracts.

Allergens↗

PubMed2000

Hyperpolarization-activated cation currents in stellate and pyramidal neurons of rat entorhinal cortex.

Properties of hyperpolarization-activated cation currents (I(h)) were investigated in neurons of juvenile rat entorhinal cortex using the patch-clamp technique. A rat brain slice preparation containing the entorhinal cortex was used for whole-cell recordings of I(h) in pyramidal cells from layer IV and in stellate cells from layer II of the entorhinal cortex. In both stellate and pyramidal cells, I(h) activated at potentials more negative than -60 mV and did not show any time-dependent inactivation. Half-maximal activation of I(h) was achieved at -95.3 mV in pyramidal cells and at -95.0 mV in stellate cells. The channels were permeable for sodium and potassium ions. I(h) of pyramidal and stellate neurons was reduced by about 50% in the presence of 100 microM ZD7288. Extracellularly applied 1 mM Cs(+) decreased I(h) of pyramidal cells by 92%, whereas I(h) of stellate cells was only reduced by 70%. In both pyramidal and stellate neurons, I(h) was not significantly changed during the application of 1 mM Ba(2+). 8-Bromo-c-AMP increased amplitudes of I(h) in stellate cells, while I(h) of pyramidal cells remained unchanged. It is suggested that different types of hyperpolarization-activated cation channels are expressed in pyramidal and stellate cells of the entorhinal cortex.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2000

Vanadate induces calcium signaling, Ca2+ release-activated Ca2+ channel activation, and gene expression in T lymphocytes and RBL-2H3 mast cells via thiol oxidation.

Using ratiometric Ca2+ imaging and patch-clamp measurement of Ca2+ channel activity, we investigated Ca2+ signaling induced by vanadium compounds in Jurkat T lymphocytes and rat basophilic leukemia cells. In the presence of external Ca2+, vanadium compounds produced sustained or oscillatory Ca2+ elevations; in nominally Ca2+-free medium, a transient Ca2+ rise was generated. Vanadate-induced Ca2+ signaling was blocked by heparin, a competitive inhibitor of the 1,4, 5-inositol trisphosphate (IP3) receptor, suggesting that Ca2+ influx is secondary to depletion of IP3-sensitive Ca2+ stores. In Jurkat T cells, vanadate also activated the Ca2+-dependent transcription factor, NF-AT. Intracellular dialysis with vanadate activated Ca2+ influx through Ca2+ release-activated Ca2+ (CRAC) channels with kinetics comparable to those of dialysis with IP3. Neither phosphatase inhibitors nor nonhydrolyzable nucleotide analogues modified CRAC channel activation. The action of vanadate, but not IP3, was prevented by the thiol-reducing agent DTT. In addition, the activation of CRAC channels by vanadate was mimicked by the thiol-oxidizing agent chloramine T. These results suggest that vanadate enhances Ca2+ signaling via thiol oxidation of a proximal element in the signal transduction cascade.

Adenosine Triphosphate↗

PubMed2000

Prognostic value of genomic alterations in minimal residual cancer cells purified from the blood of breast cancer patients.

The prognostic value of disseminated tumour cells derived from 353 breast cancer patients was evaluated. Disseminated tumour cells were purified from blood using a newly established method and nucleic acids were subsequently isolated. We investigated genomic imbalances (GI) such as mutation, amplification and loss of heterozygosity of 13 tumour suppressor genes and 2 proto-oncogenes using DNA from isolated minimal residual cancer cells. Significant correlations were found between genomic alterations of the DCC - and c-erbB-2 genes in disseminated breast cancer cells and actuarial relapse-free survival. Furthermore, increasing numbers of genomic imbalances measured in disseminated tumour cells were significantly associated with worse prognosis of recurrent disease. Logistic regression and Cox multivariate analysis led to the identification of genomic imbalances as an independent prognostic factor. Determination of disseminated tumour cells by genotyping of oncogenes and tumour suppressor genes seems not only to be a useful adjunct in follow up of carcinoma patients but provides also valuable additional individualized prognostic and predictive information in breast cancer patients beyond the TNM system.

Adult↗

PubMed2000

Properties of entorhinal cortex projection cells to the hippocampal formation.

There are multiple connections from the entorhinal cortex (EC) to the hippocampus that carry the information from the EC to the hippocampus. Layer II cells of the medial EC innervating the dentate gyrus (DG)-molecular layer possess K(+)-outward currents and inward rectifier currents that are potentially modulated by changes in intracellular second messengers. Layer II cells responded to synaptic stimulation with a rather flat input-output curve, and much stronger stimuli are required to generate action potentials in these neurons than in EC layer III cells. During repetitive stimulation at frequencies of 10 Hz and more, EC layer II cells respond with increased likelihood to generate action potentials. Two different NMDA conductances can be demonstrated in these neurons. A slow, less Mg, less voltage-dependent component is responsible for the transient depolarization between the fast and slow IPSP. A second group of neurons also projects to the DG. These are either pyramidal or nonpyramidal cells in the deep layers of the EC. At least part of these neurons also possess rhythmogenic properties. In contrast to layer II cells, layer III neurons have a steep input-output curve and show during repetitive synaptic activation a tendency to repolarize and to display long-lasting inhibitions dependent on GABAB-, atropine-, and naloxone-sensitive components. As a consequence, they are readily activated during low frequency stimulation, but project only a few action potentials to area CA1 initially during higher (more than 10 Hz) frequency synaptic stimulation.

Animals↗