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Biomedical subjects

M Krauss

Publications and source records attributed to M Krauss.

At least 19 recordsLinked to original sources
PubMed2006

Spin-flip processes and ultrafast magnetization dynamics in Co: Unifying the microscopic and macroscopic view of femtosecond magnetism.

The femtosecond magnetization dynamics of a thin cobalt film excited with ultrashort laser pulses has been studied using two complementary pump-probe techniques, namely, spin-, energy-, and time-resolved photoemission and the time-resolved magneto-optical Kerr effect. Combining the two methods, it is possible to identify the microscopic electron spin-flip mechanisms responsible for the ultrafast macroscopic magnetization dynamics of the cobalt film. In particular, we show that electron-magnon excitation does not affect the overall magnetization even though it is an efficient spin-flip channel on the sub-200 fs time scale. Instead, we find experimental evidence for the relevance of Elliott-Yafet-type spin-flip processes for the ultrafast demagnetization taking place on a time scale of 300 fs.

Journal Article↗
PubMed2006

Spermidine synthase is prominently expressed in the striatal patch compartment and in putative interneurones of the matrix compartment.

The ubiquitous polyamines spermidine and spermine are known as modulators of glutamate receptors and inwardly rectifying potassium channels. They are synthesized by a set of specific enzymes in which spermidine synthase is the rate-limiting step catalysing the formation of the spermine precursor spermidine from putrescine. Spermidine and spermine were previously localized to astrocytes, probably reflecting storage rather than synthesis in these cells. In order to identify the cellular origin of spermidine and spermine synthesis in the brain, antibodies were raised against recombinant mouse spermidine synthase. As expected, strong spermidine synthase-like immunoreactivity was obtained in regions known to express high levels of spermidine and spermine, such as the hypothalamic paraventricular and supraoptic nuclei. In the striatum, spermidine synthase was found in neurones and the neuropil of the patch compartment (striosome) as defined by expression of the micro opiate receptor. The distinct expression pattern of spermidine synthase, however, only partially overlapped with the distribution of the products spermidine and spermine in the striatum. In addition, spermidine synthase-like immunoreactivity was seen in patch compartment-apposed putative interneurones. These spermidine synthase-positive neurones did not express any marker characteristic of the major striatal interneurone classes. The neuropil labelling in the patch compartment and in adjacent putative interneurones may indicate a role for polyamines in intercompartmental signalling in the striatum.

Animals↗
PubMed2001

Biomimetic extraction of PAHs and PCBs from soil with octadecyl-modified silica disks to predict their availability to earthworms.

We developed a model to predict the availability of PAHs and PCBs to earthworms (Lumbricus terrestris L.) in soils. We related the uptake of PAHs and PCBs by earthworms to the extraction with octadecyl-modified silica disks (C18 disks). Eleven soils (data set A) were used to develop the model, and 14 additional soils (data set B) were used to validate it independently. The biota-to-soil accumulation factors (BSAFs) of higher molecular weight PAHs (> or =202 g mol(-1)) and PCBs were higher than the corresponding Cl8 disk-soil partition coefficients (Kdisk) in the soils of data set A. This suggested that PAHs and PCBs were not only partitioned between soil and earthworms but also selectively ingested or metabolized. Nevertheless, we could predict the BSAFs of individual PAHs and PCBs for data set A by regression equations of log BSAF on log Kdisk (r=0.47-0.87). To predict the BSAFs of all PAHs and PCBs, respectively, we derived a model for each compound class that uses Kdisk and K(ow) values. Both the compound and the compound-class specific model were suitable to predict the BSAFs of PAHs and PCBs in data set B within a factor of 10-15.

Animals↗
PubMed2001

Active site structure and mechanism of human glyoxalase I-an ab initio theoretical study.

The structure of the active site of human glyoxalase I and the reaction mechanism of the enzyme-catalyzed conversion of the thiohemiacetal, formed from methylglyoxal and glutathione, to S-D-lactoylglutathione has been investigated by ab initio quantum chemical calculations. To realistically represent the environment of the reaction center, the effective fragment potential methodology has been employed, which allows systems of several hundred atoms to be described quantum mechanically. The methodology and the active site model have been validated by optimizing the structure of a known enzyme-inhibitor complex, which yielded structures in good agreement with the experiment. The same crystal structure has been used to obtain the quantum motif for the investigation of the glyoxalase I reaction. The results of our study confirm that the metal center of the active site zinc complex plays a direct catalytic role by binding the substrate and stabilizing the proposed enediolate reaction intermediate. In addition, our calculations yielded detailed information about the interactions of the substrate, the reaction intermediates, and the product with the active site of the enzyme and about the mechanism of the glyoxalase I reaction. The proton transfers of the reaction proceed via the two highly flexible residues Glu172 and Glu99. Information about the structural and energetic effect of the protein on the first-shell complex has been attained by comparison of the structures optimized in the local protein environment and in a vacuum. The environment of the zinc complex disturbs the Cs symmetry found for the complex in a vacuum, which suggests an explanation for the stereochemical behavior of glyoxalase I.

Catalytic Domain↗
PubMed2001

Human stoned B interacts with AP-2 and synaptotagmin and facilitates clathrin-coated vesicle uncoating.

Synaptic vesicle biogenesis involves the recycling of synaptic vesicle components by clathrin-mediated endocytosis from the presynaptic membrane. stoned B, a protein encoded by the stoned locus in Drosophila melanogaster has been shown to regulate vesicle recycling by interacting with synaptotagmin. We report here the identification and characterization of a human homolog of stoned B (hStnB). Human stoned B is a brain-specific protein which co-enriches with other endocytic proteins such as AP-2 in a crude synaptic vesicle fraction and at nerve terminals. A domain with homology to the medium chain of adaptor complexes binds directly to both AP-2 and synaptotagmin and competes with AP-2 for the same binding site within synaptotagmin. Finally we show that the mu 2 homology domain of hStnB stimulates the uncoating of both clathrin and AP-2 adaptors from clathrin-coated vesicles. We hypothesize that hStnB regulates synaptic vesicle recycling by facilitating vesicle uncoating.

Adaptor Proteins, Vesicular Transport↗
PubMed2001

Randomised trial of acupuncture compared with conventional massage and "sham" laser acupuncture for treatment of chronic neck pain.

OBJECTIVES: To compare the efficacy of acupuncture and conventional massage for the treatment of chronic neck pain. DESIGN: Prospective, randomised, placebo controlled trial. SETTING: Three outpatient departments in Germany. PARTICIPANTS: 177 patients aged 18-85 years with chronic neck pain. INTERVENTIONS: Patients were randomly allocated to five treatments over three weeks with acupuncture (56), massage (60), or "sham" laser acupuncture (61). MAIN OUTCOME MEASURES PRIMARY OUTCOME MEASURE: maximum pain related to motion (visual analogue scale) irrespective of direction of movement one week after treatment. SECONDARY OUTCOME MEASURES: range of motion (3D ultrasound real time motion analyser), pain related to movement in six directions (visual analogue scale), pressure pain threshold (pressure algometer), changes of spontaneous pain, motion related pain, global complaints (seven point scale), and quality of life (SF-36). Assessments were performed before, during, and one week and three months after treatment. Patients' beliefs in treatment were assessed. RESULTS: One week after five treatments the acupuncture group showed a significantly greater improvement in motion related pain compared with massage (difference 24.22 (95% confidence interval 16.5 to 31.9), P=0.0052) but not compared with sham laser (17.28 (10.0 to 24.6), P=0.327). Differences between acupuncture and massage or sham laser were greater in the subgroup who had had pain for longer than five years (n=75) and in patients with myofascial pain syndrome (n=129). The acupuncture group had the best results in most secondary outcome measures. There were no differences in patients' beliefs in treatment. CONCLUSIONS: Acupuncture is an effective short term treatment for patients with chronic neck pain, but there is only limited evidence for long term effects after five treatments.

Acupuncture Analgesia↗
PubMed2001

Predicting soil-water partitioning of polycyclic aromatic hydrocarbons and polychlorinated biphenyls by desorption with methanol-water mixtures at different temperatures.

We evaluated a method to determine organic carbon-normalized soil-water partition coefficients (Koc) of 20 PAHs and 12 PCBs by desorption in the presence of a cosolvent (methanol fractions of 0.1-0.9) and at different temperatures (20-80 degrees C). The Koc values, the deviation factor from ideal sorption alpha, and the desorption enthalpies delta Hdes were estimated by nonlinear regression of log Koc on the methanol fractions and on T. The Koc values of individual compounds varied up to a factor of 100 among the studied 11 urban soils. The calculated alpha and delta Hdes of individual compounds varied considerably among the soils (coefficients of variation 5-20% and 20-30%, respectively), alpha increased with increasing hydrophobicity of the compounds. A sequential extraction with four temperature/methanol fraction combinations followed by a nonlinear regression allowed for the direct determination of the Koc, alpha, and delta Hdes. The use of less temperature/methanol fraction combinations requires a suitable estimation of alpha and delta Hdes, as their choice may change the obtained Koc values by up to a factor of 10. The proposed method is suitable for a routine determination of Koc values of PAHs and PCBs for small soil samples (2-6 g) and low concentrations (down to 0.3 mg kg-1 of sigma 20 PAHs and 1.2 micrograms kg-1 of sigma 12 PCBs).

Environmental Monitoring↗
PubMed2001

The knee joint in early juvenile idiopathic arthritis. An ROC study for evaluating the diagnostic accuracy of contrast-enhanced MR imaging.

PURPOSE: Diagnosis of juvenile idiopathic arthritis (JIA) remains difficult due to unspecific clinical and laboratory findings, especially in early stages of the disease. The purpose of our study was to determine the sensitivity and specificity of MR imaging in diagnosing JIA of the knee joints. MATERIAL AND METHODS: Forty children (3-17 years old) clinically diagnosed with JIA (follow-up > 1 year) of a knee joint and a control group of 40 children with painful knee joints (MR diagnosis: bone bruise of the knee (n = 7), normal knee joint (n = 12), osteomyelitis (n = 6), septic arthritis (n = 2), bone tumor (n = 7) and miscellaneous bone lesions (n = 6)) were examined using a 1.5 T MR unit. T1-weighted spin-echo (SE), T2-weighted fast SE, contrast-enhanced T1-weighted SE and 2D gradient echo sequences were performed. The receiver operating characteristic (ROC) curves evaluation was conducted by 5 independent radiologists. RESULTS: The positive criteria for diagnosing JIA were joint effusions (n = 40), contrast-enhancing synovitis (n = 39), cartilage lesions (n = 15), subchondral erosions and bony destruction (n = 1). Sensitivity and specificity were 93.5% and 92.5%, respectively. Both cases of septic arthritis were misdiagnosed as JIA by all radiologists. CONCLUSION: Contrast-enhanced MR imaging seems to be a highly sensitive tool in establishing the diagnosis of JIA.

Adolescent↗
PubMed2000

Binding properties of agonists and antagonists to distinct allosteric states of the nicotinic acetylcholine receptor are incompatible with a concerted model.

Recent work has shown that the nicotinic acetylcholine receptor (nAChR) can be fixed in distinct conformations by chemical cross-linking with glutardialdehyde, which abolishes allosteric transitions in the protein. Here, two conformations that resemble the desensitized and the resting states were compared with respect to their affinities for different classes of ligands. The same ligands were tested for their ability to convert the nAChR from a conformation with low affinity to a conformation with high affinity for acetylcholine. As expected, agonists were found to bind with higher affinity to the desensitized state-like conformation and to induce a shift of the nAChR to this high affinity state. In contrast, although most antagonists tested bound preferentially to the desensitized receptor as well they failed to induce a change of the affinity for acetylcholine. These observations sharply contradict basic predictions of the concerted model, including the postulate of a preformed equilibrium between the different states of the nAChR in the absence of agonist. With a similar approach we could show that the non-competitive inhibitor ethidium is displaced in a non-allosteric manner by other well characterized channel blockers from the cross-linked nAChR. These results require revision of current models for the mechanisms underlying non-competitive antagonism at the nAChR.

Acetylcholine↗
PubMed2000

Environmental tobacco smoke and lung cancer: a case-control study in Germany.

To assess the association between exposure to environmental tobacco smoke (ETS) and lung cancer, the authors personally interviewed 292 lifelong nonsmoking lung cancer cases (recruited from 15 hospitals in the study area) and 1,338 nonsmoking controls (randomly selected by population registries) between 1990 and 1996 in Germany. Subjects were asked by a standardized questionnaire about exposure to ETS in childhood, by spouse, at work, and in transportation and social settings. Several indicators of these different sources of exposure were investigated, using not or low exposed subjects as the reference category. The most informative quantification index was weighted duration of exposure (hours x level of smokiness). No effect of ETS exposure during childhood and no clear effect of spousal ETS were observed. However, for the highest category of exposure, clear effects of ETS at the workplace (odds ratio (OR) = 1.93; 95% confidence interval (CI): 1.04, 3.58), in vehicles (OR = 2.64; 95% CI: 1.30, 5.36), and from all sources combined (OR = 1.39; 95% CI: 0.96, 2.01) were found. Adjustment for occupational carcinogens, radon, and diet did not appreciably change the results. These findings suggest that exposures to high levels of ETS at the workplace and in other public indoor settings appear to be important risk factors for lung cancer risk in nonsmokers.

Aged↗
PubMed2000

Effective fragment potentials and the enzyme active site.

Optimization of the binding conformation of a substrate in an enzyme active site using ab initio quantum chemistry methods are intractable since the active site comprises several hundred atoms. However, the active site can be decomposed into an active and spectator region where the spectator residues are represented by effective fragment potentials and reducing the number of all-electron atoms involved in the chemistry to a reasonable level. The effective fragment potentials for electrostatics and polarization are implemented in GAMESS but the repulsive and charge transfer potentials are fit to interaction energies of water with models of the residues. These repulsive/charge transfer potentials are generated for the protein residues and the EFP are then used to optimize binding of a transition state analogue to chorismate mutase (B. subtilis) and small dianions to ribonuclease A. For chorismate mutase the calculated binding conformation compares well to the comparable X-ray structure. The binding of the inhibitor to the glutamate/glutamine mutant active site is then predicted with the optimization including the glutamine residue constrained only at the C alpha atom. The binding conformations suggest important roles for tyr108 and arg63, which have not been noted earlier. The electrostatic stabilization of the transition state by the active site charge distribution has to be augmented by a specific electronic activation by glu78. In ribonuclease A, the protons are found to move to provide a clustering of the charges to bind the small dianions, phosphate, thiophosphate, and sulfate.

Binding Sites↗
PubMed2000

Polycyclic aromatic hydrocarbons and polychlorinated biphenyls in forest soils: depth distribution as indicator of different fate.

We determined 20 polycyclic aromatic hydrocarbons (PAHs) and 12 polychlorinated biphenyls (PCBs) in Oi, Oe, and Oa horizons and at 0-5 and 15-20 cm mineral soil depth of 16 Norway spruce (Picea abies) stands in north Bavaria. The sum of PAH concentrations increased along the line Oi (mean+/-SD: 841+/-330 microg kg(-1))<Oe (4117+/-3093)<Oa (9272+/-5721) while that of PCBs was higher in Oe (39.1+/-19.4 microg kg(-1)) than in Oi (12.1+/-6.5) but similar in Oe and Oa (46.0+/-39.4). The sum of both PAH (0-5 cm: 666+/-707/15-20 cm: 95+/-165) and PCB concentrations (1.7+/-1.5/0.28+/-0.20) decreased sharply in the mineral soil. The concentration ratios of an individual compound in the Oe to that in the Oi (enrichment factor, e(Oe/Oi)) and the analogously calculated e(Oa/Oe) correlated significantly (p<0.001) with the octanol-water partition coefficient (K(ow), r=0.94 and 0.93 for PAHs; r=0.91 and 0.83 for PCBs, respectively). The enrichment factors of PAHs were consistently higher than those of PCBs with comparable K(ow). This may be explained by a higher volatilisation rate of the PCBs or a stronger sorption of PAHs to soil. In the mineral soil, the concentrations of most PAHs and PCBs decreased with increasing depth, except those of naphthalene and the PCBs 8, 20, 28, and 52. In the mineral soil, the enrichment factors e(0-5/Oa) and e(15-20/0-5) of the PCBs 8, 20, 28, and 52 were, on average, 10 times higher than those of PAHs with similar K(ow) values indicating a more pronounced leaching of PCBs than of PAHs. The results demonstrate that the fate of PAHs in forest soils is markedly different from that of PCBs.

Journal Article↗
PubMed2000

Structure-activity relationship and site of binding of polyamine derivatives at the nicotinic acetylcholine receptor.

Several wasp venoms contain philanthotoxins (PhTXs), natural polyamine amides, which act as noncompetitive inhibitors (NCIs) on the nicotinic acetylcholine receptor (nAChR). Effects of varying the structure of PhTXs and poly(methylene tetramine)s on the binding affinity have been investigated. Using the fluorescent NCI ethidium in a displacement assay Kapp values of these compounds have been determined. We found that an increase in size of the PhTX's hydrophobic head group significantly increased the binding affinity, while inserting positive charge almost completely destroyed it. Elongating the PhTX polyamine chain by introducing an additional aminomethylene group decreased the binding affinity, whereas a terminal lysine improved it. In general, poly(methylene tetramine)s showed higher binding affinities than PhTX analogues. The stoichiometry of PhTX binding was determined to be two PhTX molecules per receptor monomer. PhTXs appeared to bind to a single class of nonallosterically interacting binding sites and bound PhTX was found to be completely displaced by well-characterized luminal NCIs. To elucidate the site of PhTX binding, a photolabile, radioactive PhTX derivative was photocross-linked to the nAChR in its closed channel conformation resulting in labeling yields for the two alpha and the beta, gamma and delta subunits of 10.4, 11.1, 4.0 and 7.4%, respectively. Based on these findings we suggest that PhTXs and poly(methylene tetramine)s enter the receptor's ionic channel from the extracellular side. The hydrophobic head groups most likely bind to the high-affinity NCI site, while the positively charged polyamine chains presumably interact with the negatively charged selectivity filter located deep in the channel lumen.

Binding Sites↗
PubMed2000

[3D vascular imaging with power mode in planning and controlling percutaneously implanted abdominal aortic stent grafts].

PURPOSE: Evaluation of the reliability of vascular ultrasound with power mode and 3D-power mode for preinterventional planning before endovascular treatment of abdominal aortic aneurysms and postoperative follow-up after endografting. MATERIAL AND METHOD: A new real-time 3D technique with power mode flow imaging was used in a prospective study of 75 patients with infrarenal aortic aneurysms, in 25 cases before and in 50 cases after stentgraft implantation. The results of vascular ultrasound with color-coded duplex sonography (CCDS), power mode and 3D power mode were compared with CTA and DSA in all cases. RESULTS: Only the length and diameter of the aneurysm could be reliably measured by sonography. Additional 3D reconstructions could show flow parameters in the aneurysm more clearly, but imaging of the proximal and distal anchoring zone was only achieved insufficiently. After stentgraft implantation, possible complications like thrombus formation in the graft (4/50) and endoleaks (15/50) were clearly seen by power sonography. 9 anchoring leaks and 6 side-branch endoleaks were found. 3D power mode made localizing and imaging of aneurysm reperfusion easier. Detection of the origin of side-branch endoleaks was achieved only by DSA. Stent frame fractures (4/50) were difficult to see by ultrasound. CONCLUSIONS: Vascular ultrasound with power mode and 3D power mode makes the imaging of complications after endoaortic stentgraft implantation like endoluminal thrombus formation or endoleaks and the documentation of aneurysm reperfusion easier compared to CCDS. 3D reconstructions show the dimensions of the aneurysm but are not able to substitute CTA and DSA with measuring catheter for preinterventional planning.

Aged↗
PubMed2000

Aortic aneurysm size and graft behavior after endovascular stent-grafting: clinical experiences and observations over 3 years.

PURPOSE: To assess the long-term safety and efficacy of aortic endografts in terms of clinical outcome, continuing aneurysm exclusion, and changes of aneurysm size and graft configuration. METHODS: Between August 1994 and July 1997, 190 patients (176 men; mean age 68.7 years, range 40-87) with aortic and aortoiliac aneurysms were treated with endovascular stent-grafts (Stentor, Vanguard, and EGS) in a tertiary care municipal hospital setting. Follow-up involved clinic visits every 3 to 6 months with contrast-enhanced computed tomography (CT), color duplex, and plain abdominal radiographs at regular intervals; angiography was used selectively. All data were collected prospectively and entered into a computerized database. RESULTS: Implantation was possible in 188 (98.9%) patients. Early conversion to open surgical repair was required in 14 (7.4%) patients. Primary endoleaks were detected in 32 (16.8%) patients. Perioperative mortality was 0.53% (1/190). During follow-up, 17 (8.9%) additional patients were converted to open repair over a mean 20.9 months. Thirty-seven secondary procedures to treat endoleaks and pelvic outflow occlusions were performed in 30 (15.8%) patients. Changes in stent configuration suggestive of endograft disintegration were observed in 31 (29.8%) of 104 abdominal radiographs. Intraluminal layering of thrombus was seen on contrast-enhanced CT images in 20 patients. A significant trend (chi(2)4 = 12.34, p < 0.025) toward aneurysm enlargement was seen in patients with persistent endoleaks at a mean 18-month follow-up. CONCLUSIONS: Although endoleaks after aortic stent-graft placement tend to cause ongoing aneurysm growth, we have also observed aneurysm shrinkage despite ongoing endoleak. The presence or absence of an endoleak in itself may be a poor predictor of successful stent-graft therapy. Lifelong surveillance is needed to assure successful aneurysm exclusion and stability or shrinkage of the aneurysm sac. Technical improvements in stent materials and design are necessary to guarantee long-term stability and safety of the device.

Adult↗
PubMed1999

How do acetylcholine receptor ligands reach their binding sites?

The access pathway to the binding sites for large competitive antagonists of the nicotinic acetylcholine receptor from Torpedo californica electric tissue was analyzed by binding and photolabeling experiments with alpha-neurotoxins. Binding assays with [125I]alpha-bungarotoxin showed an increase in the number of accessible binding sites upon stepwise solubilization of the receptor-rich membranes. Similarily, ligand binding is facilitated upon fluidization of the membrane by increasing the temperature. The access to the binding sites seems to be sterically 'hindered' in the densely packed membrane state. Using a novel series of large biotinylated photoactivatable derivatives of neurotoxin II, we observed that the accessibility to the alpha/gamma- but not to the alpha/delta-binding site was considerably decreased for some derivatives under native conditions. This effect was less apparent at higher temperatures and could be abolished by complete solubilization. These observations support the nonequivalence of the receptor's binding sites. Together, our data suggest (a) that alpha-neurotoxins approach their binding sites from the membrane-facing periphery of the receptor's extramembrane domain rather than through the channel mouth and (b) that different entrance pathways to each binding site exist which vary in their sensitivity to the physical state of the plasma membrane.

Animals↗
PubMed1999

Virtual 3D cutting for bone segment extraction in maxillofacial surgery planning.

An important step toward our main goal of a completely computer-based maxillofacial surgical planning system is the availability of tools for the surgeon to define bone segments from skull and jaw bones. We have developed an easy-to-handle user interface that employs visual and force-feedback devices to define subvolumes of a patient's volume dataset. This interface is a main component of our maxillofacial surgical planning tool MeVisTo-Jaw [1]. The defined subvolumes together with their spatial arrangements lead to an operation plan.

Humans↗