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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 94 (2005), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Minocycline is neuroprotective in animal models of a number of acute CNS injuries and neurodegenerative diseases. While anti-inflammatory and anti-apoptotic effects of minocycline have been characterized, the molecular basis for the neuroprotective effects of minocycline remains unclear. We report here that minocycline and a number of antioxidant compounds protect mixed neuronal cultures in an oxidative stress assay. To evaluate the role of minocycline's direct antioxidant properties in neuroprotection, we determined potencies for minocycline, other tetracycline antibiotics, and reference antioxidant compounds using a panel of in vitro radical scavenging assays. Data from in vitro rat brain homogenate lipid peroxidation and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays show that minocycline, in contrast to tetracycline, is an effective antioxidant with radical scavenging potency similar to vitamin E. Our findings suggest that the direct antioxidant activity of minocycline may contribute to its neuroprotective effects in some cell-based assays and animal models of neuronal injury.
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 91 (2004), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Opioid receptors are expressed in neuronal and immune cells and regulated in response to immunological processes. Herein, we demonstrate up-regulation of the δ-opioid receptor gene by interleukin-4 in immune cells (primary T and polymorphonuclear leukocytes, Jurkat E6 T cells), and in NG 108–15 neuronal cells. We identified an interleukin-4-responsive element at nt −671 on the murine gene promoter, to which the transcription factor STAT6 binds, as shown by reporter gene analysis and STAT6/DNA interaction studies in living cells with transcription factor decoy oligonucleotides. STAT6 normally binds to palindromic DNA motifs with a 5′-TTC…GAA-3′ core. Notably, the δ-opioid receptor STAT6 site (5′-TTC…GGA-3′) is an imperfect palindrome with a mismatch within this core sequence. A systematic analysis of possible mismatch 5′-TTC…GAA-3′ motifs revealed that STAT6 also binds to the sequence 5′-TTA…GAA-3′. This motif occurs as a polymorphism in the human µ-opioid receptor gene (Kraus et al. 2001 J. Biol. Chem 276, 43901–43908). We show that this mutated element has a significantly reduced STAT6 binding activity which correlates to its reduced interleukin (IL)-4 inducibility. In contrast, the non-canonical STAT6 site of the δ-opioid receptor binds STAT6 with similar high activity as a perfectly palindromic STAT6 site and is strongly inducible by IL-4.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford UK : Blackwell Science Ltd
    Journal of neurochemistry 74 (2000), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Prodynorphin, the precursor of the dynorphin opioid peptides, has been shown to play an important role in several aspects of human diseases and complex traits, e.g., drug abuse, epilepsy, and mood disorders. The objective of this study was to identify polymorphisms in the 5′ control region of the human prodynorphin gene and to relate these polymorphisms to prodynorphin gene expression. Within the core promoter region, a 68-bp sequence was found to occur as a polymorphic element, either singular or as tandemly repeated element two, three, or four times. This 68-bp repeat element contains an AP-1 transcription factor binding site as demonstrated by electrophoretic mobility shift assay. Reporter gene assays were performed and provided evidence for allele dependent different promoter activity. Dynorphin was found to be involved in many pathophysiological processes so that the described prodynorphin alleles may correlate with the occurrence of several diseases, for example, drug addiction. However, prodynorphin allelic distributions were not significantly different in heroin addicts and control subjects.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Sedimentology 51 (2004), S. 0 
    ISSN: 1365-3091
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geosciences
    Notes: Mudrock-dominated channel fills are common features of the fluvial Palaeogene Willwood Formation of Wyoming. These fills are small, on average 30 m wide and 3 m deep, and they vary from simple plugs to more lithologically complex fills with internal scour surfaces. Some fills preserve plant material, and others show pedogenic modification. All fills are located within metre-thick intervals of weakly pedogenically modified mudstones that surround ribbon sandstones. The intervals have previously been attributed to channel avulsion; the fine-grained channel fills are interpreted as crevasse-splay feeder channels within these avulsion deposits.Variation in fill type, particularly the presence of pedogenic features, appears to be related to floodplain drainage. Possible factors that influenced drainage were basin position of the fills and Palaeogene climate fluctuations, although the role of either is not unequivocal. In general, channel fills with sombre colours and preserved plant detritus, indicating poorly drained conditions, dominate locations that were proximal to the Palaeogene basin axes. Fills that contain root traces, red and yellow-brown matrix colours and mottling, which indicate pedogenic modification and episodic subaerial exposure of the sediment, dominate locations that were more distal to the Palaeogene basin axes. Eocene climate fluctuations, particularly episodes of global warming, may have been a secondary control on the kind of fill that developed. Mudrock-dominated channel fills have not been described previously from ancient avulsion deposits. Their common presence in the Willwood Formation suggests that they are a typical component of avulsion belts and that similar channel fills in other stratigraphic units should be considered with regard to channel avulsion. The variety of fills observed in the Willwood Formation indicates that avulsion belt channels can experience very different fill histories. The descriptive details of fills provided here should help in their recognition elsewhere. In addition, the nature of the channel fill provides important information on ancient drainage conditions in the avulsion belt. Pedogenically modified channel fills have been recognized only rarely from the stratigraphic record. Their presence throughout the Willwood Formation suggests that they should exist in other alluvial successions and may have been overlooked previously. They indicate that periods of sediment exposure alternated with episodic influxes of water and sediment in an active avulsion belt.
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford BSL : Blackwell Science Ltd
    Molecular microbiology 30 (1998), S. 0 
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The catabolite control protein CcpA is the central regulator of carbon catabolite repression in Bacilli and other Gram-positive bacteria. A comparison of 12 CcpA-like sequences with regulators from the LacI/GalR family defines a CcpA subfamily based on extensive similarities found among CcpAs and not in 32 other members of the family. These amino acids are clustered in three blocks in the CcpA sequence. Their interpretation, assuming a PurR-like fold, reveals that almost all of them are surface exposed and form a continuous patch on the N-terminal subdomain of the protein core extending into the DNA reading head. We introduced nine single amino acid exchanges in the subfamily specific residues of CcpA from Bacillus megaterium. Six mutants, namely CcpA47RS, 79AE, 89YE, 295YR, 299YE and 303RD, are inactive or severely impaired in catabolite repression, underlining their relevance for CcpA function. They are negatively transdominant over wild-type CcpA demonstrating their ability to correctly fold for dimerization. Five of them are unable or impaired in binding HPr-Ser-46-P in vitro, establishing a correlation between catabolite repression efficiency and HPr-Ser-46-P binding. These results support the hypothesis that the conserved region in CcpA is the HPr-Ser-46-P binding site.
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Molecular microbiology 48 (2003), S. 0 
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Cell wall integrity is crucial for fungal growth, development and stress survival. In the model yeast Saccharomyces cerevisiae, the cell integrity Mpk1/Slt2 MAP kinase and calcineurin pathways monitor cell wall integrity and promote cell wall remodelling under stress conditions. We have identified the Cryptococcus neoformans homologue of the S. cerevisiae Mpk1/Slt2 MAP kinase and have characterized its role in the maintenance of cell integrity in response to elevated growth temperature and in the presence of cell wall synthesis inhibitors. C. neoformans Mpk1 is required for growth at 37°C in vitro, and this growth defect is suppressed by osmotic stabilization. C. neoformans mutants lacking Mpk1 are attenuated for virulence in the mouse model of cryptococcosis. Phosphorylation of Mpk1 is induced in response to perturbations of cell wall biosynthesis by the antifungal drugs nikkomycin Z (a chitin synthase inhibitor), caspofungin (a β-1,3-glucan synthase inhibitor), or FK506 (a calcineurin inhibitor), and mutants lacking Mpk1 display enhanced sensitivity to nikkomycin Z and caspofungin. Lastly, we show that calcineurin and Mpk1 play complementing roles in regulating cell integrity in C. neoformans. Our studies demonstrate that pharmacological inhibition of the cell integrity pathway would enhance the activity of antifungal drugs that target the cell wall.
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 66 (1996), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The actions of exogenous and endogenous opioids are mediated by at least three different opioid receptors, called μ, κ, and δ. Recently, we have detected a new variant of the rat μ-opioid receptor, which we termed rMOR1B and which differs from rMOR1 (now also called rMOR1A) in the amino acid sequence at the C-terminus. Both isoforms were proposed to be splicing variants of the same gene. To elucidate the molecular mechanism leading to the formation of the new variant, the exon/intron structure of the rat μ-opioid receptor gene in the respective area has been determined by analyzing a genomic P1 phage clone. In addition, we have investigated the putative promoter region of this gene. The present study revealed that rMOR1B is generated by an alternative splicing event whereby a previously unknown exon will be placed behind exon 3 to form rMOR1B mRNA, which is separated from the latter by an intron. Therefore, this new exon has to be called exon 4, whereas the former exon 4, which encodes the C-terminus of MOR1A, now becomes exon 5. Examination of the putative rat promoter region revealed a high degree of nucleotide sequence homology to the mouse gene. Using an RNase protection approach, one single transcription initiation site could be located at 230 bp upstream of the translation start. This is similar to the situation in the mouse, where four major transcription start sites were reported to lie close together around 270 bp upstream of the protein coding region.
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Histopathology 37 (2000), S. 0 
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Histopathology 35 (1999), S. 0 
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: To present the clinical light microscopic and immunophenotypic features of a distinctive vascular neoplasm of the spleen.〈section xml:id="abs1-2"〉〈title type="main"〉Methods and resultsTwo of the splenic lesions arose in children, and one was found in an adult. They ranged from 19 to 40 mm diameter and histologically were quite similar. Sheets of large epithelioid cells with a spectrum of nuclear configurations ranging from oval and vesicular to twisted and hyperchromatic were noted in each case. Distinct or prominent nucleoli were present in many cells, and occasional cells had nuclear pseudoinclusions. In two cases, bands of basophilic, fibroblast-rich stroma with scattered chronic inflammatory cells were present. The mitotic rate ranged from 0/10 high-power fields (HPF) to 0.5/10 HPF in these epithelioid cells. The vascular nature of these tumours was manifested as a sieve-like array of round, erythrocyte-filled spaces, most with attenuated and cytologically bland lining cells. The polygonal, epithelioid cells exhibited the following phenotype: smooth muscle actin (SMA)+, muscle specific actin (MSA)+, vimentin+, CD31−, CD34−, CD21−, CD8−, CD68− (2/3 cases), S100−, while the lining cells were CD34+, vimentin+ and SMA−, with variable CD31 and factor VIII related antigen expression. Elongated SMA+, MSA+ cell processes were evident in one case, reminiscent of previously characterized myoid elements of the normal spleen. An uneventful follow-up was noted for all three patients.〈section xml:id="abs1-3"〉〈title type="main"〉ConclusionsThe histology and immunophenotype set these neoplasms apart from classic hamartomas, haemangiomas and previously characterized (haem)angioendotheliomas of the spleen, and may represent proliferations of myoid elements native to the spleen.
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Histopathology 35 (1999), S. 0 
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The distinction between nontuberculous mycobacterial (NTM) lymphadenitis and other causes of cervical lymphadenitis is critical, as different entities call for different treatments. Despite modern diagnostic techniques for NTM infections their prompt and accurate diagnosis is still difficult. We assessed the value of different histological features in diagnosing clinically suggestive NTM cervical lymphadenitis in cases of granulomatous cervical lymphadenitis.〈section xml:id="abs1-2"〉〈title type="main"〉Methods and resultsA retrospective study of 30 patients with a clinical diagnosis of NTM cervical lymphadenitis was carried out. The patients were divided into three subgroups and several histological parameters were examined in each subgroup. A comparison was made with cases of proven tuberculous lymphadenitis. Four histological features (presence of microabscesses, ill-defined granulomas, noncaseating granulomas and a small number of giant cells) were found with significant statistical difference when comparison was made between the NTM group and the tuberculosis group.〈section xml:id="abs1-3"〉〈title type="main"〉ConclusionsA rapid and accurate diagnostic procedure for NTM lymphadenitis is not yet available. Therefore, in the presence of a suggestive clinical picture for NTM lymphadenitis, we propose four histological features which support this diagnosis, thus allowing prompt therapeutic intervention.
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