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  • 1
    ISSN: 1573-0972
    Keywords: DNA probe ; heat-stable enterotoxin ; NAG-ST ; Vibrio ; Vibrio mimicus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Using a 0.27 kb DNA probe specific for the heat-stable enterotoxin gene (nag-st) of Vibrio cholerae non-O1, 1109 strains representing 17 species of the genus Vibrio, isolated from clinical and environmental sources were examined. The nag-st gene was preponderantly associated with strains classified as V. mimicus; 16.8% of these strains hybridized. It was more frequent in the clinical isolates (22.6%) than in the environmental isolates (13.7%). The incidence of nag-st gene-positive strains of V. mimicus isolated from different countries was uniformly high and ranged between 8.7% (Bangladesh) and 57.1% (environmental strains from USA). The incidence of the nag-st gene was much lower among strains of V. cholerae non-O1 (3.6%). Probe-positive and-negative strains of V. mimicus and V. cholerae non-O1 were used to evaluate the performance of the conventional suckling mouse assay for detection of the NAG-ST enterotoxin. Of the 31 probe-positive strains, only five (16.1%) yielded a positive fluid accumulation ratio (FA ratio) when neat heated culture supernatant was used to perform the suckling mouse assay. All the 31 probe-positive strains gave a positive FA ratio when 20-fold concentrated and heated culture supernatants of the strains were used to perform the suckling mouse assay. The need to concentrate (by at least 20-fold) the culture supernatant of strains of V. mimicus and V. Cholerae non-O1 was identified as an important step to obtain consistent results when using the suckling mouse assay for detection of NAG-ST.
    Type of Medium: Electronic Resource
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  • 2
    Publication Date: 2013-04-19
    Description: Background Triple-negative breast cancer (TNBC) may be more sensitive to platinum. This study was to compare platinum-based regimen with nonplatinum regimen in the first-line treatment of advanced TNBC. Patients and methods Eligible metastatic TNBC (mTNBC) women without prior treatment for advanced disease were randomized (1 : 1) to receive either docetaxel–cisplatin (TP) or docetaxel –capecitabine (TX) q3w for up to 6 cycles, until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) and the secondary end points included progression-free survival (PFS) and overall survival (OS). In total 53 patients were enrolled. Results The median follow-up was 24 months. ORR was higher in the TP group than in the TX group (63.0% versus 15.4%, P = 0.001). PFS was more than doubled (10.9 months versus 4.8 months, P 〈 0.001) and median OS was also greatly improved (32.8 months versus 21.5 months, P = 0.027). Toxic effects were not different except G3/4 vomiting and G2/3 hand-foot syndrome. Conclusions This study suggested that cisplatin-based chemotherapy was superior to capecitabine-based regimen in the first-line treatment of mTNBC, as measured by ORR, PFS and OS. Further large-scale study should be warranted. These results are not sufficient to change clinical practice.
    Print ISSN: 0923-7534
    Electronic ISSN: 1569-8041
    Topics: Medicine
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  • 3
    Publication Date: 2012-11-17
    Description: Let H be a Krull monoid with class group G and suppose that every class contains a prime divisor. The set of distances ( H ) of H is the set of all d N with the following property: there are irreducible elements u 1 , ..., u k , v 1 , ..., v k + d such that u 1 ·...· u k = v 1 ·...· v k + d , but u 1 ·...· u k cannot be written as a product of l irreducible elements for any l with k 〈 l 〈 k + d . We show that ( H ) is an interval.
    Print ISSN: 0024-6093
    Electronic ISSN: 1469-2120
    Topics: Mathematics
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  • 4
    Publication Date: 2013-07-23
    Description: Aims Oxidative stress is implicated in the pathology of pulmonary arterial hypertension (PAH). Previously, we demonstrated that vardenafil, a phosphodiesterase-5 inhibitor, has potential as therapy for PAH, although the mechanism remained uncharacterized. Here, we aimed to determine baseline levels of oxidative stress in PAH and investigate whether vardenafil affects oxidative stress levels while improving PAH. Methods and results Sprague–Dawley rats with monocrotaline-induced PAH were administered oral vardenafil 1 mg kg –1 day –1 for 21 days ( n = 12). Treatment-naive patients ( n = 15) with PAH were treated with vardenafil 5 mg twice daily for 3 months. Haemodynamic data and plasma levels of nitrate/nitrite and products of oxidative damage were determined in rats and patients. Histopathology, immunohistochemistry, and assessments of oxidative/anti-oxidative enzyme expression were performed in rat lung tissue. Compared with baseline (patients) or untreated controls (rats), vardenafil significantly reduced pulmonary vascular resistance and increased cardiac output (CO). In rats, vardenafil suppressed proliferation and enhanced apoptosis of pulmonary artery smooth muscle cells, attenuating small pulmonary artery remodelling, and right ventricular hypertrophy. Vardenafil significantly reduced levels of oxidative stress biomarkers, such as 8-iso-prostaglandin-F2α and 3-nitrotyrosine, and significantly increased nitric oxide (NO) levels in rats and patients. Furthermore, vardenafil significantly increased endothelial NO synthase expression and superoxide dismutase activity, and down-regulated nicotinamide adenine dinucleotide phosphate oxidase expression in rat lung tissue. Conclusion Vardenafil reduces oxidative stress in rats and humans while improving PAH, warranting investigation of oxidative stress pathways as targets for PAH therapy.
    Print ISSN: 0008-6363
    Electronic ISSN: 1755-3245
    Topics: Medicine
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  • 5
    Publication Date: 2012-06-28
    Description: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. The understanding of its gene expression regulation and molecular mechanisms still remains elusive. Started from experimentally verified T-ALL-related miRNAs and genes, we obtained 120 feed-forward loops (FFLs) among T-ALL-related genes, miRNAs and TFs through combining target prediction. Afterwards, a T-ALL miRNA and TF co-regulatory network was constructed, and its significance was tested by statistical methods. Four miRNAs in the miR-17–92 cluster and four important genes (CYLD, HOXA9, BCL2L11 and RUNX1) were found as hubs in the network. Particularly, we found that miR-19 was highly expressed in T-ALL patients and cell lines. Ectopic expression of miR-19 represses CYLD expression, while miR-19 inhibitor treatment induces CYLD protein expression and decreases NF-B expression in the downstream signaling pathway. Thus, miR-19, CYLD and NF-B form a regulatory FFL, which provides new clues for sustained activation of NF-B in T-ALL. Taken together, we provided the first miRNA-TF co-regulatory network in T-ALL and proposed a model to demonstrate the roles of miR-19 and CYLD in the T-cell leukemogenesis. This study may provide potential therapeutic targets for T-ALL and shed light on combining bioinformatics with experiments in the research of complex diseases.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 6
    Publication Date: 2016-05-13
    Description: Background: China reduced hepatitis B virus (HBV) infection by 90% among children under 5 years old with safe and effective hepatitis B vaccines (HepB). In December 2013, this success was threatened by widespread media reports of infant deaths following HepB administration. Seventeen deaths and one case of anaphylactic shock following HBV vaccination had been reported. Methods: We conducted a telephone survey to measure parental confidence in HepB in eleven provinces at four points in time; reviewed maternal HBV status and use of HepB for newborns in birth hospitals in eight provinces before and after the event; and monitored coverage with hepatitis B vaccine and other programme vaccines in ten provinces. Results: HepB from the implicated company was suspended during the investigation, which showed that the deaths were not caused by HepB vaccination. Before the event, 85% respondents regarded domestic vaccines as safe, decreasing to 26.7% during the event. During the height of the crisis, 30% of parents reported being hesitant to vaccinate and 18.4% reported they would refuse HepB. Use of HepB in the monitored provinces decreased by 18.6%, from 53 653 doses the week before the event to 43 688 doses during the week that Biokangtai HepB was suspended. Use of HepB within the first day of life decreased by 10% among infants born to HBsAg-negative mothers, and by 6% among infants born to HBsAg-positive mothers. Vaccine refusal and HepB birth dose rates returned to baseline within 2 months; confidence increased, but remained below baseline. Conclusions: The HBV vaccine event resulted in the suspension of a safe vaccine, which was associated with a decline of parental confidence, and refusal of vaccination. Suspension of a vaccine can lead to loss of confidence that is difficult to recover. Timely and credible investigation, accompanied by proactive outreach to stakeholders and the media, may help mitigate negative impact of future coincidental adverse events following immunization.
    Print ISSN: 0300-5771
    Electronic ISSN: 1464-3685
    Topics: Medicine
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  • 7
    Publication Date: 2013-09-26
    Description: Serine integrases catalyze the integration of bacteriophage DNA into a host genome by site-specific recombination between ‘attachment sites’ in the phage ( attP ) and the host ( attB ). The reaction is highly directional; the reverse excision reaction between the product attL and attR sites does not occur in the absence of a phage-encoded factor, nor does recombination occur between other pairings of attachment sites. A mechanistic understanding of how these enzymes achieve site-selectivity and directionality has been limited by a lack of structural models. Here, we report the structure of the C-terminal domains of a serine integrase bound to an attP DNA half-site. The structure leads directly to models for understanding how the integrase-bound attP and attB sites differ, why these enzymes preferentially form attP x attB synaptic complexes to initiate recombination, and how attL x attR recombination is prevented. In these models, different domain organizations on attP vs. attB half-sites allow attachment-site specific interactions to form between integrase subunits via an unusual protruding coiled-coil motif. These interactions are used to preferentially synapse integrase-bound attP and attB and inhibit synapsis of integrase-bound attL and attR . The results provide a structural framework for understanding, testing and engineering serine integrase function.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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