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991.
Graffe CC Bech JN Pedersen EB 《American journal of physiology. Renal physiology》2012,302(2):F264-F275
The degree of water transport via aquaporin-2 (AQP2) water channels in renal collecting duct principal cells is reflected by the level of the urinary excretion of AQP2 (u-AQP2). In rats, the AQP2 expression varies with sodium intake. In humans, the effect of sodium intake on u-AQP2 and the underlying mechanisms have not previously been studied. We measured the effect of 4 days of high sodium (HS) intake (300 mmol sodium/day; 17.5 g salt/day) and 4 days of low sodium (LS) intake (30 mmol sodium/day; 1.8 g salt/day) on u-AQP2, fractional sodium excretion (FE(Na)), free water clearance (C(H2O)), urinary excretion of PGE(2) (u-PGE(2)) and cAMP (u-cAMP), and plasma concentrations of vasopressin (AVP), renin (PRC), ANG II, aldosterone (Aldo), atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) in a randomized, crossover study of 21 healthy subjects, during 24-h urine collection and after hypertonic saline infusion. The 24-h urinary sodium excretion was significantly higher during HS intake (213 vs. 41 mmol/24 h). ANP and BNP were significantly lower and PRC, ANG II, and Aldo were significantly higher during LS intake. AVP, u-cAMP, and u-PGE(2) were similar during HS and LS intake, but u-AQP2 was significantly higher during HS intake. The increases in AVP and u-AQP2 in response to hypertonic saline infusion were similar during HS and LS intake. In conclusion, u-AQP2 was increased during HS intake, indicating that water transport via AQP2 was increased. The effect was mediated by an unknown AVP-independent mechanism. 相似文献
992.
BackgroundIncreasing incidences of malignant small bowel tumours have been reported, but data from European populations are limited. This study aimed to clarify the incidence patterns of malignant small bowel tumours in Sweden.MethodsPatients with a first and primary malignant small bowel tumour were identified from the Swedish Cancer Register during the study period 1960–2009. Sex-specific and age-standardised incidence rates of these tumours were calculated by their anatomical location and histological type in different time periods. Figures were plotted to show the proportions and incidence rates over time, and joinpoint loglinear regression models were estimated to assess any time trends.ResultsA total of 6604 patients with malignant small bowel tumours were identified. The age-standardised incidence of all malignant small bowel tumours increased from 14.2 to 19.7 per 1,000,000 person-years during the study period. The incidence of duodenal cancer increased more than 3-fold (from 1.6 to 5.4 per 1,000,000 person-years), which was mainly expained by a dramatical rising trend of adenocarcinoma of the duodenum (from 0.7 to 4.2 per 1,000,000 person-years). Malignant tumours of small bowel with unspecified anatomical locations showed a slight increase (from 7.0 to 7.9 per 1,000,000). The incidence of small bowel tumours in other locations or of other histological types was more stable.ConclusionsThe incidence of small bowel malignancies has increased during the period 1960–2009. Among the specific types of small bowel cancer, a particularly rapid increase was found for duodenal adenocarcinoma. 相似文献
993.
E Nobili MD Salvado L Folkersen L Castiglioni J Kastrup A Wetterholm E Tremoli GK Hansson L Sironi JZ Haeggström A Gabrielsen 《PloS one》2012,7(7):e41786
Background
Cysteinyl-leukotrienes (cys-LT) are powerful spasmogenic and immune modulating lipid mediators involved in inflammatory diseases, in particular asthma. Here, we investigated whether cys-LT signaling, in the context of atherosclerotic heart disease, compromises the myocardial microcirculation and its response to hypoxic stress. To this end, we examined Apoe−/− mice fed a hypercholesterolemic diet and analysed the expression of key enzymes of the cys-LT pathway and their receptors (CysLT1/CysLT2) in normal and hypoxic myocardium as well as the potential contribution of cys-LT signaling to the acute myocardial response to hypoxia.Methods and principal findings
Myocardial biopsies from Apoe−/− mice demonstrated signs of chronic inflammation with fibrosis, increased apoptosis and expression of IL-6, as compared to biopsies from C57BL/6J control mice. In addition, we found increased leukotriene C4 synthase (LTC4S) and CysLT1 expression in the myocardium of Apoe−/− mice. Acute bouts of hypoxia further induced LTC4S expression, increased LTC4S enzyme activity and CysLT1 expression, and were associated with increased extension of hypoxic areas within the myocardium. Inhibition of cys-LT signaling by treatment with montelukast, a selective CysLT1 receptor antagonist, during acute bouts of hypoxic stress reduced myocardial hypoxic areas in Apoe−/− mice to levels equal to those observed under normoxic conditions. In human heart biopsies from 14 patients with chronic coronary artery disease mRNA expression levels of LTC4S and CysLT1 were increased in chronic ischemic compared to non-ischemic myocardium, constituting a molecular basis for increased cys-LT signaling.Conclusion
Our results suggest that CysLT1 antagonists may have protective effects on the hypoxic heart, and improve the oxygen supply to areas of myocardial ischemia, for instance during episodes of sleep apnea. 相似文献994.
Gene silencing by RNA interference (RNAi) can be achieved by the ectopic expression of tailored short hairpin RNAs (shRNAs) which after export to the cytoplasm are processed by Dicer and incorporated into the RNA induced silencing complex (RISC). Design rules for shRNAs have been the focus of several studies, but only a few reports have turned the attention to the sequence of the loop-region. In this work we selected high-functional and low-functional shRNA loops from retroviral hairpin-loop-libraries in an RNAi reporter assay. The procedure revealed a very significant and stem sequence-dependent effect of the loop on shRNA function and although neither strong consensus loop sequence nor structural motifs could be identified, a preferred loop sequence (5'-UGUGCUU-3') was found to support robust knock down with little stem sequence dependency. These findings will serve as a guide for designing shRNAs with improved knock down capacity. 相似文献
995.
Jesper S. Oeemig Carina Lynggaard Daniel H. Knudsen Frederik T. Hansen Kent D. N?rgaard Tanja Schneider Brian S. Vad Dorthe H. Sandvang Line A. Nielsen S?ren Neve Hans-Henrik Kristensen Hans-Georg Sahl Daniel E. Otzen Reinhard Wimmer 《The Journal of biological chemistry》2012,287(50):42361-42372
Antimicrobial peptides are a new class of antibiotics that are promising for pharmaceutical applications because they have retained efficacy throughout evolution. One class of antimicrobial peptides are the defensins, which have been found in different species. Here we describe a new fungal defensin, eurocin. Eurocin acts against a range of Gram-positive human pathogens but not against Gram-negative bacteria. Eurocin consists of 42 amino acids, forming a cysteine-stabilized α/β-fold. The thermal denaturation data point shows the disulfide bridges being responsible for the stability of the fold. Eurocin does not form pores in cell membranes at physiologically relevant concentrations; it does, however, lead to limited leakage of a fluorophore from small unilamellar vesicles. Eurocin interacts with detergent micelles, and it inhibits the synthesis of cell walls by binding equimolarly to the cell wall precursor lipid II. 相似文献
996.
Jensen MO Jensen H Honge JL Hans N Hasenkam JM Nielsen SL 《Journal of biomechanics》2012,45(5):908-912
BackgroundForce measurements on the mitral valve apparatus have been reported from in vivo and in vitro studies. Recent reparative techniques for ischemic mitral valve insufficiency call for papillary muscle relocation. This study describes a device to measure forces generated on traction sutures utilized for this purpose.MethodsThe transducer design was based on a modified caliper with strain gauges attached. Finite element computer simulation was employed to optimize the signal output. The system was designed to facilitate investigation of the effects of shortening GoreTex traction suture that was extended from near the fibrous trigones of the mitral valve through the papillary muscles. The suture was exteriorized out through the left ventricle in a porcine setup (n=11) and attached to the dedicated device for simultaneous papillary muscle relocation and traction suture force measurement.ResultsThe transducer demonstrated excellent signal strength, linearity, and durability. Peak force was seen at the onset of the systolic isovolumic contraction (p<0.001). Initial results indicated that this external approach can document force magnitudes comparable to previous internally measured forces in the mitral valve apparatus.ConclusionsIt has been proven feasible to measure forces in the mitral valve papillary muscle relocation sutures with an external device. The results from using this equipment will provide insight into the biomechanical requirements of relocation traction sutures and other devices utilized for papillary muscle relocation. 相似文献
997.
Hamming OJ Kang L Svensson A Karlsen JL Rahbek-Nielsen H Paludan SR Hjorth SA Bondensgaard K Hartmann R 《The Journal of biological chemistry》2012,287(12):9454-9460
IL-21 is a class I cytokine that exerts pleiotropic effects on both innate and adaptive immune responses. It signals through a heterodimeric receptor complex consisting of the IL-21 receptor (IL-21R) and the common γ-chain. A hallmark of the class I cytokine receptors is the class I cytokine receptor signature motif (WSXWS). The exact role of this motif has not been determined yet; however, it has been implicated in diverse functions, including ligand binding, receptor internalization, proper folding, and export, as well as signal transduction. Furthermore, the WXXW motif is known to be a consensus sequence for C-mannosylation. Here, we present the crystal structure of IL-21 bound to IL-21R and reveal that the WSXWS motif of IL-21R is C-mannosylated at the first tryptophan. We furthermore demonstrate that a sugar chain bridges the two fibronectin domains that constitute the extracellular domain of IL-21R and anchors at the WSXWS motif through an extensive hydrogen bonding network, including mannosylation. The glycan thus transforms the V-shaped receptor into an A-frame. This finding offers a novel structural explanation of the role of the class I cytokine signature motif. 相似文献
998.
Maja D. Kaspersen Peter B. Larsen Emil Kofod-Olsen Jens Fedder Jesper Bonde Per H?llsberg 《PloS one》2012,7(11)
An analysis of all known human herpesviruses has not previously been reported on sperm from normal donors. Using an array-based detection method, we determined the cross-sectional frequency of human herpesviruses in semen from 198 Danish sperm donors. Fifty-five of the donors had at least one ejaculate that was positive for one or more human herpesvirus. Of these 27.3% (n = 15) had a double herpesvirus infection. If corrected for the presence of multiple ejaculates from some donors, the adjusted frequency of herpesviruses in semen was 27.2% with HSV-1 in 0.4%; HSV-2 in 0.1%; EBV in 6.3%; HCMV in 2.7%; HHV-6A/B in 13.5%; HHV-7 in 4.2%, whereas none of the samples had detectable VZV or HHV-8. Subsequently, we examined longitudinally data on ejaculates from 11 herpesvirus-positive donors. Serial analyses revealed that a donor who tested positive for herpesvirus at one time point did not necessarily remain positive over time. For the most frequently found herpesvirus, HHV-6A/B, we examined its association with sperm. For HHV-6A/B PCR-positive semen samples, HHV-6A/B could be detected on the sperm by flow cytometry. Conversely, PCR-negative semen samples were negative by flow cytometry. HHV-6B was shown to associate with sperm within minutes in a concentration dependent manner. Confocal microscopy demonstrated that HHV-6B associated with the sperm head, but only to sperm with an intact acrosome. Taken together, our data suggest that HHV-6A/B could be transported to the uterus via binding to the sperm acrosome. Moreover, we find a 10 times higher frequency of HHV-7 in semen from healthy individuals than previously detected. Further research is required to determine the potential risk of using herpesvirus-positive donor semen. Longitudinally analyses of ejaculate series indicate that implementation of quarantine for a donor shown to shed a herpesvirus is not a tenable solution. 相似文献
999.
Christian Leukel Jesper Lundbye-Jensen Mark Schram Christensen Albert Gollhofer Jens Bo Nielsen Wolfgang Taube 《PloS one》2012,7(9)
Part of the sensory information is processed by our central nervous system without conscious perception. Subconscious processing has been shown to be capable of triggering motor reactions. In the present study, we asked the question whether visual information, which is not consciously perceived, could influence decision-making in a choice reaction task. Ten healthy subjects (28±5 years) executed two different experimental protocols. In the Motor reaction protocol, a visual target cue was shown on a computer screen. Depending on the displayed cue, subjects had to either complete a reaching movement (go-condition) or had to abort the movement (stop-condition). The cue was presented with different display durations (20–160 ms). In the second Verbalization protocol, subjects verbalized what they experienced on the screen. Again, the cue was presented with different display durations. This second protocol tested for conscious perception of the visual cue. The results of this study show that subjects achieved significantly more correct responses in the Motor reaction protocol than in the Verbalization protocol. This difference was only observed at the very short display durations of the visual cue. Since correct responses in the Verbalization protocol required conscious perception of the visual information, our findings imply that the subjects performed correct motor responses to visual cues, which they were not conscious about. It is therefore concluded that humans may reach decisions based on subconscious visual information in a choice reaction task. 相似文献
1000.