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Biomedical subjects

P Müller

Publications and source records attributed to P Müller.

At least 19 recordsLinked to original sources
PubMed2006

A European interlaboratory testing of three well-known procedures for immunocytochemical detection of epithelial cells in bone marrow. Results from analysis of normal bone marrow.

BACKGROUND: This investigation intended to study the unspecific background to be expected in normal bone marrow (BM), comparing three well recognized protocols for immunocytochemical detection of disseminated carcinoma cells. The interlaboratory variation in screening and evaluation of stained cells was analyzed and different screening methods were compared. METHODS: BM mononuclear cells (BM MNC) from 48 normal BMs were immunostained in parallel by three participating laboratories. The protocols, based on three different anti-cytokeratin antibodies, have all been in common use for detection of disseminated carcinoma cells: the A45-B/B3 protocol (Hamburg), the CK2 protocol (Augsburg) and the AE1AE3 protocol (Oslo). For all protocols, the immunostained cells were visualized by the same alkaline-phosphatase (AP) detection system (APAAP) followed by detection of the cells by manual screening and by two different automated screening systems (ACIS from Chromavision and MDS1 from Applied Imaging). Detected AP-visualized cells were morphologically classified into unambiguous hematopoietic (Uhc) and questionable cells (Qc, potentially interpreted as tumor cells). RESULTS: Seven of 48 BMs (15%) harbored > or = 1 AP-visualized cell(s) among 1 x 10(6) BM MNC, both for the A45-B/B3- and for the AE1AE3 protocol, while for CK2 a higher proportion of BMs (21 BMs; 44%) harbored AP-visualized cells (P < 0.01, McNemar's test). The number of Qc was, for all protocols, 1 log lower than the total number of AP-visualized cells. On average, the frequency of Qc was 0.04, 0.08, and 0.02 per 10(6) BM MNC with A45-B/B3, CK2 and AE1AE3, respectively, and the number of Qc-positive BMs 1, 4, and 1. The MDS1 screening sensitivity was similar to manual screening, while ACIS detected fewer cells (P < 0.001, McNemar's test). CONCLUSIONS: All protocols resulted in AP-visualization of occasional hematopoietic cells. However, morphological classification brings the specificity to a satisfactory high level. Approximately 10% of AP-visualized cells were categorized "questionable". The CK2 protocol turned out less specific than the A45-B/B3 and AE1AE3 protocols.

Adult↗
PubMed2006

Enhanced macroscopic quantum tunneling in Bi2Sr2CaCu2O8 + delta intrinsic Josephson-junction stacks.

We have investigated macroscopic quantum tunneling in Bi(2)Sr(2)CaCu(2)O(8 + delta) intrinsic Josephson junctions at millikelvin temperatures using microwave irradiation. Measurements show that the escape rate for uniformly switching stacks of Nu junctions is about Nu(2) times higher than that of a single junction having the same plasma frequency. We argue that this gigantic enhancement of the macroscopic quantum tunneling rate in stacks is boosted by current fluctuations which occur in the series array of junctions loaded by the impedance of the environment.

Journal Article↗
PubMed2006

Cytology and mRNA expression analysis of fine needle aspirates of thyroid nodules in an East German region with borderline iodine deficiency.

Fine needle aspiration cytology (FNAC) is widely recommended as an important tool for pre-operative identification of malignancy in patients with nodular thyroid disease. To assess the diagnostic contribution of FNAC and the potential of quantitative mRNA analysis in fine needle aspirates in daily practice, we conducted a prospective study in thyroid clinics (n=2) and endocrine practices (n=3), respectively in an East German region with borderline iodine deficiency. Two-hundred and forty-four consecutive FNACs were obtained over a period of 2 years (2002-2004) from euthyroid patients presenting for first evaluation of a solitary thyroid nodule. The mean nodule size for FNAC was 27 mm (range: 10-79 mm). In 55% of patients FNAC was performed after scintiscan detection of a cold or normal functioning thyroid nodule (CTN), while in the remainder FNAC was performed as a primary investigation. FNAC outcomes were: 57.8% benign, 22.1% indeterminate, 2.5% suspicious for malignancy, 17.6% non-diagnostic. Messenger RNA levels for a house keeping gene (beta-actin) and a thyroid specific marker (thyroglobulin, Tg) were studied as basic molecular markers using real-time PCR. Both in the IN VIVO and EX VIVO FNA series, beta-actin and Tg mRNA levels were positively correlated with the thyrocyte cell yield/respective FNA smear. However, subgroup analysis showed that FNAC with histologically confirmed follicular thyroid cancer and/or microfollicular adenoma exhibited significantly lower Tg mRNA expression despite high beta-actin levels. Sufficient mRNA quantities were obtained in >90% of FNA specimen to allow quantitative mRNA analysis of at least 5 further genes. In conclusion, quantitative mRNA analysis is feasible in FNA on a routine basis and provides a perspective for a molecular distinction of thyroid nodules, once specific marker genes have been defined for benign and malignant thyroid tumours respectively.

Actins↗
PubMed2006

Disjunct distributions during glacial and interglacial periods in mountain butterflies: Erebia epiphron as an example.

Over several decades, the distribution patterns and evolution of alpine disjunct species has become an increasingly discussed subject. Large scale genetic analysis has allowed the resolution of the past range changes and intraspecific evolution of many species, in Europe especially of Mediterranean origin. However, the phylogeographic structures of species with arctic-alpine disjunct distribution patterns are relatively poorly studied. The existing phylogeographic analysis (mostly of alpine plant species) supports disjunct distributions during glacial as well as post-glacial periods for a number of species. However, several questions still remain unresolved and we therefore analysed the Mountain Ringlet Erebia epiphron as a model for such alpine disjunct species. We found strong differentiation into five different lineages supporting five differentiation centres: (i) the eastern Pyrenees, (ii) the mountain ranges between the central Pyrenees and south-western Alps, (iii, iv) two areas along the southern Alps margin and (v) the northern Alps margin. We propose that these patterns evolved due to the humidity requirements of this species, which did not allow survival in the dry glacial steppes, but along the margins of the wetter glaciated high mountain ranges.

Animals↗
PubMed2005

[Medical aspects of diving in the tropics].

Scuba diving vacations in tropical surroundings belong to the repertoire of most divers. In addition to carefully making travel plans and taking care of the necessary vaccinations and appropriate malaria prophylaxis, the following points also must be observed. The flight itself affects diving safety. In particular, a too short time interval between diving and the return flight can lead to decompression problems. Because most of the diving areas are reached by ship, many divers need a prophylaxis against motion sickness. Moreover, external otitis occurs more frequently while diving in the tropics. Finally, there is potential danger from the sea inhabitants, primarily from scorpion fishes, Portuguese Man-of-Wars, box jellyfishes as well as cone snails.

Animals↗
PubMed2005

Sb/Si(111) adsorption: hidden phase transitions behind Langmuir-like isotherms.

The experimental study of the thermodynamic and kinetic properties of the Sb/Si(111) interface reveals a surprising behavior: a 2D phase condensates when the Sb coverage increases, indicating strong attractive Sb-Sb interactions, whereas the isotherms present a quasi-Langmuir shape, suggesting that these interactions should be negligible. Ab initio calculations raise this contradiction: while the adsorption site evolves from ternary towards the on-top position with increasing coverage, the character of the Sb-Sb effective interactions changes from repulsive towards attractive, resulting in an almost constant average adsorption energy. A simple (Langmuir) thermodynamic behavior can then be the consequence of a surface phase transition.

Journal Article↗
PubMed2005

Antiproliferative activity of olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor.

The study describes the protein kinase selectivity profile, as well as the binding mode of olomoucine II in the catalytic cleft of CDK2, as determined from cocrystal analysis. Apart from the main cell cycle-regulating kinase CDK2, olomoucine II exerts specificity for CDK7 and CDK9, with important functions in the regulation of RNA transcription. In vitro anticancer activity of the inhibitor in a panel of tumor cell lines shows a wide potency range with a slight preference for cells harboring a wild-type p53 gene. Cell-based assays confirmed activation of p53 protein levels and events leading to accumulation of p21(WAF1). Additionally, in olomoucine II-treated cells, Mdm2 was found to form a complex with the ribosomal protein L11, which inhibits Mdm2 ubiquitin ligase function. We conclude that perturbations in RNA synthesis may lead to activation of p53 and that this contributes to the antiproliferative potency of cyclindependent kinase inhibitors.

Antineoplastic Agents↗
PubMed2004

A H2O2-producing glyoxal oxidase is required for filamentous growth and pathogenicity in Ustilago maydis.

In the phytopathogenic fungus Ustilago maydis the mating-type loci control the transition from yeast-like to filamentous growth required for pathogenic development. In a large REMI (restriction enzyme mediated integration) screen, non-pathogenic mutants were isolated in a haploid strain that had been engineered to be pathogenic. In one of these mutants, which showed a specific morphological phenotype, the tagged gene, glo1 , was found to encode a product that is highly homologous to a glyoxal oxidase gene from the wood-rot fungus Phanerochaete chrysosporium. Glyoxal oxidase homologues are found in human, plant pathogenic fungi and in plants, but not in other mammals or yeasts. To confirm the function of the glo1 gene, null mutations were generated in compatible haploid U. maydis strains. In crosses null mutants were unable to generate filamentous dikaryons, and were completely non-pathogenic. Using a Glo1-overproducing strain we demonstrated that Glo1 is membrane bound, oxidizes a series of small aldehydes (< C4) and produces H2O2. The enzyme needs to be activated, presumably by auto-oxidation, to show full activity. A potential role for Glo1 during filamentous growth and pathogenic development of U. maydis is proposed.

Alcohol Oxidoreductases↗
PubMed2004

Context-dependent stimulus presentation to freely moving animals in 3D.

The presentation of controllable, dynamic sensory stimuli provides a powerful experimental paradigm, which has been extensively applied to explore sensory processing in walking and tethered flying insects. Recent advances in computer hardware and software technology provide the opportunity to track the 3D flight path of free-flying insects and process these data in real-time, opening up the possibility to present dynamic stimuli to free-flying animals. To accommodate for the increased complexity relating to 3D space, we partitioned experimental design, real-time data acquisition and stimulus control into multiple self-contained modules. 3D experimental scenarios were created in a stand-alone application by forging multiple 3D space-stimulus relationships. The use of dynamic cues is illustrated by an experiment, in which dynamic acoustic cues were presented to a free-flying parasitoid fly in a large 3D environment. The combination of loosely coupled modules provides robust and flexible solutions, allowing new paradigms to be readily implemented based on existing technologies. We demonstrate this with a test system that displayed a complex visual stimulus, controlled in real-time by the 2D position and orientation of a test object. The presented methods are applicable in a variety of novel experimental paradigms, including learning paradigms, for various sensory modalities in walking, swimming and flying animals.

Animals↗
PubMed2004

Counting individual 41Ca atoms with a magneto-optical trap.

Atom trap trace analysis, a novel method based upon laser trapping and cooling, is used to count individual atoms of 41Ca present in biomedical samples with isotopic abundance levels between 10(-8) and 10(-10). The method is calibrated against resonance ionization mass spectrometry, demonstrating good agreement between the two methods. The present system has a counting efficiency of 2x10(-7). Within 1 h of observation time, its 3-sigma detection limit on the isotopic abundance of 41Ca reaches 4.5x10(-10).

Calcium Radioisotopes↗
PubMed2004

Use of the multipurpose transposon Tn KPK2 for the mutational analysis of chromosomal regions upstream and downstream of the sipF gene in Bradyrhizobium japonicum.

The DNA regions upstream and downstream of the Bradyrhizobium japonicum gene sipF were cloned by in vivo techniques and subsequently sequenced. In order to study the function of the predicted genes, a new transposon for in vitro mutagenesis, Tn KPK2, was constructed. This mutagenesis system has a number of advantages over other transposons. Tn KPK2 itself has no transposase gene, making transposition events stable. Extremely short inverted repeats minimize the length of the transposable element and facilitate the determination of the nucleotide sequence of the flanking regions. Since the transposable element carries a promoterless ' phoA reporter gene, the appearance of functional PhoA fusion proteins indicates that Tn KPK2 has inserted in a gene encoding a periplasmic or secreted protein. Although such events are extremely rare, because the transposon has to insert in-frame, in the correct orientation, and at an appropriate location in the target molecule, a direct screening procedure on agar indicator plates permits the identification of candidate clones from large numbers of colonies. In this study, Tn KPK2 was used for the construction of various symbiotic mutants of B. japonicum. One of the mutant strains, A2-10, which is defective in a gene encoding a protein that comigrates with bacterioferritin ( bcpB), was found to induce the formation of small and ineffective nodules.

Amino Acid Sequence↗
PubMed2004

[Relevance of p53 protein and its mutations for novel strategies in cancer therapy].

Mutational inactivation of the p53 gene products is one of the most common genetic events that occur in human cancer confirming the central role of p53 as a tumour suppressor. The wild type p53 protein acts as a powerful transcription factor binding as many as 300 different promoter sequences in the genome. As a transcription factor, p53 can broadly alter patterns of specific gene expression leading to cell-cycle arrest and/or apoptosis. The transcriptional activity of the p53 protein is precisely regulated and its basal activity is enhanced in cells exposed to a wide variety of stress signals. This stress regulated transactivation function of p53 is driven by its sequence-specific DNA-binding domain and is co-ordinated by specific protein-protein interactions that can be modulated by covalent and non-covalent modifications. The mutant forms of p53 protein are defective in sequence specific DNA-binding because the missense mutation affects one or all of the assembly pathways. Analysis of p53 mutant has shown that different conformational classes of mutants exist and the reactivation of each class requires a different strategy depending on the mechanism of p53 protein misfolding. Potential reactivation of both wild type and mutant p53 protein in vivo raises our hopes of developing anti-cancer drugs useful in combination with sophisticated diagnostics for the treatment of cancer.

Apoptosis↗
PubMed2003

Josephson behavior of phase-slip lines in wide superconducting strips.

Phase-slip lines can be viewed as dynamically created Josephson junctions in a homogeneous superconducting film. In contrast to phase-slip centers, phase-slip lines occur in wide superconducting strips, where the order parameter may vary in two dimensions. We investigated phase-slip lines in two different materials using several methods. We observed Shapiro steps under microwave radiation, which shows that the frequency of the order parameter oscillation is equal to Josephson frequency. A periodic oscillation of a critical current versus the applied magnetic field was found in strips with a hole in the middle. The latter effect provides a clear evidence of macroscopic quantum interference across a phase-slip line. We have used low temperature scanning laser microscopy to visualize the phase-slip lines and to distinguish them from possible local inhomogeneities in the films.

Journal Article↗
PubMed2003

Recurrent spinal cord astrocytoma with intraventricular seeding.

PATIENT: We report on an unusual case of a recurrent and progressive spinal pilocytic astrocytoma with metastatic spreading to the hypothalamus in a 14-year-old boy. TREATMENT AND RESULTS: The patient underwent resection of an intramedullary atypical pilocytic astrocytoma classified as WHO grade II at the level of Th11/12 in 1997 and received local photon beam irradiation. Three years later, a second operation was necessary for a recurrent tumour at the same level. Seventeen months later, a second recurrent tumour with spinal seeding as well as an intracranial tumour in the third ventricle and hypothalamus was detected. He was shunted for an occlusive hydrocephalus and a stereotactic biopsy of the hypothalamic lesion was performed. The tumour was classified as anaplastic pilocytic astrocytoma (WHO grade III). He received chemotherapy with ifosfamide, cisplatin and etoposide (HIT-GBM-C-protocol), craniospinal radiation, and is still alive 60 months after the first operative intervention without neurological deficits.

Adolescent↗
PubMed2003

Is interval medication a successful treatment regimen for schizophrenic patients with critical attitudes towards treatment?

In neuroleptic long-term medication, only part of the patients accept regular intake of neuroleptic drugs. The question is whether an interval medication regimen as opposed to continuous medication can help to reduce drop outs in patients with critical attitudes towards long-term medication. In a 2-year prospective study, 122 patients were randomised to an interval and 164 to a continuous neuroleptic medication regimen. The drop out rates were 62.5% in the interval and 53.7% in the continuous medication group. Drop outs generally show more negative attitudes towards treatment. Patients with negative attitudes do not do better under interval medication. Moreover, this regimen even requires more cooperation and trust in terms of the necessity of medication on the part of the patient compared to the continuous medication regimen. Interval medication therefore is a strategy which can only be successful in highly cooperative, but not in treatment-reluctant patients.

Antipsychotic Agents↗