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排序方式: 共有113条查询结果,搜索用时 15 毫秒
61.
62.
Fiona E Yull Wei Han E Duco Jansen M Brett Everhart Ruxana T Sadikot John W Christman Timothy S Blackwell 《The journal of histochemistry and cytochemistry》2003,51(6):741-749
We investigated the effects of Gram-negative bacterial lipopolysaccharide (LPS) on luciferase expression in transgenic reporter mice in which luciferase expression is driven by the nuclear factor kappaB (NF-kappaB)-dependent portion of the human immunodeficiency virus-1 (HIV-1) long terminal repeat (HIV-1 LTR). Using these mice, we dissected the sources of luciferase activity at the organ level by (a) assessing luciferase activity in organ homogenates, (b) bioluminescence imaging in vivo, and (c) bioluminescence imaging of individual organs ex vivo. Luciferin dosage was a critical determinant of the magnitude of photon emission from these reporter mice. Photon emission increased at doses from 0.5-6 mg of luciferin given by intraperitoneal (IP) injection. The differential between basal and LPS-induced bioluminescence was maximal at 3-6 mg of luciferin. Luciferase expression was highly inducible in lungs, liver, spleen, and kidneys after a single IP injection of LPS, as assessed by luciferase activity measurements in organ homogenates. Luciferase activity was also induced in the forebrain by treatment with IP LPS. In contrast, aerosolized LPS produced a response localized to the lungs as assessed by both bioluminescence and ex vivo luciferase assay measurements. These studies demonstrate the utility of luciferase reporter mice for determining organ-specific gene expression in response to local and systemic stimuli. 相似文献
63.
64.
JS Agerholm O Andersen MB Almskou C Bendixen J Arnbjerg GP Aamand US Nielsen F Panitz AH Petersen 《Acta veterinaria Scandinavica》2004,45(3):133
To investigate the congenital complex vertebral malformation syndrome (CVM) in Holstein calves, two breeding studies were
performed including 262 and 363 cows, respectively. Cows were selected from the Danish Cattle Database based on pedigree and
insemination records. Selected cows were progeny of sires with an established heterozygous CVM genotype and pregnant after
insemination with semen from another sire with heterozygous CVM genotype. Following calving the breeders should state, if
the calf was normal and was requested to submit dead calves for necropsy. In both studies, significantly fewer CVM affected
calves than expected were obtained; a finding probably reflecting extensive intrauterine mortality in CVM affected foetuses.
The findings illustrate increased intrauterine mortality as a major potential bias in observational studies of inherited disorders. 相似文献
65.
Sadikot RT Han W Everhart MB Zoia O Peebles RS Jansen ED Yull FE Christman JW Blackwell TS 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(2):1091-1098
To determine whether NF-kappaB activation is sufficient to generate lung inflammation in vivo, we selectively expressed a constitutively active form of IkappaB kinase 1 (cIKK1) or IkappaB kinase 2 (cIKK2) in airway epithelium. After intratracheal administration of adenoviral vectors expressing cIKK1 or cIKK2 to transgenic reporter mice that express Photinus luciferase under the control of an NF-kappaB-dependent promoter, we detected significantly increased luciferase activity over time (up to 96 h). Compared with control mice treated with adenoviral vectors expressing beta-galactosidase, lung bioluminescence and tissue luciferase activity were increased in NF-kappaB reporter mice treated with adenovirus (Ad)-cIKK1 or Ad-cIKK2. NF-kappaB activation in lungs of Ad-cIKK1- and Ad-cIKK2-treated mice was confirmed by immunoblots for RelA and EMSA from lung nuclear protein extracts. Mice treated with Ad-cIKK1 or Ad-cIKK2 showed induction of mRNA expression of several chemokines and cytokines in lung tissue. In lung lavage fluid, mice treated with Ad-cIKK1 or Ad-cIKK2 showed elevated concentrations of NF-kappaB-dependent chemokines macrophage-inflammatory protein 2 and KC and increased numbers of neutrophils. Coadministration of adenoviral vectors expressing a transdominant inhibitor of NF-kappaB with Ad-cIKK1 or Ad-cIKK2 resulted in abrogated NF-kappaB activation and other parameters of lung inflammation, demonstrating that the observed inflammatory effects of Ad-cIKK1 and Ad-cIKK2 were dependent on NF-kappaB activation by these kinases. These data show that selective expression of IkappaB kinases in airway epithelium results in NF-kappaB activation, inflammatory mediator production, and neutrophilic lung inflammation. Therapies targeted to NF-kappaB in lung epithelium may be beneficial in treating inflammatory lung diseases. 相似文献
66.
Elevated ammonium concentrations in the medium of cultivated cells have
been shown to increase the intracellular levels of uridine-5'-diphospho-
N-acetylglucosamine (UDP-GlcNAc) and uridine-5'-diphospho-N-
acetylgalactosamine (UDP-GalNAc; Ryll et al., 1994). These sugar
nucleotides are substrates for glycosyltransferases in the glycosylation
pathway. In our experiments, recombinant Chinese hamster ovary cells
producing an immunoadhesin glycoprotein (GP1-IgG) have been cultivated
under controlled cell culture conditions in the presence of different
ammonium concentrations.15N-Labeled ammonium chloride (15NH4Cl) was added
exogenously to the cell culture media to determine if ammonium was
incorporated into UDP-GlcNAc and cytidine-5'-
monophospho-N-acetylneuraminic acid (CMP-NANA) pools, and subsequently
incorporated into GP1-IgG as N-linked glycans. The intracellular pools of
UDP-activated hexosamines (UDP-GNAc) were followed during the time course
of the experiment. To assess the extent of15NH4+incorporation into the
glycans of GP1-IgG, the glycoprotein was first purified to homogeneity by
protein A chromatography. Enzymatically released N- glycans were then
analyzed by matrix-assisted laser desorption/ionization time-of-flight mass
spectrometry. N-Glycans synthesized in the presence of15NH4Cl revealed an
N-glycan-dependent increase in mass-to-charge of 2.5-4.8 Da. These results
indicate that 60-70% of the total nitrogen containing monosaccharides had
incorporated15N. Presumably,15NH4+was incorporated into GlcNAc and N-
acetylneuraminic acid as proposed earlier (Ryll et al., 1994). This might
be a universal and previously not described reaction in mammalian cells
when exposed to nonphysiological but in cell culture commonly found
concentrations of ammonium. The data presented here are of significance for
glycoprotein production in mammalian cell culture, since it has been shown
previously that elevated levels of UDP- activated hexosamines affect
N-glycan characteristics such as branching and degree of amino sugar
incorporation. In addition, our results demonstrate that isotope labeling
in combination with MALDI-TOF-MS can be used as an alternate tool to
radioactive labeling of sugar substrates in metabolic studies.
相似文献
67.
CYCLIC CHANGES IN THE CELL SURFACE : I. Change in Thymidine Transport and Its Inhibition by Cytochalasin B in Chinese Hamster Ovary Cells 总被引:2,自引:3,他引:2
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Cytochalasin B (CB) shows a marked concentration-dependent inhibition of the incorporation of [3H]thymidine into Chinese hamster ovary cells. This inhibition was shown to result from an inhibition of thymidine uptake, not from an inhibition of DNA synthesis. Cells normally acquire the capacity to transport thymidine as they move from the G1 stage of the cell cycle into the S phase. If CB is added to cells while they are in G1, they do not acquire the ability to transport thymidine as they enter S. However, the addition of CB to cells that are already in S has no effect on their ability to transport thymidine. These results are discussed in terms of a model in which elements involved in thymidine transport enter the cell surface membrane as the cells move from G1 to S. It is proposed that CB prevents this structural transition by binding to the cell surface. 相似文献
68.
This study examined the application of previously characterized microparticles composed of hyaluronan (HA) and chitosan hydroglutamate (CH) as well as novel microparticles consisting of both polymers (HA/CH) to improve the nasal delivery of a model drug. The rabbit bioavailabilities of gentamicin incorporated in HA, CH, and HA/CH microparticles were increased 23-, 31-, and 42-fold, respectively, compared with the control intranasal solution of gentamicin, indicating that all test microparticles were retained for longer periods on the nasal mucosa of the rabbits as supported by previous in vitro dissolution as well as frog palate mucoadhesion studies, thereby improving drug absorption. The higher bioavailabilities of CH-based formulations (CH and HA/CH) suggest the penetration-enhancing effects of CH may also be partially responsible for the improvement. A model was developed, based on a glass impinger device, to deliver dry powder formulations reproducibly onto the surface of cultured cell monolayers. In vitro permeability and fluorescence microscopy studies on the tight junctions of the 16HBE14o- cell lines further confirmed the ability of CH-based formulations to enhance penetration. Furthermore, the in vitro absorption profile from cell culture studies was consistent with those determined from in vivo studies. The complementary effect from the mucoadhesive nature of HA coupled with the penetration-enhancing effects of CH makes the novel HA/CH formulation a promising nasal delivery system. 相似文献
69.
Background
Helicobacter pylori colonizes the human stomach and is associated with gastritis, peptic ulcer, and gastric cancer. This ubiquitous association between H. pylori and humans is thought to be present since the origin of modern humans. The H. pylori genome encodes for an exceptional number of restriction and modifications (R-M) systems. To evaluate if R-M systems are an adequate tool to determine the geographic distribution of H. pylori strains, we typed 221 strains from Africa, America, Asia, and Europe, and evaluated the expression of different 29 methyltransferases. 相似文献70.
Madlen Stange Alfredo Mari Tim Roloff Helena MB Seth-Smith Michael Schweitzer Myrta Brunner Karoline Leuzinger Kirstine K. Sgaard Alexander Gensch Sarah Tschudin-Sutter Simon Fuchs Julia Bielicki Hans Pargger Martin Siegemund Christian H. Nickel Roland Bingisser Michael Osthoff Stefano Bassetti Rita Schneider-Sliwa Manuel Battegay Hans H. Hirsch Adrian Egli 《PLoS pathogens》2021,17(3)
The first case of SARS-CoV-2 in Basel, Switzerland was detected on February 26th 2020. We present a phylogenetic study to explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26th until March 23rd. We sequenced SARS-CoV-2 naso-oropharyngeal swabs from 746 positive tests that were performed at the University Hospital Basel during the study period. We successfully generated 468 high quality genomes from unique patients and called variants with our COVID-19 Pipeline (COVGAP), and analysed viral genetic diversity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny. Epidemiological data from patient questionnaires was used to facilitate the interpretation of phylogenetic observations. The early outbreak in Basel was dominated by lineage B.1 (83·6%), detected first on March 2nd, although the first sample identified belonged to B.1.1. Within B.1, 68·2% of our samples fall within a clade defined by the SNP C15324T (‘Basel cluster’), including 157 identical sequences at the root of the ‘Basel cluster’, some of which we can specifically trace to regional spreading events. We infer the origin of B.1-C15324T to mid-February in our tri-national region. The other genomes map broadly over the global phylogenetic tree, showing several introduction events from and/or dissemination to other regions of the world via travellers. Family transmissions can also be traced in our data. A single lineage variant dominated the outbreak in the Basel area while other lineages, such as the first (B.1.1), did not propagate. A mass gathering event was the predominant initial source of cases, with travel returners and family transmissions to a lesser extent. We highlight the importance of adding specific questions to epidemiological questionnaires, to obtain data on attendance of large gatherings and their locations, as well as travel history, to effectively identify routes of transmissions in up-coming outbreaks. This phylogenetic analysis in concert with epidemiological and contact tracing data, allows connection and interpretation of events, and can inform public health interventions.Trial Registration: ClinicalTrials.gov . NCT04351503相似文献