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H Meier

Publications and source records attributed to H Meier.

At least 19 recordsLinked to original sources
PubMed2004

RAxML-III: a fast program for maximum likelihood-based inference of large phylogenetic trees.

MOTIVATION: The computation of large phylogenetic trees with statistical models such as maximum likelihood or bayesian inference is computationally extremely intensive. It has repeatedly been demonstrated that these models are able to recover the true tree or a tree which is topologically closer to the true tree more frequently than less elaborate methods such as parsimony or neighbor joining. Due to the combinatorial and computational complexity the size of trees which can be computed on a Biologist's PC workstation within reasonable time is limited to trees containing approximately 100 taxa. RESULTS: In this paper we present the latest release of our program RAxML-III for rapid maximum likelihood-based inference of large evolutionary trees which allows for computation of 1.000-taxon trees in less than 24 hours on a single PC processor. We compare RAxML-III to the currently fastest implementations for maximum likelihood and bayesian inference: PHYML and MrBayes. Whereas RAxML-III performs worse than PHYML and MrBayes on synthetic data it clearly outperforms both programs on all real data alignments used in terms of speed and final likelihood values. Availability SUPPLEMENTARY INFORMATION: RAxML-III including all alignments and final trees mentioned in this paper is freely available as open source code at http://wwwbode.cs.tum/~stamatak CONTACT: stamatak@cs.tum.edu.

Algorithms↗
PubMed2004

Discovery and optimization of 2-aryl oxazolo-pyrimidines as adenosine kinase inhibitors using liquid phase parallel synthesis.

Adenosine kinase inhibition is an attractive therapeutic approach for several conditions for example, neurodegeneration, seizures, ischemia, inflammation and pain. Several nucleosidic and non-nucleosidic inhibitors are available. Using a virtual screening approach, we have discovered that 2-aryl oxazolo-pyrimidines are adenosine kinase inhibitors. Subsequent high throughput derivatization enabled the optimization of this new inhibitor chemotype resulting in highly potent derivatives. A variety of analogues were produced by applying liquid phase parallel synthesis to vary the 7-amino residues as well as the 2-aryl moiety.

Adenosine Kinase↗
PubMed2001

exo-2-(Pyridazin-4-yl)-7-azabicyclo[2.2.1]heptanes: syntheses and nicotinic acetylcholine receptor agonist activity of potent pyridazine analogues of (+/-)-epibatidine.

A new strategy for the straightforward synthesis of novel racemic epibatidine analogues is presented, in which the 2-chloropyridinyl moiety of epibatidine is bioisosterically replaced by differently substituted pyridazine rings. A key step of the new syntheses is the inverse type Diels-Alder reaction of the electron-rich enol ether 13 with the electron-deficient diazadiene systems of the 1,2,4, 5-tetrazines 14a-d to yield the novel pyridazine analogues of (+/-)-epibatidine 18, 19, 22, and 24. In addition preparation of the N-substituted derivatives, such as 26 and 28, is described. The structures of the novel epibatidine analogues were assigned on the basis of spectral data, that of compound 24 being additionally verified by X-ray crystallography exhibiting two racemic solid-state conformations in the crystal lattice and representing the first X-ray structure of an unprotected 7-azabicyclo[2.2.1]heptane moiety. The nAChR agonist activity of the racemic compounds 18, 19, 22, 24, and 28 was assayed in vitro by whole-cell current recordings from Xenopus oocytes expressing different recombinant nicotinic receptors from the rat. Among the compounds synthesized and tested, the pyridazine analogue 24 of (+/-)-epibatidine and its N-methyl derivative 28 were found to be the most active ones retaining much of the potency of natural epibatidine but with a substantially improved selectivity ratio between the alpha4beta2 and alpha3beta4 subtypes.

Animals↗
PubMed2001

Investigation of praziquantel metabolism in isolated rat hepatocytes.

Isolated rat hepatocytes were used to elucidate the metabolism of praziquantel (PZQ). Our studies were designed to investigate mainly qualitative differences in the biotransformation of PZQ enantiomers. Additionally, the main metabolites cis- and trans-4-hydroxypraziquantel were determined semiquantitatively. For this purpose, racemic PZQ and both enantiomers were incubated with isolated rat hepatocytes. The incubation mixtures were investigated using high-performance liquid chromatography/mass spectrometry. Hepatocytes prepared from male Wistar rats were incubated in Krebs-Ringer buffer at 37 degrees C for 4 h. Aliquots were withdrawn hourly throughout 4 h of incubation. We found that hepatocytes converted both enantiomers of PZQ to the major metabolites cis- and trans-4-hydroxypraziquantel. Additional metabolites were detected after incubating the S-(+)-enantiomer. These minor metabolites were identified by means of their mass/charge ratio as monohydroxypraziquantel metabolites of different, unknown structure.

Animals↗
PubMed2001

Large-needle biopsy versus thin-needle biopsy in diagnostic pathology of liver diseases.

BACKGROUND/AIMS: A study was carried out to determine whether thin-needle biopsy (TNB) yields enough material to study diffuse liver diseases. METHODS: Using TNB (20G and 21G) and a conventional Menghini-type large-needle biopsy (LNB; 17G), the amounts of tissue obtained and the histopathological diagnoses were compared. The biopsies were obtained by surgeons with a several-stroke method (17GS) and by physicians with a single-strike method (17GP, 20GP, 21GP). A total of 343 biopsy specimens from 258 patients were included in the study. RESULTS: A comparison of the mean values for the length of the core biopsy, as well as the mean numbers of portal tracts and terminal hepatic veins among the four groups showed significant differences (p<0.001): the mean number of portal tracts obtained with 17GS was 13.8+/-6.5, with 17GP it was 9.7+/-5.9, with 20GP it was 6.7+/-4.4, and with 21GP it was 4.0+/-3.1. A comparison of the histopathological diagnoses showed no major differences between 17GP and 20GP; the diversity and frequencies of the diagnoses were similar. CONCLUSION: We suggest that the use of TNB, particularly 20G-size needles, could be extended to the investigation of diffuse liver diseases in which LNB carries a high risk of complications or is contraindicated, and when the diagnosis is the primary reason for the biopsy rather than grading or staging of a known diffuse disease.

Adolescent↗
PubMed2000

Capillary electrophoresis-mass spectrometry, liquid chromatography-mass spectrometry and nanoelectrospray-mass spectrometry of praziquantel metabolites.

Capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography-mass spectrometry (LC-MS) coupling was used for the investigation of metabolites of the anthelmintic drug praziquantel. Human urine samples and microsomal incubation mixtures were investigated after preparation by solid-phase extraction. CE- and LC-MS coupling was performed using an electrospray ionization interface. An ion trap mass spectrometer equipped with a laboratory-made nanoelectrospray ion source was used for the investigation of the glucuronide conjugates by consecutive fragmentations. The nanoelectrospray interface offers the opportunity to perform complicated MSn spectrometric investigations. Different phase I metabolites of praziquantel and their glucuronidated and sulfated conjugates were detected.

Animals↗
PubMed2000

Stilbenoid dendrimers

The first five generations of the stilbenoid dendrimers 1(n) (n = 1-5) have been prepared by a combined coupled synthesis (between the generations of the dendrons 8-12) and convergent synthesis. Wittig-Horner reactions together with a protecting group technique yield monodisperse compounds of high constitutional and configurational purity. The solubility of the stiff molecules, which have primarily a disklike shape in the first and second generations and a cylindrical shape in the third, fourth, and fifth generations, is governed by the alkoxy chains that are attached to the peripheral benzene rings. The number of stilbene building blocks increases according to the formula 3(2(n)-1) from 3 in the first generation (n = 1) to 93 in the fifth generation (n = 5). Consequently, the molecular mass reaches 24,000 in 1(5)b which contains 144 hexyloxy chains. An exact measurement of the mass is provided by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. In solution, the stilbenoid dendrimers 1(n) exhibit a strong tendency to aggregate, which increases from generation to generation. In the pure state, columnar mesophases Col(hd) (1(1)b, 1(1)c, 1(2)b, and 1(2)c) and Col(ob) (1(2)b, 1(2)c) are formed; intramolecular steric hindrance prevents such ordered arrangements in higher generations 1(n) (n = 3, 4, 5).

Journal Article↗
PubMed2000

A nested array of rRNA targeted probes for the detection and identification of enterococci by reverse hybridization.

Complete 23S and almost complete 16S rRNA gene sequences were determined for the type strains of the validly described Enterococcus species, Melissococcus pluton and Tetragenococcus halophilus. A comprehensive set of rRNA targeted specific oligonucleotide hybridization probes was designed according to the multiple probe concept. In silico probe design and evaluation was performed using the respective tools of the ARB program package in combination with the ARB databases comprising the currently available 16S as well as 23S rRNA primary structures. The probes were optimized with respect to their application for reverse hybridization in microplate format. The target comprising 16S and 23S rDNA was amplified and labeled by PCR (polymerase chain reaction) using general primers targeting a wide spectrum of bacteria. Alternatively, amplification of two adjacent rDNA fragments of enterococci was performed by using specific primers. In vitro evaluation of the probe set was done including all Enterococcus type strains, and a selection of other representatives of the gram-positive bacteria with a low genomic DNA G+C content. The optimized probe set was used to analyze enriched drinking water samples as well as original samples from waste water treatment plants.

Base Sequence↗
PubMed2000

Taxonomic characterization of Ochrobactrum sp. isolates from soil samples and wheat roots, and description of Ochrobactrum tritici sp. nov. and Ochrobactrum grignonense sp. nov.

A large collection of bacterial strains, immunotrapped from soil and from the wheat rhizoplane, was subjected to polyphasic taxonomy by examining various pheno- and genotypic parameters. Strains were grouped on (inter) repetitive extragenic palindromic DNA (REP) PCR profiles at the intraspecies level. Pheno- and genotypic characters were assessed for representatives from 13 different REP groups. Strains of nine REP groups constituting two physiological BIOLOG clusters fell in the coherent DNA-DNA reassociation group of Ochrobactrum anthropi. Strains of two REP groups constituting a separate BIOLOG cluster fell in the coherent DNA-DNA reassociation group of Ochrobactrum intermedium. Additional phenotypic characters differentiating O. anthropi and O. intermedium were found. REP group K strains constituted a different BIOLOG cluster, a separate DNA-DNA reassociation group and a distinct phylogenetic lineage in 165 rDNA homology analysis, indicating that REP group K strains represent a new species. Diagnostic phenotypic characters were found. Closest relatives were Ochrobactrum species. The name Ochrobactrum grignonense sp. nov. is proposed (type strain OgA9aT = LMG 18954T = DSM 13338T). REP group J strains again constituted a different BIOLOG cluster, a separate DNA-DNA reassociation group and showed, as a biological particularity, a strict preference for the rhizoplane as habitat. Diagnostic phenotypic characters were found. This indicated that REP group J strains represent a further new species, although phylogenetic analyses using 16S rDNA homology were not able to separate the cluster of REP group J sequences significantly from 16S rDNA sequences of Ochrobactrum anthropi. The name Ochrobactrum tritici sp. nov. is proposed (type strain SCII24T = LMG 18957T = DSM 13340T).

Alphaproteobacteria↗
PubMed1999

[Occupationally-induced contact dermatitis and bronchial asthma in a unusual delayed reaction to hydroxychloroquine].

We report the case of a a 60 year-old worker in the pharmaceutical industry who suffered from recurring contact dermatitis. Initially the contact dermatitis was limited to the hands; later on it became generalized. The patient had been working on a drug filling line in a pharmaceutical plant for more than 20 years. Eight years after starting this job he had developed allergic hand dermatitis to 2,6-diaminopyridine (patch test positive); this healed upon cessation of exposure. Ten years later he again developed hand dermatitis which progressed to generalized dermatitis and conjunctivitis. Under systemic and local therapy with corticosteroids and cessation of work, it healed nearly completely. Four months after returning to work, the patient experienced a first episode of severe asthma and generalized dermatitis with conjunctivitis following exposure to hydroxychloroquine the day before. The asthma and dermatitis improved after systemic corticosteroid therapy and stopping work. His condition continued to fluctuate, when though the patient was transferred at work and now wore rubber gloves. Eight months later he again developed a generalized dermatitis. Patch testing revealed delayed-type sensitizations to hydroxychloroquine (tested in concentrations of 0. 1%, 0.5%, 1% and 2%). Equivalent tests in five healthy volunteers were negative. The patch test reactions were pustular, while a biopsy was interpreted as a multiform contact dermatitis reaction. Bronchial exposure with hydroxychloroquine dust produced a delayed bronchial obstruction over the next 20 hours, which progressed to fever and generalized erythema (hematogenous contact dermatitis). After removing exposure to 2,6-diaminopyridine and hydroxychloroquine, the patient went on to develop a contact dermatitis to latex (patch test positive). However, skin prick tests with latex and patch tests with rubber additiva were negative. Hydroxychloroquine is well known to cause drug reactions. To our knowledge, contact dermatitis to this substance has not yet been reported. It is noteworthy that the patch test reactions were pustular and of multiform morphology and that bronchial exposure to the allergen resulted in asthma and a generalized drug reaction. Pathogenetically the asthmatic reaction seems to be on a delayed-type mechanism as is also seen with ampicillin, cobalt and nickel induced asthma.

Asthma↗
PubMed1999

Specific oligonucleotide probes for in situ detection of a major group of gram-positive bacteria with low DNA G + C content.

Almost one thousand 16S rRNA sequences of Gram-positive bacteria with a low DNA G + C content from public databases were analyzed using the ARB software package. A signature region was identified between positions 354 and 371 (E. coli numbering) for the Bacillus sub-branch of the Gram-positive bacteria with a low DNA G + C content, the former orders Bacillales and Lactobacillales. Three oligonucleotide probes, namely LGC354A, LGC354B, and LGC354C, were designed to target this diagnostic site. Their fluorescent derivatives were suitable for whole cell detection by fluorescence in situ hybridization (FISH). Hybridization conditions were adjusted for differentiation of target and related non-target reference species. When applying FISH to whole bacterial cells in a sample of activated sludge from a communal wastewater treatment plant, members of the Bacillus sub-branch were detected at levels from 0.01% of cells in samples fixed with paraformaldehyde to over 8 percent in the same samples fixed with ethanol and treated with lysozyme. The problems of quantitative in situ analysis of Gram-positive bacteria with a low DNA G + C content in biofilm flocs are discussed and recommendations made. Members of the Bacillus sub-branch were detected in different abundances in activated sludge samples from different wastewater plants.

Bacillus↗
PubMed1999

In situ analysis of the bacterial communities associated to farmed eel by whole-cell hybridization.

Bacterial communities in water samples and eel slime were investigated by fluorescence in situ hybridization of whole bacterial cells in an eel intensive culture system over 1 year. A newly developed probe, matching 27 Vibrio spp., and a specific probe for Vibrio vulnificus were used. Phylogenetic probes complementary to selected regions of the 16S and 23S ribosomal RNA revealed that Proteobacteria of the alpha and beta subclass were predominant in water and eel slime. Members of the gamma subclass (e.g. vibrios and aeromonads) were more abundant in eel slime, although no V. vulnificus was detected.

Alphaproteobacteria↗
PubMed1998

Application of 23S rDNA-targeted oligonucleotide probes specific for enterococci to water hygiene control.

Identification of enterococci species by hybridization with recently designed species-specific and group-specific 23S rDNA-targeted oligonucleotide probes was superior to results obtained with a common biochemical test panel. Considering these findings, a molecular biological procedure for the detection of enterococci in water samples was developed. A short enrichment is followed by an amplification step and a hybridization reaction in microtiter plate format. The detection limit is about 1 CFU/ml, and results are available within 26 h.

Bacterial Typing Techniques↗
PubMed1998

Detection of hemolysin variants of Shiga toxin-producing Escherichia coli by PCR and culture on vancomycin-cefixime-cefsulodin blood agar.

The presence of a hemolysin-encoding gene, elyA or hlyA, from Shiga toxin-producing Escherichia coli (STEC) was detected by PCR in each of 95 strains tested. PCR products of elyA from human STEC isolates of serovars frequently detected in Germany, such as O157:H-, O103:H2, O103:H-, O26:H11, and O26:H-, showed nucleotide sequences identical to previously reported ones for O157:H7 and O111:H- strains. Compared to them, four elyA amplicons derived from human isolates of rare STEC serovars showed identity of about 98% but lacked an AluI restriction site. However, the nucleotide sequence of an amplicon derived from a porcine O138:K81:H- STEC strain was identical to the corresponding region of hlyA, encoding alpha-hemolysin, from E. coli. This hlyA amplicon showed 68% identity with the nucleotide sequence of the corresponding elyA fragment. It differed from the elyA PCR product in restriction fragments generated by AluI, EcoRI, and MluI. Of the 95 representative STEC strains, 88 produced hemolysin on blood agar supplemented with vancomycin (30 mg/liter), cefixime (20 micrograms/liter), and cefsulodin (3 mg/liter) (BVCC). The lowest added numbers of two to six STEC CFU per g of stool or per ml of raw milk were detectable on BVCC plates after seeding of the preenrichment broth, modified tryptic soy broth (mTSB) supplemented with novobiocin (10 mg/liter), with 16 STEC strains. These strains represented the seven prevailing serovars diagnosed from German patients. However, with ground-beef samples, PCR was essential to identify the lowest added numbers of two to six STEC CFU among colonies of hemolyzing Enterobacteriaceae, such as Serratia spp. and alpha-hemolysin-producing E. coli. We conclude that preenrichment of stool and food samples in mTSB for 6 h followed by overnight culturing on BVCC is a simple method for the isolation and presumptive identification of STEC.

Bacterial Toxins↗
PubMed1997

Effect of structural modification of enol-carboxamide-type nonsteroidal antiinflammatory drugs on COX-2/COX-1 selectivity.

Meloxicam (5), an NSAID in the enol-carboxamide class, was developed on the basis of its antiinflammatory activity and relative safety in animal models. In subsequent screening in microsomal assays using human COX-1 and COX-2, we discovered that it possessed a selectivity profile for COX-2 superior to piroxicam and other marketed NSAIDs. We therefore embarked on a study of enol-carboxamide type compounds to determine if COX-2 selectivity and potency could be dramatically improved by structural modification. Substitution at the 6- and 7-positions of the 4-oxo-1,2-benzothiazine-3-carboxamide, alteration of the N-methyl substituent, and amide modification were all examined. In addition we explored several related systems including the isomeric 3-oxo-1,2-benzothiazine-4-carboxamides, thienothiazines, indolothizines, benzothienothiazines, naphthothiazines, and 1,3- and 1,4-dioxoisoquinolines. While a few examples were found with greater potency in the COX-2 assay, no compound tested had a better COX-2/COX-1 selectivity profile than that of 5.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

[Cannabis poisoning after eating salad].

We describe 4 patients who suffered gastrointestinal disorders and psychological effects after eating salad prepared with hemp seed oil. The concentration of tetrahydrocannabinol (THC) in this oil far exceeded the recommended tolerance dose. Our observations prompted the Swiss Federal Office of Public Health to publish warnings in the press concerning consumption of this oil. We describe the symptoms of orally ingested THC and point out unresolved problems connected with food containing hemp.

Adult↗