| 1. |
- Benktander, John, et al.
(författare)
-
The Repertoire of Glycosphingolipids Recognized by Vibrio cholerae
- 2013
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- The binding of cholera toxin to the ganglioside GM1 as the initial step in the process leading to diarrhea is nowadays textbook knowledge. In contrast, the knowledge about the mechanisms for attachment of Vibrio cholerae bacterial cells to the intestinal epithelium is limited. In order to clarify this issue, a large number of glycosphingolipid mixtures were screened for binding of El Tor V. cholerae. Several specific interactions with minor complex non-acid glycosphingolipids were thereby detected. After isolation of binding-active glycosphingolipids, characterization by mass spectrometry and proton NMR, and comparative binding studies, three distinct glycosphingolipid binding patterns were defined. Firstly, V. cholerae bound to complex lacto/neolacto glycosphingolipids with the GlcNAcβ3Galβ4GlcNAc sequence as the minimal binding epitope. Secondly, glycosphingolipids with a terminal Galα3Galα3Gal moiety were recognized, and the third specificity was the binding to lactosylceramide and related compounds. V. cholerae binding to lacto/neolacto glycosphingolipids, and to the other classes of binding-active compounds, remained after deletion of the chitin binding protein GbpA. Thus, the binding of V. cholerae to chitin and to lacto/neolacto containing glycosphingolipids represents two separate binding specificities.
|
|
| 2. |
- Bergstrand, Sara, et al.
(författare)
-
Existence of Tissue Blood Flow in Response to External Pressure in the Sacral Region of Elderly Individuals - Using an Optical Probe Prototype
- 2010
-
Ingår i: MICROCIRCULATION. - : Taylor and Francis. - 1073-9688 .- 1549-8719. ; 17:4, s. 311-319
-
Tidskriftsartikel (refereegranskat)abstract
- Pandgt;Objective: The aim was to investigate the existence of sacral tissue blood flow at different depths in response to external pressure and compression in elderly individuals using a newly developed optical probe prototype. Methods: The tissue blood flow and tissue thickness in the sacral area were measured during load in 17 individuals using laser Doppler flowmetry and photoplethysmography in a combined probe, and digital ultrasound. Results: The mean age was 68.6 +/- 7.0 years. While loading, the mean compression was 60.3 +/- 11.9%. The number of participants with existing blood flow while loading increased with increased measurement depth. None had enclosed blood flow deep in the tissue and at the same time an existing more superficial blood flow. Correlation between tissue thickness and BMI in unloaded and loaded sacral tissue was shown: r = 0.68 (P = 0.003) and r = 0.68 (P = 0.003). Conclusions: Sacral tissue is highly compressed by external load. There seems to be a difference in responses to load in the different tissue layers, as occluded blood flow in deeper tissue layers do not occur unless the blood flow in the superficial tissue layers is occluded.
|
|
| 3. |
- Che, K. F., et al.
(författare)
-
Interleukin-26 in Antibacterial Host Defense of Human Lungs Effects on Neutrophil Mobilization
- 2014
-
Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 190:9, s. 1022-1031
-
Tidskriftsartikel (refereegranskat)abstract
- Rationale: The role of the presumed Th17 cytokine IL-26 in antibacterial host defense of the lungs is not known. Objectives: To characterize the role of IL-26 in antibacterial host defense of human lungs. Methods: Intrabronchial exposure of healthy volunteers to endotoxin and vehicle was performed during bronchoscopy and bronchoalveolar lavage (BAL) samples were harvested. Intracellular IL-26 was detected using immunocytochemistry and immunocytofluorescence. This IL-26 was also detected using flow cytometry, as was its receptor complex. Cytoldnes and phosphorylated signal transducer and activator of transcription (STAT) 1 plus STAT3 were quantified using ELISA. Gene expression was analyzed by real-time polymerase chain reaction and neutrophil migration was assessed in vitro. Measurements and Main Results: Extracellular IL-26 was detected in BAL samples without prior exposure in vivo and was markedly increased after endotoxin exposure. Alveolar macrophages displayed gene expression for, contained, and released IL-26. Th and cytotoxic T cells also contained IL-26. In the BAL samples, IL-26 concentrations and innate effector cells displayed a correlation. Recombinant IL-26 potentiated neutrophil chemotaxis induced by IL-8 and fMLP but decreased chemokinesis for neutrophils. Myeloperoxidase in conditioned media from neutrophils was decreased. The IL-26 receptor complex was detected in neutrophils and IL-26 decreased phosphorylated STAT3 in these cells. In BAL and bronchial epithelial cells, IL-26 increased gene expression of the IL-26 receptor complex and STAT1 plus STAT3. Finally, IL-26 increased the release of neutrophil-mobilizing cytokines in BAL but not in epithelial cells. Conclusions: This study implies that alveolar macrophages produce IL-26, which stimulates receptors on neutrophils and focuses their mobilization toward bacteria and accumulated immune cells in human lungs.
|
|
| 4. |
- Dahlhoff, Maik, et al.
(författare)
-
A new mouse model for studying EGFR-dependent gastric polyps.
- 2012
-
Ingår i: Biochimica et biophysica acta. - : Elsevier BV. - 0006-3002. ; 1822:8, s. 1293-1299
-
Tidskriftsartikel (refereegranskat)abstract
- Hyperactivation of the epidermal growth factor receptor (EGFR) in gastric cells due to excess of its ligand transforming growth factor-α (TGFA) is associated with hyperplastic lesions in Ménétrier's disease patients and in transgenic mice. Other EGFR ligands, however, have never been associated with stomach diseases. Here, we report that overexpression of the EGFR ligand betacellulin (BTC) results in a severe, age-dependent hyperplasia of foveolar epithelium. The stomach weight of affected mice reached up to 3g representing more than 10% of total body weight. The preexisting corpus mucosa was severely depleted, and both parietal and chief cells were replaced by proliferating foveolar epithelium. The lesions were more severe in male as compared to female transgenic mice, and partially regressed in the former after castration-mediated androgen removal. The gastric hyperplasia fully disappeared when BTC-tg mice were crossed into the Egfr(Wa5) background expressing a dominant-negative EGFR, indicating that the phenotype is EGFR-dependent. This is, to our knowledge, the first report of hyperplastic gastric lesions due to the overexpression of an EGFR ligand other than TGFA. BTC-tg mice are therefore a new, promising model for studying EGFR-dependent gastric polyps.
|
|
| 5. |
- Gustafsson, Jenny K, 1981, et al.
(författare)
-
Dynamic changes in mucus thickness and ion secretion during Citrobacter rodentium infection and clearance.
- 2013
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
-
Tidskriftsartikel (refereegranskat)abstract
- Citrobacter rodentium is an attaching and effacing pathogen used as a murine model for enteropathogenic Escherichia coli. The mucus layers are a complex matrix of molecules, and mucus swelling, hydration and permeability are affected by many factors, including ion composition. Here, we used the C. rodentium model to investigate mucus dynamics during infection. By measuring the mucus layer thickness in tissue explants during infection, we demonstrated that the thickness changes dynamically during the course of infection and that its thickest stage coincides with the start of a decrease of bacterial density at day 14 after infection. Although quantitative PCR analysis demonstrated that mucin mRNA increases during early infection, the increased mucus layer thickness late in infection was not explained by increased mRNA levels. Proteomic analysis of mucus did not demonstrate the appearance of additional mucins, but revealed an increased number of proteins involved in defense responses. Ussing chamber-based electrical measurements demonstrated that ion secretion was dynamically altered during the infection phases. Furthermore, the bicarbonate ion channel Bestrophin-2 mRNA nominally increased, whereas the Cftr mRNA decreased during the late infection clearance phase. Microscopy of Muc2 immunostained tissues suggested that the inner striated mucus layer present in the healthy colon was scarce during the time point of most severe infection (10 days post infection), but then expanded, albeit with a less structured appearance, during the expulsion phase. Together with previously published literature, the data implies a model for clearance where a change in secretion allows reformation of the mucus layer, displacing the pathogen to the outer mucus layer, where it is then outcompeted by the returning commensal flora. In conclusion, mucus and ion secretion are dynamically altered during the C. rodentium infection cycle.
|
|
| 6. |
- Hagblad, Jimmie, et al.
(författare)
-
A technique based on laser Doppler flowmetry and photoplethysmography for simultaneously monitoring blood flow at different tissue depths
- 2010
-
Ingår i: Medical and Biological Engineering and Computing. - : Springer Science Business Media. - 0140-0118 .- 1741-0444. ; 48:5, s. 415-422
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to validate a non-invasive optical probe for simultaneous blood flow measurement at different vascular depths combining three photoplethysmography (PPG) channels and laser Doppler flowmeter (LDF). Wavelengths of the PPG were near-infrared 810 nm with source-to-detector separation of 10 and 25 mm, and green 560 nm with source-to-detector separation of 4 mm. The probe is intended for clinical studies of pressure ulcer aetiology. The probe was placed over the trapezius muscle, and depths from the skin to the trapezius muscle were measured using ultrasound and varied between 3.8 and 23 mm in the 11 subjects included. A provocation procedure inducing a local enhancement of blood flow in the trapezius muscle was used. Blood flows at rest and post-exercise were compared. It can be concluded that this probe is useful as a tool for discriminating between blood flows at different vascular tissue depths. The vascular depths reached for the different channels in this study were at least 23 mm for the near-infrared PPG channel (source-to-detector separation 25 mm), 10-15 mm for the near-infrared PPG channel (separation 10 mm), and shallower than 4 mm for both the green PPG channel (separation 4 mm) and LDF.
|
|
| 7. |
- Hemdan, Tammer, et al.
(författare)
-
The prognostic value and therapeutic target role of stathmin-1 in urinary bladder cancer
- 2014
-
Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 111:6, s. 1180-1187
-
Tidskriftsartikel (refereegranskat)abstract
- Background:The oncoprotein-18/stathmin 1 (STMN1), involved in cell progression and migration, is associated with clinical outcome in breast cancer. Here we aim to investigate its clinical significance in urinary bladder cancer and its possibilities as a therapeutic target.Methods:Immunohistochemical analyses of STMN1 protein expression were performed in three patient cohorts: cohort I (n=115 Ta, n=115 T1, n=112 T2-4 stages), cohort II, based on randomised controlled trials (n=239 T1-T4), and cohort III of primary tumour/matched metastasis (n=90 T1-T4). The effects of STMN1 on cell proliferation and migration were evaluated in the urinary bladder cancer cell line, T24, by inhibiting STMN1-cellular expression using siRNA.Results:In cohort I, high STMN1 expression correlated to shorter disease-specific survival hazard ratio (HR)=2.04 (95% confidence interval (CI) 1.13-3.68; P=0.02), elevated p53- (P<0.001) and Ki67-protein levels (P<0.001). The survival result was validated in cohort II: HR=1.76 (95% CI 1.04-2.99; P=0.03). In the metastatic bladder cancer material, 70% of the patients were STMN1-positive in both the primary tumour and matched metastases. In vitro, the growth and migration of the T24 cells were significantly reduced (P<0.01, P<0.0001, respectively), when transfecting the cells with STMN1-siRNA.Conclusions:STMN1 protein expression has prognostic significance but is primarily a potential treatment target in urinary bladder cancer.
|
|
| 8. |
- Kenny, Diarmuid T., et al.
(författare)
-
Presence of terminal N-acetylgalactosamineβ1-4N-acetylglucosamine residues on O-linked oligosaccharides from gastric MUC5AC: involvement in Helicobacter pylori colonization?
- 2012
-
Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 22:8, s. 1077-85
-
Tidskriftsartikel (refereegranskat)abstract
- Isolation of MUC5AC mucins from the gastric mucosa from two secretor individuals (one from normal mucosa from a patient with gastric cancer and one from a control) showed different abilities to bind and induce the proliferation of the Helicobacter pylori strain J99. Analysis of the released O-linked oligosaccharides by LC-MS from these individuals showed a very heterogeneous mixture of species from the cancer patient containing both neutral and sialylated structures, whereas the normal sample showed dominating neutral blood group H terminating structures as well as neutral structures containing the di-N-acetyllactosamine (lacdiNAc) unit GalNAcβ1-4GlcNAcβ1- on the C-6 branch of the reducing end GalNAc. The linkage configuration of these epitopes were determined using C-4-specific fragmentation for the GalNAcβ1-4GlcNAcβ1- glycosidic linkage, comparison of the MS(3) fragmentation with standards for linkage configuration and N-acetylhexosamine type as well as exoglycosidase treatment. It was also shown that the lacdiNAc epitope is present in both human and porcine gastric mucins, indicating that this is an epitope preserved between species. We hypothesize that the termination on gastric MUC5AC with lacdiNAc is in competition with complex glycosylation such as the Le(b) and H type 1 as well as complex sialylated structures. These are epitopes known to bind the H. pylori BabA and SabA adhesins.
|
|
| 9. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 10. |
- Legrand, Sara-Ann, et al.
(författare)
-
Prevalence of alcohol, illicit drugs and psychoactive medicines in killed drivers in four European countries
- 2013
-
Ingår i: International Journal of Injury Control and Safety Promotion. - : Taylor & Francis. - 1745-7300 .- 1745-7319. ; 21:1, s. 17-28
-
Tidskriftsartikel (refereegranskat)abstract
- Our objective was to determine the presence of psychoactive substances in blood of drivers killed in road crashes in four European countries. Data from 1118 drivers of car and vans, killed between 2006 and 2009, were collected in Finland, Norway, Portugal and Sweden. The prevalence of any psychoactive substance ranged between 31 and 48%.Alcohol (>= 0.1 g/L) was the most common finding, 87% had a blood alcohol concentration (BAC)>=.5 g/L. Benzodiazepines (1.8-13.3%) and amphetamines (0-7.4%) were the most prevalent psychoactive medicines and illicit drugs, respectively. Alcohol-drug and drug-drug combinations were rather prevalent. Differences in alcohol/drug findings seemed to reflect differences in use in the countries. More research should be done to develop preventive strategies to reduce the number of alcohol- and drug-related traffic accidents targeting at-risk groups, such as drivers with very high BACs and novice drivers.
|
|
