Search PubMed⌕ Search

Biomedical subjects

M Müller

Publications and source records attributed to M Müller.

At least 235 records · Page 13Linked to original sources

Interface localization-delocalization transition in a symmetric polymer blend: a finite-size scaling Monte Carlo study.

Using extensive Monte Carlo simulations, we study the phase diagram of a symmetric binary (AB) polymer blend confined into a thin film as a function of the film thickness D. The monomer-wall interactions are short ranged and antisymmetric, i.e., the left wall attracts the A component of the mixture with the same strength as the right wall does the B component, and this gives rise to a first order wetting transition in a semi-infinite geometry. The phase diagram and the crossover between different critical behaviors is explored. For large film thicknesses we find a first order interface localization-delocalization transition, and the phase diagram comprises two critical points, which are the finite film width analogies of the prewetting critical point. Using finite-size scaling techniques we locate these critical points, and present evidence of a two-dimensional Ising critical behavior. When we reduce the film width the two critical points approach the symmetry axis straight phi=1/2 of the phase diagram, and for D approximately 2R(g) we encounter a tricritical point. For an even smaller film thickness the interface localization-delocalization transition is second order, and we find a single critical point at straight phi=1/2. Measuring the probability distribution of the interface position, we determine the effective interaction between the wall and the interface. This effective interface potential depends on the lateral system size even away from the critical points. Its system size dependence stems from the large but finite correlation length of capillary waves. This finding gives direct evidence of a renormalization of the interface potential by capillary waves in the framework of a microscopic model.

Journal Article↗

Negative regulation of Ros receptor tyrosine kinase signaling. An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1.

Male "viable motheaten" (me(v)) mice, with a naturally occurring mutation in the gene of the SH2 domain protein tyrosine phosphatase SHP-1, are sterile. Known defects in sperm maturation in these mice correlate with an impaired differentiation of the epididymis, which has similarities to the phenotype of mice with a targeted inactivation of the Ros receptor tyrosine kinase. Ros and SHP-1 are coexpressed in epididymal epithelium, and elevated phosphorylation of Ros in the epididymis of me(v) mice suggests that Ros signaling is under control of SHP-1 in vivo. Phosphorylated Ros strongly and directly associates with SHP-1 in yeast two-hybrid, glutathione S-transferase pull-down, and coimmunoprecipitation experiments. Strong binding of SHP-1 to Ros is selective compared to six other receptor tyrosine kinases. The interaction is mediated by the SHP-1 NH(2)-terminal SH2 domain and Ros phosphotyrosine 2267. Overexpression of SHP-1 results in Ros dephosphorylation and effectively downregulates Ros-dependent proliferation and transformation. We propose that SHP-1 is an important downstream regulator of Ros signaling.

3T3 Cells↗

Spectral statistics of the two-body random ensemble revisited.

Using longer spectra we reanalyze spectral properties of the two-body random ensemble studied 30 years ago. At the center of the spectra the old results are largely confirmed, and we show that the nonergodicity is essentially due to the variance of the lowest moments of the spectra. The longer spectra allow us to test and reach the limits of validity of French's correction for the number variance. At the edge of the spectra we discuss the problems of unfolding in more detail. With a Gaussian unfolding of each spectrum the nearest-neighbor spacing distribution between ground state and first exited state is shown to be stable. Using such an unfolding the distribution tends toward a semi-Poisson distribution for longer spectra. For comparison with the nuclear table ensemble we could use such unfolding obtaining similar results as in the early papers, but an ensemble with realistic splitting gives reasonable results if we just normalize the spacings in accordance with the procedure used for the data.

Journal Article↗

Specificity of signaling by STAT1 depends on SH2 and C-terminal domains that regulate Ser727 phosphorylation, differentially affecting specific target gene expression.

Complete activation of signal transducer and activator of transcription 1 (STAT1) requires phosphorylation at both Y701 and a conserved PMS(727)P sequence. S727 phosphorylation of STAT1 in interferon-gamma (IFN-gamma)-treated mouse fibroblasts occurred without a need for p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1 and 2 or c-Jun kinases, and required both an intact SH2 domain and phosphorylation of Y701. In contrast, UV irradiation-induced STAT1 phosphorylation on S727 required p38MAPK, but no SH2 domain- phosphotyrosine interactions. Mutation of S727 differentially affected IFN-gamma target genes, at the level of both basal and induced expression. Particularly strong effects were noted for the GBP1 and TAP1 genes. The PMS(727)P motif of STAT3 was phosphorylated by stimuli and signaling pathways different from those for STAT1 S727. Transfer of the STAT3 C-terminus to STAT1 changed the stimulus and pathway specificity of STAT1 S727 phosphorylation to that of STAT3. Our data suggest that STAT C-termini contribute to the specificity of cellular responses by linking individual STATs to different serine kinase pathways and through an intrinsically different requirement for serine phosphorylation at different target gene promoters.

3T3 Cells↗

New insights into endotoxin-induced activation of macrophages: involvement of a K+ channel in transmembrane signaling.

LPS (endotoxins) activate cells of the human immune system, among which are monocytes and macrophages, to produce endogenous mediators. These regulate the immune response, but may also cause severe harm leading to septic shock. The activation of monocytes/macrophages by LPS is mediated by a membrane-bound LPS receptor, mCD14. As mCD14 lacks a transmembrane domain, a further protein is required for the signal transducing step to the cell interior. Here we show, using excised outside-out membrane patches, that activation of a high-conductance Ca(2+)- and voltage-dependent potassium channel is an early step in the transmembrane signal transduction in macrophages. The channel is activated by endotoxically active LPS in a dose-dependent manner. Channel activation can be completely inhibited by LPS antagonists and by anti-CD14 Abs. Activation of the channel is essential for LPS-induced cytokine production as shown by its inhibition by selective K(+) channel blockers.

Antibodies, Blocking↗

Differential effects of TNF and LTalpha in the host defense against M. bovis BCG.

Signaling via TNF receptor type 1 (TNFR1) was shown to be crucial in host defense against the intracellular pathogens L. monocytogenes, M. tuberculosis and M. bovis. To investigate the function of TNF and LTalpha in host defense against M. bovis, mice double deficient for TNF and LTalpha (TNF / LTalpha (- / -)), TNF / LTalpha (- / -) mice complemented with a murine LTalpha transgene (TNF(- / -)) and LTalpha (- / -) mice were infected with BCG and the ensuing pathology was investigated. Control mice showed a normal host defense with early clearance of bacteria. The granulomatous reaction in the liver was accompanied by recruitment of activated macrophages characterized by their acid phosphatase positivity and differentiation into epithelioid cells as well as a coordinated expression of proinflammatory transcripts. In contrast, TNF / LTalpha (- / -) mice showed no comparable recruitment of activated macrophages in the liver. Furthermore, these mice showed extensive necrotic pulmonary lesions with massive growth of acid fast bacilli. Reintroduction of LTalpha as a transgene into TNF / LTalpha (- / -) mice prolonged survival but did not restore resistance to BCG. This, at least partially protective role of LTalpha was further supported by data demonstrating that LTalpha -deficient mice as well were susceptible to BCG infection. In contrast to the deleterious effect of TNF / LTalpha deficiency in BCG infection, BCG-infected TNF / LTalpha (- / -) mice were tolerant to LPS-induced shock. These results demonstrate that TNF as well as LTalpha are involved in murine host defense against BCG and that absence of TNF / LTalpha protects BCG-infected mice from LPS mediated shock.

Animals↗

Two-dimensional separation of [7]helicene enantiomers on Cu(111).

The adsorption of heptahelicene, a helically shaped polyaromatic hydrocarbon (C(30)H(18)), on a Cu(111) surface was studied by means of thermal desorption mass spectrometry (TDMS) and low energy electron diffraction (LEED) at temperatures between 130-1,000 K under ultrahigh vacuum (UHV) conditions. The molecule in the monolayer remains intact up to 400 K. Above that temperature it decomposes in several steps into carbon and hydrogen, desorbing subsequently as H(2). In the saturated monolayer of the racemate the enantiomers are separated into two different domains on the surface which are mirror images of each other. After adsorption of one enantiomer only, no mirror domains were observed.

Journal Article↗

Quantitative structure-transformation relationships of phenylurea herbicides.

Quantitative relationships between the structure of phenylurea herbicides and their transformation in different matrices have been developed. Experimental data on microbial transformation by pure and mixed cultures of soil micro-organisms in inoculated and native soil, as well as on chemical transformation by hydrolysis in sterile soil and water, were available from previous studies. Around 60 experimental or calculated descriptors were used. Quantum chemical calculations were performed with three different semi-empirical methods. Models developed with multiple linear regression were generally easier to interpret than those derived with partial least-squares projection to latent structures. Quite simple and interpretable models could be found to predict transformation rates by pure cultures from lipophilicity, by mixed cultures from adsorption distribution coefficients, and by chemical or enzymatic hydrolysis from electronic properties. Transformation in inoculated soil could not be predicted, but for native soil the use of a quantum chemical descriptor for reactivity (energy of LUMO) together with molar refraction resulted in a general model.

Adsorption↗

[Veno-occlusive liver disease after total infradiaphragmatic lymphoid irradiation. A rare complication].

BACKGROUND: Radiotherapy is potentially curative in early stages of follicle center lymphoma. Frequent side effects are pancytopenia, nausea and abdominal discomfort. A radiation-induced liver injury with serious clinical symptoms and changes in liver function is a rare complication. CASE REPORT: Whole abdomen was irradiated in a 49-year-old patient with a centrocytic-centroblastic lymphoma, stage IA (localization: left inguinal region). A total dose of 30 Gy was delivered in a weekly fractionation of five times 1.5 Gy. Kidneys were protected by shielding after a dose of 13.5 Gy, liver blocks were positioned after 25 Gy. During the last 2 days of therapy the patient presented with weight gain, ascites, dyspnoea and elevated liver enzymes. Diagnostics revealed hepatosplenomegaly, ascites and an increased portosystemic pressure gradient. Liver biopsy specimen showed a veno-occlusive disease. Complete relief of symptomatology was achieved within 7 days following placement of a transjugular intrahepatic portosystemic stent-shunt (TIPSS), heparinization and diuretics. Liver enzymes are in the normal range. CONCLUSION: Veno-occlusive disease of the liver (VOD) is a very rare side effect of primary abdominal irradiation of follicle center lymphoma. This complication should be taken into consideration if a patient presents with upper right quadrant pain, ascites and elevation of liver enzymes especially within 4 months following radiotherapy. Genesis of veno-occlusive disease, diagnostics, therapy and a review of the literature are presented.

Angiography↗

[Xerostomia after radiotherapy. More effective treatment by a mucin-containing spray?].

INTRODUCTION: After radiotherapy (XRT) for head and neck tumors, xerostomia is observed as a chronic side effect. We investigated whether the topical use of a mucin-containing spray can help patients to cope with this problem. PATIENTS AND METHODS: A total of 73 patients with xerostomia post XRT received a bottle of the mucin spray (Saliva medac) and a questionnaire, 59 of which were completed and returned. RESULTS: All patients had received some form of prior treatment, which had been applied 16 times/day on average (median: 15 times/day). The mucin spray had to be used less frequently, i.e., 11 times/day (median: 5 times/day), (p < 0.001, Wilcoxon's rank test). Additionally, they reported being able to sleep significantly better when using the mucin spray (2.9 vs 3.9 in the German school grading system: 1 = very good, 6 = poor; p < 0.001, Wilcoxon's rank test). The spray was well accepted by the patients. CONCLUSIONS: The spray was useful against xerostomia in irradiated patients.

Administration, Oral↗

Microstructural homogeneity of support silk spun by Eriophora fuliginea (C.L. Koch) determined by scanning X-ray microdiffraction.

Scanning X-ray microdiffraction (SXD) permits the 'imaging' in-situ of crystalline phases, crystallinity and texture in whole biopolymer samples on the micrometre scale. SXD complements transmission electron microscopy (TEM) techniques, which reach sub-nanometre lateral resolution but require thin sections and a vacuum environment. This is demonstrated using a support thread from a web spun by the orb-weaving spider Eriophora fuliginea (C.L. Koch). Scanning electron microscopy (SEM) shows a central thread composed of two fibres to which thinner fibres are loosely attached. SXD of a piece of support thread approximately 60 microns long shows in addition the presence of nanometre-sized crystallites with the beta-poly(L-alanine) structure in all fibres. The crystallinity of the thin fibres appears to be higher than that of the central thread, which probably reflects a higher polyalanine content of the fibroins. The molecular axis of the polymer chains in the central thread is orientated parallel to the macroscopic fibre axis, but in the thin fibres the molecular axis is tilted by about 71 degrees to the macroscopic fibre axis. A helical model is tentatively proposed to describe this morphology. The central thread has a homogeneous distribution of crystallinity along the macroscopic fibre axis.

Animals↗

[Minimally invasive bone anchor in therapy of female stress incontinence. A good concept?].

Transvaginal pubic bone anchoring represents a minimally invasive technique for cystourethropexy or urethral sling suspension. This study assesses the results of this procedure. Cystourethropexy was performed in 4 and a sling procedure in 13 of 17 patients. The stress incontinence showed a median improvement from grade 2 to 1.35 (p = 0.01). Nine patients had impaired vaginal wound healing with urge symptoms. Revision was necessary in eight of them. An unfavorable outcome could not be significantly correlated with the surgical technique, the surgeon, the patient's age or the number of previous operations. The technique of minimally invasive bone anchoring must be regarded as unsuitable in view of the largely poor wound healing associated with irritation symptoms.

Adult↗

High-performance liquid chromatography/fluorescence detection of S-methylglutathione formed by glutathione-S-transferase T1 in vitro.

Glutathione-S-transferase T1 (GSTT1-1) is a major isoenzyme for the biotransformation of halomethanes. The enzyme activity is located, among other places, in human liver and erythrocytes and is subject to a genetic polymorphism. Metabolism of the halomethanes via GSTT1-1 yields S-methylglutathione (MeSG). A new HPLC assay for the enzymatic formation of MeSG was developed. The glutathione conjugate was derivatized with 9-fluorenylmethyl chloroformate, followed by reverse-phase HPLC with gradient elution and fluorescence detection. The limit of detection was as low as about 39 pmol MeSG on-column. Including derivatization and HPLC analysis, samples could be run at 42-min intervals, thus enabling a high sample throughput. The entire method was validated for analyte recovery (78.2%) and for variations in detector response with replicated injections (11.8%) and with analyses on each of 11 consecutive days (15.2%) with erythrocyte lysate incubations as the matrix. The time-, protein-, and substrate-dependences of the enzymatic catalysis with the model substrates methyl bromide (MeBr) and methyl chloride (MeCl) were studied. Due to its strong electrophilic character, MeBr caused a high level of spontaneous MeSG formation from glutathione in a protein-free medium and a substrate-trapping side reaction in the presence of proteins. Therefore, enzymatic MeSG formation rates may only be determined with MeBr concentrations of at least 3000 ppm in the presence of limited amounts of protein (e.g. 100 microl erythrocyte lysate). In contrast, MeCl showed a lower alkylating potential allowing enzymatic catalysis to be the dominant reaction in incubations with 10,000 ppm MeCl and 2 ml erythrocyte lysate.

Chromatography, High Pressure Liquid↗

Pharmacokinetics of emedastine difumarate, a new anti-histaminic agent in patients with renal impairment.

OBJECTIVE: Emedastine difumarate is a new H1 receptor antagonist with well defined pharmacokinetic and pharmacodynamic profiles in healthy volunteers. However, to date it is not known whether impaired renal function in patients with chronic renal insufficiency affects its pharmacokinetics and probably also its tolerability. Therefore, we here set out to compare the pharmacokinetics of emedastine difumarate in patients suffering from different degrees of renal failure with a control group of healthy volunteers. METHODS AND RESULTS: For this purpose we conducted an open, single-centre, comparative parallel group study in patients and healthy volunteers. Emedastine difumarate 2 mg was administered orally to the study population in single and seven repetitive doses twice daily (b.i.d.). Pharmacokinetics differed markedly between volunteers (n = 6) and patients (n = 17). The maximum serum concentration of emedastine (Cmax), area under the serum concentration-time curve, mean residence time and terminal disposition half-life were significantly higher in patients (P < 0.05), while time to reach Cmax and apparent volume of disposition were not statistically different after single and repeated (steady-state) oral administrations. Blood pressure and heart rate were also not affected by the study medication. CONCLUSION: The present study shows that impaired renal function alters the pharmacokinetics of emedastine in plasma. Thus, dose adjustment of emedastine difumarate is advisable in patients with impaired renal function.

Administration, Oral↗

Microdialysis. A novel tool for clinical studies of anti-infective agents.

In vivo microdialysis (MD) is an innovative clinical technique that has been employed in preclinical research and metabolic studies in patients for more than a decade. Recently, MD has been adopted for human drug studies and has opened up the opportunity to quantify tissue drug distribution in vivo. The particular advantage of MD for the anti-infective field relates to the fact that MD allows for online measurement of the unbound, pharmacologically active drug fraction in the interstitial space fluid (ISF), the anatomically defined target site for most bacterial infections. The aim of this review is to provide an overview of the current literature about MD in anti-microbial drug studies. It will be shown that MD has become feasible in most human tissues including brain and lung. So far, several MD studies have demonstrated that anti-microbial concentrations at the effect site may be subinhibitory, although effective concentrations are attained in serum, a finding that has significant impact on clinical decision making. In addition to its property as a pharmacokinetic sampling technique, MD offers unique opportunities in pharmacokinetic-pharmacodynamic (PK-PD) research and has the potential to streamline the decision process on proper drug dosing in drug development.

Anti-Infective Agents↗

[The role of pychosocial care and bereavement counselling].

Within their psychosocial problems, badly ill patients and their families often feel left alone by caregivers, as there are physicians and nurses. It is the caregiver's task to allow patients to communicate all their feelings, not seeking to mollify, or banish them by attempting to cheer up or distract the patient. Sharing means to communicate the patient's and his family's anger, sorrows, social pains, spiritual questions, anxiety, as well as their hope and special aims to reach. The first step for the caregiver is, to set up a profound psychosocial diagnosis and to establish some kind of a hierarchy among all the needs. Both of them, caregiver and patient have to find out their primary goals and challenges in the process of dying and come to an agreement. Communicating with a dying patient and being with him in the last period of his life presupposes a deepened communication with oneself and the own hopes and fears.

Attitude to Death↗

[Postoperative analgesic effect after intra-articular morphine or ropivacaine following knee arthroscopy - a prospective randomized, doubleblinded study].

INTRODUCTION: Recent studies for postoperative pain relief after arthroscopy by intraarticular morphine or bupivacaine showed controversial results. The aim of the study was to evaluate the analgesic effect of intraarticular morphine and ropivacaine. METHODS: 135 patients were randomized into 9 groups (n=15) after standardized knee-arthroscopy. They received either 1 mg or 5 mg morphine or 150 mg ropivacaine or a combination of 5 mg morphine and 75 mg ropivacaine. Drains were opened either after 10 or 30 minutes. A control-group received isotonic saline. Pain was assesed 1 h and 4 h after surgery, at 8 pm on the day of the operation and at 8am and 4 pm the following two days by a VAS scale. Tramadol consumption as rescue medication was registred. RESULTS: Ropivacaine showed the best pain relief after surgery. After 24 h the pain intensity approximated in all groups and after 48 h there was no difference. Tramadol consumption was highest in the control group and lowest in the ropivacaine group (p<0,05). Ropivacaine showed better pain reduction than morphine. An influence of the time, when drains were opened, could only be demostrated for the 75 mg ropivacain combination group. CONCLUSION: Intraarticular ropivacaine following elective knee-arthroscopy reduces postoperative analgetic consumption significantly and improves patient comfort.

Adult↗