In vivo compartmentalization of functionally distinct, rapidly responsive antigen-specific T-cell populations in DNA-immunized or Salmonella enterica serovar Typhimurium-infected mice

The location and functional properties of antigen-specific memory T-cell populations in lymphoid and nonlymphoid compartments following DNA immunization or infection with Salmonella were investigated. Epitope-specific CD8+-T-cell expansion and retention during the memory phase were analyzed for DNA-immunized mice by use of a 5-h peptide restimulation assay. These data revealed that epitope-specific gamma interferon (IFN-{gamma})-positive CD8+ T cells occur at higher frequencies in the spleen, liver, and blood than in draining or peripheral lymph nodes during the expansion phase. Moreover, this distribution is maintained into long-term memory. The location and function of both CD4+ and CD8+ Salmonella-specific memory T cells in mice who were given a single dose of Salmonella enterica serovar Typhimurium was also quantitated by an ex vivo restimulation with bacterial lysate to detect the total Salmonella-specific memory pool. Mice immunized up to 6 months previously with S. enterica serovar Typhimurium had bacterium-specific CD4+ T cells that were capable of producing IFN-{gamma} or tumor necrosis factor alpha (TNF-{alpha}) at each site analyzed. Similar findings were observed for CD8+ T cells that were capable of producing IFN-{gamma}, while a much lower frequency and more restricted distribution were associated with TNF-{alpha}-producing CD8+ T cells. This study is the first to assess the frequencies, locations, and functions of both CD4+ and CD8+ memory T-cell populations in the same Salmonella-infected individuals and demonstrates the organ-specific functional compartmentalization of memory T cells after Salmonella infection

Are there differences in all-cause and coronary heart disease mortality between immigrants in Sweden and in their country of birth? A follow-up study of total populations

BACKGROUND: Mortality from cardiovascular diseases is higher among immigrants than native Swedes. It is not clear whether the high mortality persists from the country of birth or is a result of migration. The purpose of the present study was to analyse whether all-cause and coronary heart disease mortality differ between immigrants in Sweden and in the country of birth. METHODS: Two cohorts including the total population from Swedish national registers and WHO were defined. All-cause and CHD mortality are presented as age-adjusted incidence rates and incidence density ratios (IDR) in eight immigrant groups in Sweden and in their country of birth. The data were analysed using Poisson regression. RESULTS: The all-cause mortality risk was lower among seven of eight male immigrant groups (IDR 0.39–0.97) and among six of eight female immigrant groups (IDR 0.42–0.81) than in their country of birth. The CHD mortality risk was significantly lower in male immigrants from Norway (IDR = 0.84), Finland (IDR = 0.91), Germany (IDR = 0.84) and Hungary (IDR = 0.59) and among female immigrants from Germany (IDR = 0.66) and Hungary (IDR = 0.54) than in their country of birth. In contrast, there was a significantly higher CHD mortality risk in male immigrants from Southern Europe (IDR = 1.23) than in their country of birth. CONCLUSION: The all-cause mortality risk was lower in the majority of immigrant groups in Sweden than in their country of birth. The differences in CHD mortality risks were more complex. For countries with high CHD mortality, such as Finland and Hungary, the risk was lower among immigrants in Sweden than in their country of birth. For low-risk countries in South Europe, the risk was higher in immigrants in Sweden than in South Europe

Enhanced M1 Macrophage Polarization in Human Helicobacter pylori-Associated Atrophic Gastritis and in Vaccinated Mice

Background: Infection with Helicobacter pylori triggers a chronic gastric inflammation that can progress to atrophy and gastric adenocarcinoma. Polarization of macrophages is a characteristic of both cancer and infection, and may promote progression or resolution of disease. However, the role of macrophages and their polarization during H. pylori infection has not been well defined. Methodology/Principal Findings: By using a mouse model of infection and gastric biopsies from 29 individuals, we have analyzed macrophage recruitment and polarization during H. pylori infection by flow cytometry and real-time PCR. We found a sequential recruitment of neutrophils, eosinophils and macrophages to the gastric mucosa of infected mice. Gene expression analysis of stomach tissue and sorted macrophages revealed that gastric macrophages were polarized to M1 after H. pylori infection, and this process was substantially accelerated by prior vaccination. Human H. pylori infection was characterized by a mixed M1/M2 polarization of macrophages. However, in H. pylori-associated atrophic gastritis, the expression of inducible nitric oxide synthase was markedly increased compared to uncomplicated gastritis, indicative of an enhanced M1 macrophage polarization in this pre-malignant lesion. Conclusions/Significance: These results show that vaccination of mice against H. pylori amplifies M1 polarization of gastric macrophages, and that a similar enhanced M1 polarization is present in human H. pylori-induced atrophic gastritis

Patterns and correlates of physical activity: a cross-sectional study in urban Chinese women

<p>Abstract</p> <p>Background</p> <p>Inactivity is a modifiable risk factor for many diseases. Rapid economic development in China has been associated with changes in lifestyle, including physical activity. The purpose of this study was to investigate the patterns and correlates of physical activity in middle-aged and elderly women from urban Shanghai.</p> <p>Methods</p> <p>Study population consisted of 74,942 Chinese women, 40–70 years of age, participating in the baseline survey of the Shanghai Women's Health Study (1997–2000), an ongoing population-based cohort study. A validated, interviewer-administered physical activity questionnaire was used to collect information about several physical activity domains (exercise/sports, walking and cycling for transportation, housework). Correlations between physical activity domains were evaluated by Spearman rank-correlation coefficients. Associations between physical activity and socio-demographic and lifestyle factors were evaluated by odds ratios derived from logistic regression.</p> <p>Results</p> <p>While more than a third of study participants engaged in regular exercise, this form of activity contributed only about 10% to daily non-occupational energy expenditure. About two-thirds of women met current recommendations for lifestyle activity. Age was positively associated with participation in exercise/sports and housework. Dietary energy intake was positively associated with all physical activity domains. High socioeconomic status, unemployment (including retirement), history of chronic disease, small household, non-smoking status, alcohol and tea consumption, and ginseng intake were all positively associated with exercise participation. High socioeconomic status and small household were inversely associated with non-exercise activities.</p> <p>Conclusion</p> <p>This study demonstrates that physical activity domains other than sports and exercise are important contributors to total energy expenditure in women. Correlates of physical activity are domain-specific. These findings provide important information for research on the health benefits of physical activity and have public health implications for designing interventions to promote participation in physical activity.</p

Diet and body constitution in relation to subgroups of breast cancer defined by tumour grade, proliferation and key cell cycle regulators

BACKGROUND: The general lack of clear associations between diet and breast cancer in epidemiological studies may partly be explained by the fact that breast cancer is a heterogeneous disease that may have disparate genetic associations and different aetiological bases. METHOD: A total of 346 incident breast cancers in a prospective cohort of 17,035 women enrolled in the Malmö Diet and Cancer study (Sweden) were subcategorized according to conventional pathology parameters, proliferation and expression of key cell cycle regulators. Subcategories were compared with prediagnostic diet and body measurements using analysis of variance. RESULTS: A large hip circumference and high body mass index were associated with high grade tumours (P = 0.03 and 0.009, respectively), whereas low energy and unadjusted fat intakes were associated with high proliferation (P = 0.03 and 0.004, respectively). Low intakes of saturated, monounsaturated and polyunsaturated fatty acids were also associated with high proliferation (P = 0.02, 0.004 and 0.003, respectively). Low energy and unadjusted fat intakes were associated with cyclin D(1 )overexpression (P = 0.02 and 0.007, respectively), whereas cyclin E overexpression was positively correlated with fat intake. Oestrogen receptor status and expression of the tumour suppressor gene p27 were not associated with either diet or body constitution. CONCLUSION: Low energy and low total fat (polyunsaturated fatty acids in particular) intakes, and high body mass index were associated with relatively more malignant breast tumours. Dietary behaviours and body constitution may be associated with specific types of breast cancer defined by conventional pathology parameters and cyclin D(1 )and cyclin E expression. Further studies including healthy control individuals are needed to confirm our results

Dendritic cell maturation and death during Salmonella infection. Role of pro-inflammatory cytokines and MyD88

The costimulatory molecules CD80 and CD86 are required for the ability of dendritic cells (DC) to induce both tolerance and immunity. This thesis investigates the control of CD80/CD86 upregulation in vivo on DC during Salmonella infection. After oral Salmonella infection, DC in Peyer´s patches (PP), mesenteric lymph nodes (MLN) and spleen upregulated costimulatory molecules almost simultaneously despite differential seeding of these organs with bacteria. Costimulatory molecules were also induced on TNF/iNOS-producing CD11cintCD11b+ DC that accumulated in infected organs. The CD11cintCD11b+ DC were efficient at bacterial uptake but, in contrast to conventional DC, failed to process and present Salmonella Ag on MHC-II. Using different gene-deficient mice, the pathways controlling CD80/86 upregulation on DC during Salmonella infection were dissected. Upregulation of CD80 was strictly dependent on the Toll-like receptor adaptor MyD88, whereas upregulation of CD86 was mediated by both MyD88-dependent and -independent factors. The pro-inflammatory cytokine TNF was identified as one MyD88-dependent factor required for optimal upregulation of CD80/86 in the MLN. In the absence of MyD88, upregulation of CD86 was mediated by type I interferons. However, the contribution of type I interferons to CD86 upregulation in wild type mice is only marginal, since mice lacking the type I interferon receptor (IFN-αβR) showed no major defects in CD80/86 upregulation. Despite the abrogated upregulation of CD80/86 on DC of TNFR1-/-, MyD88-/- or MyD88-/-IFN-αβR-/- mice, DC directly associated with bacteria upregulated costimulatory molecules independently of these factors. Pro-inflammatory signaling not only upregulated costimulatory molecules on DC during Salmonella infection, but also mediated DC death. Thus, MyD88-dependent production of TNF induced DC death in Salmonella-infected mice. CD8α+ DC were most susceptible to infection-induced cell death as assessed directly ex vivo by Annexin-V and 7AAD staining, whereas recruited CD11cintCD11b+ DC were completely resistant. Thus, the inflammatory environment imprints a distinct pattern of costimulatory molecules on DC, with MyD88-dependent factors controlling the upregulation of CD80. However, MyD88-dependent factors also induce DC death during Salmonella infection, which is likely to have a negative impact on anti-bacterial immunity

Observaciones sobre traducción de literatura infantil —Un estudio de la traducción al español de cuentos de Astrid Lindgren—

Síntesis: Esta tesina trata de dificultades que se presentan en la traducción de literatura infantil. Para analizar las traducciones españolas de cuatro novelas infantiles de Astrid Lindgren, he investigado cómo se traducen los nombres propios, los topónimos (nombres geográficos), las palabras inventadas por la autora y los fenómenos específicos de la cultura sueca. La cuestión central ha sido ver si se pierde algo del estilo de la traductora o de lo específico sueco en la traducción de esos tipos de palabras. La conclusión es que sí, se pierde algo del estilo personal de la autora y lo típico sueco, pero esto no se puede evitar, ya que la traducción de literatura consiste en hacer un texto inteligible para otras culturas. Además, el estilo de Astrid Lindgren es muy original y por eso es difícil traducir sus textos. El primer capítulo contiene el trasfondo científico y, en él, se tratan problemas de traducción, tanto generales como los de traducir nombres propios, topónimos, palabras inventadas y fenómenos específicos de una cultura. En el segundo capítulo presento los resultados de mi investigación. Rindo cuenta de todas las palabras que he encontrado, junto con sus traducciones, divididas en grupos según el tipo de traducción. En el cuarto capítulo analizo las traducciones y discuto las pérdidas de significado y, también, del estilo de la autora y de lo típico sueco. El quinto capítulo contiene mis conclusiones, basadas en las discusiones del capítulo anterior. Hipótesis: La hipótesis de esta tesina es que, en la traducción de literatura infantil, se pierde mucho de lo que es específico para la cultura a la que pertenece la novela, y también de lo que es específico para el autor. Pienso que ello ocurre porque muchas veces se traducen nombres propios, topónimos, palabras inventadas y fenómenos específicos de una cultura en la literatura infantil para que los niños entiendan mejor las historias. Mi hipótesis está basada, en primer lugar, en mi propia sospecha y, también, en el conocimiento de que el trabajo de traducir es algo muy difícil; la traducción de literatura infantil es, por lo menos, tan difícil como cualquier otro tipo de traducción. Objetivo y propósito: El objetivo de esta tesina es comparar algunos libros de Astrid Lindgren en sueco con sus traducciones en español. Voy a concentrar mi investigación en nombres propios, topónimos, palabras inventadas por la autora y fenómenos específicos de la cultura sueca. Empezaré con Ronja Rövardotter (Ronja, hija del bandolero) y seguiré con Mio min Mio (Mío, mi pequeño Mío), Emil i Lönneberga (Miguel el Travieso) y Pippi Långstrump (Pippi Calzaslargas). He elegido estas novelas porque en ellas se pueden encontrar muchos nombres de personas y sitios, junto con fenómenos suecos y palabras inventadas. El propósito de esta comparación es tratar de establecer cómo se tratan los nombres propios, topónimos, palabras inventadas y fenómenos específicos de la cultura sueca en la traducción. El asunto que voy a tratar en esta tesina es el problema de traducir o no traducir algunos elementos especiales y, también, cómo traducirlos. La cuestión central es si se pierde algo del estilo personal del autor, o de la cultura, en traducciones de literatura infantil

Dendritic cell maturation and death during Salmonella infection. Role of pro-inflammatory cytokines and MyD88

The costimulatory molecules CD80 and CD86 are required for the ability of dendritic cells (DC) to induce both tolerance and immunity. This thesis investigates the control of CD80/CD86 upregulation in vivo on DC during Salmonella infection. After oral Salmonella infection, DC in Peyer?s patches (PP), mesenteric lymph nodes (MLN) and spleen upregulated costimulatory molecules almost simultaneously despite differential seeding of these organs with bacteria. Costimulatory molecules were also induced on TNF/iNOS-producing CD11cintCD11b+ DC that accumulated in infected organs. The CD11cintCD11b+ DC were efficient at bacterial uptake but, in contrast to conventional DC, failed to process and present Salmonella Ag on MHC-II. Using different gene-deficient mice, the pathways controlling CD80/86 upregulation on DC during Salmonella infection were dissected. Upregulation of CD80 was strictly dependent on the Toll-like receptor adaptor MyD88, whereas upregulation of CD86 was mediated by both MyD88-dependent and -independent factors. The pro-inflammatory cytokine TNF was identified as one MyD88-dependent factor required for optimal upregulation of CD80/86 in the MLN. In the absence of MyD88, upregulation of CD86 was mediated by type I interferons. However, the contribution of type I interferons to CD86 upregulation in wild type mice is only marginal, since mice lacking the type I interferon receptor (IFN-??R) showed no major defects in CD80/86 upregulation. Despite the abrogated upregulation of CD80/86 on DC of TNFR1-/-, MyD88-/- or MyD88-/-IFN-??R-/- mice, DC directly associated with bacteria upregulated costimulatory molecules independently of these factors. Pro-inflammatory signaling not only upregulated costimulatory molecules on DC during Salmonella infection, but also mediated DC death. Thus, MyD88-dependent production of TNF induced DC death in Salmonella-infected mice. CD8?+ DC were most susceptible to infection-induced cell death as assessed directly ex vivo by Annexin-V and 7AAD staining, whereas recruited CD11cintCD11b+ DC were completely resistant. Thus, the inflammatory environment imprints a distinct pattern of costimulatory molecules on DC, with MyD88-dependent factors controlling the upregulation of CD80. However, MyD88-dependent factors also induce DC death during Salmonella infection, which is likely to have a negative impact on anti-bacterial immunity