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Biomedical subjects

Peter Müller

Publications and source records attributed to Peter Müller.

68 records · Page 4Linked to original sources
PubMed2002

Is patient satisfaction a unidimensional construct? Factor analysis of the Munich Patient Satisfaction Scale (MPSS-24).

Although patients' satisfaction with treatment has gained much attention, conceptual and methodological issues are not sufficiently investigated. Consequently, well-validated satisfaction scales are rare. In order to respond to methodological requirements being associated with the measurement of patient satisfaction, the Munich Patient Satisfaction Scale (MPSS-24) was developed for psychiatric in-patients. The scale was validated on the basis of three independent samples (n=85, n= 161, n=91), and the effects of moderating variables were controlled. In several steps of item selection the initial pool of 133 items was reduced to 24 items, which were subjected to factor analysis. The MPSS-24 demonstrates one major principal component with two minor factors which indicates that doctor-patient communication is the essential source for patient satisfaction. The instrument is of high internal consistency and reliability, and convergent validity is satisfactory.

Adult↗
PubMed2002

Rapid transbilayer movement of the fluorescent sterol dehydroergosterol in lipid membranes.

This study establishes a new assay for measuring the transbilayer movement of dehydroergosterol (DHE) in lipid membranes. The assay is based on the rapid extraction of DHE by methyl-beta-cyclodextrin (M-CD) from liposomes. The concentration of DHE in the liposomal membrane was measured by using fluorescence resonance energy transfer (FRET) from DHE to dansyl-phosphatidylethanolamine, which is not extracted from liposomes by M-CD. The method was applied to small (SUV) and large (LUV) unilamellar vesicles of different compositions and at various temperatures. From the kinetics of FRET changes upon extraction of DHE from membranes, rates of M-CD mediated extraction and flip-flop of DHE could be deduced and were found to be dependent on the physical state of the lipid phase. For egg phosphocholine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine in the liquid-crystalline state, halftimes of extraction and transbilayer movement were <5 s and approximately 20-50 s, respectively, at 10 degrees C. For 1,2-dimyristoyl-sn-glycero-3-phosphocholine-SUV being in the gel state at 10 degrees C, the respective halftimes were 28 s and 5-8 min. Surprisingly, DHE could not be extracted from LUV consisting of 1,2-dimyristoyl-sn-glycero-3-phosphocholine. This might be an indication of specific interactions between DHE molecules in membranes depending on the phospholipid composition of the membrane.

Biophysical Phenomena↗
PubMed2002

Transbilayer movement of phospholipids at the main phase transition of lipid membranes: implications for rapid flip-flop in biological membranes.

The transbilayer movement of fluorescent phospholipid analogs in liposomes was studied at the lipid phase transition of phospholipid membranes. Two NBD-labeled analogs were used, one bearing the fluorescent moiety at a short fatty acid chain in the sn-2 position (C(6)-NBD-PC) and one headgroup-labeled analog having two long fatty acyl chains (N-NBD-PE). The transbilayer redistribution of the analogs was assessed by a dithionite-based assay. We observed a drastic increase of the transbilayer movement of both analogs at the lipid phase transition of DPPC (T(c) = 41 degrees C) and DMPC (T(c) = 23 degrees C). The flip-flop of analogs was fast at the T(c) of DPPC with a half-time (t(1/2)) of ~6-10 min and even faster at the T(c) of DMPC with t(1/2) on the order of <2 min, as shown for C(6)-NBD-PC. Suppressing the phase transition by the addition of cholesterol, the rapid transbilayer movement was abolished. Molecular packing defects at the phase transition are assumed to be responsible for the rapid transbilayer movement. The relevance of those defects for understanding of the activity of flippases is discussed.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2002

Rapid transbilayer movement of spin-labeled steroids in human erythrocytes and in liposomes.

The transbilayer movement and distribution of spin-labeled analogs of the steroids androstane (SLA) and cholestane (SLC) were investigated in the human erythrocyte and in liposomes. Membranes were labeled with SLA or SLC, and the analogs in the outer leaflet were selectively reduced at 4C using 6-O-phenylascorbic acid. As shown previously, 6-O-phenylascorbic acid reduces rapidly nitroxides exposed on the outer leaflet, but its permeation of membranes is comparatively slow and thus does not interfere with the assay. From the reduction kinetics, we infer that transbilayer movement of SLA in erythrocytes is rapid at 4C with a half-time of approximately 4.3 min and that the probe distributes almost symmetrically between both halves of the plasma membrane. We have no indication that a protein-mediated transport is involved in the rapid transbilayer movement of SLA because 1) pretreatment of erythrocytes with N-ethyl maleimide affected neither flip-flop nor transbilayer distribution of SLA and 2) flip-flop of SLA was also rapid in pure lipid membranes. The transbilayer dynamics of SLC in erythrocyte membranes could not be resolved by our assay. Thus, the rate of SLC flip-flop must be on the order of, or even faster than, that of probe reduction rate on the exoplasmic leaflet (half-time approximately 0.5 min). The results are discussed with regard to the transbilayer dynamics of cholesterol.

Androstanes↗
PubMed2002

Evolutionary conservation of the chromatin modulator Polycomb in the jellyfish Podocoryne carnea.

Polycomb-group (PcG) proteins form chromatin-associated multimeric complexes, which are responsible for the maintenance of the transcriptionally repressive state of regulatory genes during development. We have isolated a Polycomb homologue of the hydrozoan Podocoryne carnea by a PCR-based approach. Our results demonstrate that structure and function of Polycomb-group proteins have been conserved in evolution from cnidarians to vertebrates since Podocoryne Polycomb interacts in yeast with mouse dinG/RING1B, an interaction partner of the mouse Polycomb homologue MPc3. Polycomb is expressed throughout the life cycle of Podocoryne. In situ hybridization reveals a differential expression pattern in proliferating and differentiating tissues of the developing medusa bud. In the transdifferentiation of activated isolated striated muscle of the medusa to smooth muscle and RFamide-positive nerve cells, Polycomb expression is strongly increased when differentiation into nerve cells occurs.

Amino Acid Sequence↗
PubMed2002

[Prognosis of schizophrenia from the viewpoint of patients and relatives. An explorative study].

OBJECTIVE: This study is aimed at exploring what schizophrenic patients and their closest relatives expect the further course of the illness will be like and how it can be influenced. METHOD: Problem-centered interviews were conducted with 31 schizophrenic patients and their closest relatives at discharge from hospital treatment. The verbatim transcripts of the interviews were analyzed by means of structuring qualitative content analysis. RESULTS: Most frequently, the respondents expected an improvement of the illness or they were unsure whether the actual recovery from psychosis will persist or whether a further relapse will occur. Less frequently, the respondents were sure that this will be the case or that the illness will take a chronic, eventually deteriorating course. The majority was convinced that the course of the illness can be influenced, by psychiatric treatment as well as by the patients themselves. As concerns the social situation in the near future, particularly changes of the occupational status were hoped for. CONCLUSION: The assessment of the prognosis of the schizophrenic illness by most patients and relatives appears quite realistic. Rather than considering themselves as helpless victims they see opportunities for influencing the further course of the illness. This should have a positive influence on the readiness to use mental health service and to comply with treatment recommendations.

Adult↗
PubMed2002

[The risk of rehospitalisation during therapy with atypical and typical neuroleptics--a contribution to differential indication].

Atypical neuroleptics have a lot of advantages compared with conventional substances. It is still disadvantageous that a depot-medication is missing. The role of the form of application has been studied in a schizophrenia-out-patient department. In 25 out-patients under therapy with atypical neuroleptics the time of rehospitalisation per year was retrospectively determined and compared with that of 25 out-patients receiving depot-medication. Both groups were comparable with regard to some patient-characteristics and predictors of the course of the disease. It turned out that for patients with depot-neuroleptics the time spent in hospital per year was half of that for patients under atypical drugs. It had been in the same range in both groups 4 to 6 years ago and had decreased until the last year of the catamnesis in patients with depot-medication, but not in those with atypics. Typical neuroleptics as oral medication are disadvantageous in this respect. Despite efforts to reach a good compliance in all patients, preferable effects of atypical drugs with regard to negative symptoms are opposed by less favourable rehospitalisation times. This has to be taken into consideration in differential indication.

Administration, Oral↗
PubMed2002

Delayed retrograde aortic dissection after endovascular stenting of the descending thoracic aorta.

A 66-year-old patient underwent emergency endovascular repair of a descending thoracic aneurysm because of suspected aortic rupture. Two weeks later, a small saccular aneurysm of the aortic arch was treated with open surgery. An unexpected intraoperative finding was retrograde dissection of the aortic arch and of the ascending aorta that was not seen on the postprocedural computed tomographic scans after endografting. The ascending aorta, the aortic arch, and the proximal part of the descending thoracic aorta were successfully replaced with a Dacron graft with deep hypothermia, circulatory arrest, and retrograde cerebral perfusion. Awareness that this life-threatening complication that necessitates extensive cardiovascular surgery can occur not only during or immediately after endovascular stenting of the thoracic aorta but also as much as several days or perhaps even weeks after the procedure is important.

Aged↗
PubMed2002

A novel two-component system of Bradyrhizobium japonicum: ElmS and ElmR are encoded in diverse orientations.

By completely sequencing the Bradyrhizobium japonicum insert of cosmid C27, a pair of genes was identified which was found to be highly similar to prokaryotic two-component systems. The genes of the putative regulator protein (214 aa), elmR, and the putative sensor histidine kinase (470 aa), elmS, are divergently oriented with their putative translational start sites separated by only 85 nucleotides. This new locus is located about 10 kb upstream of the sipS signal peptidase allele. The highest similarities were found to regulatory proteins of methylotrophic bacteria. Genetically defined B. japonicum mutants were tested for their growth on different monocarbon compounds and for the symbiotic interactions with soybeans. Because no obvious phenotype could be observed the functional importance of this sensor/regulator-pair remains to be determined.

Amino Acid Sequence↗
PubMed2002

A combinatorial approach to protein docking with flexible side chains.

Rigid-body docking approaches are not sufficient to predict the structure of a protein complex from the unbound (native) structures of the two proteins. Accounting for side chain flexibility is an important step towards fully flexible protein docking. This work describes an approach that allows conformational flexibility for the side chains while keeping the protein backbone rigid. Starting from candidates created by a rigid-docking algorithm, we demangle the side chains of the docking site, thus creating reasonable approximations of the true complex structure. These structures are ranked with respect to the binding free energy. We present two new techniques for side chain demangling. Both approaches are based on a discrete representation of the side chain conformational space by the use of a rotamer library. This leads to a combinatorial optimization problem. For the solution of this problem, we propose a fast heuristic approach and an exact, albeit slower, method that uses branch-and-cut techniques. As a test set, we use the unbound structures of three proteases and the corresponding protein inhibitors. For each of the examples, the highest-ranking conformation produced was a good approximation of the true complex structure.

Algorithms↗
PubMed2002

Validation of the phenylalanine/tyrosine ratio determined by tandem mass spectrometry: sensitive newborn screening for phenylketonuria.

The efficacy of the tandem mass spectrometry as a tool for the newborn screening of phenylketonuria, an inherited metabolic disorder, was investigated. Precision, reproducibility, selectivity and sensitivity were validated for phenylalanine and tyrosine measurements from dried blood spots. Bland-Altman plots were used to assess the agreement with conventional methods like fluorometry and ion exchange chromatography. The utility of the phenylalanine/tyrosine ratio for discrimination between mild hyperphenylalaninemia and classical types of phenylketonuria was investigated. Depending on concentration levels of phenylalanine and tyrosine the within-run and between-run assay variability ranged between 4.2% and 12.7%. Higher recoveries and a lower detection limit were found for the mass spectrometric method when compared to the fluorometric method. Pearson correlation coefficients of 0.91 for tandem mass spectrometry vs. fluorometric method, as well as 0.95 for tandem mass spectrometry vs. ion exchange chromatography were calculated. The closest agreement between methods was observed between tandem mass spectrometry and ion exchange chromatography. The results demonstrate a high efficacy of the tandem mass spectrometric method for quantitative determination of phenylalanine and tyrosine from dried blood spots. The phenylalanine/tyrosine ratio is crucial to improve the specificity and positive predictive value for the diagnosis of classical phenylketonuria.

Blood Specimen Collection↗
PubMed1997

Squalene-hopene cyclase from Bradyrhizobium japonicum: cloning, expression, sequence analysis and comparison to other triterpenoid cyclases.

With the help of a PCR-based screening method, the gene encoding squalenehopene cyclase (SHC) of Bradyrhizobium japonicum USDA 110 was isolated from a cosmid library. The SHC catalyses the cyclization of squalene to hopanoids, a class of triterpenoid lipids recently discovered in nitrogen-fixing, root-nodule-forming Bradyrhizobium bacteria. Hybridization experiments showed that the gene is present in bacteria of all Bradyrhizobium strains tested and in photosynthetic bacteria forming stem nodules on tropical legumes of the genus Aeschynomene. The Bradyrhizobium shc gene is 1983 bp in length and encodes a protein of 660 amino acid residues with a calculated molecular mass of 73671 Da. Comparison of the deduced amino acid sequence with the sequences of other SHCs revealed highest similarity (70%) to the SHC from the Gram-negative Zymomonas mobilis and lower similarity (48%) to the SHCs from the Gram-positive Alicyclobacillus acidocaldarius and Alicyclobacillus acidoterrestris. Bradyrhizobium SHC also showed similarity (38-43%) to eukaryotic oxidosqualene cyclases. The B. japonicum shc gene was expressed in Escherichia coli. The recombinant SHC catalysed the cyclization of squalene to the hopanoids hopene and diplopterol in vitro. However, the formation of the gammacerane derivative tetrahymanol, which is produced in addition to hopanoids in B. japonicum strains in vivo, could not be detected in vitro. Therefore, the presence of a second squalene cyclase in B. japonicum can be assumed. Sequence analysis of 0.5 kb upstream from the shc gene identified a partial ORF with significant similarity to the C-terminus of an ORF located immediately upstream from the shc gene in Z. mobilis. Both ORFs also showed similarity to phytoene desaturases from cyanobacteria and plants. The 3'-end of this ORF from B. japonicum overlaps with 13 bp at the 5'-end of shc. The close proximity of this ORF to shc suggests that shc and this ORF may be part of an operon.

Amino Acid Sequence↗
PubMedDate not supplied

Activation of the lymphotoxin-beta receptor induces NFkappaB-dependent interleukin-6 and MIP-2 secretion in mouse fibrosarcoma cells.

Activation of the lymphotoxin beta-receptor (LTbetaR), a member of the tumor necrosis factor receptor family, plays a crucial role in lymphoid organogenesis and tumor development. Lymphotoxin alpha(1)beta(2) (LTalpha(1)beta(2)) and LIGHT have been identified as membrane anchored ligands for the LTbetaR. While LTbetaR is expressed on a wide range of cell types e.g. fibroblasts and monocytes, the ligands are expressed only on activated lymphocytes and NK cells. In order to characterize LTbetaR expression and the biological consequences of LTbetaR activation rat anti-mouse LTbetaR monoclonal antibodies were generated. These antibodies recognized a mouse LTbetaR-Ig fusion protein as well as endogenous LTbetaR on a variety of mouse fibroblast and fibrosarcoma cell lines. Specificity was demonstrated by the lack of binding to LTbetaR-deficient embryonic fibroblasts. Competitive binding studies revealed that three different epitopes were recognized by the monoclonal antibodies. Two of the monoclonals activated the LTbetaR and induced activation of NFkappaB and secretion of MIP-2 and IL-6 in L929 mouse fibroblast cells. MIP-2 and IL-6 secretion was NFkappaB-dependent because IkappaB-transfected cells released significantly reduced amounts of both mediators.

Animals↗