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M Beyeler

Publications and source records attributed to M Beyeler.

9 recordsLinked to original sources
PubMed2005

Compartmental bone morphometry in the mouse femur: reproducibility and resolution dependence of microtomographic measurements.

Microcomputed tomography (microCT) is widely used for nondestructive bone phenotyping in small animals, especially in the mouse. Here, we investigated the reproducibility and resolution dependence of microCT analysis of microstructural parameters in three different compartments in the mouse femur. Reproducibility was assessed with respect to precision error (PE%CV) and intraclass correlation coefficient (ICC). We examined 14 left femurs isolated postmortem from two strains of mice (seven per group). Measurements and analyses were repeated five times on different days. In a second step, analysis was repeated again five times for a single measurement. Resolution dependence was assessed by high-resolution measurements (10 microm) in one strain and subsequent image degrading. Reproducibility was better in full bone compartment and in cortical bone compartment in the diaphysis (PE%CV = 0.06-2.16%) than in trabecular compartment in the distal metaphysis (PE(%CV) = 0.59-5.24%). Nevertheless, ICC (0.92-1.00) showed a very high reliability of the assessed parameters in all regions, indicating very small variances within repeated measurements compared to the population variances. Morphometric indices computed from lower- and higher-resolution images displayed in general only weak dependence and were highly correlated with each other (R2 = 0.91-0.99). The results show that parameters in the full and cortical compartments were very reproducible, whereas precision in the trabecular compartment was somewhat lower. Nevertheless, all compartmental analysis methods were very robust, as shown by the high ICC values, demonstrating high suitability for application in inbred strains, where highest precision is needed due to small population variances.

Animals↗
PubMed2004

[Cutaneous lymphoma].

Cutaneous lymphomas are uncommon. They must be distinguished from secondary skin manifestations of primary nodal lymphomas. Primary cutaneous lymphomas are divided into B-cell- and T-cell cutaneous lymphoma and commonly have good prognosis. Therapy is based on the stage of the disease. Since cure is not possible, the aim of treatment is to control the disease and reduce symptoms. A variety of new and promising therapeutic modalities have been introduced in recent years.

Antineoplastic Agents↗
PubMed2004

The spectrum of mesenchymal skin neoplasms reflected by the new WHO classification.

Mesenchymal tumors are a heterogeneous group of tumors often arising in the skin and soft tissue. The tumors have been reclassified by the WHO in 2002. Benign mesenchymal tumors are about a hundred times more frequent than malignant mesenchymal tumors. Clinically, mesenchymal tumors often present as skin-colored nodes. Overall, elderly persons are more affected than younger individuals. The etiology is often unknown, sometimes there is an association with insults such as radiation, scars, or lymphedematous or venous stasis. Whereas some years ago a wide excision with a margin of 3-5 cm was performed for malignant variants, today micrographic surgery is preferred, as it can avoid mutilating procedures. Early detection and removal is critical since mesenchymal skin tumors often cannot be cured by radiation or chemotherapy.

Humans↗
PubMed2003

[Cutaneous neoplasms].

The skin is the organ most commonly affected by malignancies. Various cancers of the skin show a dramatic increase in incidence over the last decades. Epithelial skin tumors are most frequently, e.g., basal cell carcinoma and the squamous cell carcinoma with its precursors, the actinic keratoses. Melanoma, which is extremely difficult to treat in advanced tumor stages, is dreaded. Besides that, there are other epithelial malignant diseases, e.g. Morbus Bowen and adnexal tumors originating from the skin appendices. Mesenchymal malignant neoplasias such as Morbus Kaposi, angiosarcomas and other dermal sarcomas, are rare. Since the majority of malignant neoplasms is removable and curable by a simple surgical intervention, the knowledge of the different skin tumors is essential for non-dermatologist.

Adjuvants, Immunologic↗
PubMed2003

[Standard and experimental therapy of cutaneous T-cell lymphoma].

Cutaneous T-cell lymphoma represent a heterogeneous group of diseases characterized by skin invasion of monoclonal T-lymphocytes. These cutaneous T-cell lymphomas are divided into 3 groups based on clinical, histological and immunohistological characteristics: Indolent with a survival time of over 10 years, aggressive with a survival time less than 10 years and provisional (EORTC classification). Standard treatments such as PUVA, total skin electron beam, methotrexate, polychemotherapy regimens, retinoids and photopheresis have been used for years. Bexarotene is a newly registered drug. To achieve better response rates, several new drugs are being evaluated in clinical trails, including imiquimod, denileukon-diftitox, liposomal doxorubicin, adeno-interferon-gamma and various combination approaches.

Adrenal Cortex Hormones↗
PubMed1997

The global activator GacA of Pseudomonas aeruginosa PAO positively controls the production of the autoinducer N-butyryl-homoserine lactone and the formation of the virulence factors pyocyanin, cyanide, and lipase.

The global activator GacA, a highly conserved response regulator in Gram-negative bacteria, is required for the production of exoenzymes and secondary metabolites in Pseudomonas spp. The gacA gene of Pseudomonas aeruginosa PAO1 was isolated and its role in cell-density-dependent gene expression was characterized. Mutational inactivation of gacA resulted in delayed and reduced formation of the cell-density signal N-butyryl-L-homoserine lactone (BHL), of the cognate transcriptional activator RhIR (VsmR), and of the transcriptional activator LasR, which is known to positively regulate RhIR expression. Amplification of gacA on a multicopy plasmid caused precocious and enhanced production of BHL, RhIR and LasR. In parallel, the gacA gene dosage markedly influenced the BHL/RhIR-dependent formation of the cytotoxic compounds pyocyanin and cyanide and the exoenzyme lipase. However, the concentrations of another known cell-density signal of P. aeruginosa, N-oxododecanoyl-L-homoserine lactone, did not always match BHL concentrations. A model accounting for these observations places GacA function upstream of LasR and RhIR in the complex, cell-density-dependent signal-transduction pathway regulating several exoproducts and virulence factors of P. aeruginosa via BHL.

4-Butyrolactone↗
PubMed1997

Biosynthesis of pyochelin and dihydroaeruginoic acid requires the iron-regulated pchDCBA operon in Pseudomonas aeruginosa.

The high-affinity siderophore salicylate is an intermediate in the biosynthetic pathway of pyochelin, another siderophore and chelator of transition metal ions, in Pseudomonas aeruginosa. The 2.5-kb region upstream of the salicylate biosynthetic genes pchBA was sequenced and found to contain two additional, contiguous genes, pchD and pchC, having the same orientation. The deduced amino acid sequence of the 60-kDa PchD protein was similar to those of the EntE protein (2,3-dihydroxybenzoate-AMP ligase) of Escherichia coli and other adenylate-forming enzymes, suggesting that salicylate might be adenylated at the carboxyl group by PchD. The 28-kDa PchC protein showed similarities to thioesterases of prokaryotic and eukaryotic origin and might participate in the release of the product(s) formed from activated salicylate. One potential product, dihydroaeruginoate (Dha), was identified in culture supernatants of iron-limited P. aeruginosa cells. The antifungal antibiotic Dha is thought to arise from the reaction of salicylate with cysteine, followed by cyclization of cysteine. Inactivation of the chromosomal pchD gene by insertion of the transcription and translation stop element omega Sm/Sp abolished the production of Dha and pyochelin, implying that PchD-mediated activation of salicylate may be a common first step in the synthesis of both metabolites. Furthermore, the pchD::omega Sm/Sp mutation had a strong polar effect on the expression of the pchBA genes, i.e., on salicylate synthesis, indicating that the pchDCBA genes constitute a transcriptional unit. A full-length pchDCBA transcript of ca. 4.4 kb could be detected in iron-deprived, growing cells of P. aeruginosa. Transcription of pchD started at tandemly arranged promoters, which overlapped with two Fur boxes (binding sites for the ferric uptake regulator) and the promoter of the divergently transcribed pchR gene encoding an activator of pyochelin biosynthesis. This promoter arrangement allows tight iron-mediated repression of the pchDCBA operon.

Amino Acid Sequence↗
PubMed1995

Structural genes for salicylate biosynthesis from chorismate in Pseudomonas aeruginosa.

Salicylate is a precursor of pyochelin in Pseudomonas aeruginosa and both compounds display siderophore activity. To elucidate the salicylate biosynthetic pathway, we have cloned and sequenced a chromosomal region of P. aeruginosa PAO1 containing two adjacent genes, designated pchB and pchA, which are necessary for salicylate formation. The pchA gene encodes a protein of 52 kDa with extensive similarity to the chorismate-utilizing enzymes isochorismate synthase, anthranilate synthase (component I) and p-aminobenzoate synthase (component I), whereas the 11 kDa protein encoded by pchB does not show significant similarity with other proteins. The pchB stop codon overlaps the presumed pchA start codon. Expression of the pchA gene in P. aeruginosa appears to depend on the transcription and translation of the upstream pchB gene. The pchBA genes are the first salicylate biosynthetic genes to be reported. Salicylate formation was demonstrated in an Escherichia coli entC mutant lacking isochorismate synthase when this strain expressed both the pchBA genes, but not when it expressed pchB alone. By contrast, an entB mutant of E. coli blocked in the conversion of isochorismate to 2,3-dihydro-2,3-dihydroxybenzoate formed salicylate when transformed with a pchB expression construct. Salicylate formation could also be demonstrated in vitro when chorismate was incubated with a crude extract of P. aeruginosa containing overproduced PchA and PchB proteins; salicylate and pyruvate were formed in equimolar amounts. Furthermore, salicylate-forming activity could be detected in extracts from a P. aeruginosa pyoverdin-negative mutant when grown under iron limitation, but not with iron excess. Our results are consistent with a pathway leading from chorismate to isochorismate and then to salicylate plus pyruvate, catalyzed consecutively by the iron-repressible PchA and PchB proteins in P. aeruginosa.

Amino Acid Sequence↗