Biomedical subjects

K Schneider

Publications and source records attributed to K Schneider.

At least 37 records · Page 2Linked to original sources

PubMed2004

[5 years of "concerted action dose reduction in CT" -- what has been achieved and what remains to be done?].

In May 1998, the German "Concerted Action Dose Reduction in CT" was founded by all parties involved in CT. Its intention was to achieve a significant reduction of the radiation exposure caused by CT, a matter that has increasingly been considered a major challenge since the early nineties. As a result of a number of joint efforts, the essential preconditions have been established by now. The fifth anniversary of the Concerted Action gave rise for both retrospection and outlook on the tasks that have already been accomplished and those that still need to be done. For this purpose, a one-day symposium took place in Berlin on November 4, 2003. The contents of a total of 18 contributions will be outlined here in brief.

Adult↗

PubMed2003

Angiogenic capacity of endothelial cells in islets of Langerhans.

Transplantation of pancreatic islets reconstitutes glucose homeostasis in diabetes mellitus. Before transplantation, islets are disrupted from the surrounding blood vessels by the isolation procedure, with the grafted tissue being subject to ischemic damage. The survival of transplanted islets is assumed to depend on effective revascularization. Perfusion studies suggest that newly formed microvessels supplying the graft with nutrients are exclusively rebuilt by the host. It is generally not known whether isolated islets contain endothelial cells (EC), which potentially participate in the revascularization process. Therefore, we tried to detect immature EC in isolated islets by transformation with polyoma middle T antigen. Endothelioma cells were generated, implicating the presence of de-differentiated EC within isolated islets. When embedded in a fibrin gel, the islets developed cellular cords consisting of EC, whereas FGF-2 and VEGF stimulated the formation of cord-like structures. Furthermore, we studied the presence of donor EC in islet grafts by using transgenic mice with an EC lineage-specific promotor-LacZ reporter construct (Tie-2LacZ). Following islet transplantation, Tie-2LacZ-positive EC of both donor and recipient were identified in the vicinity of or within the graft up to 3 wk after transplantation. In conclusion, EC and/or their progenitors with angiogenic capacity reside within isolated islets of different species, and their proliferative potential can be stimulated by various inducers. These graft-related endothelia persist after islet transplantation and are integrated within newly formed microvessels.

Animals↗

PubMed2003

[Are titanium implants superior to gold implants in the tympanic cavity?].

BACKGROUND: Gold implants in reconstructive surgery of the middle ear have proved to work sufficiently: That applies to tympanic cavity conditions without signs of chronic inflammation as also to the bacterially infected middle ear. For some years titanium implants are also in the use and established as well. The biocompatibility of titanium, the clinical and the audiological results are satisfactory. When using gold-prostheses in stapes surgery however, the still unsolved problem of occasional deafness has to be considered. PATIENTS: The clinical and functional results of middle ear surgery were examined retrospectively. There was no preselection of patients. 53 patients underwent middle ear surgery with titanium prostheses, 42 patients with gold prostheses. RESULTS: Due to their material properties and due to their delicate shape titanium prostheses (PORP, TORP) can be inserted into the tympanic cavity more simply and with better fit. The audiological results of gold and titanium prostheses are comparable. The extruding rate of the gold prostheses is substantial, whereas the extruding rate of titanium is negligible. CONCLUSION: The functional results of both materials are comparable. Due to the high extruding rates of gold prostheses titanium is clearly superior.

Auditory Threshold↗

PubMed2003

Epicardial treatment of atrial fibrillation using cryoablation in an acute off-pump sheep model.

BACKGROUND: The purpose of this study was to test the feasibility and effectiveness of cryoablation therapy (SurgiFrost trade mark CryoCath, Endocare Inc., Irvine, California, USA) for linear epicardial treatment of atrial fibrillation in an acute off-pump sheep model. METHODS: After thoracotomy, we performed epicardial cryoablation (2 min intervals at -160 degrees C) with pacing electrodes positioned at the left atrial appendage (LAA), the pulmonary veins (PVs), the right atrial appendage (RAA), and the vena cava cranialis (VCC) in 8 sheep. Circular epicardial ablations were performed with online temperature measurement in the ascending aorta and in the esophagus. The sheep were sacrificed two hours after ablation procedure, and heart, lungs, and esophagus were retrieved for histological examination. Out of all 8 sheep, histo-pathological analysis was performed on the RAA and VCC in 6 sheep and on the CAA and PV in all 8 sheep. RESULTS: Thin-walled structures such as PVs and VCC showed electrical isolation. No significant changes in temperature in the descending aorta and the esophagus were observed. There was evidence of extensive transmural alteration including vascular lesions, myocardial degeneration and necrosis as well as epi- and endocardial necrosis in the left atria in three of 8 cases, in the right atria in 5 of 6 cases, in the VCC in 6 of 6 cases, and in the PV in 5 of 8 cases. Mild lesions of the muscular layer of the esophagus were found in 7 of 8 cases. CONCLUSIONS: Epicardial cryoablation is not effective on thicker tissues like LAA and RAA due to the rewarming of the current blood flow. However, thin tissues like VCC and PV can be isolated. Further chronic studies are necessary to evaluate the potential for regeneration of adjacent structures.

Animals↗

PubMed2002

[Role of radiotherapy in non-small cell lung cancer].

Lung cancer has the highest cancer mortality in Switzerland. 80% of all lung cancer patients are patients with non-small cell lung cancer. Despite advances in the pre-treatment evaluation and treatment strategies, cure for non-small cell lung cancer ist still rare. Multimodality approaches specifically for locally advanced non-small cell lung cancer are among the most promising strategies to improve long term tumour control. In this paper we discuss the role of radical primary and adjuvant radiotherapy for a stage one to four non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗

PubMed2002

Mapping neutralizing and non-neutralizing epitopes on the capsid protein of feline calicivirus.

Neutralizing epitopes on feline calicivirus (FCV) capsid protein were mapped using chimeric capsid proteins recombinant between two FCV isolates that do not show any cross-neutralization. The three chimeric proteins examined were expressed in murine L929 cells employing an MVA/T7 vaccinia virus expression system and inoculated into major histocompatibility complex haplotype-matched C3/HN mice. Based on the neutralizing antibody titre the neutralizing epitope(s) could be mapped to the 5' hypervariable region of the E region or potentially to the C region. The epitopes of some non-neutralizing antibodies were mapped with the same chimeric proteins to the regions B or D and F of the FCV capsid protein.

Animals↗

PubMed2002

Time extrapolation and interspecies extrapolation for locally acting substances in case of limited toxicological data.

In the case of substances with a limited toxicological data base there is often (i) a lack of qualified human toxicological data; and (ii) a paucity of studies with adequate exposure duration. Hence, several extrapolations have to be performed to arrive at appropriate risk assessments or derive occupational exposure limits. The present paper deals with the possibilities for extrapolating the change in effect concentrations over time (time extrapolation, e.g. from subacute to chronic exposure) and for interspecies extrapolation (from animal to human) in connection with locally acting substances (respiratory toxicants). To justify the time extrapolation factors, 46 technical reports produced by the US National Toxicology Program (NTP) involving studies with subacute, subchronic and chronic exposure duration were evaluated. On the basis of geometric mean values, decreases in effect concentrations by factors of 3.2 (subacute --> subchronic), 2.7 (subchronic --> chronic) and 6.6 (subacute --> chronic) were found. Differentiation according to animal species (mouse, rat), sex or substance properties did not result in any relevant changes of the mean value. NTP studies with less than lifetime exposure periods (subacute, subchronic) in many cases showed different locations of respiratory effects compared with chronic studies, and thus offered limited possibilities for qualitative prediction of long-term respiratory effects (occurrence of effects in certain regions of the respiratory tract). With regard to interspecies extrapolation, gaseous and particulate substances were evaluated separately. With some modifications (e.g. consideration of the clearance of particles of low solubility), the 1994 US Environmental Protection Agency (EPA) model for deriving reference concentrations for humans on the basis of experimental data in animals is proposed for inhalable particulate substances. In the case of gaseous substances, the assumptions of the EPA model do not seem to consider sufficiently the local inhomogeneity in substance distribution and anatomical and histological differences between the upper respiratory tracts of rodents and humans. Considerable uncertainty would attach to a default factor for interspecies extrapolation for gaseous substances.

Administration, Inhalation↗

PubMed2001

Coherent vortex extraction in 3D turbulent flows using orthogonal wavelets.

This Letter presents a wavelet technique for extracting coherent vortices from three-dimensional turbulent flows, which is applied to a homogeneous isotropic turbulent flow at resolution N = 256(3). The coherent flow is reconstructed from only 3%N wavelet coefficients that retain the vortex tubes, and 98.9% of the energy with the same k(-5/3) spectrum as the total flow. In contrast, the remaining 97%N wavelet coefficients correspond to the incoherent flow which is structureless, decorrelated, and whose effect can therefore be modeled statistically.

Journal Article↗

PubMed2001

The Fe-only nitrogenase from Rhodobacter capsulatus: identification of the cofactor, an unusual, high-nuclearity iron-sulfur cluster, by Fe K-edge EXAFS and 57Fe Mössbauer spectroscopy.

Samples of the dithionite-reduced FeFe protein (the dinitrogenase component of the Fe-only nitrogenase) from Rhodobacter capsulatus have been investigated by 57Fe Mössbauer spectroscopy and by Fe and Zn EXAFS as well as XANES spectroscopy. The analyses were performed on the basis of data known for the FeMo cofactor and the P cluster of Mo nitrogenases. The prominent Fourier transform peaks of the Fe K-edge spectrum are assigned to Fe-S and Fe-Fe interactions at distances of 2.29 A and 2.63 A, respectively. A significant contribution to the Fe EXAFS must be assigned to an Fe backscatterer shell at 3.68 A, which is an unprecedented feature of the trigonal prismatic arrangement of iron atoms found in the FeMo cofactor of nitrogenase MoFe protein crystal structures. Additional Fe...Fe interactions at 2.92 A and 4.05 A clearly indicate that the principal geometry of the P cluster is also conserved. Mössbauer spectra of 57Fe-enriched FeFe protein preparations were recorded at 77 K (20 mT) and 4.2 K (20 mT, 6.2 T), whereby the 4.2 K high-field spectrum clearly demonstrates that the cofactor of the Fe-only nitrogenase (FeFe cofactor) is diamagnetic in the dithionite-reduced ("as isolated") state. The evaluation of the 77 K spectrum is in agreement with the assumption that this cofactor contains eight Fe atoms. In the literature, several genetic and biochemical lines of evidence are presented pointing to a significant structural similarity of the FeFe, the FeMo and and the FeV cofactors. The data reported here provide the first spectroscopic evidence for a structural homology of the FeFe cofactor to the heterometal-containing cofactors, thus substantiating that the FeFe cofactor is the largest iron-sulfur cluster so far found in nature.

Ferredoxins↗

PubMed2001

Evidence that inhibition of cathepsin-B contributes to the neuroprotective properties of caspase inhibitor Tyr-Val-Ala-Asp-chloromethyl ketone.

During the use of tetrapeptide and other proprietary caspase inhibitors in the study of neurodegeneration, we had concluded that mechanisms other than the inhibition of caspases contributed to the protective effects of certain caspase inhibitors. Here we report our studies to identify a target for and hence a mechanism by which the tetrapeptide inhibitor tyrosine-valine-alanine-aspartate-chloromethyl ketone (Ac-YVAD-cmk) is able to rescue neuronal cell cultures from cell death. Ac-YVAD-cmk rescued neuronal cells from cell death in response to oxidative stress and oxygen/glucose deprivation. Affinity labeling with biotinylated YVAD-cmk demonstrated distinct binding proteins for the inhibitor in cells from the central nervous system versus Jurkat cells. Binding to the novel target protein was displaced by class-specific protease inhibitors and suggested that the target is a cysteine protease. Affinity purification and sequencing identified the target as cathepsin-B. Cathepsin-B inhibitors competed with biotinylated YVAD-cmk for the target protein. The availability of the target for binding was reduced in cells that had been rescued by unlabeled inhibitor. Cathepsin-B inhibitors rescue hippocampal slices from cell death induced by oxygen/glucose deprivation. These data provide evidence to support a role for cathepsin-B in neuronal cell death, particularly that following ischemia.

Amino Acid Chloromethyl Ketones↗

PubMed2001

Prodomain processing of Asp1 (BACE2) is autocatalytic.

Generation of the amyloid peptide through proteolytic processing of the amyloid precursor protein by beta- and gamma-secretases is central to the etiology of Alzheimer's disease. The highly elusive beta-secretase was recently identified as a transmembrane aspartic proteinase, Asp2 (BACE). The Asp2 homolog Asp1 (BACE2/DRAP) has also been reported to exhibit beta-secretase cleavage of amyloid precursor protein. Most aspartic proteinases are generated as inactive proenzymes, requiring removal of the prodomain to generate active proteinase. Here we show that prodomain processing of Asp1 occurs between Leu(62) and Ala(63) and is autocatalytic. Asp1 cleaved a maltose-binding protein-Asp1 prodomain fusion protein and a synthetic peptide at this site. Mutation of one of the conserved catalytic aspartic acid residues in the active site of Asp1 to asparagine (D110N) abolished this cleavage. Mutation of P(1)' and P(2)' residues in the substrate to phenylalanine reduced cleavage at this site. Asp1 expressed in cells was the mature form, and prodomain processing occurred intramolecularly within the endoplasmic reticulum/early Golgi. Interestingly, a proportion of mature Asp1 was expressed on the cell surface. When full-length Asp1(D110N) was expressed in COS-7 cells, it was not processed, suggesting that no other proteinase can activate Asp1 in these cells.

Amino Acid Sequence↗

PubMed2001

Relative biological efficiency for the induction of various gene mutations in normal and enriched with 10B Tradescantia cells by neutrons from 252Cf source.

The effectiveness of neutrons from a Californium-252 source in the induction of various abnormalities in the Tradescantia clone 4430 stamen hair cells (Trad-SH assay) were studied. A special attention was paid to check whether any enhancement in effects is visible in the cells enriched with boron ions. Inflorescences, normal or pretreated with chemicals containing boron, were irradiated in the air with neutrons from a 252Cf source at KAERI, Taejon, Korea. To estimate the relative biological effectiveness (RBE) of the beam under the study, numbers of Tradescantia inflorescence without chemical pretreatment were irradiated with various doses of X-rays. The ranges of radiation doses used for neutrons were 0-1.0Gy and for X-rays 0-0.5Gy. Following the culturing according to standard procedures screening of gene and lethal mutations in somatic cells of stamen hairs was done in the extended period, between days 7 and 19 after exposures. Maximal RBE values for the induction of pink, colorless and lethal mutations were evaluated from comparison of the slopes in linear parts of the dose response curves obtained after irradiation with X-rays and californium source. The RBE(max) value or the induction of gene mutation was estimated as 7.2 comparing the value 5.6 in the studies reported earlier. The comparison of dose-response curves and its alteration, due to changes in the cells and plants environment during and after irradiation, explains the observed differences. Inflorescence pretreated with borax responded to neutrons differently depending on the biological end points. Although, for the induction of pink mutations no significant difference was observed, though, in the case of cell lethality, pretreated with boron ion plants have shoved a statistically significant increase of the RBE value from 5.5 to 34.7, and in the case of colorless mutations from 1.6 to 5.6.

Boron↗

PubMed2001

The PDB data uniformity project.

The Protein Data Bank (PDB; http://www.rcsb.org/pdb/) is the single worldwide archive of structural data of biological macromolecules. This paper describes the data uniformity project that is underway to address the inconsistency in PDB data.

Databases, Factual↗

PubMed2001

Paediatric fluoroscopy--a survey of children's hospitals in Europe. I. Staffing, frequency of fluoroscopic procedures and investigation technique.

BACKGROUND: Fluoroscopy is an important, sometimes vital radiological procedure in paediatric patients with high variability in frequency and technique. OBJECTIVE: To obtain data on paediatric fluoroscopy practice in Europe using a simple questionnaire mailed to 191 children's hospitals. RESULTS: Eighty-eight radiology departments in 21 European countries participated in the survey. There was great variation in the size of paediatric hospitals in Europe and, consequently, the numbers of staff members (radiographers and radiologists). The total number of fluoroscopy procedures varied widely; the mean value was 1,073 examinations per year. The most frequent fluoroscopic examination was the micturating cystourethrogram, comprising 40% of total fluoroscopies. For all types of investigations there were enormous differences in the number of spot film images routinely obtained. Only a few departments have prepared protocols for junior doctors or radiographers. CONCLUSIONS: Although the number of fluoroscopic investigations per radiologist does not reflect real workload (the difficulty of the investigation was not requested), it can be stated that a considerable percentage of children's hospitals are understaffed. These results also clearly demonstrate that fluoroscopy guidelines for the most common investigations in paediatric patients are needed to improve the quality of examinations and limit radiation exposure to the patients.

Europe↗

PubMed2001

Retinal detachment and cataract, facial dysmorphism, generalized osteoporosis, immobile spine and platyspondyly in a consanguinous kindred--a possible new syndrome.

We report on a consanguineous family with 6 children (out of 7) affected by a spondylo-ocular syndrome. Clinical features include cataract, loss of vision due to retinal detachment, facial dysmorphism, facial hypotonia, normal height with disproportional short trunk, immobile spine with thorakal kyphosis and reduced lumbal lordosis. On ophthalmological examination of the index patient, a dense cataract and complete retinal detachment could be detected on the right eye. On the left eye, an absent lens nucleus was found, but no retinal detachment. On radiological examination, there was generalized moderate osteoporosis; the spine showed marked platyspondyly and the bone age was advanced. On laboratory investigations, a normal excretion of amino acids, mucopolysaccharides and oligosaccharides could be found. The phenotypical spectrum observed in the 6 affected individuals was rather uniform. The karyotype was normal in all affected children. This hitherto undescribed combination of oculo-skeletal symptoms shows most resemblance with connective tissue disorders, suggesting a range of candidate genes for mutation analysis.

Abnormalities, Multiple↗

PubMed2001

A conscious-rabbit model to study vardenafil hydrochloride and other agents that influence penile erection.

Experimental models to study the effect of agents on penile erection usually include electrical stimulation of peripheral nerves in anesthetized animals combined with systemic or intracavernous injection of drugs. The objective of this study was to demonstrate that conscious rabbits can be used as a simple and quantitative model for the assessment of compounds that show potential for the treatment of erectile dysfunction. Erection was assessed by measuring the length of uncovered penile mucosa before and after the intravenous (i.v.) administration of agents. Animals did not require anesthesia during the course of the study. The phosphodiesterase 5 (PDE5) inhibitors vardenafil x HCl (hereafter called vardenafil) and sildenafil were given intravenously, and measurements were taken for 0-5 h. The effects of phentolamine and milrinone were also evaluated. Vardenafil (0.1-3 mg/kg) induced dose-dependent penile erections in conscious rabbits following i.v. administration. The efficacy of vardenafil was potentiated, and the minimal effective dose was reduced significantly to 0.01 mg/kg by simultaneous administration of the nitric oxide (NO) donor sodium nitroprusside (SNP). Administration of the NO-synthase inhibitor L-NAME abolished the effect. Sildenafil was effective in this model after i.v. administration. The alpha-adrenergic receptor antagonist phentolamine (0.1, 0.3 and 1 mg/kg i.v.) induced erections with a slower t(max) compared with vardenafil and sildenafil. Intravenous administration of the PDE3 inhibitor milrinone (1 mg/kg i.v.) was less effective than the PDE5 inhibitor vardenafil. The conscious rabbit is a suitable and reliable model for the evaluation of compounds with potential for the treatment of erectile dysfunction. This was demonstrated using compounds that target different signaling pathways that induce smooth muscle relaxation in the penis.

Adrenergic alpha-Antagonists↗

PubMed2001

FeMo cofactor biosynthesis in a nifE- mutant of Rhodobacter capsulatus.

In all diazotrophic micro-organisms investigated so far, mutations in nifE, one of the genes involved in the biosynthesis of the FeMo cofactor (FeMoco), resulted in the accumulation of cofactorless inactive dinitrogenase. In this study, we have found that strains of the phototrophic non-sulfur purple bacterium Rhodobacter capsulatus with mutations in nifE, as well as in the operon harbouring the nifE gene, were capable of reducing acetylene and growing diazotrophically, although at distinctly lower rates than the wild-type strain. The diminished rates of substrate reduction were found to correlate with the decreased amounts of the dinitrogenase component (MoFe protein) expressed in R. capsulatus. The in vivo activity, as measured by the routine acetylene-reduction assay, was strictly Mo-dependent. Maximal activity was achieved under diazotrophic growth conditions and by supplementing the growth medium with molybdate (final concentration 20-50 microM). Moreover, in these strains a high proportion of ethane was produced from acetylene ( approximately 10% of ethylene) in vivo. However, in in vitro measurements with cell-free extracts as well as purified dinitrogenase, ethane production was always found to be less than 1%. The isolation and partial purification of the MoFe protein from the nifE mutant strain by Q-Sepharose chromatography and subsequent analysis by EPR spectroscopy and inductively coupled plasma MS revealed that FeMoco is actually incorporated into the protein (1.7 molecules of FeMoco per tetramer). On the basis of the results presented here, the role of NifNE in the biosynthetic pathway of the FeMoco demands reconsideration. It is shown for the first time that NifNE is not essential for biosynthesis of the cofactor, although its presence guarantees formation of a higher content of intact FeMoco-containing MoFe protein molecules. The implications of our findings for the biosynthesis of the FeMoco will be discussed.

Acetylene↗

PubMed2001

Chicken interleukin-6. cDNA structure and biological properties.

Suppression subtractive hybridization technology was used to identify differentially expressed genes in spleens of chickens that had been treated with the synthetic immune modifier S-28463. One induced chicken gene encoded a protein with about 35% sequence identity to human interleukin-6 (IL-6). It consists of 241 amino acids including a putative N-terminal signal peptide of 47 residues. Bacterially expressed chicken IL-6 (ChIL-6) carrying a histidine tag in place of the signal peptide was biologically active: it induced proliferation of the IL-6-dependent murine hybridoma cell line 7TD1. The concentration of ChIL-6 required for half-maximal proliferative response was approximately 60 pg.mL-1. When injected intravenously into adult chickens, purified recombinant ChIL-6 induced an increase in serum corticosterone levels. Supernatants of chicken LMH and monkey COS-7 cells transiently transfected with a ChIL-6 expression construct induced proliferation of 7TD1 cells, demonstrating that recombinant ChIL-6 from eukaryotic cells is also active.

Amino Acid Sequence↗