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  • 1
    Publication Date: 2013-04-13
    Description: Type I interferons (IFN-I) are critical for antiviral immunity; however, chronic IFN-I signaling is associated with hyperimmune activation and disease progression in persistent infections. We demonstrated in mice that blockade of IFN-I signaling diminished chronic immune activation and immune suppression, restored lymphoid tissue architecture, and increased immune parameters associated with control of virus replication, ultimately facilitating clearance of the persistent infection. The accelerated control of persistent infection induced by blocking IFN-I signaling required CD4 T cells and was associated with enhanced IFN-gamma production. Thus, we demonstrated that interfering with chronic IFN-I signaling during persistent infection redirects the immune environment to enable control of infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704950/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704950/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, Elizabeth B -- Yamada, Douglas H -- Elsaesser, Heidi -- Herskovitz, Jonathan -- Deng, Jane -- Cheng, Genhong -- Aronow, Bruce J -- Karp, Christopher L -- Brooks, David G -- 8UL1TR000077-04/TR/NCATS NIH HHS/ -- AI060567/AI/NIAID NIH HHS/ -- AI082975/AI/NIAID NIH HHS/ -- AI085043/AI/NIAID NIH HHS/ -- HL108949/HL/NHLBI NIH HHS/ -- P30 AI028697/AI/NIAID NIH HHS/ -- P50 AR063020/AR/NIAMS NIH HHS/ -- R01 AI047868/AI/NIAID NIH HHS/ -- R01 AI056154/AI/NIAID NIH HHS/ -- R01 AI085043/AI/NIAID NIH HHS/ -- R01 HL108949/HL/NHLBI NIH HHS/ -- U01 AI082975/AI/NIAID NIH HHS/ -- UL1 TR000077/TR/NCATS NIH HHS/ -- New York, N.Y. -- Science. 2013 Apr 12;340(6129):202-7. doi: 10.1126/science.1235208.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Immunology and Molecular Genetics and the UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23580528" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/immunology ; Antigens, CD274/metabolism ; Arenaviridae Infections/*immunology/*virology ; CD4-Positive T-Lymphocytes/immunology ; Cytokines/immunology/metabolism ; Dendritic Cells/immunology ; Gene Expression Profiling ; Immune Tolerance ; Interferon Type I/genetics/*immunology/*metabolism ; Interferon-gamma/immunology/metabolism ; Interleukin-10/metabolism ; Lymphocytic choriomeningitis virus/*immunology/*physiology ; Mice ; Oligonucleotide Array Sequence Analysis ; Receptor, Interferon alpha-beta/antagonists & inhibitors/genetics/metabolism ; *Signal Transduction ; Virus Replication
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    ISSN: 1432-0738
    Keywords: Trichloroethylene ; Longterm inhalation ; Carcinogenicity ; Lymphomas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pure trichloroethylene (tri), stabilized by an amine base, was administered by inhalation at 0, 100, and 500 ppm for 6 h/day, 5 days/week, for 18 months to mice, rats and Syrian hamsters of both sexes. No significant increase in tumor formation was observed in any species or dosing group, except in malignant lymphomas, which were increased in female mice in the following incidence rates: 9/29 (controls), 17/30 (100 ppm), and 18/28 (500 ppm). Whether or not this high occurrence of lymphomas, which is peculiar to this strain of mice (NMRI) has any relationship to tri-exposure, cannot be decided upon by the present experiment. It is concluded that from these findings no indication for a carcinogenic potential of pure trichloroethylene can be deduced.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    The astronomy and astrophysics review 5 (1993), S. 165-237 
    ISSN: 1432-0754
    Keywords: Stars: pre-main sequence ; Stars: mass loss ; Interstellar medium: out-flows
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Summary Young bipolar nebulae are those rather rare exceptions among deeply embedded pre-main sequence objects driving bipolar outflows, which are amenable to detailed optical studies — by that means they provide unique information about this whole class of objects. The aim of this review is to work out, what their observations have told us about their structure and about the winds of young stars and their interaction with circumstellar matter. While the emphasis lies on the discussion of the optical observations, the large body of infrared and radio data is also considered. First, four of the best studied examples, S 106, Cep A, R Mon, and L 1551 IRS 5, are analyzed in depth. Then, recent observational results about disks and winds of T Tauri stars are considered, which shed new light also on the essential structural elements of young bipolar nebulae. After the description of some peculiar cases, the common properties characterizing the whole class of young bipolar nebulae are worked out. We are led to a unified picture of the bipolar winds causing both, the broad optically bright reflection lobes and molecular outflows, as well as the highly collimated optical jets observed in some cases on their polar axes; structure and dynamics of the bipolar winds are determined by the close interaction between the central stars and their massive circumstellar disks. Finally, current theoretical concepts about the mechanisms driving the winds are discussed, and present ideas about the evolution of bipolar nebulae are described. The Appendix includes a catalog of young bipolar nebulae.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Human pancreatic tissue was investigated by immunohistochemistry using a polyclonal antibody against the actin binding protein villin, which participates in the formation of actin filament bundles in the microvilli. In cells of the different parts of the pancreatic duct system as well as in the acinar cells villin immunoreactivity was located mainly at the apical cell surface. This was confirmed by the ultrastructural demonstration of microvilli on the surface of duct and acinar cells, which exhibited the typical actin bundles. In chronic pancreatitis the staining for villin in duct-like structures of degenerative pancreatic tissue was irregular or even absent. This correlated with the electron microscopic observation of duct-like structures known as tubular complexes composed of cells devoid of microvilli at the apical cell surface. At the light microscopical level degenerative structures without lumen and of unknown origin showed a strong staining for villin at their basal cell surface.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2307
    Keywords: Hyaluronate ; HA-binding protein ; Pancreatic adenocarcinoma ; Metastasis ; Invasion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A biotinylated hyaluronate (HA)-binding protein isolated from bovine cartilage was used to analyze the distribution of HA in nude mouse xenografts derived from human pancreatic adenocarcinoma cell lines as well as in primary human pancreatic adenocarcinomas. The most reproducible results for the localisation of HA were obtained using cryostat sections. When the biotinylated HA-binding protein was applied to histological sections of nude mouse xenografts, the specific staining found could be inhibited by preincubating the HA-binding protein with an excess of HA or by hyaluronidase treatment of the tissue before staining. The highest HA concentration was found at the tumor boundaries, while in the central part of the tumor staining was slight or absent. In cryostat sections of primary tumors HA was found predominantly in the connective tissue immediately around tumor cells or at the border between the tumor and normal pancreatic tissue.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0630
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 171 (1953), S. 1066-1067 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Lines of equal density for electrons and dust particles in the planetary system in a plane perpendicular to the ecliptic. Position of sun and inner planets marked by their symbols The spatial densities of electrons and dust particles were derived from the observed values of brightness and ...
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1440
    Keywords: Digitalis ; testosterone ; estradiol ; cortisol ; cardiac index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Digoxin was studied to see whether it impairs adrenal function and feminizes male subjects by changing plasma sexual hormones; both have been reported on previously. In eight healthy male subjects neither estrone (38.7±7.7 vs 35.4±3.2 pg/ml) nor estradiol (35.8±6.4 vs 32.2±3.9 pg/ml) nor testosterone (6.32±0.74 vs 6.45±0.73 ng/ml) were found to be altered by digoxin administration (plasma levels 1.55±0.27 ng/ml) lasting 35 days. The same was true of free testosterone (147±24 vs 142±19 pg/ml) and free estradiol (657±77 vs 615±78 fg/ml). Even maximal stimulation of the adrenal and gonadal glands by adrenocorticotropic hormone (ACTH) and human chorionic gonadotropin (hCG) did not exhibit any digoxin-induced alterations in the synthesizing capacity of steroid hormones, as shown by plasma cortisol (increase from 128±18 to 389±18 ng/ml) and testosterone (from 5.96±0.90 to 10.33±1.19 ng/ml). Furthermore, seven subjects on digoxin were observed over a period of 150–210 days; they did not show any increase of estrogens. This was also found in three subjects when estrogen levels were elevated initially due to extreme obesity. Also, 35 patients who took β-methyldigoxin (n=8), β-acetyldigoxin (n=20) and digitoxin (n=7) from 1 to 9 (x:1.9) years demonstrated normal plasma concentrations of gonadal and adrenal steroids, irrespective of duration of application or the digitalis compound. However, our studies showed that sexual hormones are correlated to cardiac performance: with decreasing cardiac index, testosterone (r: 0.86;P〈0.01) and estradiol (r: 0.68;P〈0.05) decreased significantly. We conclude that digoxin does not exert any influence on plasma sexual steroids. Since no competition between digoxin and estradiol receptors was found, it may even be the digitalis compound of choice when feminization is expected due to other complications. Furthermore, on digoxin the adrenal gland is capable of synthesizing cortisol sufficiently.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1335
    Keywords: Trichloroethylene ; Epichlorohydrin ; 1,2-Epoxybutane ; Carcinogencity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous analytical studies of industrial samples of trichloroethylene (TRI) have revealed the presence of mutageneic and carcinogenic epoxides which, it was proposed, might be responsible for the carcinogenicity of such samples, as demonstrated with mice in other laboratories. To test this hypothesis, Swiss mice (ICR/HA) of both sexes, bred and kept in SPF conditions, were dosed daily with TRI in corn oil by gavage (males: 2.4 g/kg, females: 1.8 g/kg) with or without the addition of epichlorohydrin (EPC, 0.8%, w/w), 1,2-epoxybutane (BO, 0,8%), or EPC+BO (0.25%+0,25%) for 18 months. The ensuing observation period terminated at 106 weeks (from start of experiment). Gross and microscopic examination of all organs revealed a statistically significant increase in the incidence of forestomach papillomas and carcinomas after EPC-, BO-, and (EPC+BO)-stabilized samples of TRI, but not after pure, amine base-stabilized TRI. This type of tumor is believed to be induced by the direct alkylating epoxides epichlorohydrin and epoxybutane, whose industrial use in stabilizing chlorinated aliphatic hydrocarbons should be discontinued. No other significant increase in tumor incidences was found. Again, this study does not support the suggestion that trichloroethylene itself is carcinogenic under realistic exposure conditions.
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  • 10
    ISSN: 1432-0878
    Keywords: Pancreas, exocrine ; Acinar cells ; Proliferation ; Proliferating cell nuclear antigen (PCNA) ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The monoclonal antibody PC10 raised against the proliferating cell nuclear antigen (PCNA) was used to study acinar cell replication in the pancreas of rats under different functional conditions. In Western blots, the antibody recognized a single band of 37 kDa in pancreatic homogenates indicating its specificity in this particular species and organ. Three conditions of growth were chosen for immunohistochemical analysis: pancreatic preand postnatal development, pancreatic regeneration after injury, and cholecystokinin-stimulated acinar cell proliferation. The time course of acinar cell replication under each condition was the same as that obtained after tritiated thymidine incorporation with subsequent autoradiography, indicating that the percentage of PCNA-positive cells reflects the pool of cycling cells in the models investigated. However, the absolute number of PCNA-positive cells was two to ten times higher than comparable labeling indices from 3H-thymidine autoradiography. This finding might reflect the half life of PCNA, which exceeds the duration of the S-phase. Thus, PCNA-positive cells not only represent S-phase cells, but also cells that have recently completed the cell cycle.
    Type of Medium: Electronic Resource
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