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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Acetylcholine release stimulated by nicotinic agonists was measured as radioactivity released from perfused synaptosomes prepared from mouse interpeduncular nucleus (IPN) that had been loaded with [3H]choline. Agonist-stimulated release was dependent upon external calcium and over 90% of released radioactivity was acetylcholine. The release process was characterized by dose response curves for 13 agonists and inhibition curves for six antagonists. α-Conotoxin MII did not inhibit this release, while α-conotoxin AuIB inhibited 50% of agonist-stimulated release. Comparison of this process with [3H]dopamine release from mouse striatal synaptosomes indicated that different forms of nicotinic acetylcholine receptors (nAChRs) may mediate these processes. This was confirmed by assays using mice homozygous for the β2 subunit null mutation. The deletion of the β2 subunit had no effect on agonist-stimulated acetylcholine release, but abolished agonist-stimulated release of dopamine from striatal synaptosomes. Mice heterozygous for the β2 subunit null mutation showed decreased dopamine release evoked by l-nicotine with no apparent change in EC50 value, as well as similar decreases in both transient and persistent phases of release with no changes in desensitization rates.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature medicine 7 (2001), S. 655-656 
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Cancer is one of the most feared diseases in modern society. Approximately 50% of cancer patients die because the initial tumor becomes metastatic, spreading beyond the site of origin. Studies have demonstrated a positive correlation between cancer progression and expression of extracellular ...
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  • 3
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] We screened cDNAs with homology to conserved regions in matrix metalloproteinase (MMP) genes (Fig. 1 legend) and iso-lated a unique 3.4-kilobase (kb) cDNA fragment (MMP-X1) from a human placenta cDNA library. This cDNA encodes a unique protein of 582 amino acids (Mr 66K) which can be closely ...
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Annals of biomedical engineering 26 (1998), S. 190-199 
    ISSN: 1573-9686
    Keywords: Particle residence time ; In vitro model ; Artery: carotid ; Artery: coronary ; Stenosis ; Particle motion ; Model ; Artery: stenosed
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Asymmetric 75% and 95% area reduction, transparent Sylgard stenotic models were operated under internal carotid artery (ICA) (Womersley parameter, α=5.36, Remean=213 and 180, respectively, and Repeak=734 and 410, respectively) and left anterior descending coronary artery (LAD) flow wave forms (α=2.65,Remean=59 and 57, respectively, and Repeak=137 and 94, respectively) to evaluate the effect of these conditions on particle residence times downstream of the stenoses. Amberlite particles (1.05 g/cm3, 400 μm) were added to the fluid to simulate platelets and their motion through the stenotic region and were traced using a laser light sheet flow visualization method with pseudo-color display. Two-dimensional (2D) particle motions were recorded and particle washout in the stenotic throat and downstream section were computed for all cases. All four model cases demonstrated jetting through the stenosis which followed an arching pattern around a large separation zone downstream. Considerable mixing was observed within these vortex regions during high flow phases. Particle washout profiles showed no clear trend between the degrees of stenosis although particles downstream of the stenoses tended to remain longer for LAD conditions. The critical washout cycle (1% of particles remaining downstream of the stenosis), however, was longer for the 95% stenoses cases under each flow condition due to the larger protected region immediately downstream and maximal for the LAD 95% case. Results of this study suggest that particle residence times downstream of 75% and 95% stenoses (~ 3–6 s for ICA and ~ 8–10 s for LAD) exceed the minimum time for platelet adhesion (~ 1 s) for at least 1% of cells and, thus, may be sufficient to initiate thrombus formation under resting conditions. © 1998 Biomedical Engineering Society. PAC98: 8745Hw, 8722-q, 4727Wg, 4732Cc
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Annals of biomedical engineering 27 (1999), S. 298-312 
    ISSN: 1573-9686
    Keywords: In vivo ; Incipient cell rolling ; Transient contact ; Drag force ; Modeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract The mechanics of leukocyte [white blood cell (WBC)] deformation and adhesion to endothelial cells (EC) in shear flow has been investigated. Experimental data on transient WBC–EC adhesion were obtained from in vivo measurements. Microscopic images of WBC–EC contact during incipient WBC rolling revealed that for a given wall shear stress, the contact area increases with time as new bonds are formed at the leading edge, and then decreases with time as the trailing edge of the WBC membrane peels away from the EC. A two-dimensional model (2D) was developed consisting of an elastic ring adhered to a surface under fluid stresses. This ring represents an actin-rich WBC cortical layer and contains an incompressible fluid as the cell interior. All molecular bonds are modeled as elastic springs distributed in the WBC–EC contact region. Variations of the proportionality between wall shear stress (τ w ) in the vicinity of the WBC and the resulting drag force (F s ), i.e., Fs/τw, reveal its decrease with WBC deformation and increasing vessel channel height (2D). The computations also find that the peeling zone between adherent WBC and EC may account for less than 5% of the total contact interface. Computational studies describe the WBC–EC adhesion and the extent of WBC deformation during the adhesive process. © 1999 Biomedical Engineering Society. PAC99: 8717-d, 8719Tt, 8717Aa
    Type of Medium: Electronic Resource
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  • 6
    Publication Date: 2014-08-30
    Description: Background: The 90-kDa heat shock protein HSP90AA1 is critical for the stability of several proteins that are important for tumor progression and thus, is a promising target for cancer therapy. Selenosemicarbazone metal complexes have been shown to possess anticancer activity through an unknown molecular mechanism. Methods: The MTT assay, fluorescence-activated cell sorting, and fluorescent microscopy were used to analyze the mechanism of the anti-cancer activity of the selenosemicarbazone metal complexes. Additionally, RNA-seq was applied to identify transcriptional gene changes, and in turn, the signaling pathways involved in the process of 2-24a/Cu-induced cell death. Last, the expression of HSP90AA1, HSPA1A, PIM1, and AKT proteins in 2-24a/Cu-treated cells were investigated by western blot analysis. Results: A novel selenosemicarbazone copper complex (2-24a/Cu) efficiently induced G2/M arrest and was cytotoxic in cancer cells. 2-24a/Cu significantly induced oxidative stress in cancer cells. Interestingly, although RNA-seq revealed that the transcription of HSP90AA1 was increased in 2-24a/Cu-treated cells, western blotting showed that the expression of HSP90AA1 protein was significantly decreased in these cells. Furthermore, down-regulation of HSP90AA1 led to the degradation of its client proteins (PIM1 and AKT1), which are also cancer therapy targets. Conclusion: Our results showed that 2-24a/Cu efficiently generates oxidative stress and down-regulates HSP90AA1 and its client proteins (PIM1, AKT1) in U2os and HeLa cells. These results demonstrate the potential application of this novel copper complex in cancer therapy.
    Electronic ISSN: 1471-2407
    Topics: Medicine
    Published by BioMed Central
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  • 7
    Publication Date: 2016-04-04
    Description: Hantavirus is a tripartite negative-sense RNA virus. It can infect humans through contaminated rodent excreta and causes two types of fatal human diseases: hemorrhagic fever with renal syndrome (HFRS) and hant...
    Electronic ISSN: 1746-6148
    Topics: Medicine
    Published by BioMed Central
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  • 8
    Publication Date: 2016-08-02
    Description: Krüppel-like factor 8 (KLF8) is highly expressed in hepatocellular carcinoma (HCC) and contributes to tumor initiation and progression by promoting HCC cell proliferation and invasion. However, the role of KLF8 in liver cancer stem cells (LCSCs) is not known. In the current study, we investigated the role of KLF8 in LCSCs to determine if KLF8 is a novel marker of these cells. We found that KLF8 was highly expressed in primary HCC tumors, distant migrated tissues, and LCSCs. Patients with high KLF8 expression had a poor prognosis. KLF8 promoted stem cell-like features through activation of the Wnt/β-catenin signaling pathway. Cell apoptosis was significantly increased in HCC cells with knockdown of KLF8 compared with the control cells when treated with the same doses of sorafenib or cisplatin. Taken together, our study shows that KLF8 plays a potent oncogenic role in HCC tumorigenesis by maintaining stem cell-like features through activation of the Wnt/β-catenin signaling pathway and promoting chemoresistance. Thus, targeting KLF8 may provide an effective therapeutic approach to suppress tumorigenicity of HCC. This article is protected by copyright. All rights reserved
    Print ISSN: 0899-1987
    Electronic ISSN: 1098-2744
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 9
    Publication Date: 2013-06-22
    Description: Background: There is a strong need for early assessment of tumor response to chemotherapy in order to avoid the adverse effects of unnecessary chemotherapy and to allow early transition to second-line therapy. The purpose of this study was to determine the feasibility of ultrasonic spectral analysis for the in vivo characterization of changes in tumor microstructure in the evaluation of tumor response to chemotherapy using diagnostic ultrasound. Methods: Experiments were approved by the regional animal care committee. Twenty-four MCF-7 breast cancer bearing nude mice were treated with adriamycin or sterile saline administered by intraperitoneal injection. Ultrasonic radio-frequency (RF) data was collected using a clinically available ultrasound scanner (6-MHz linear transducer). Linear regression parameters (spectral slope and midband-fit) regarding the calibrated power spectra from the RF signals were tested to monitor tumor response to treatment. The section equivalent to the ultrasound imaging plane was stained with hematoxylin and eosin to allow for assessment of the density of tumor cell nuclei. Results: Treatment with adriamycin significantly reduced tumor growth in comparison with the control group (p = 0.003). Significant changes were observed in the ultrasonic parameters of the treated relative to the untreated tumors (p 〈 0.05). The spectral slope increased by 48.5%, from -10.66 +/- 2.96 to -5.49 +/- 2.69; the midband-fit increased by 12.8%, from -57.10 +/- 7.68 to -49.81 +/- 5.40. Treated tumors were associated with a significant decrease in the density of tumor cell nuclei as compared with control tumors (p 〈 0.001). Conclusions: Ultrasonic spectral analysis can detect changes in tumor microstructure after chemotherapy, and this will be helpful in the early evaluation tumor response to chemotherapy.
    Electronic ISSN: 1471-2407
    Topics: Medicine
    Published by BioMed Central
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  • 10
    Publication Date: 2014-06-11
    Description: Depression is a major mental health problem during adolescence. This study, using a sample of Chinese adolescents, examined the separate and combined effects of perceived school-related stress and of family socioeconomic status (SES) on the prevalence of depressive symptoms. A total of 1774 Chinese students from Grades 7–12 were recruited into our questionnaire survey. School-related stress was measured by the Effort-Reward Imbalance Questionnaire-School Version, family SES was assessed by a standardized question, and depressive symptoms were evaluated by the Center for Epidemiological Studies Depression Scale for Children. Multivariate logistic regression was applied, adjusting for age, gender, grade, smoking, alcohol drinking and physical activity. It was found that high school-related stress and low family SES were associated with elevated odds of depressive symptoms, respectively. The effect of school-related stress was particularly strong in low SES group. In adolescents with both high stress at school and low SES, the odds ratio was 9.18 (95% confidence interval = 6.53–12.89) compared to the reference group (low stress at school and high SES). A significant synergistic interaction effect was observed (synergy index = 2.28, 95% confidence interval = 1.56–3.32). The findings indicated that perceived school-related stress, in terms of effort-reward imbalance, was related to depressive symptoms in this sample of Chinese adolescents. The strong interaction with family SES suggests that health promoting efforts in school settings should be targeted specifically at these socially deprived groups.
    Print ISSN: 1661-7827
    Electronic ISSN: 1660-4601
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Published by MDPI Publishing
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