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- Ekman-Ordeberg, G, et al.
(författare)
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Low molecular weight heparin stimulates myometrial contractility and cervical remodeling in vitro
- 2009
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Ingår i: Acta Obstet Gynecol Scand. - : Wiley. ; 88:9, s. 984-989
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The low molecular weight heparin, Dalteparin, shortens human labor time. The aim of this study was to investigate if the mechanism behind this effect involves myometrial contractility and cervical ripening and if the anticoagulative activity is necessary for its effect. DESIGN: Experimental in vitro study. SETTING: Lund University and Karolinska Institute, Sweden. METHODS: The effect of low molecular weight heparins with or without anticoagulative properties on myometrial contractility was measured in vitro on smooth muscle strips from biopsies obtained at elective cesarean sections. The effects on cervical ripening were assessed in cervical fibroblasts cultured from explants of cervical biopsies obtained at delivery. MAIN OUTCOME MEASURES: Mean force and number of contractions in uterine smooth muscle strips and interleukin-8 (IL-8) secretion in cervical fibroblasts. RESULTS: Myometrial smooth muscle strips pretreated with low molecular weight heparins showed increased contractile activity compared to untreated smooth muscle strips. Secretion of IL-8 from cultured cervical fibroblasts was significantly increased after treatment with low molecular weight heparin. Both these effects were independent of anticoagulative activity of the low molecular weight heparin. CONCLUSIONS: A possible underlying mechanism for the shortened labor time after low molecular weight heparin treatment is enhanced myometrial contractility and an increased IL-8 secretion in cervical fibroblast, mimicking the final cervical ripening in vivo. Our data support the notion that anticoagulant activity is not required to promote labor.
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- Hajjar, Adeline M, et al.
(författare)
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Lack of in vitro and in vivo recognition of Francisella tularensis subspecies lipopolysaccharide by Toll-like receptors.
- 2006
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 74:12, s. 6730-8
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Tidskriftsartikel (refereegranskat)abstract
- Francisella tularensis is an intracellular gram-negative bacterium that is highly infectious and potentially lethal. Several subspecies exist of varying pathogenicity. Infection by only a few organisms is sufficient to cause disease depending on the model system. Lipopolysaccharide (LPS) of gram-negative bacteria is generally recognized by Toll-like receptor 4 (TLR4)/MD-2 and induces a strong proinflammatory response. Examination of human clinical F. tularensis isolates revealed that human virulent type A and type B strains produced lipid A of similar structure to the nonhuman model pathogen of mice, Francisella novicida. F. novicida LPS or lipid A is neither stimulatory nor an antagonist for human and murine cells through TLR4 or TLR2. It does not appear to interact with TLR4 or MD-2, as it is not an antagonist to other stimulatory LPS. Consistent with these observations, aerosolization of F. novicida LPS or whole bacteria induced no inflammatory response in mice. These results suggest that poor innate recognition of F. tularensis allows the bacterium to evade early recognition by the host innate immune system to promote its pathogenesis for mammals.
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- Pettersson, B. M. Fredrik, 1974-
(författare)
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tRNA Gene Structures in Bacteria
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In bacteria, tRNA molecules are produced as precursors with additional nucleotides both upstream and downstream of the tRNA coding sequence. To generate a mature tRNA, the endoribonuclease RNase P removes the upstream sequence, while a number of enzymes can remove the downstream sequence. In this thesis, the influence of such upstream and downstream sequences on the expression of mature functional tRNA was studied. It was found that in Escherichia coli, the presence of an upstream sequence positively influences tRNA expression. Furthermore, it was shown that the identity of the nucleotide immediatedly 5' of the canonical RNase P cleavage site in a tRNA precursor influenced RNase P cleavage site selection in vivo in E. coli, but not in Pseudomonas aeruginosa. Additionally, a stem-loop in the precursor just downstream of the tRNA increased this "miscleavage". This stem-loop resembled a rho-independent transcription terminator and overlapped the trpT gene in P. aeruginosa, but it only marginally influenced the expression of the downstream secE gene. The trpT and secE genes were found to be cotranscribed. The trpT-secE gene order was also conserved in the majority of bacteria investigated. The expression of tRNA genes during development in Streptomyces coelicolor was also studied. Here, the expression of most tRNA genes tested increased with time during development. Similarly, the expression of the RNase P RNA increased. The relative increase was quantified and correlated with different criteria related to gene structure and gene organisation, but no significant differences could be found. Moreover, a tRNALeuCAA UUA codon suppressor as well as the cognate bldA tRNA could restore differentiation to a developmentally blocked bldA deletion strain. For both tRNAs, the efficiency of restoration depended on the 5'- and 3'-flanks. In conclusion, both 5'- and 3'-flanking sequences influence tRNA expression, and bacteria respond differently to changes in their tRNA gene structures.
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