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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cell biology and toxicology 15 (1999), S. 19-29 
    ISSN: 1573-6822
    Keywords: anthrax lethal toxin ; cytotoxicity ; macrophage ; phospholipase A2 ; protein kinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The molecular mechanism of cytotoxic effect exerted by the lethal toxin (LeTx) of Bacillus anthracis is not well understood. In the present study, using primary culture of mouse peritoneal macrophages, we have investigated possible cytotoxic mechanisms. LeTx was not found to induce high levels of nitric oxide (NO) production for NO-mediated toxicity. Fragmentation of DNA, a biochemical marker of apoptosis, was not observed in LeTx-treated cells. Pretreatment of cells with antioxidants such as melatonin and dehydroepiandrosterone (DHEA) did not protect the LeTx-induced cytotoxicity. However, addition of phospholipase A2 (PLA2) inhibitors (quinacrine, p-bromophenacyl bromide, manoalide, butacaine) to the culture medium resulted in the inhibition of cytotoxicity of LeTx in a dose-dependent manner. LeTx-induced cytotoxicity was also inhibited by the tyrosine-specific protein kinase inhibitor genistein, but not by the protein kinase C inhibitors staurosporine or H-7. The results of these studies indicate a role for PLA2 and protein kinase in the cytotoxic mechanism of macrophages by anthrax lethal toxin.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-6822
    Keywords: anthrax lethal toxin ; cytokine ; dehydroepiandrosterone ; melatonin ; tumor necrosis factor α
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The lethal toxin of Bacillus anthracis, which is composed of two separate proteinaceous exotoxins, namely protective antigen and lethal factor, is central to the pathogenesis of anthrax. Low levels of this toxin are known to induce release of cytokines such as tumor necrosis factor α (TNF-α). In the present study we investigated the effect of dehydroepiandrosterone (DHEA), melatonin (MLT), or DHEA + MLT on production of lethal toxin-induced TNF-α in mouse peritoneal macrophages. We found that treatment with DHEA significantly inhibited the TNF-α production caused by anthrax lethal toxin. Exposure of MLT to anthrax lethal toxin-treated macrophages also decreased the release of TNF-α to the extracellular medium as compared to the control. However, combined use of DHEA and MLT also inhibited TNF-α release, but not more than single therapies. These results suggest that DHEA and MLT may have a therapeutic role in reducing the increased cytokine production induced by anthrax lethal toxin.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-6822
    Keywords: anthrax lethal toxin ; cytotoxicity ; intracellular calcium antagonist ; macrophage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The lethal toxin ofBacillus anthracis is central to the pathogenesis of anthrax. Using primary cultures of mouse peritoneal macrophages, we have demonstrated that intracellular calcium release inhibitors protect against anthrax lethal toxin-induced cytotoxicity. The cytolytic effect of anthrax lethal toxin was markedly reduced by dantrolene, an inhibitor of calcium release from intracellular calcium stores. Pretreatment of macrophages with cyclosporin A, which has been shown to be a potent inhibitor of calcium release from mitochondria, also protected cells against cytotoxicity. These results indicate that calcium release from intracellular store may be an essential step for the propagation of anthrax lethal toxin-induced cell damage in macrophages. Thus our findings suggest that dantrolene, cyclosporin A, and possibly other drugs affecting intracellular calcium pools might be effectively preventing the toxicity from anthrax lethal toxin.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1435-232X
    Keywords: Key words Y chromosome ; DYS287 ; DXYS5Y ; SRY465 ; DYS19 ; DXYS156Y ; East Asians ; Koreans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We have examined variations of five polymorphic loci (DYS287, DXYS5Y, SRY465, DYS19, and DXYS156Y) on the Y chromosome in samples from a total of 1260 males in eight ethnic groups of East Asia. We found four unique haplotypes constructed from three biallelic markers in these samples of East Asians. The Japanese population was characterized by a relatively high frequency of either the haplotype I-2b (−/Y2/T) or II-1 (+/Y1/C). These dual patterns of the distribution of Y chromosomes (I-2b/II-1) were also found in Korea, although they were present at relatively low frequencies. The haplotype II-1 was present in Northeast Asian populations (Chinese, Japanese, Koreans, and Mongolians) only, except for one male from the Thai population among the Southeast Asian populations (Indonesians, Philippines, Thais, and Vietnamese). The Japanese were revealed to have the highest frequency of this haplotype (27.5%), followed by Koreans (2.9%), Mongolians (2.6%), and mainland Chinese (2.2%). In contrast, the frequency of the haplotype I-2b was found to be 17.1% in the Japanese, 9.5% in Indonesian, 6.3% in Korean, 3.8% in Vietnamese, and 2.7% in Thai samples. These findings suggested that the chromosomes of haplotype I-2b were likely derived from certain areas of Northeast Asia, the region closest to Southeast Asia. Phylogenetic analysis using the neighbor-joining tree also reflected a general distinction between Southeast and Northeast Asian populations. The phylogeny revealed a closer genetic relationship between Japanese and Koreans than to the other surveyed Asian populations. Based on the result of the dual patterns of the haplotype distribution, it is more likely that the population structure of Koreans may not have evolved from a single ancient population derived from Northeast Asians, but through dual infusions of Y chromosomes entering Korea from two different waves of East Asians.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Journal of human genetics 43 (1998), S. 195-198 
    ISSN: 1435-232X
    Keywords: Keyword Y Chromosome ; DYS287 ; DYS19 ; Chinese ; Japanese ; Korean
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The Y Alu polymorphic (YAP) element (DYS287) and the Y-linked tetranucleotide microsatellite locus DYS19 were examined in samples from a total of 455 unrelated males in the Korean population. The frequency of the YAP + allele was found to be 1.3% (6/455) in the Korean population. These results are consistent with previous reports that showed the YAP element to be absent in most Asian populations, with the exception of the high frequency of the YAP + allele in the Japanese population. All five common alleles at the DYS19 locus were identified in this study. The C allele was the most frequent (197/455), followed by the D (119/455), B (78/455), E (41/455), and A (20/455) alleles. Seven combination haplotypes (DYS287/DYS19) were found, and the mean combination haplotype diversity in the Korean population appeared to be 0.71. Based on results of these two loci, Japanese and Korean populations may share some common genetic structure that could reflect recent gene flow and some amount of admixture of Y chromosomes between these two populations.
    Type of Medium: Electronic Resource
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