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  • 1
    Electronic Resource
    Electronic Resource
    Detection of all anti-factor VIII antibodies in haemophilia A patients by the Bethesda assay and a more sensitive immunoprecipitation assay (2001)
    Oxford UK : Blackwell Science Ltd
    Haemophilia 7 (2001), S. 0 
    Details
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Plasmas from 40 haemophilia A patients enrolled in a study by the paediatric group of the German Society on Thrombosis and Hemostasis were tested by the Bethesda assay for inhibitor antibodies and by a more sensitive immunoprecipitation assay (IP) for all antifactor VIII antibodies. Of the 26 severe, 11 moderate and three mild haemophiliacs, 18, two, and none, respectively, had positive Bethesda titres after several factor VIII infusions. In 275 plasmas with Bethesda titres of 0, 0.6–1.0, 〉 1–5, and 〉 5–655, the IP responses were 0–238, 0–61, 0–786, and 43–6141, respectively, and a reliable positive IP titre was 〉 4.2. The overlapping ranges of IP titres indicated large differences in the ratio of inhibitory to noninhibitory antibodies in individual plasmas. In five of seven patients with Bethesda titres of 0.6–1, the IP titres were 〈 4.2, suggesting a lack of precision of Bethesda titres ≤ 1. Detection of the primary immune response was found in only three patients by IP assay before a positive Bethesda assay. This precludes early, reliable testing of which patients will be immunologically responsive. In four patients undergoing immune tolerance therapy, antifactor VIII antibodies were still detectable by the IP assay in the absence of a Bethesda titre, which indicates that antibodies were completely eradicated in none of the patients. Our results show that the use of both the Bethesda and IP assays can provide more accurate detection of antifactor VIII antibodies in all patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2516.2001.00456.x
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  • 2
    Electronic Resource
    Electronic Resource
    Phosphorylation of the flagellar regulatory protein FlrC is necessary for Vibrio cholerae motility and enhanced colonization (2000)
    Oxford, UK : Blackwell Science Ltd
    Molecular microbiology 35 (2000), S. 0 
    Details
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The human pathogen Vibrio cholerae specifically expresses virulence factors within the host, including cholera toxin (CT) and the toxin co-regulated pilus (TCP), which allow it to colonize the intestine and cause disease. V. cholerae is a highly motile organism by virtue of a polar flagellum, and motility has been inferred to be an important aspect of virulence, yet the exact role of motility in pathogenesis has remained undefined. The two-component regulatory system FlrB/FlrC is required for polar flagellar synthesis; FlrC is a σ54-dependent transcriptional activator. We demonstrate that the transcriptional activity of FlrC affects both motility and colonization of V. cholerae. In a purified in vitro reaction, FlrB transfers phosphate to the wild-type FlrC protein, but not to a mutant form in which the aspartate residue at amino acid position 54 has been changed to alanine (D54A), consistent with this being the site of phosphorylation of FlrC. The wild-type FlrC protein, but not the D54A protein, activates σ54-dependent transcription in a heterologous system, demonstrating that phospho-FlrC is the transcriptionally active form. A V. cholerae strain containing a chromosomal flrCD54A allele did not synthesize a flagellum and had no detectable levels of transcription of the critical σ54-dependent flagellin gene flaA. The V. cholerae flrCD54A mutant strain was also defective in its ability to colonize the infant mouse small intestine, approximately 50-fold worse than an isogenic wild-type strain. Another mutation of FlrC (methionine 114 to isoleucine; M114I) confers constitutive transcriptional activity in the absence of phosphorylation, but a V. cholerae flrCM114I mutant strain, although flagellated and motile, was also defective in its ability to colonize. The strains carrying D54A or M114I mutant FlrC proteins expressed normal levels of CT and TCP under in vitro inducing conditions. Our results show that FlrC ‘locked’ into either an inactive (D54A) or an active (M114I) state results in colonization defects, thereby demonstrating a requirement for modulation of FlrC activity during V. cholerae pathogenesis. Thus, the σ54-dependent transcriptional activity of the flagellar regulatory protein FlrC contributes not only to motility, but also to colonization of V. cholerae.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2958.2000.01745.x
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  • 3
    Electronic Resource
    Electronic Resource
    The absence of a flagellum leads to altered colony morphology, biofilm development and virulence in Vibrio cholerae O139 (2001)
    Oxford, UK : Blackwell Science Ltd
    Molecular microbiology 39 (2001), S. 0 
    Details
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Throughout most of history, epidemic and pandemic cholera was caused by Vibrio cholerae of the serogroup O1. In 1992, however, a V. cholerae strain of the serogroup O139 emerged as a new agent of epidemic cholera. Interestingly, V. cholerae O139 forms biofilms on abiotic surfaces more rapidly than V. cholerae O1 biotype El Tor, perhaps because regulation of exopolysaccharide synthesis in V. cholerae O139 differs from that in O1 El Tor. Here, we show that all flagellar mutants of V. cholerae O139 have a rugose colony morphology that is dependent on the vps genes. This suggests that the absence of the flagellar structure constitutes a signal to increase exopolysaccharide synthesis. Furthermore, although exopolysaccharide production is required for the development of a three-dimensional biofilm, inappropriate exopolysaccharide production leads to inefficient colonization of the infant mouse intestinal epithelium by flagellar mutants. Thus, precise regulation of exopolysaccharide synthesis is an important factor in the survival of V. cholerae O139 in both aquatic environments and the mammalian intestine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2958.2001.02195.x
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  • 4
    Electronic Resource
    Electronic Resource
    The novel σ54- and σ28-dependent flagellar gene transcription hierarchy of Vibrio cholerae (2001)
    Oxford, UK : Blackwell Science, Ltd
    Molecular microbiology 39 (2001), S. 0 
    Details
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The human pathogen Vibrio cholerae is a highly motile organism by virtue of a polar flagellum. Flagellar transcriptional regulatory factors have been demonstrated to contribute to V. cholerae virulence, but the role these factors play in the transcription hierarchy controlling flagellar synthesis has been unclear. The flagellar genes revealed by the V. cholerae genome sequence are located in three large clusters, with the exception of the motor genes, which are found in three additional locations. It had previously been demonstrated that the alternative sigma factor σ54 and the σ54-dependent activators FlrA and FlrC are necessary for flagellar synthesis. The V. cholerae genome sequence revealed the presence of a fliA gene, which is predicted to encode the alternative flagellar sigma factor σ28. A V. choleraeΔfliA mutant strain is non-motile, and synthesizes a truncated flagellum. Vibrio cholerae FliA complements both V. cholerae and Salmonella typhimurium fliA mutants for motility, consistent with its function as an alternative flagellar sigma factor. Analysis of lacZ transcriptional fusions of the V. cholerae flagellar promoters in both V. cholerae and S. typhimurium identified σ28-, σ54-, FlrA- and FlrC-dependent promoters, as well as promoters that were independent of all these factors. Our results support a model of V. cholerae flagellar gene transcription as a novel hierarchy composed of four classes of genes. Class I is composed solely of the gene encoding the σ54-dependent activator FlrA, which along with the σ54-holoenzyme form of RNA polymerase activates expression of Class II genes. These genes include structural components of the MS ring, switch and export apparatus, as well as the genes encoding both FliA and FlrC. FlrC, along with σ54-holoenzyme, activates expression of Class III genes, which include basal body, hook and filament genes. Finally, σ28-holoenzyme activates expression of Class IV genes, which include additional filament genes as well as motor genes. Thus, this novel V. cholerae flagellar hierarchy has incorporated elements from both the σ54-dependent Caulobacter crescentus polar flagellar hierarchy and the σ28-dependent S. typhimurium peritrichous flagellar hierarchy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2958.2001.02348.x
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  • 5
    Electronic Resource
    Electronic Resource
    Lipid-induced filamentous growth in Ustilago maydis (2004)
    Oxford, UK : Blackwell Science Ltd
    Molecular microbiology 52 (2004), S. 0 
    Details
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The phytopathogenic fungus Ustilago maydis is obligately dependent on infection of maize to complete the sexual phase of its life cycle. Mating interactions between haploid, budding cells establish an infectious filamentous cell type that invades the host, induces large tumours and eventually forms large masses of black spores. The ability to switch from budding to filamentous growth is therefore critical for infection and completion of the life cycle, although the signals that influence the transition have not been identified from the host or the environment. We have found that growth in the presence of lipids promotes a filamentous phenotype that resembles the infectious cell type found in planta. In addition, the ability of the fungus to respond to lipids is dependent on both the cAMP signalling pathway and a Ras/MAPK pathway; these pathways are known to regulate mating, filamentous growth and pathogenesis in U. maydis. Overall, these results lead us to hypothesize that lipids may represent one of the signals that promote and maintain the filamentous growth of the fungus in the host environment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2958.2004.04019.x
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  • 6
    Electronic Resource
    Electronic Resource
    Genetic analysis of the mouse brain proteome (2002)
    [s.l.] : Nature Publishing Group
    Nature genetics 30 (2002), S. 385-393 
    Details
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Proteome analysis is a fundamental step in systematic functional genomics. Here we have resolved 8,767 proteins from the mouse brain proteome by large-gel two-dimensional electrophoresis. We detected 1,324 polymorphic proteins from the European collaborative interspecific backcross. Of these, we ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/ng861
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  • 7
    Electronic Resource
    Electronic Resource
    Cholesterol lowering effect of dietary weight loss and orlistat treatment – efficacy and limitations (2004)
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 19 (2004), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : Orlistat reduces energy uptake by the impairment of fat digestion and some evidence indicates it also lowers plasma cholesterol.Aim : To examine total, low-density lipoprotein- and high-density lipoprotein cholesterol during a weight reducing regimen, and assess the effect of orlistat in lowering cholesterol levels independent of its weight reducing efficacy.Methods : A total of 448 patients with elevated cholesterol according to cardiovascular risk factors entered a 2 week single-blind run-in period on a hypocaloric diet. Of 384 patients were subsequently assigned double-blind treatment with orlistat (3 × 120 mg/day) or placebo for 6 months in conjunction with the hypocaloric diet.Results : Weight loss in the orlistat group was 7.4 kg vs. 4.9 kg with placebo. Total and low-density lipoprotein cholesterol decreased by 25–30 mg/dL vs. 10–15 mg/dL with placebo. Reduction of cholesterol with orlistat was significantly greater than anticipated from weight loss alone. In patients with cardiovascular risk factors entering the study with lower cholesterol values orlistat was also superior to placebo. On the contrary, reduction of cholesterol concentrations never exceeded 20%.Conclusion : Orlistat has a cholesterol lowering efficacy independent of its weight reducing effect. Because of the limited therapeutic effectiveness, patients at high cardiovascular risk should receive rather early additional cholesterol lowering medication during weight loss programmes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2036.2004.01966.x
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  • 8
    Electronic Resource
    Electronic Resource
    Mouse models for neurodegenerative diseases and a theory of proteomics (2003)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 85 (2003), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Proteome analysis is usually performed by separating complex cellular protein extracts by two-dimensional-electrophoresis followed by protein identification using mass spectrometry. In this way proteins are compared from normal and diseased tissue in order to detect disease related protein changes. In a strict sense, however, this procedure cannot be called proteome analysis: the tools of proteomics are used just to detect some interesting proteins which are then investigated by protein chemistry as usual. Real proteome research would be studying the cellular proteome as a whole, its composition, organization and its kind of action. At present however, we have no idea how a proteome works as a whole; we have not even a theory about that. If we would know how the proteome of a cell type is arranged, we probably would alter our strategy to detect and analyze disease-related proteins. I will present a theory of proteomics and show some results from our laboratory which support this theory. The results come from investigations of the mouse brain proteome and include mouse models for neurodegenerative diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.85.s2.8_1.x
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  • 9
    Electronic Resource
    Electronic Resource
    A pseudo-trigonal bipyramidally coordinated Pt atom in dicarbonylbis(octacarbonyl-μ-dicyclohexylphosphidodirhenio)platinum(II) (2001)
    Oxford [u.a.] : International Union of Crystallography (IUCr)
    Acta crystallographica 57 (2001), S. 810-811 
    Details
    ISSN: 1600-5759
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: In the title compound, [PtRe4(C12H22P)2(CO)18] or [(μ-PCy2)(CO)8Re2]2Pt(CO)2 (Cy is cyclohexyl), two phosphido-bridged dirhenium groups are linked by a Pt(CO)2 unit and show different bonding patterns for stereochemical reasons. The Re—Re distances are 3.2620 (15) and 3.0739 (15) Å, and the Pt—Re distances are 2.9165 (12), 2.9025 (15) and 2.8548 (13) Å.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1107/S0108270101007399
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  • 10
    Electronic Resource
    Electronic Resource
    A very energetic supernova associated with the γ-ray burst of 29 March 2003 (2003)
    [s.l.] : Macmillian Magazines Ltd.
    Nature 423 (2003), S. 847-850 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Over the past five years evidence has mounted that long-duration (〉2 s) γ-ray bursts (GRBs)—the most luminous of all astronomical explosions—signal the collapse of massive stars in our Universe. This evidence was originally based on the probable association of one ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nature01750
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