Functional specialization of gut CD103+ dendritic cells in the regulation of tissue-selective T cell homing

Gut-associated lymphoid tissue (GALT) dendritic cells (DCs) display a unique ability to generate CCR9+alpha4beta7+ gut-tropic CD8+ effector T cells. We demonstrate efficient induction of CCR9 and alpha4beta7 on CD8+ T cells in mesenteric lymph nodes (MLNs) after oral but not intraperitoneal (i.p.) antigen administration indicating differential targeting of DCs via the oral route. In vitro, lamina propria (LP)-derived DCs were more potent than MLN or Peyer's patch DCs in their ability to generate CCR9+alpha4beta7+ CD8+ T cells. The integrin alpha chain CD103 (alphaE) was expressed on almost all LP DCs, a subset of MLN DCs, but on few splenic DCs. CD103+ MLN DCs were reduced in number in CCR7-/- mice and, although CD8+ T cells proliferated in the MLNs of CCR7-/- mice after i.p. but not oral antigen administration, they failed to express CCR9 and had reduced levels of alpha4beta7. Strikingly, although CD103+ and CD103- MLN DCs were equally potent at inducing CD8+ T cell proliferation and IFN-gamma production, only CD103+ DCs were capable of generating gut-tropic CD8+ effector T cells in vitro. Collectively, these results demonstrate a unique function for LP-derived CD103+ MLN DCs in the generation of gut-tropic effector T cells.     

Effect of Increased Blood Oxygen Affinity on Work Performance of Rats

Influence of altered blood oxygen affinity on maximal performance ability was evaluated in trained rats exercising to exhaustion in a graded treadmill test. Modification of blood oxygen affinity was achieved both by 2,3-diphosphoglycerate depletion, accomplished by exposure of animals to CO(2) and by exchange transfusion with blood exposed to bisulfite or stored in acid citrate dextrose, and by carbamylation of hemoglobin, produced by exchange transfusion of blood incubated with potassium cyanate. A decrease in oxygen tension at half-saturation of hemoglobin (P(50)) from 36 to 23 mm Hg produced a decrease in resting central venous oxygen pressure of about 12 mm Hg. During exercise it caused an average decrease in work performance of about 10%, which was equivalent to that performance decrement caused by a decrease in hemoglobin concentration of approximately 10%. When superimposed on anemia, this change in blood oxygen affinity again caused a similar decrease in performance over and above that due to anemia alone. A marked rightward shift of the in vivo oxygen dissociation curve during severe exercise may have compensated for the reduced in vitro P(50).     

High Proportions of Proinflammatory Bacteria on the Colonic Mucosa in a Young Patient with Ulcerative Colitis as Revealed by Cloning and Sequencing of 16S rRNA Genes

The pathogenesis of ulcerative colitis (UC) remains unknown. It is thought to be due to an abnormal and uncontrolled immune response to normally occurring constituents of the intestine. Microbial agents appear to be involved in the pathogenesis and intestinal bacteria seem to be an important factor in the development and chronicity. The aim of this study was to investigate the colonic microbiota of a patient with UC. The colonic tissues were taken during surgery from a 12-year-old girl suffering from UC. The microbiota on the colonic samples was studied by cloning and sequencing of amplified 16S rRNA genes. Compared with healthy subjects, alteration of the dominant bacterial group was observed in the UC patient. We found a high incidence of Enterobacteriaceae, Bacteroides fragilis, and the single phylotype of the Faecalibacterium prausnitzii-like “Butyrate-producing bacterium” L2-6. Furthermore, there was a substantial presence of Pseudomonas aeruginosa in the present case of UC. The high proportion of adverse proinflammatory species is striking in the present case compared with more normal situations. Even if those bacteria are not the cause of the UC, they most probably enhance the symptoms of the disease.     

Effects of 17-day spaceflight on electrically evoked torque and cross-sectional area of the human triceps surae

The effects of spaceflight on triceps surae muscle torque and cross-sectional area (CSA) were investigated on four astronauts using electrically evoked contractions to by-pass neural control. Muscle twitch characteristics, ankle joint angle–twitch torque relation, frequency–torque relation, tetanic torque and fatigability were assessed before, during and after a 17-day Space Shuttle flight (STS-78). Muscle plus bone cross-sectional area (CSAm+b) was evaluated before and after the flight. Whereas no changes in muscle function were observed during the flight, marked alterations were found during the recovery period. Peak twitch (PTw) and tetanic torques at 50 Hz (PT₅₀) continued to fall up to the 8th recovery day (R+8) on which losses in PTw and PT₅₀ were 24.4% (P<0.01) and 22.0% (P<0.01), respectively. The decline in PTw was not joint-angle-specific. Post-flight, especially on R+8, torque decreased at all stimulation frequencies (1, 20, 30 and 50 Hz); however the shape of the frequency–torque curve, normalised for PT₅₀, was not modified. Similarly, no changes in twitch kinetics were observed. Post- flight, an 8% (P<0.01) reduction in CSAm+b was found on R+2. Normalisation of PT₅₀ values for CSAm+b showed a progressive loss in specific torque (PT₅₀/CSAm+b), which was maximal on R+2 (19.5%, P<0.05). Also, fatigability during 2-min intermittent stimulation at 20 Hz increased throughout recovery, reaching a nadir of 16.4% (P<0.01) on R+15. In conclusion, 17 days of spaceflight resulted in significant changes in muscle function during the recovery phase, but not in microgravity. The disproportionate loss of torque compared with that of muscle size suggests the presence of muscle damage due to reloading in 1 g.     

TNF-α receptor 1 deficiency reduces antigen-presenting capacity of Schwann cells and ameliorates experimental autoimmune neuritis in mice

Tumor necrosis factor-α (TNF-α) is a pleiotropic pro-inflammatory cytokine with potentially neurodestructive effects and plays a pivotal role in autoimmune demyelinating disease. To address the role of TNF-α in the pathogenesis of experimental autoimmune neuritis (EAN), the current study investigated the antigen-presenting capacity of Schwann cells (SCs) in EAN induced by P0 protein peptide 106–125 in TNF-α recepter 1 deficient (TNFR1^−/−) mice. The antigen-presenting capacity of SCs was assessed by the expression of MHC class II (MHCII), CD40, CD80 and CD86 molecules on activated SCs as well as by induction of T cell proliferation in co-cultures of P0 protein peptide 106–125 specific T cells with activated SCs. In addition, the expression of inducible nitric oxide synthase (iNOS) was measured in activated SCs by flow cytometry. TNFR1^−/− EAN mice developed significantly delayed and reduced clinical signs of EAN compared to wild type EAN mice. In parallel, the expression of MHCII, CD80 and iNOS on SCs were decreased in TNFR1^−/− mice compared to wild type mice. Likewise, proliferation of P0 protein peptide 106–125 specific T cells simulated by activated SCs of TNFR1^−/− EAN mice was lower than that of wild type EAN mice. Our data suggest that TNF-α may exert pro-inflammatory effects in EAN via TNFR1 by up-regulating the antigen-presenting function and iNOS production of SCs.     

Experiences of Kurdish war-wounded refugees in communication with Swedish authorities through interpreter

Objective

To study experiences of war-wounded Kurdish refugees with respect to cross-cultural communication through interpreters.

Method

Semi-structured interviews were conducted with ten men, aged 31–42. Content analysis was used for analysis and interpretation of data.

Result

War-wounded Kurdish refugees experienced a number of difficulties regarding communication through interpreters, mainly related to the insufficient language link to the Swedish authorities, particularly health care personnel. In many instances, interpreters were selected based on the immigrant's citizenship rather than mother tongue, leading to a more complex, tri-lingual interpretation situation. Differences in cultural background, fear, suspicion and lack of confidence in interpreters were addressed as other problems by the participants.

Conclusion

Interpreter competence and patient confidence in the interpreter are essential for an adequate cross-cultural health communication. Assignment of interpreters should be based on knowledge of the patient's/client's mother tongue, rather than citizenship, and the outcome is improved by a common ethnic and cultural background of interpreter and patient/client. Our study should be considered as a pilot study, and the results should be validated in larger cohorts as well as in other ethnic and language groups.

Practice implications

In order to minimize communication misunderstandings, complicated tri-lingual interpretation situations should be avoided. Interpreters should ideally be assigned according to patient's/client's mother tongue rather than citizenship. Interpreters’ competence and patient's/client's confidence in interpreter may have significant impact on communication outcome.     

P-selectin glycoprotein ligand-1-mediated leukocyte recruitment regulates hepatocellular damage in acute obstructive cholestasis in mice

Objective  

Leukocytes mediate hepatocellular injury in obstructive cholestasis. The aim of the present study was to define the role of P-selectin glycoprotein ligand-1 (PSGL-1) in cholestasis-induced leukocyte recruitment and liver damage.