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  • 1
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    p38 mitogen-activated protein kinase determines the susceptibility to cigarette smoke-induced emphysema in mice (2014)
    BioMed Central
    Details
    Publication Date: 2014-05-08
    Description: Background: There is a need for agents that suppress inflammation and progression of chronic obstructive pulmonary disease. p38 mitogen-activated protein kinase (p38 MAPK) has been associated with this disorder, and several inhibitors of this cascade are in clinical trials for its treatment, but their efficacy and utility are unknown. This study evaluated the relationship between p38 MAPK activation and susceptibility to cigarette smoke (CS)-induced emphysema, and whether its inhibition ameliorated the lung inflammation and injury in murine models of cigarette smoke exposure. Methods: In acute and chronic CS exposure, the activation and expression of p38 MAPK in the lungs, as well as lung inflammation and injury (proteinase production, apoptosis, and oxidative DNA damage), were compared between two mouse strains: C57BL/6 (emphysema-susceptible) and NZW (emphysema-resistant). The selective p38 MAPK inhibitor SB203580 (45 mg/kg) was administrated intra-peritoneally to C57BL/6 mice, to examine whether it ameliorated cigarette smoke-induced lung inflammation and injury. Results: Acute CS-induced lung inflammation (neutrophil infiltration, mRNA expressions of TNF-alpha and MIP-2), proteinase expression (MMP-12 mRNA), apoptosis, and oxidative DNA damage were significantly lower in NZW than C57BL/6 mice. p38 MAPK was significantly activated and up-regulated by both acute and chronic CS exposure in C57BL/6 but not NZW mice. mRNA expression of p38 MAPK was also upregulated in C57BL/6 by chronic CS exposure and tended to be constitutively suppressed in NZW mice. SB203580 significantly attenuated lung inflammation (neutrophil infiltration, mRNA expressions of TNF-alpha and MIP-2, protein levels of KC, MIP-1alpha, IL-1beta, and IL-6), proteinase expression (MMP-12 mRNA), oxidative DNA damage, and apoptosis caused by acute CS exposure. Conclusions: cigarette smoke activated p38 MAPK only in mice that were susceptible to cigarette smoke-induced emphysema. Its selective inhibition ameliorated lung inflammation and injury in a murine model of cigarette smoke exposure. p38 MAPK pathways are a possible molecular target for the treatment of chronic obstructive pulmonary disease.
    Electronic ISSN: 1471-2466
    Topics: Medicine
    Published by BioMed Central
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  • 2
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    Autoimmunity against M2 muscarinic acetylcholine receptor induces myocarditis and leads to a dilated cardiomyopathy-like phenotype (2012)
    Wiley-Blackwell
    Details
    Publication Date: 2012-04-05
    Description: Patients with dilated cardiomyopathy (DCM) often have autoantibodies against cardiac antigens including the M 2 muscarinic acetylcholine receptor (M 2 R). To elucidate the role of autoimmunity against M 2 R in disease development, we induced an immune response against M 2 R by adoptive transfer into Rag2 −/– mice of splenocytes from M 2 R −/– mice immunized with a recombinant M 2 R protein. T lymphocytes transiently infiltrated the heart in recipient mice followed by morphological changes in cardiomyocytes. These mice produced IgG antibodies against M 2 R which bound to cardiomyocytes in vivo and decreased the amplitude of calcium signals in isolated rat cardiomyocytes in vitro. Recipient mice showed increased heart weights associated with increased intraventricular diameter, decreased systolic function and increased action potential duration, which are characteristics of DCM. Our results suggest that myocarditis and DCM associated with the presence of anti-M 2 R antibodies are autoimmune diseases with a risk of progressing to the terminal stage. Our mouse model will be useful in the analysis of the molecular mechanisms of disease progression and the development of new therapies for DCM.
    Print ISSN: 0014-2980
    Electronic ISSN: 1521-4141
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 3
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    Autoimmunity against M2 muscarinic acetylcholine receptor induces myocarditis and leads to a dilated cardiomyopathy-like phenotype (2012)
    Wiley-Blackwell
    Details
    Publication Date: 2012-04-25
    Description: Patients with dilated cardiomyopathy (DCM) often have autoantibodies against cardiac antigens including the M 2 muscarinic acetylcholine receptor (M 2 R). To elucidate the role of autoimmunity against M 2 R in disease development, we induced an immune response against M 2 R by adoptive transfer into Rag2 −/– mice of splenocytes from M 2 R −/– mice immunized with a recombinant M 2 R protein. T lymphocytes transiently infiltrated the heart in recipient mice followed by morphological changes in cardiomyocytes. These mice produced IgG antibodies against M 2 R which bound to cardiomyocytes in vivo and decreased the amplitude of calcium signals in isolated rat cardiomyocytes in vitro. Recipient mice showed increased heart weights associated with increased intraventricular diameter, decreased systolic function and increased action potential duration, which are characteristics of DCM. Our results suggest that myocarditis and DCM associated with the presence of anti-M 2 R antibodies are autoimmune diseases with a risk of progressing to the terminal stage. Our mouse model will be useful in the analysis of the molecular mechanisms of disease progression and the development of new therapies for DCM.
    Print ISSN: 0014-2980
    Electronic ISSN: 1521-4141
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 4
    Electronic Resource
    Electronic Resource
    Interface-trap generation at ultrathin SiO2 (4–6 nm)-Si interfaces during negative-bias temperature aging (1995)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 77 (1995), S. 1137-1148 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: This article reports an investigation of the negative-bias temperature instability in metal-oxide-silicon (MOS) systems with gate oxide thickness (Tox) in the range of 4.2–30 nm. The bias temperature aging was performed on p-type samples with applied negative oxide fields (1.6–5.0 MV/cm) over a temperature range of 150–290 °C. The maximum aging time was 5000 h. The interface-trap distribution was evaluated by the conductance technique. This time-consuming method yields reliable results even in ultrathin oxides, if appropriate corrections are made. The interface-trap generation and the concurrent fixed oxide charge can be expressed by simple empirical expressions. Their characteristic features are the inverse proportionality to oxide thickness (Tox) for the generated interface-trap density (Nit) and no thickness dependence for the fixed charge generation. A general phenomenological model is proposed to explain these empirical expressions in terms of the diffusion-reaction chemistry between hydrogenated trivalent silicon and the diffusing species. It is developed for the uncharged (neutral) and positively charged cases of diffusing species. Experimental results support the neutral-species (molecular hydrogen) model and the observed T−1ox dependence of Nit generation implies that the negative-bias temperature instability becomes more severe for ultrathin gate oxide MOS devices. © 1995 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.358977
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  • 5
    Electronic Resource
    Electronic Resource
    Neutral electron trap generation in SiO2 by hot holes (1990)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 56 (1990), S. 1329-1331 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Experimental evidence for neutral electron trap generation in SiO2 caused by injected holes is presented. The neutral electron traps are detected by Fowler–Nordheim (FN) tunneling electron injection after avalanche hole injection. The density of generated neutral traps increases with the number of injected holes, but does not saturate with that of the trapped holes. The centroid of generated neutral traps is found to be in the middle of the oxide. These results suggest that neutral traps are generated by the holes and not only by the recombination of electrons with trapped holes. The origin of neutral traps is considered to be associated with dipolar defects formed by SiO bond breaking under hole transport in the oxide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.103200
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  • 6
    Electronic Resource
    Electronic Resource
    Interface-trap generation induced by hot-hole injection at the Si-SiO2 interface (1992)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 61 (1992), S. 807-809 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The individual role of hot holes, hot electrons, and their recombination in interface-trap generation at the Si-SiO2 interface during hot-carrier injection has been investigated with an emphasis on its oxide thickness dependence (7–30 nm). Hot holes are found to be able to generate interface traps and to be much more effective for interface-trap generation at low-level injections than both hot electrons and electron-hole recombination. The experimental evidence of no thickness dependence of the hot-hole-induced interface-trap generation suggests that this is an interfacial process occurring at the Si-SiO2 interface.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.107751
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  • 7
    Electronic Resource
    Electronic Resource
    Maintenance of broad host range vector pKT230 in marine unicellular cyanobacteria (1992)
    Oxford, UK : Blackwell Publishing Ltd
    FEMS microbiology letters 99 (1992), S. 0 
    Details
    ISSN: 1574-6968
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Abstract The host range of pKT230 in marine unicellular cyanobacteria was investigated. The broad host range vector, pKT230, was successfully transferred by transconjugation to Synechococcus sp. PCC7335, NKBG15031a and Synechocystis 7a. pKT230 was found to be maintained as an autonomous replicon in strains NKBG15031a and 7a. pKT230 stability in Synechococcus sp. NKBG15041c, in which pKT230 was found to be maintained as an autonomous replicon in our previous report [1], was also studied. In the absence of selection pressure, after 120 h of cultivation, about 50% of cells lost the plasmid. In the presence of selection pressure (kanamycin 25 μg ml−), after 120 h of cultivation, more than 90% of the cells harboured the plasmid.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1574-6968.1992.tb05544.x
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  • 8
    Electronic Resource
    Electronic Resource
    Fibrous support for immobilization of enzymes (1982)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Applied Polymer Science 27 (1982), S. 1665-1674 
    Details
    ISSN: 0021-8995
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: A poly(vinyl alcohol) (PVA) fiber support incorporating various aminoacetal functional groups has been developed for immobilizing enzymes. The aminated PVA fiber seems to adsorb enzymes with electrostatic force of attraction; thus the immobilization procedure is simple. By the use of this fiber having immobilized enzymes, the reaction between enzymes and substrates is nearly independent of the size of subtstrates. This newly developed type of fiber, which is formed by a mass superfine fibers (SFF), each measuring 1 μm or less in diameter, permits much more increased surface area than the conventional enzyme immobilization supports. Our studies of the properties of the fiber for immobilization of enzymes show the following results: (1) SFF has a greater ability for the immobilization of invertase than ordinary fibers; (2) dimethyl-aminated SFF has the best performance for the immobilization of invertase. From these results, it is concluded that the dimethyl-aminated SFF is an excellent support for the immobilization of invertase.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/app.1982.070270523
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  • 9
    Electronic Resource
    Electronic Resource
    Thermal stabilities of homopolymers of amino acids (1969)
    New York : Wiley-Blackwell
    Journal of Polymer Science Part A-1: Polymer Chemistry 7 (1969), S. 1415-1424 
    Details
    ISSN: 0449-296X
    Keywords: Physics ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In order to study the thermal stabilities of the α-helical polyamino acids in the solid state, measurements of the infrared spectra at high temperature, weight loss by thermogravimetry, and the expansion of the α-helix by x-ray diffractometry were carried out on poly(γ-methyl D-glutamate), poly(γ-benzyl L-glutamate), poly-L-alanine, poly(β-benzyl L-aspartate), poly-δ-carbobenzoxy-L-ornithine and poly-ε-carbobenzoxy-L-lysine. The thermal degradation temperatures of these polymers lie between 140°C and 230°C. The α-helical conformation is stable at high temperature in these polyamino acids, except for poly(β-benzyl L-asparatate), unless thermal degradation takes place. As temperature rises, the amide A and the amide I bands of the infrared spectra shift slightly to higher frequencies and the amide II band to lower frequencies. At the same time, the intensities of these amide bands decrease. These changes differ among the different molecules. From the x-ray measurement, it was found that the α-helix expands along the helical axis with temperature. It is expected that the intramolecular hydrogen bonds of the α-helix become weak with increasing temperature and that the state of the hydrogen bonds of the α-helices depends upon the molecules.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/pol.1969.150070605
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