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Biomedical subjects

M Preuss

Publications and source records attributed to M Preuss.

At least 19 recordsLinked to original sources

Coulombic amino group-metal bonding: adsorption of adenine on Cu110.

The interaction between molecular amino groups and metal surfaces is analyzed from first-principles calculations using the adsorption of adenine on Cu110 as a model case. The amino group nitrogens are found to adsorb on top of the surface copper atoms. However, the bonding clearly cannot be explained in terms of covalent interactions. Instead, we find it to be largely determined by mutual polarization and Coulomb interaction between substrate and adsorbate.

Adenine↗

Optical absorption of water: coulomb effects versus hydrogen bonding.

The optical spectrum of water is not well understood. For example, the main absorption peak shifts upwards by 1.3 eV upon condensation, which is contrary to the behavior expected from aggregation-induced broadening of molecular levels. We investigate theoretically the effects of electron-electron and electron-hole correlations, finding that condensation leads to delocalization of the exciton onto nearby hydrogen-bonded molecules. This reduces its binding energy and has a dramatic impact on the line shape. The calculated spectrum is in excellent agreement with experiment.

Journal Article↗

Long-term outcome and quality of care of patients with Staphylococcus aureus bacteremia.

To assess the long-term outcome and influence of clinical management of patients with Staphylococcus aureus bacteremia (SAB), 229 patients with blood cultures positive for Staphylococcus aureus between January 1997 and December 2000 were retrospectively identified and followed up. Risk factors, source of infection, treatment, clinical course, and outcome were recorded by chart review. For the assessment of 1-year survival, a questionnaire was sent to family doctors and government registration offices. Time of initial antibiotic therapy, duration of antibiotic treatment and performance of echocardiography were regarded as indicators of the quality of the clinical management of SAB. Among the 229 patients studied, 218 were evaluable for 1-year survival. Crude mortality after 1 year was 37.6% year. Within 30 days 43 (19.7%) patients had died, and 39 (17.9%) additional patients died thereafter. Using multivariate analysis, the following variables were associated with death: malignant disease (odds ratio [OR] 4.8; 95% confidence interval [CI], 2.6-8.9), pneumonia (OR, 3.6; 95%CI, 1.2-10.2), age >60 years (OR, 2.6; 95%CI, 1.5-4.5), and known source of infection (OR, 2.3; 95%CI, 1.3-4.1). Among 160 patients with a completely assessable treatment course 73 (46%) had received antibiotics for at least 14 days. A delay of antibiotic treatment of 1 day or more after microbiological diagnosis was observed in 28.3% of patients (i.e., 60 of 212 patients who received at least 1 dose of antibiotics). Echocardiography was performed in 101 (44.1%) cases. Overall, the findings indicate that standard guidelines for the management of SAB are followed only in part in clinical practice. In order to reduce the considerable mortality associated with SAB and to improve short- and long-term outcome, efforts should be made to increase adherence to recommendations.

Adult↗

Ground- and excited-state properties of DNA base molecules from plane-wave calculations using ultrasoft pseudopotentials.

We present equilibrium geometries, vibrational modes, dipole moments, ionization energies, electron affinities, and optical absorption spectra of the DNA base molecules adenine, thymine, guanine, and cytosine calculated from first principles. The comparison of our results with experimental data and results obtained by using quantum chemistry methods show that in specific cases gradient-corrected density-functional theory (DFT-GGA) calculations using ultrasoft pseudopotentials and a plane-wave basis may be a numerically efficient and accurate alternative to methods employing localized orbitals for the expansion of the electron wave functions.

DNA↗

[Transumbilical laparoscopic-assisted "one-trocar" appendectomy -- TULAA -- as an alternative operation method in the treatment of appendicitis].

INTRODUCTION: Appendectomy is one of the most commonly performed surgical procedures in general surgery and laparoscopic appendectomy represents the beginning of minimal invasive era in visceral surgery. But until yet, laparoscopic appendectomy is not the standard method for removal of the appendix and the discussion about the value and the advantages of laparoscopic appendectomy is still going on between the opponents and advocates of this method. In this article we present the transumbilical laparoscopic assisted "one-trocar" appendectomy (TULAA) as an alternative procedure for appendectomy and our experiences with this technique, which is up to now not very well known in Germany. METHOD: From November 1, 2000 to December 31, 2002, we performed appendectomy in 350 patients. 163 patients (46.6 %) underwent TULAA in the technique of Begin. All of them were examined two weeks and three months after surgery. RESULTS: In 94.5 % the "one-trocar" appendectomy was successful and there were no intraoperative complications. The mortality was 0 %. Conversion to the open procedure was necessary in 3 patients (1.8 %), respectively introduction of accessory trocars was necessary in 6 patients (3.7 %). In 111 from 163 patients (68.1 %) appendectomy was performed because of acute appendicitis. In 14.1 % we detected additional secondary findings during the laparoscopy. The postoperative complication rate was 3.6 %. CONCLUSION: The transumbilical laparoscopic assisted "one-trocar" appendectomy complements the minimal invasive procedures in visceral surgery. The operating technique combines the simplicity and the safety of conventional appendectomy with the survey of laparoscopic appendectomy. It minimizes the trauma of surgery and shows a perfect cosmetic result.

Acute Disease↗

[Adequate management of stab and gunshot wounds].

BACKGROUND: It is difficult to verify the treatment of stab and gunshot wounds with prospective randomized studies. That is why the results of observational studies are so important. MATERIAL: From 1 January 1989 to 31 December 1998, we saw 74 patients because of stab (64) and gunshot (ten) wounds. RESULTS: Most of the patients, whose injuries were caused mainly for criminal reasons (criminal 54, autoaggressive 14, accidental 4, unknown 2), came to hospital on weekends. We saw 38 abdominal, 23 thoracic, and 13 mixed injuries. On average, 3.8 h passed between the time of injury and getting first aid. Concerning abdominal injuries, we counted 21 negative intraoperative results. Two of 12 thoracic injuries showed no further damage. The patients stayed in hospital for 13.1 days on average. The morbidity was 28.38%, and mortality was 5.41%. CONCLUSIONS: Abdominal gunshot wounds need immediate surgical treatment. Concerning stab wounds, obligatory as well as selective surgical methods are both acceptable. Because of valid diagnostic options, thoracic stab wounds allow several ways of treatment.

Abdominal Injuries↗

Monitoring of water content and water distribution in ischemic hearts.

We determined water content and water distribution by fitting dielectric spectra of ischemic canine hearts between 5 MHz and 3 GHz with a newly developed model which describes heart cells and subcellular organelles as rotational ellipsoids filled with electrolyte enclosed by an isolating membrane. The fraction of dry material is modelled by spherical particles with a small dielectric permittivity. Free model parameters were water content, cell volume fraction, and the conductivity of the electrolytes. Resulting model parameters were compared to data from tissue desiccation and to conductivity changes produced by protons and lactate ions. We investigated hearts in two states: during ischemia after interruption of blood flow (pure ischemia, PI, n=5) and during ischemia after resuscitation with Tyrode's solution (IAR, n=14). The difference between water content determined by tissue desiccation and by dielectric spectroscopy was less than 0.5%. During 360 min of ischemia, water content in IAR decreased from 85+/-1.6% to 83+/-2.2% and in PI from 80+/-0.8% to 78+/-1.5%. Cellular volume fraction in IAR increased from 0.47+/-0.045 to 0.63+/-0.031 and in PI from 0.62+/-0.014 to 0.73+/-0.013, which is consistent with published morphometric data. After 180 min of ischemia, the increase of the cytosolic conductivity was 0.14+/-0.02 S/m as calculated from the dielectric spectrum and was similar to the conductivity increase which was roughly estimated on the basis of tissue lactate concentration. In conclusion, dielectric spectroscopy combined with our model analysis facilitates the monitoring of water content and distribution by means of nondestructive surface probes.

Animals↗

Comparison of two in vitro dendritic cell maturation models for screening contact sensitizers using a panel of methacrylates.

Allergen-induced emigration and maturation of dendritic cells (DC) are pivotal steps in sparking off allergic contact dermatitis. In vitro models, reflecting these steps, may provide tools for assessment of sensitizing capacities of putative contact allergens. Here, we evaluated the applicability of such models for a panel of methacrylate congeners, the sensitizing properties of which were established previously in clinical and experimental animal studies. First, using interleukin-4 (IL-4)/granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced, blood monocyte-derived DC, hapten-induced up-regulation of maturation/ activation markers, including CD80, CD83, CD86, chemokine receptors CXCR4 and CCR5, as well as the drug resistance related molecules P-glycoprotein (Pgp) and lung resistance protein (LRP), were monitored by flow cytometry. Of note, whereas CD86 and CXCR4 were most sensitive in discriminating between the contact sensitizers and irritants included in the panel, i.e. sodium dodecyl sulphate (SDS) and croton oil (CO), assessment of CD83 and LRP expression reflected the relatively lower sensitizing capacity of methyl methacrylate. Second, using ex vivo skin explant cultures, allergen-induced LC migration from epidermal to basal membranous and dermal skin structures was most reliably monitored by CDla, as compared with Pgp, LRP, HLA-DR or CD54 staining. The extent of CD1a+ LC migration was found to closely correlate with the sensitizing capacities of the panel of test compounds. These results support the view that both in vitro models can provide valuable data on contact sensitizing properties, and add chemokine receptors and drug resistance related molecules to the list of DC membrane markers revealing allergenic signaling.

Cell Movement↗

X-ray tomographic imaging of Ti/SiC composites.

In this paper, high-resolution tomographic synchrotron X-ray imaging is applied to study the occurrence and evolution of damage in Ti-6Al-4V/SCS6 SiC fibre composite materials. Three composite morphologies of increasing complexity have been studied, namely single fibre, single-ply and multi-ply composites. The single fibre composite was strained to full fibre fragmentation and the progressive introduction of damage monitored. For the single-ply composite, damage was introduced deliberately by laser drilling to establish the effect of damaged fibres on their neighbours, whereas for the multi-ply composite the morphology of a fibre bridging fatigue crack was studied. In addition to traditional mode I fibre fractures, subsequent fibre wedge cracks were observed presumably nucleating from damage introduced into the fibre surface by the first fracture event. In addition to these crack morphologies, spiral defects were observed for the single ply during failure. Finally, for the multi-ply composite, the matrix crack front showed a number of characteristic features, including advancement in fibre-free regions, crack bifurcation near fibres and different crack plane heights either side of a fibre.

Alloys↗

[Primary and secondary aortoiliac reconstructions in patients with coexistent horseshoe and pelvic kidney].

The coexistence of dystopic kidney and abdominal aortic aneurysm or aortoiliac occlusive arterial disease is uncommon (0.12-0.15 %) and constitutes a technical challenge to vascular surgeons. Between 1997 and 1999 we performed 249 aortoiliac reconstructions and encountered four patients (1.6 %) with dystopic kidneys. The aortoiliac reconstructions were performed successfully in all patients while maintaining renal blood supply. Aortoiliac reconstructions in patients with horseshoe or pelvic kidney show similar results as regular reconstructions on the condition that optimal preoperative diagnosis and operative technique are used considering atypical renal vessels. Nevertheless, pelvic kidneys can lead to serious complications as we describe in this report. On the basis of our patients anatomy, embryology and surgical management of this entity.

Aged↗

Mba1, a novel component of the mitochondrial protein export machinery of the yeast Saccharomyces cerevisiae.

The biogenesis of mitochondria requires the integration of many proteins into the inner membrane from the matrix side. The inner membrane protein Oxa1 plays an important role in this process. We identified Mba1 as a second mitochondrial component that is required for efficient protein insertion. Like Oxa1, Mba1 specifically interacts both with mitochondrial translation products and with conservatively sorted, nuclear-encoded proteins during their integration into the inner membrane. Oxa1 and Mba1 overlap in function and substrate specificity, but both can act independently of each other. We conclude that Mba1 is part of the mitochondrial protein export machinery and represents the first component of a novel Oxa1-independent insertion pathway into the mitochondrial inner membrane.

Cell Division↗

A superfamily of variant genes encoded in the subtelomeric region of Plasmodium vivax.

The malarial parasite Plasmodium vivax causes disease in humans, including chronic infections and recurrent relapses, but the course of infection is rarely fatal, unlike that caused by Plasmodium falciparum. To investigate differences in pathogenicity between P. vivax and P. falciparum, we have compared the subtelomeric domains in the DNA of these parasites. In P. falciparum, subtelomeric domains are conserved and contain ordered arrays of members of multigene families, such as var, rif and stevor, encoding virulence determinants of cytoadhesion and antigenic variation. Here we identify, through the analysis of a continuous 155,711-base-pair sequence of a P. vivax chromosome end, a multigene family called vir, which is specific to P. vivax. The vir genes are present at about 600-1,000 copies per haploid genome and encode proteins that are immunovariant in natural infections, indicating that they may have a functional role in establishing chronic infection through antigenic variation.

Adult↗

Docosahexaenoic acid synthesis from n-3 polyunsaturated fatty acids in differentiated rat brain astrocytes.

DHA, the main n-3 PUFA in the brain, is synthesized from n-3 PUFA precursors by astrocytes. To assess the potential of this process to supply DHA for the brain, we investigated whether the synthesis in astrocytes is dependent on DHA availability. Rat brain astrocytes differentiated with dibutyryl cAMP and incubated in media containing 10% fetal bovine serum synthesized DHA from alpha-linolenic acid ([1-(14)C]18:3n-3), docosapentaenoic acid ([3-(14)C]22:5n-3), tetracosapentaenoic acid ([3-(14)C]24:5n-3), and tetracosahexaenoic acid ([3-(14)C]24:6n-3). When DHA was added to media containing a 5 microM concentration of these (14)C-labeled n-3 PUFA, radiolabeled DHA synthesis was reduced but not completely suppressed even when the DHA concentration was increased to 15 microM. Radiolabeled DHA synthesis also was reduced but not completely suppressed when the astrocytes were treated with 30 microM DHA for 24 h before incubation with 5 microM [1-(14)C]18:3n-3.These findings indicate that although the DHA synthesis in astrocytes is dependent on DHA availability, some synthesis continues even when the cells have access to substantial amounts of DHA. This suggests that DHA synthesis from n-3 PUFA precursors is a constitutive process in the brain and, therefore, is likely to have an essential function.

Animals↗

Role of antioxidant enzyme expression in the selective cytotoxic response of glioma cells to gamma-linolenic acid supplementation.

We hypothesized that the cytotoxic effect of GLA observed in glioma but not normal glial cells reflects differences in GLA metabolism and/or antioxidant enzyme levels between these cells. The PUFA content of unsupplemented glioma cells was approximately 50% of that seen in unsupplemented astrocytes. Supplementation with 20 microM GLA for 24 h led to a 230 and 22% increase in glioma and astrocyte PUFA content, respectively, such that both supplemented cell types contained similar levels of PUFA. No major differences were seen in terms of GLA metabolites retained in the cells or secreted into the media following incubation with [(3)H]-GLA. No significant differences were observed in activity of MnSOD or CuZn-SOD between the cells. However, CAT and GPx activity in the glioma cells was significantly higher and lower, respectively, than observed in normal astrocytes. GLA supplementation resulted in a significant increase in CAT activity in normal astrocytes; glioma CAT activity was unchanged. No significant change was seen in the other antioxidant enzymes following GLA supplementation. These results suggest that the cytotoxic effect of GLA on glioma cells reflects both increased PUFA content and an inability to upregulate CAT.

Animals↗

The affinity of the GroEL/GroES complex for peptides under conditions of protein folding.

The affinity of four short peptides for the Escherichia coli molecular chaperone GroEL was studied in the presence of the co-chaperone GroES and nucleotides. Our data show that binding of GroES to one ring enhances the interaction of the peptides with the opposite GroEL ring, a finding that was related to the structural readjustments in GroEL following GroES binding. We further report that the GroEL/GroES complex has a high affinity for peptides during ATP hydrolysis when protein substrates would undergo repeated cycles of assisted folding. Although we could not determine at which step(s) during the cycle our peptides interacted with GroEL, we propose that successive state changes in GroEL during ATP hydrolysis may create high affinity complexes and ensure maximum efficiency of the chaperone machinery under conditions of protein folding.

Adenosine Diphosphate↗

Interaction with GroEL destabilises non-amphiphilic secondary structure in a peptide.

The Escherichia coli molecular chaperone GroEL can functionally interact with non-native forms of many proteins. An inherent property of non-native proteins is the exposure of hydrophobic residues and the presence of secondary structure elements. Whether GroEL unfolds or stabilises these structural elements in protein substrates as a result of binding has been the subject of extended debate in the literature. Based on our studies of model peptides of pre-formed helical structure, we conclude that the final state of a GroEL-bound substrate is dependent on the conformational flexibility of the substrate protein and the distribution of hydrophobic residues, with optimal association when these are able to present a cluster of hydrophobic residues in the binding interface.

Chaperonin 60↗

Secondary structure forming propensity coupled with amphiphilicity is an optimal motif in a peptide or protein for association with chaperonin 60 (GroEL).

The interactions of GroEL with six dansyl peptides were investigated by means of our previously established fluorescence binding assay [Hutchinson, J. P., Oldham, T. C., El-Thaher, T. S. H., and Miller, A. D. (1997) J. Chem. Soc., Perkin Trans. 2, 279-288]. Three peptides (AMPH series) were constructed with a hierarchy of alpha-helix-forming propensities and amphiphilic characteristics. The remaining three peptides (NON-AMPH series) were prepared with a reordered amino acid sequence designed to form peptides of differing non-amphiphilic alpha-helix-forming propensity. Of these six peptides, two (AMPH(+) and NON-AMPH(+)) were N-capped with an S-form alpha-helix-inducing template (Ro 47-1615, Hoffmann-La Roche), two (AMPH(-) and NON-AMPH(-)) were N-capped with an R-form non-inducing template (Ro 47-1614, Hoffmann-La Roche), and two (AMPH(R) and NON-AMPH(R)) were without N-cap modification. This paper describes how the known strength of interaction of an unfolded protein substrate with the molecular chaperone GroEL (K(d) micromolar to nanomolar) may be emulated with a single peptide (AMPH(+)) (apparent K(d) 5 nM) which has a high propensity to form an amphiphilic alpha-helical structure in solution. Secondary structure forming propensity is not, in and of itself, an important contributor to the strength of interaction with GroEL. However, secondary structure forming propensity coupled with amphiphilicity may be sufficient to account for most, if not all, of the interaction strength between GroEL and an unfolded peptide or protein substrate.

Binding, Competitive↗

Heterogeneous transmural gene expression of calcium-handling proteins and natriuretic peptides in the failing human heart.

OBJECTIVE: Human heart failure is associated with a disturbed intracellular calcium (Ca2+) homeostasis. In this regard, ventricular wall stress is considered to be a determinant for expression of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a). In the present study, we analyzed the transmural protein and/or mRNA levels of SERCA2a, other Ca(2+)-handling proteins, and of atrial and brain natriuretic peptides (ANP and BNP) in the human heart. METHODS: Subepicardial (epi), midmyocardial (mid), and subendocardial (endo) sections of the left ventricular free wall from end-stage failing (n = 17) and nonfailing (n = 5) human hearts were analyzed by Western blot for immunoreactive protein levels of SERCA2a, phospholamban (PLN), and calsequestrin (CS). Subepi- and subendocardial sections were analyzed by Northern blot for steady-state mRNA levels of SERCA2a, Na(+)-Ca2+ exchanger (NCX1), ANP, and BNP. RESULTS: SERCA2a protein and mRNA levels were reduced by 40 +/- 5% (P < 0.01) and 25 +/- 7% (P < 0.05) in endo compared to epi in the failing heart and by 27 +/- 14% and 16 +/- 12% (non-significant) in the nonfailing heart, respectively. PLN protein levels were reduced by 23 +/- 6% (P < 0.05) in endo compared to epi in the failing heart and by 17 +/- 25% (non-significant) in the nonfailing heart, whereas CS protein levels and NCX1 mRNA levels were similar across the left ventricular wall. Strikingly, in the failing heart, both BNP and ANP mRNA levels were upregulated predominantly in endo. CONCLUSIONS: In the failing human heart, SERCA2a and PLN, as well as natriuretic peptides but not CS and NCX1 are differentially expressed across the left ventricular wall, implicating (1) different susceptibility of subendocardium and subepicardium to factors affecting expression of these proteins and (2) differences in regulation of the distinct calcium-cycling proteins.

Adult↗