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Biomedical subjects

Thomas Müller

Publications and source records attributed to Thomas Müller.

At least 109 records · Page 6Linked to original sources
PubMed2003

Acquisition of neuronal and glial markers by neural crest-derived cells in the mouse intestine.

Enteric neurons and glia arise from the neural crest. The phenotype of crest-derived cells was examined as they differentiated into neurons or glia in the mouse small and large intestine. Previous studies have shown that undifferentiated enteric crest-derived cells are Phox2b(+)/Ret(+)/p75(+)/Sox10(+), and at embryonic day (E) 10.5, about 10-15% of the crest-derived cells in the small intestine have started to differentiate into neurons. In the current study, by E12.5 and E14.5, about 25% and 47%, respectively, of Phox2b(+) cells in the small intestine were immunoreactive to the pan-neuronal protein, ubitquitin hydrolase (PGP9.5), and the percentage did not change dramatically from E14.5 onward. The differentiation of crest-derived cells into neurons in the colon lagged behind that in the small intestine by several days. Differentiating enteric neurons showed high Ret, low p75, and undetectable Sox10 immunostaining. Glial precursors were identified by the presence of brain-specific fatty acid binding protein (B-FABP) and detected first in the fore- and rostral midgut at E11.5. Glial precursors appeared to be B-FABP(+)/Sox10(+)/p75(+) but showed low Ret immunostaining. S100b was not detected until E14.5. Adult glial cells were B-FABP(+)/Sox10(+)/p75(+)/S100b(+). A nucleic acid stain (to identify all ganglion cells) was combined with immunostaining for PGP9.5 and S100b to detect neurons and glial cells, respectively, in the postnatal intestine. At postnatal day 0, fewer than 5% and 10% of cells in myenteric ganglia of the small and large intestine, respectively, were neither PGP9.5(+) nor S100b(+). Because some classes of neurons are not present in significant numbers until after birth, the expression of PGP9.5 by developing enteric neurons appeared to precede the expression of neuron type-specific markers.

Animals↗
PubMed2003

Assessment of complex movements reflects dysfunction in Huntington's disease.

Results of various complex instrumental tools, rating scales, caudate atrophy and CAG repeat length may reflect the severity of Huntington's disease (HD). A simple assessment task for dysfunction due to disease is the standardized, computer based performance of peg insertion. The objectives of our study were to compare scored HD symptoms, computed bicaudate diameter ratio (BDR), age related genetic disease load (CAG index = [CAG-35.5 x age]) and peg insertion scores between asymptomatic 34 HD gene carriers, 89 previously untreated HD patients with psychiatric or motor symptoms, or both, and 51 treated HD patients. We measured the period of the total time taken to insert 25 pegs from a rack into a series of appropriate holes, calculated the CAG index, estimated the bicaudate diameter ratio (BDR) of a current brain CT and scored the HD patients under blind conditions. Times for the peg insertion task significantly differed between HD patients and controls, but not between HD gene carriers and controls. BDR and CAG index reflected the increase of symptoms in HD. Peg insertion results and scored severity of HD, BDR and CAG index significantly correlated with each other. Peg insertion scores are not specific diagnostic markers for HD, but they reflect clinical symptoms of neurodegeneration. The performance of peg insertion involves visuospatial cognition, self-elaboration of internal strategies, sorting and planning of movement. Therefore peg insertion particularly reflects executive dysfunction in early HD and additionally motor impairment in advanced HD.

Adult↗
PubMed2003

The canine copper toxicosis gene MURR1 does not cause non-Wilsonian hepatic copper toxicosis.

BACKGROUND: Non-Wilsonian hepatic copper toxicosis includes Indian childhood cirrhosis (ICC), endemic Tyrolean infantile cirrhosis (ETIC) and the non-Indian disease known as idiopathic copper toxicosis (ICT). These entities resemble the hepatic copper overload observed in livers of Bedlington terriers with respect to their clinical presentation and biochemical and histological findings. We recently cloned the gene causing copper toxicosis in Bedlington terriers, MURR1, as well as the orthologous human gene on chromosome 2p13-p16. AIM: To study the human orthologue of the canine copper toxicosis gene as a candidate gene for ICC, ETIC, and ICT. METHODS: We sequenced the exons and the intron-exon boundaries of the human MURR1 gene in 12 patients with classical ICC, one patient with ETIC, and 10 patients with ICT to see whether these patients display any mutations in the human orthologue of the canine copper toxicosis gene. RESULTS: No mutations in the MURR1 gene, including the intron-exon boundaries, were identified in a total of 23 patients with non-Wilsonian hepatic copper toxicosis. CONCLUSIONS: Our results demonstrate that copper toxicosis in Bedlington terriers is not an animal model for the non-Wilsonian hepatic copper toxicosis described in this study.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Evidence for genetic heterogeneity in lymphedema-cholestasis syndrome.

Lymphedema-cholestasis syndrome (LCS, Aagenaes syndrome) is the only known form of hereditary lymphedema associated with cholestasis. A locus, LCS1, has recently been mapped to chromosome 15q in a Norwegian kindred. In a consanguine Serbian Romani family with a neonate who had a combination of lymphedema and cholestasis with features atypical for Norwegian LCS, haplotype and linkage analysis of markers spanning the LCS1 region argue that a second LCS locus may exist. The infant may represent an instance of a previously undescribed lymphedema-cholestasis syndrome.

Cholestasis↗
PubMed2003

Diversity of culturable phyllosphere bacteria on beech and oak: the effects of lepidopterous larvae.

The community composition of epiphytic heterotrophic bacteria on leaves of beech and oak, which were either damaged by lepidopterous larvae or remained undamaged, was investigated. In addition, the ability of these bacteria to utilize inorganic nitrogen was studied. The bacteria were isolated on nutrient agar and systematically identified with biochemical and physiological tests. Rarefaction plots and the Shannon-Wiener function revealed that species diversity was significantly higher on leaves of damaged beech compared to undamaged leaves, but no differences were found on leaves of oak. The portion of bacterial isolates showing a strong response to ammonia and nitrate was significantly larger on leaves of oak than on those of beech. Furthermore, significantly more isolates with a high capability to assimilate both nitrogen compounds were found on leaves attacked by the folivorous larvae compared to those not attacked on oak. It is suggested that the changes in the microbial community in response to folivorous insects might affect the extent of nutrient cycling exceeding eventually the scale of a leaf.

Ammonia↗
PubMed2003

A medical humanities special study module on principles of medical theory and practice at the Charité, Humboldt University, Berlin, Germany.

The authors are members of a committee in charge of a special study module (SSM) entitled Principles of Medical Theory and Practice in a problem-based and integrated reformed curriculum track at the Charité, the medical school and university hospital of the Humboldt University, Berlin, Germany. The SSM contextualizes medicine by highlighting the societal contexts of the doctor-patient relationship and the medical profession. Integrating the humanities into medical education helps students develop an awareness of the strengths and limitations of modern medicine, develop their own personalities and sense of social responsibility, and generally broaden their outlook. Teachers in the SSM seminars are from different disciplines, such as the history of medicine, bioethics, sociology, anthropology, and complementary medicine. Once a week, one or two teachers meet with as many as 21 students per group for a 90-minute course. Twelve courses constitute a seminar. Students are required to participate in four seminars during five years of studies. They can choose different topics from a set range. Although this SSM has been largely successful, some problems have occurred. Results from the course evaluations and experiences show that the seminars differ from one another in many ways. Financial restraints and the departmental structure of the faculty have influenced implementation of the SSM. However, the SSM is a new concept and is continuously reviewed and renewed. Future plans will be to specify outcomes, continue to discuss reasonable seminar topics, establish continuous support and training for teachers, and motivate students to become actively involved in the seminar discussions.

Berlin↗
PubMed2003

Absence of exon 10 of the human luteinizing hormone (LH) receptor impairs LH, but not human chorionic gonadotropin action.

The LH receptor (LHR) mediates the actions of LH and human chorionic gonadotropin (hCG). In vivo data showed that deletion of exon 10 does not affect hCG action, whereas LH action is impaired. To investigate the role of exon 10 in LH/hCG action in vitro we created stable COS-7 cells expressing the LHR with (wt) or without (-ex10) exon 10. Binding experiments showed that the affinities of LH and hCG to the LHR wt and -ex10 were similar. Stimulation of wt with hCG or LH resulted in increased cAMP. cAMP production was significantly impaired in -ex10 stimulated with LH. This response was not altered by pertussis toxin, excluding that G(i) becomes activated in LHR -ex10. In desensitization experiments, intracellular cAMP of LHR wt and -ex10 declined to approximately 30%. No difference in intracellular cAMP was detected between LHR wt or -ex10 after recovery and restimulation with hCG or LH. These experiments show that impaired cAMP production of LHR -ex10 stimulated with LH is not due to anomalous receptor coupling or desensitization. We conclude that although exon 10 of the LHR plays no role in ligand binding, it is important for receptor activation by LH by a mechanism probably involving extracellular conformational changes.

Animals↗
PubMed2003

Effect of antenatal corticosteroid administration on Doppler flow velocity parameters in pregnancies with absent or reverse end-diastolic flow in the umbilical artery.

OBJECTIVE: Evaluation of alterations of Doppler flow velocity waveforms after antenatal corticosteroid therapy. METHODS: Pulsatility index of the umbilical artery, middle cerebral artery and ductus venosus waveforms was measured in high-risk pregnancies complicated by umbilical AREDV directly prior to and within 24 or 48 hours after application of the first dose of a steroid treatment course. RESULTS: Return of a positive end-diastolic flow after umbilical AREDV or conversion of REDV into zero-flow was detected in 9 of 20 (45%) pregnancies after steroid application. Neither in the group which showed altered umbilical end-diastolic flow nor in the total of patients investigated was there any significant change in the PI of the umbilical artery or the ductus venosus waveforms. In contrast, there was an overall drop of pulsatility in the middle cerebral artery. CONCLUSIONS: Antenatal corticosteroid administration could increase cerebral perfusion but has no influence on umbilical and venous blood flow.

Adrenal Cortex Hormones↗
PubMed2003

Treatment benefit correlates with increase of daily drug costs in Parkinson's disease clinics.

BACKGROUND: There is a move towards treatment of Parkinson's disease (PD) patients in specialized units, however, data on the outcome and on daily antiparkinsonian drug costs are rare. OBJECTIVE: The objective of this study was to elucidate relationships between costs of drug treatment and efficacy of drug titration in a PD clinic. SUBJECTS AND METHODS: We calculated costs of drug therapy and scored severity of PD of 63 consecutively referred in-patients initially and at the end of their hospital stay under standardized conditions. RESULTS: Titration of antiparkinsonian drugs significantly induced a decrease of PD symptoms and an increase of daily drug costs. There were significant correlations between the degree of (i) improvement of the UPDRS score, (ii) increase of dopaminergic agents and (iii) change of corresponding daily antiparkinsonian drug costs. CONCLUSION: Our results demonstrate the effectiveness of treatment in PD clinics, which results in increased daily antiparkinsonian drug costs due to elevated dopaminergic substitution.

Aged↗
PubMed2003

[From Basel to Bad Nassau. The fate of the psychoanalyst Arthur Muthmann (1875-1957)].

Arthur Muthmann is known as a pioneer of psychoanalysis in German-speaking countries. He published on the clinical application of psychoanalysis as well as an article explaining the matter to laymen. His Freiburg years and later work have already been portrayed, while his academic failure in Switzerland and his directorship of a private sanatorium at the famous Hessian spa of Bad Nassau have hardly been looked at. Historians of psychoanalysis reported on Muthmann's definite split from the psychoanalytic movement after 1909 due to the fiasco about his professoral thesis at Basel. His contribution to the spreading of psychoanalytic knowledge of the time has been judged upon harshly by known historians. Both hypotheses will be scrutinised here.

Academic Dissertations as Topic↗
PubMed2002

A core-shell structured BaTiO3 precursor preparation, characterization and potential.

A new procedure for the preparation of a core-shell-structured BaTiO(3) precursor (core=TiO(2); shell=BaCO(3)) will be described. The structure of this precursor is characterized by electron microscopy (environmental scanning electron microscopy; energy disperse X-ray spectroscopy), whereas the development of phases during thermal treatment is followed by X-ray powder diffraction.

Journal Article↗
PubMed2002

Chemistry of the aromatic 9-germafluorenyl dianion and some related silicon and carbon species.

Dipotassio-9-germafluorenyl dianion (3b) was synthesized by reduction of 9,9-dichloro-9-germafluorene (4b) with sodium/potassium alloy in tetrahydrofuran. The X-ray crystal structure of 3b, like that for the analogous silicon compound 3a, shows C-C bond length equalization in the five-membered metallole rings and C-C bond length alternation in the six-membered benzenoid rings, indicating aromatic delocalization of electrons into the germole ring of 3b. Calculated nucleus independent chemical shift (NICS) values indicate that the five-membered ring is more aromatic than the six-membered rings in 3a and 3b. Derivatization of 3b with Me(3)SiCl gave 9,9-bis(trimethylsilyl)-9-germafluorene (5). Controlled oxidation of 3b yielded dipotassio-9,9'-digerma-9,9'-bifluorenyl dianion (6). Reaction of 6 with MeOH yielded 9,9'-digerma-9,9'-bifluorene (7). The X-ray structure of 6 indicates C-C bond length alternation in the five-membered rings. Thus dianion 6, like its silicon analogue 8, has the negative charges localized at metal atoms and no aromatic character. Dipotassio-9,9'-bifluorenyl dianion (9), the carbon analogue of 6, exhibits aromaticity with its X-ray crystal structure showing the C-C bond length equalization in both the five- and six-membered rings. Derivatization of 9 with MeI gave 9,9'-dimethyl-9,9'-bifluorene (10). The structure of 10 shows that the two fluorenyl rings are cis to each other with a torsional angle of 59 degrees and a long C-C single bond (1.60 A) connecting them.

Journal Article↗
PubMed2002

Regulation of epithelial cell migration and tumor formation by beta-catenin signaling.

Cell migration requires precise control, which is altered or lost when tumor cells become invasive and metastatic. beta-catenin plays a dual role in this process: as a member of adherens junctions it is essential to link cadherins to the cytoskeleton thereby allowing tight intercellular adhesion, and as a member of the Wnt-signaling pathway, beta-catenin is translocated into the nucleus and serves together with the LEF1/TCF-transcription factors to drive gene expression necessary for the epithelial-to-mesenchymal transition (EMT). Activated beta-catenin signaling has been implicated in the genesis of a variety of tumors. Here we demonstrate a pivotal function for beta-catenin signaling in epithelial cell migration and tumorigenesis. Hepatocyte growth factor (HGF) and epidermal growth factor (EGF) induce beta-catenin signaling under conditions where they stimulate cell motility. Ectopic expression of either stabilized beta-catenin or a regulatable form of activated beta-catenin induces cell migration in different cell types and cooperates with EGF and HGF in this process. Activation of beta-catenin signaling induces expression of the new target gene osteopontin during migration. Cells expressing stabilized beta-catenin also exhibit significantly increased capability to form tumors in a nude mouse xenograft model. The data suggest that a critical threshold of beta-catenin signaling, activated by cooperative mechanisms, may be important during the EMT and tumorigenesis.

Animals↗
PubMed2002

Mass spectrometric characterization and gas-phase chemistry of self-assembling supramolecular squares and triangles.

A detailed mass spectrometric characterization of self-assembling polynuclear metal complexes is described. The complexes can only be ionized as intact species under a surprisingly narrow range of conditions by electrospray ionization. Comparison with the results from NMR experiments shows that several solution-phase features of these squares and triangles (such as trends in bond energies, ligand-exchange reactions, or square-triangle equilibria) are qualitatively reflected in the gas-phase data. Consequently, mass spectrometry represents a valuable method for the characterization of these compounds. Nevertheless, the formation of unspecific aggregates during the ionization process occurs and its implications are discussed. Beyond the chemistry in solution, the fragmentation pathways of these complexes in the gas phase have been studied by infrared multiphoton dissociation (IRMPD) experiments. The results of IRMPD studies allow us to draw conclusions with respect to the structure and energetics of fragmentation products. In this tandem MS experiment, reaction pathways can be observed directly which can hardly be analyzed in solution. According to these results, the equilibration of triangles and squares involves the supramolecular analogue of a neighboring-group effect.

Journal Article↗
PubMed2002

Progressive hearing loss, and recurrent sudden sensorineural hearing loss associated with GJB2 mutations--phenotypic spectrum and frequencies of GJB2 mutations in Austria.

Mutations of GJB2 (encoding connexin 26) are the most common cause of hearing loss (HL) in different populations, and a broad spectrum of GJB2 mutations has been identified. We screened 204 consecutive patients with non-syndromic sensorineural hearing loss for GJB2 mutations. Causative GJB2mutations were identified in 31 (15.2%) patients, and two common mutations, c.35delG and L90P (c.269T>C), accounted for 72.1% and 9.8% of GJB2 disease alleles. In four additional patients (2.0%) only one recessive GJB2 mutation was identified, making genetic counselling difficult. No genotype-phenotype correlation was established. We found, however, that homozygotes for truncating mutations were more likely to have a more severe degree of HL compared with other genotypes. Moreover, we showed by co-segregation studies that L90P is a GJB2 disease allele, and that compound heterozygotes for L90P and any recessive mutation share a mild to moderate phenotype. GJB2-associated HL was linked with progressive HL or with recurrent sudden sensorineural hearing loss (SSNHL) in three of 15 cases being analysed retrospectively. We extended the phenotypic spectrum of GJB2-related disease and recommend GJB2 mutation screening also in cases of progressive HL, and recurrent SSNHL. In addition, a carrier frequency of 1/110 (0.9%) for the most common Caucasian mutation in this gene, c.35delG, was determined in 1,212 blood donors from West-Austria, supporting the prevailing hypothesis of a Mediterranean founder mutation. Based on population and patient data, an overall GJB2 mutation carrier frequency of 1.3% was estimated for West-Austria.

Adolescent↗