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Biomedical subjects

M Müller

Publications and source records attributed to M Müller.

At least 91 records · Page 5Linked to original sources
PubMed2004

Intrafallopian transfer of gametes and early stage embryos for in vivo culture in cattle.

It may be possible to avoid inadequate in vitro culture conditions by incubating gametes or embryos in the oviducts for a short time. Ideally, an optimized procedure should be devised, combining in vitro and in vivo systems, in order to achieve synchronization in cattle. We transferred gametes as well as embryos in various stages of development and placed them into the oviducts. Embryos were recovered on Day 7 by flushing of oviducts and uterine horns. Blastocyst rates were determined on Day 7 and on Day 8. Experimental designs included transfer of in vitro matured cumulus oocyte complexes into previously inseminated heifers (COCs group), transfer of in vitro matured COCs simultaneously with capacitated spermatozoa (GIFTs group), transfer of four to eight cell stage embryos developed in vitro after IVM/IVF (Cleaved Stages group) and a group of solely in vitro produced embryos (IVP control group). Our results indicate that in vivo culture of IVM/IVF embryos in the homologous bovine oviduct has a positive influence on subsequent pre-implantation development. In addition, we have evidence that in vitro maturation and in vivo fertilization cannot be synchronized.

Animals↗
PubMed2004

Glass transition and the Coulomb gap in electron glasses.

We establish the connection between the presence of a glass phase and the appearance of a Coulomb gap in disordered materials with strongly interacting electrons. Treating multiparticle correlations in a systematic way, we show that in the case of strong disorder a continuous glass transition takes place whose Landau expansion is identical to that of the Sherrington-Kirkpatrick spin glass. We show that the marginal stability of the glass phase controls the physics of these systems: it results in slow dynamics and leads to the formation of a Coulomb gap.

Journal Article↗
PubMed2004

Impact of plasma protein binding on antimicrobial activity using time-killing curves.

OBJECTIVES: Plasma protein binding (PPB) is known to impair the antimicrobial activity of beta-lactams, but its impact on the activity of other classes of antimicrobials such as fluoroquinolones is controversial. This study was undertaken to investigate the effect of PPB on bacterial killing by selected antibiotics and moxifloxacin, which served as a model compound for the class of fluoroquinolones. METHODS: Bacterial time-killing curves were employed in the absence and presence of physiological albumin concentrations (40 g/L). Moxifloxacin, ampicillin and oxacillin were investigated. Fosfomycin, a non-protein bound antibiotic was used for comparison. Simulations were carried out by employing concentrations of antibiotics of one-fourth of the minimal inhibitory concentration (MIC), equal to the MIC and four-fold the MIC of one select bacterial strain (Staphylococcus aureus ATCC 29213). To correlate bacterial killing to the extent of PPB, bacterial time-killing curves were plotted using the calculated free and the total drug concentration. RESULTS: Bacterial killing by fosfomycin was not affected by the addition of albumin. The antimicrobial activity of oxacillin and ampicillin was reduced in the presence of albumin as expected by the calculation of the free fraction of these antibiotics. Adding albumin to moxifloxacin resulted in a significant decrease in bacterial killing of more than 1 log10 cfu/mL after a period of 8 h when the moxifloxacin concentration was equal to the respective MIC. CONCLUSIONS: Our data confirm the view that albumin substantially impairs the antimicrobial activity of antibiotics including moxifloxacin, a member of the class of fluoroquinolones.

Anti-Bacterial Agents↗
PubMed2004

Long range bond-bond correlations in dense polymer solutions.

The scaling of the bond-bond correlation function P1(s) along linear polymer chains is investigated with respect to the curvilinear distance s along the flexible chain and the monomer density rho via Monte Carlo and molecular dynamics simulations. Surprisingly, the correlations in dense three-dimensional solutions are found to decay with a power law P1(s) approximately s(-omega) with omega=3/2 and the exponential behavior commonly assumed is clearly ruled out for long chains. In semidilute solutions, the density dependent scaling of P1(s) approximately g(-omega(0))(s/g)(-omega) with omega(0)=2-2nu=0.824 (nu=0.588 being Flory's exponent) is set by the number of monomers g(rho) in an excluded volume blob. Our computational findings compare well with simple scaling arguments and perturbation calculation. The power-law behavior is due to self-interactions of chains caused by the chain connectivity and the incompressibility of the melt.

Journal Article↗
PubMed2004

Shared decision-making--results from an interdisciplinary consulting service for prostate cancer.

Locally confined prostate cancer (PCa) can be treated by various treatment options (e.g. radical prostatectomy or radiation therapy) with comparable results but different possible side effects. Therefore, treatment recommendations can vary between urologists and radiation oncologists. In 2001 the Charite-Campus Benjamin Franklin (CBF, Berlin), established the first interdisciplinary consulting service for prostate cancer patients in Germany. The aim was to offer a comprehensive and neutral consultation on all treatment options and to make treatment recommendations. The study examines what benefits may be derived from this type of consultation. A total of 362 patients presented to the consulting service between May 2001 and April 2003. Two questionnaires were used. The first one contained epidemiological questions as well as questions covering information already available on PCa. It also examined feelings and fears about the disease and possible treatment options. The second questionnaire was completed 2 weeks after the consultation to evaluate the treatment decision, determine the patient's satisfaction with the consultation and trace the development of feelings and fears. Of the patients, 334 (92.2%) were completely assessable. All patients had already obtained information about the disease and possible treatment options and wished to be involved in the decision-making process through objective and neutral consultation. Nearly all of them had a great fear of the possible side effects of therapy. Such a comprehensive consultation is time-consuming (average of 35 min) but largely received a very positive assessment in that a total of 66% found it either helpful (n=74, 22%) or very helpful (n=147, 44%). Patients felt they had been completely informed in 92% of the cases. Only 22 (9.7%) had still failed to make a decision after 2 weeks, 115 patients had stage T1c, PSA <10 ng/ml and a Gleason score < or =7. In these cases an equivalent recommendation for radical prostatectomy, percutaneous radiotherapy or permanent seed implantation was given. Of these, 49 (43.4%) decided on the surgical intervention, 48 (42.5%) on a type of radiotherapy and only 18 (15.6%) remained undecided. The histological examination of prostatectomy specimens from patients who had decided to undergo radical surgery at CBF showed a significant decrease in the rate of extracapsular disease extension (> or =T3) from 38% to 20% during the observation period. The interdisciplinary approach has made the process of deciding on an appropriate treatment much easier for the patient. The time-consuming consultation enables better selection of individual treatment modalities and their possible side effects from the point of view of both the patients and the attending physicians. In this study, patients chose either radical surgery or radiotherapy with equal frequency.

Humans↗
PubMed2004

Coordinate hypermethylation at specific genes in prostate carcinoma precedes LINE-1 hypomethylation.

In prostate carcinoma (PCa) increased DNA methylation ('hypermethylation') occurs at specific genes such as GSTP1. Nevertheless, overall methylation can be decreased ('hypomethylation') because methylation of repetitive sequences like LINE-1 retrotransposons is diminished. We analysed DNA from 113 PCa and 36 noncancerous prostate tissues for LINE-1 hypomethylation by a sensitive Southern technique and for hypermethylation at eight loci by methylation-specific PCR. Hypermethylation frequencies for GSTP1, RARB2, RASSF1A, and APC in carcinoma tissues were each >70%, strongly correlating with each other (P<10(-6)). Hypermethylation at each locus was significantly different between tumour and normal tissues (10(-11) 82% of PCas. PCa may fall into three classes, that is, with few DNA methylation changes, with frequent hypermethylation, or with additional LINE-1 hypomethylation.

Acyltransferases↗
PubMed2004

Field theoretic study of bilayer membrane fusion. I. Hemifusion mechanism.

Self-consistent field theory is used to determine structural and energetic properties of metastable intermediates and unstable transition states involved in the standard stalk mechanism of bilayer membrane fusion. A microscopic model of flexible amphiphilic chains dissolved in hydrophilic solvent is employed to describe these self-assembled structures. We find that the barrier to formation of the initial stalk is much smaller than previously estimated by phenomenological theories. Therefore its creation it is not the rate-limiting process. The relevant barrier is associated with the rather limited radial expansion of the stalk into a hemifusion diaphragm. It is strongly affected by the architecture of the amphiphile, decreasing as the effective spontaneous curvature of the amphiphile is made more negative. It is also reduced when the tension is increased. At high tension the fusion pore, created when a hole forms in the hemifusion diaphragm, expands without bound. At very low membrane tension, small fusion pores can be trapped in a flickering metastable state. Successful fusion is severely limited by the architecture of the lipids. If the effective spontaneous curvature is not sufficiently negative, fusion does not occur because metastable stalks, whose existence is a seemingly necessary prerequisite, do not form at all. However if the spontaneous curvature is too negative, stalks are so stable that fusion does not occur because the system is unstable either to a phase of stable radial stalks, or to an inverted-hexagonal phase induced by stable linear stalks. Our results on the architecture and tension needed for successful fusion are summarized in a phase diagram.

Computer Simulation↗
PubMed2004

Glassy phases in random heteropolymers with correlated sequences.

We develop an analytic approach for the study of lattice heteropolymers and apply it to copolymers with correlated Markovian sequences. According to our analysis, heteropolymers present three different dense phases depending upon the temperature, the nature of the monomer interactions, and the sequence correlations: (i) a liquid phase, (ii) a "soft glass" phase, and (iii) a "frozen glass" phase. The presence of the intermediate "soft glass" phase is predicted, for instance, in the case of polyampholytes with sequences that favor the alternation of monomers. Our approach is based on the cavity method, a refined Bethe-Peierls approximation adapted to frustrated systems. It amounts to a mean-field treatment in which the nearest-neighbor correlations, which are crucial in the dense phases of heteropolymers, are handled exactly. This approach is powerful and versatile; it can be improved systematically and generalized to other polymeric systems.

Journal Article↗
PubMed2004

Influence of pores created by laser superfinishing on osseointegration of titanium alloy implants.

The aim of this study was to assess the osseointegration of copper vapor laser-superfinished titanium alloy (Ti6Al4V) implants with pore sizes of 25, 50, and 200 microm in a rabbit intramedullary model. Control implants were prepared by corundum blasting. Each animal received all four different implants in both femora and humeri. Using static and dynamic histomorphometry, the bone-implant interface and the peri-implant bone tissue were examined 3, 6, and 12 weeks postimplantation. Among the laser-superfinished implants, total bone-implant contact was smallest for the 25-microm pores, and was similar for 50- and 200-microm pore sizes at all time points. However, all laser-superfinished surfaces were inferior to corundum-blasted (CB) control implants in terms of bone-implant contact. Within the 12-week study period, remodeling of woven bone initially formed within pores occurred only in the implants with 200-microm pores. Implants with 25-microm pores showed the highest amount of peri-implant bone volume at all time points, indicating that the amount of peri-implant bone was not correlated with the quality of the bone-implant interface. At 3 and 6 weeks postsurgery, we did not find any differences in mineral apposition rates or bone formation rates between the various implant surfaces. However, the peri-implant bone formation rate at the end of the trial was 70 and 62% higher in implants with 50- and 200-microm pores compared with CB implants, respectively. We conclude that, although laser-superfinished implants were not superior to CB control implants in terms of osseointegration, our study has provided further insights into the mechanisms of bone remodeling within pores of various sizes, and may form a basis for future experiments to design optimal implant surfaces with the help of modern laser technology.

Alloys↗
PubMed2004

Phase diagram of random heteropolymers.

We propose a new analytic approach to study the phase diagram of random heteropolymers, based on the cavity method. For copolymers we analyze the nature and phenomenology of the glass transition as a function of sequence correlations. Depending on these correlations, we find that two different scenarios for the glass transition can occur. We show that, beside the much studied possibility of an abrupt freezing transition at low temperature, the system can exhibit, upon cooling, a first transition to a soft glass phase with fully broken replica symmetry and a continuously growing degree of freezing as the temperature is lowered.

Journal Article↗
PubMed2004

Ultrastructural localization of glutathione in Cucurbita pepo plants.

Electronmicroscopic immunogold cytochemistry was used to investigate the cellular and subcellular distribution of glutathione in root and leaf cells of Styrian pumpkin (Cucurbita pepo L. subsp. pepo var. styriaca Greb.) plants. Gold particles bound to glutathione were found in various cell structures. Statistical evaluation of the gold particle density was made for different cell compartments including nuclei, mitochondria, plastids, peroxisomes, and the cytosol. In each cell type the highest level of glutathione immunoreactivity occurred in mitochondria, for which the labeling density was found to be higher in mesophyll cells of the youngest fully developed leaves (younger leaves) than in the 5th leaves (older leaves) or in root tip cells. Additionally, a statistically significant increase of gold particles bound to glutathione was observed in nuclei (22%) and the cytosol (14%) of the root cells in comparison with mesophyll cells of older (17% and 9%, respectively) and younger leaves (11% and 6%, respectively). The relevance and specificity of glutathione labeling is discussed with respect to difficulties of immunolocalization of low-molecular-weight compounds.

Cell Nucleus↗
PubMed2004

Structural polymorphism and endotoxic activity of synthetic phospholipid-like amphiphiles.

The physicochemical characteristics and in vitro biological activity of various synthetic hexaacyl phospholipid dimers were compared with the respective behavior of bacterial endotoxins (lipopolysaccharide, LPS). The structural variations of the synthetic amphiphiles include different stereochemical (R,S) configurations about their ester- and amide-linkages for the acyl chains and differences in the length of the serine backbone spacer. The temperature of the gel to liquid crystalline phase transition of the acyl chains (T(c)) lies between 10 and 15 degrees C for the compounds with the shortest backbone and decreases rapidly for the compounds with longer backbones. The phase transition enthalpies (8-16 kJ x mol(-1)) are considerably lower than those of lipid A from hexaacyl endotoxins (28-35 kJ x mol(-1)). In contrast, the dependence of T(c) on Mg(2+) and water content shows a behavior typical for endotoxins: a significant increase with increasing Mg(2+) and decreasing water concentrations. The aggregate structure is sensitively dependent not only on the length of the backbone spacer but also on the different stereochemical variations. It can be directly correlated with the biological activity of the compounds. Thus, as with natural lipid A, the capacity to induce cytokine production in mononuclear cells is directly related to the affinity to form nonlamellar cubic or inverted hexagonal H(II) aggregate structures. Together with the data on the transport and intercalation of the dimers into phospholipid liposomes mediated by the lipopolysaccharide-binding protein (LBP), our conformational concept of endotoxicity and cell activation can be applied to these non-LPS structures: endotoxically active compounds incorporate into membranes of immune cells and cause conformational changes at the site of signaling proteins such as Toll-like receptors or K(+)-channels due to their conical molecular shape.

Animals↗
PubMed2004

Preparation and adsorption of refined polyelectrolyte complex nanoparticles.

We report on bulk and surface properties of centrifuged nonstoichiometric polyelectrolyte complex (PEC) dispersions. PECs were prepared by mixing poly(diallyldimethylammonium chloride) (PDADMAC) and sodium poly(maleic acid-co-alpha-methylstyrene) (PMA-MS) at the monomolar mixing ratio of 0.6 and polymer concentration >/=1 mmol/l. Centrifugation of initial PEC dispersions revealed three phases: supernatant (SUP), coacervate (COAC), and an insoluble precipitate. Mass, turbidity, particle hydrodynamic radii (R(h)), and the titratable charge amount were determined for those phases. The turbid COAC phase consisted of 200-nm nanoparticles and carried 60% of the polymer mass and 20% of the titratable charge amount of the initial PEC dispersion. The SUP phase showed no turbidity and no such nanoparticles, but carried 80% of the initial titratable charge amount, presumably caused by excess polycations. Furthermore, linear dependences of turbidity and R(h) on COAC concentration was observed. COAC adsorption was studied at polyelectrolyte multilayer (PEM) modified silicon surfaces in dependence on both adsorption time and concentration using attenuated total-reflection-Fourier transform infrared (ATR-FTIR) spectroscopy. The adsorption data were fitted by the simple Langmuir model. Comparison of COAC particles and polystyrene latices revealed similar adsorption features. SEM and AFM measurements resulted in hemispherically shaped adsorbed COAC particles with coverages >/=25%, whose calculated volumes correlated well with those in dispersion obtained by PCS.

Journal Article↗
PubMed2004

Static properties of end-tethered polymers in good solution: a comparison between different models.

We present a comparison between results, obtained from different simulation models, for the static properties of end-tethered polymer layers in good solvent. Our analysis includes data from two previous studies--the bond fluctuation model of Wittmer et al. [J. Chem. Phys. 101, 4379 (1994)] and the off-lattice bead-spring model of Grest and Murat [Macromolecules 26, 3108 (1993)]. Additionally, we explore the properties of a similar off-lattice model simulated close to the Theta temperature. We show that the data for the bond fluctuation and the Grest-Murat model can be analyzed in terms of scaling theory because chains are swollen inside the Pincus blob. In the vicinity of the Theta point the structure of the chains is essentially Gaussian in the Pincus blob. Therefore, the data for the second off-lattice model can be compared quantitatively to the self-consistent field theory. Different ways to determine the parameters of the self-consistent field theory are discussed.

Journal Article↗
PubMed2004

Peroxisome proliferator-activated receptor alpha target genes.

Peroxisome proliferator-activated receptors (PPARs) are nuclear proteins that belong to the superfamily of nuclear hormone receptors. They mediate the effects of small lipophilic compounds such as long-chain fatty acids and their derivatives on transcription of genes commonly called PPAR target genes. Here we review the involvement of PPARalpha in peroxisomal and mitochondrial fatty acid oxidation, microsomal fatty acid hydroxylation, lipoprotein, bile and amino acid metabolism, glucose homeostasis, biotransformation, inflammation control, hepato-carcinogenesis and other pathways, through a detailed analysis of the different known or putative PPARalpha target genes.

Animals↗
PubMed2004

[Spondylodiscitis after perioperative peridural catheter].

Peridural anaesthesia is used to avoid operative, postoperative and chronic pain, especially in surgery, gynecology and urology. Complications have rarely been described but can entail serious local and systemic sequelae. Three cases with spondylitis and spondylodiscitis after peridural anaesthesia are presented. The failure to recognize the peridural catheter as the cause of vertebral pain led to therapeutic delay in two cases. The result of antimicrobial therapy and in two cases radical surgical treatment was complete recovery. The occurrence of spondylodiscitis after the use of peridural catheters is often a late manifestation of disseminated pathogens. The insidious progression of infection and non-specificity of clinical symptoms may lead to diagnostic delay. Awareness of the possibility of even delayed complications after the use of peridural anaesthesia is important.

Adult↗
PubMed2004

[Duodenum-preserving pancreas head resection-an operative technique for retaining the organ in the treatment of chronic pancreatitis].

Chronic pancreatitis is an inflammatory disease characterized by the progressive conversion of pancreatic parenchyma to fibrous tissue. The most frequent causes are alcohol overconsumption and anatomic variants such as pancreas divisum, cholelithiasis, and individual genetic predisposition. The process of fibrosis with consecutive loss of pancreatic parenchyma leads to exocrine insufficiency and maldigestion and, in advanced stages of the disease, to diabetes mellitus. Beside exocrine and endocrine malfunction, mechanical complications occur such as the formation of pancreatic pseudocysts and duodenal and common bile duct obstruction. About 50% of patients with chronic pancreatitis need surgical intervention due to untreatable chronic pain. As recent investigations suggest that the head of the pancreas triggers the chronic inflammatory process, resection of this inflammatory mass must be regarded as pivotal in any surgical intervention. Radical techniques such as the Whipple procedure are undoubtedly successful regarding pain reduction but, even in its pylorus-preserving variant, associated with high postoperative morbidity due to a large loss of pancreatic parenchyma and the absence of duodenal passage. Thirty years ago, H.G. Beger described for the first time the technique of duodenum-preserving pancreatectomy, which better combines resection of the pancreatic head with low morbidity. Over the years, different variations of the original Beger technique (Frey, Izbicky, Berne modification) have been developed, and the excellent results obtained with these methods underline that organ-sparing techniques should be preferred in the surgical treatment of chronic pancreatitis.

Chronic Disease↗