Clonal Structure of Rapid-Onset MDV-Driven CD4+ Lymphomas and Responding CD8+ T Cells

Lymphoid oncogenesis is a life threatening complication associated with a number of persistent viral infections (e.g. EBV and HTLV-1 in humans). With many of these infections it is difficult to study their natural history and the dynamics of tumor formation. Marek's Disease Virus (MDV) is a prevalent α-herpesvirus of poultry, inducing CD4+ TCRαβ+ T cell tumors in susceptible hosts. The high penetrance and temporal predictability of tumor induction raises issues related to the clonal structure of these lymphomas. Similarly, the clonality of responding CD8 T cells that infiltrate the tumor sites is unknown. Using TCRβ repertoire analysis tools, we demonstrated that MDV driven CD4+ T cell tumors were dominated by one to three large clones within an oligoclonal framework of smaller clones of CD4+ T cells. Individual birds had multiple tumor sites, some the result of metastasis (i.e. shared dominant clones) and others derived from distinct clones of transformed cells. The smaller oligoclonal CD4+ cells may represent an anti-tumor response, although on one occasion a low frequency clone was transformed and expanded after culture. Metastatic tumor clones were detected in the blood early during infection and dominated the circulating T cell repertoire, leading to MDV associated immune suppression. We also demonstrated that the tumor-infiltrating CD8+ T cell response was dominated by large oligoclonal expansions containing both “public” and “private” CDR3 sequences. The frequency of CD8+ T cell CDR3 sequences suggests initial stimulation during the early phases of infection. Collectively, our results indicate that MDV driven tumors are dominated by a highly restricted number of CD4+ clones. Moreover, the responding CD8+ T cell infiltrate is oligoclonal indicating recognition of a limited number of MDV antigens. These studies improve our understanding of the biology of MDV, an important poultry pathogen and a natural infection model of virus-induced tumor formation

The effects of interleukin-8 on airway smooth muscle contraction in cystic fibrosis

<p>Abstract</p> <p>Background</p> <p>Many cystic fibrosis (CF) patients display airway hyperresponsiveness and have symptoms of asthma such as cough, wheezing and reversible airway obstruction. Chronic airway bacterial colonization, associated with neutrophilic inflammation and high levels of interleukin-8 (IL-8) is also a common occurrence in these patients. The aim of this work was to determine the responsiveness of airway smooth muscle to IL-8 in CF patients compared to non-CF individuals.</p> <p>Methods</p> <p>Experiments were conducted on cultured ASM cells harvested from subjects with and without CF (control subjects). Cells from the 2^ndto 5^thpassage were studied. Expression of the IL-8 receptors CXCR1 and CXCR2 was assessed by flow cytometry. The cell response to IL-8 was determined by measuring intracellular calcium concentration ([Ca²⁺]_i), cell contraction, migration and proliferation.</p> <p>Results</p> <p>The IL-8 receptors CXCR1 and CXCR2 were expressed in both non-CF and CF ASM cells to a comparable extent. IL-8 (100 nM) induced a peak Ca²⁺release that was higher in control than in CF cells: 228 ± 7 versus 198 ± 10 nM (p < 0.05). IL-8 induced contraction was greater in CF cells compared to control. Furthermore, IL-8 exposure resulted in greater phosphorylation of myosin light chain (MLC₂₀) in CF than in control cells. In addition, MLC₂₀expression was also increased in CF cells. Exposure to IL-8 induced migration and proliferation of both groups of ASM cells but was not different between CF and non-CF cells.</p> <p>Conclusion</p> <p>ASM cells of CF patients are more contractile to IL-8 than non-CF ASM cells. This enhanced contractility may be due to an increase in the amount of contractile protein MLC₂₀. Higher expression of MLC₂₀by CF cells could contribute to airway hyperresponsiveness to IL-8 in CF patients.</p

Comparison of hip fracture incidence and trends between Germany and Austria 1995-2004: An epidemiological study

Mann E, Meyer G, Haastert B, Icks A. Comparison of hip fracture incidence and trends between Germany and Austria 1995-2004: an epidemiological study. BMC Public Health. 2010;10(1): 46.Background Several studies evaluated variations in hip fracture incidences, as well as trends of the hip fracture incidences. Comparisons of trends are lacking so far. We compared the incidence rates and, in particular, its trends between Austria and Germany 1995 to 2004 analysing national hospital discharge diagnosis register data. Methods Annual frequencies of hip fractures and corresponding incidences per 100,000 person years were estimated, overall and stratified for sex and age, assuming Poisson distribution. Multiple Poisson regression models including country and calendar year, age and sex were used to analyse differences in incidence and trend. The difference of annual changes between the two countries was explored using an interaction term (calender year * country). Results Overall, the increase of hip fracture risk was 1.31 fold higher (95% CI 1.29-1.34) in Austria compared to Germany, adjusted for age, sex, and calendar year. The risk increase was comparable for both sexes (males: RR 1.35 (1.32-1.37), females: RR 1.31 (1.29-1.33)). Hip fracture trend from 1995 to 2004 indicates an increase in both countries without a statistically significant difference between Austria and Germany (interaction term: p = 0.67). Conclusion In this study comparing hip fracture incidences and its trend using pooled data, the incidence in Austria was 30% higher compared to its neighbouring country Germany. For both countries a similar increasing trend of hip fracture incidence over the 10-year study period was calculated. The results need confirmation by other studies

The Oslo Health Study: Is bone mineral density higher in affluent areas?

<p>Abstract</p> <p>Background</p> <p>Based on previously reported differences in fracture incidence in the socioeconomic less affluent Oslo East compared to the more privileged West, our aim was to study bone mineral density (BMD) in the same socioeconomic areas in Oslo. We also wanted to study whether possible associations were explained by socio-demographic factors, level of education or lifestyle factors.</p> <p>Methods</p> <p>Distal forearm BMD was measured in random samples of the participants in The Oslo Health Study by single energy x-ray absorptiometry (SXA). 578 men and 702 women born in Norway in the age-groups 40/45, 60 and 75 years were included in the analyses. Socioeconomic regions, based on a social index dividing Oslo in two regions – East and West, were used.</p> <p>Results</p> <p>Age-adjusted mean BMD in women living in the less affluent Eastern region was 0.405 g/cm²and significantly lower than in West where BMD was 0.419 g/cm². Similarly, the odds ratio of low BMD (Z-score ≤ -1) was 1.87 (95% CI: 1.22–2.87) in women in Oslo East compared to West. The same tendency, although not statistically significant, was also present in men. Multivariate analysis adjusted for education, marital status, body mass index, physical inactivity, use of alcohol and smoking, and in women also use of post-menopausal hormone therapy and early onset of menopause, did hardly change the association. Additional adjustments for employment status, disability pension and physical activity at work for those below the age of retirement, gave similar results.</p> <p>Conclusion</p> <p>We found differences in BMD in women between different socioeconomic regions in Oslo that correspond to previously found differences in fracture rates. The association in men was not statistically significant. The differences were not explained by socio-demographic factors, level of education or lifestyle factors.</p

Ratio of the Isolated Photon Cross Sections at \sqrt{s} = 630 and 1800 GeV

The inclusive cross section for production of isolated photons has been measured in \pbarp collisions at $\sqrt{s} = 630$ GeV with the \D0 detector at the Fermilab Tevatron Collider. The photons span a transverse energy ($E_T$) range from 7-49 GeV and have pseudorapidity $|\eta| < 2.5$. This measurement is combined with to previous \D0 result at $\sqrt{s} = 1800$ GeV to form a ratio of the cross sections. Comparison of next-to-leading order QCD with the measured cross section at 630 GeV and ratio of cross sections show satisfactory agreement in most of the $E_T$ range.Comment: 7 pages. Published in Phys. Rev. Lett. 87, 251805, (2001

Hip fractures and area level socioeconomic conditions: a population-based study

Icks A, Haastert B, Wildner M, et al. Hip fractures and area level socioeconomic conditions: a population-based study. BMC Public Health. 2009;9(1):114.Background: Only a limited number of studies have analyzed the association between hip fracture incidence and socioeconomic conditions. Most, but not all found an association, and results are in part conflicting. The aim of our study was to evaluate the association between hip fractures and socioeconomic conditions in Germany, from 1995 to 2004, on a census tract area level. Methods: We used data from the national hospital discharge diagnosis register and data on socioeconomic and demographic characteristics of 131 census tracts from official statistics. Associations between the hip fracture incidence and socioeconomic conditions were analyzed by multiple Poisson regression models, taking overdispersion into account. Results: The risk of hip fracture decreased by 4% with a 7% increase (about one interquartile range) of non-German nationals. It decreased by 10% with a 6% increased rate of unemployment, increased by 7% with a 2% increase of the proportion of welfare recipients, and also increased by 3% with an increase of the proportion of single parent families of 1.9%. Conclusion: Our results showed weak associations between indicators of socioeconomic conditions at area level and hip fracture risk; the varied by type of indicator. We conclude that hip fracture incidence might be influenced by the socioeconomic context of a region, but further analysis using more specific markers for deprivation on a smaller scale and individual-level data are needed

Socioeconomic status and hospitalization in the very old: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Socioeconomic status could affect the demand for hospital care. The aim of the present study was to assess the role of age, socioeconomic status and comorbidity on acute hospital admissions among elderly.</p> <p>Methods</p> <p>We retrospectively examined the discharge abstracts data of acute care hospital admissions of residents in Rome aged 75 or more years in the period 1997–2000. We used the Hospital Information System of Rome, the Tax Register, and the Population Register of Rome for socio-economic data. The rate of hospitalization, modified Charlson's index of comorbidity, and level of income in the census tract of residence were obtained. Rate ratios and 95% confidence limits were computed to assess the relationship between income deciles and rate of hospitalization. Cross-tabulation was used to explore the distribution of the index of comorbidity by deciles of income. Analyses were repeated for patients grouped according to selected diseases.</p> <p>Results</p> <p>Age was associated with a marginal increase in the rate of hospitalization. However, the hospitalization rate was inversely related to income in both sexes. Higher income was associated with lower comorbidity. The same associations were observed in patients admitted with a principal diagnosis of chronic condition (diabetes mellitus, heart failure, chron obstructive pulmonary disease) or stroke, but not hip fracture.</p> <p>Conclusion</p> <p>Lower social status and associated comorbidity, more than age per se, are associated with a higher rate of hospitalization in very old patients.</p

Increased Fitness of Rice Plants to Abiotic Stress Via Habitat Adapted Symbiosis: A Strategy for Mitigating Impacts of Climate Change

Climate change and catastrophic events have contributed to rice shortages in several regions due to decreased water availability and soil salinization. Although not adapted to salt or drought stress, two commercial rice varieties achieved tolerance to these stresses by colonizing them with Class 2 fungal endophytes isolated from plants growing across moisture and salinity gradients