Patterns of CO2 and radiocarbon across high northern latitudes during International Polar Year 2008

High-resolution in situ CO2 measurements were conducted aboard the NASA DC-8 aircraft during the ARCTAS/POLARCAT field campaign, a component of the wider 2007-2008 International Polar Year activities. Data were recorded during large-scale surveys spanning the North American sub-Arctic to the North Pole from 0.04 to 12 km altitude in spring and summer of 2008. Influences on the observed CO2 concentrations were investigated using coincident CO, black carbon, CH3CN, HCN, O3, C2Cl4, and Δ14CO2 data, and the FLEXPART model. In spring, the CO2 spatial distribution from 55̊N to 90̊N was largely determined by the long-range transport of air masses laden with Asian anthropogenic pollution intermingled with Eurasian fire emissions evidenced by the greater variability in the mid-to-upper troposphere. At the receptor site, the enhancement ratios of CO2 to CO in pollution plumes ranged from 27 to 80 ppmv ppmv-1 with the highest anthropogenic content registered in plumes sampled poleward of 80̊N. In summer, the CO2 signal largely reflected emissions from lightning-ignited wildfires within the boreal forests of northern Saskatchewan juxtaposed with uptake by the terrestrial biosphere. Measurements within fresh fire plumes yielded CO2 to CO emission ratios of 4 to 16 ppmv ppmv-1 and a mean CO2 emission factor of 1698 ± 280 g kg-1 dry matter. From the 14C in CO2 content of 48 whole air samples, mean spring (46.6 ± 4.4%) and summer (51.5 ± 5%) D14CO2 values indicate a 5%seasonal difference. Although the northern midlatitudes were identified as the emissions source regions for the majority of the spring samples, depleted Δ14CO2 values were observed in <1% of the data set. Rather, ARCTAS Δ14CO2 observations (54%) revealed predominately a pattern of positive disequilibrium (1-7%) with respect to background regardless of season owing to both heterotrophic respiration and fire-induced combustion of biomass. Anomalously enriched Δ14CO2 values (101-262%) measured in emissions from Lake Athabasca and Eurasian fires speak to biomass burning as an increasingly important contributor to the mass excess in Δ14CO2 observations in a warming Arctic, representing an additional source of uncertainty in the quantification of fossil fuel CO2

Murine Models and Cell Lines for the Investigation of Pheochromocytoma: Applications for Future Therapies?

Pheochromocytomas (PCCs) are slow-growing neuroendocrine tumors arising from adrenal chromaffin cells. Tumors arising from extra-adrenal chromaffin cells are called paragangliomas. Metastases can occur up to approximately 60% or even more in specific subgroups of patients. There are still no well-established and clinically accepted “metastatic” markers available to determine whether a primary tumor is or will become malignant. Surgical resection is the most common treatment for non-metastatic PCCs, but no standard treatment/regimen is available for metastatic PCC. To investigate what kind of therapies are suitable for the treatment of metastatic PCC, animal models or cell lines are very useful. Over the last two decades, various mouse and rat models have been created presenting with PCC, which include models presenting tumors that are to a certain degree biochemically and/or molecularly similar to human PCC, and develop metastases. To be able to investigate which chemotherapeutic options could be useful for the treatment of metastatic PCC, cell lines such as mouse pheochromocytoma (MPC) and mouse tumor tissue (MTT) cells have been recently introduced and they both showed metastatic behavior. It appears these MPC and MTT cells are biochemically and molecularly similar to some human PCCs, are easily visualized by different imaging techniques, and respond to different therapies. These studies also indicate that some mouse models and both mouse PCC cell lines are suitable for testing new therapies for metastatic PCC

Treatment of glenohumeral instability in rugby players

Rugby is a high-impact collision sport, with impact forces. Shoulder injuries are common and result in the longest time off sport for any joint injury in rugby. The most common injuries are to the glenohumeral joint with varying degrees of instability. The degree of instability can guide management. The three main types of instability presentations are: (1) frank dislocation, (2) subluxations and (3) subclinical instability with pain and clicking. Understanding the exact mechanism of injury can guide diagnosis with classical patterns of structural injuries. The standard clinical examination in a large, muscular athlete may be normal, so specific tests and techniques are needed to unearth signs of pathology. Taking these factors into consideration, along with the imaging, allows a treatment strategy. However, patient and sport factors need to be also considered, particularly the time of the season and stage of sporting career. Surgery to repair the structural damage should include all lesions found. In chronic, recurrent dislocations with major structural lesions, reconstruction procedures such as the Latarjet procedure yields better outcomes. Rehabilitation should be safe, goal-driven and athlete- specific. Return to sport is dependent on a number of factors, driven by the healing process, sport requirements and extrinsic pressures

Rapid Immunomagnetic Negative Enrichment of Neutrophil Granulocytes from Murine Bone Marrow for Functional Studies In Vitro and In Vivo

Polymorphonuclear neutrophils (PMN) mediate early immunity to infection but can also cause host damage if their effector functions are not controlled. Their lack or dysfunction is associated with severe health problems and thus the analysis of PMN physiology is a central issue. One prerequisite for PMN analysis is the availability of purified cells from primary organs. While human PMN are easily isolated from peripheral blood, this approach is less suitable for mice due to limited availability of blood. Instead, bone marrow (BM) is an easily available reservoir of murine PMN, but methods to obtain pure cells from BM are limited. We have developed a novel protocol allowing the isolation of highly pure untouched PMN from murine BM by negative immunomagnetic isolation using a complex antibody cocktail. The protocol is simple and fast (∼1 h), has a high yield (5–10*106 PMN per animal) and provides a purity of cells equivalent to positive selection (>80%). Most importantly, cells obtained by this method are non-activated and remain fully functional in vitro or after adoptive transfer into recipient animals. This method should thus greatly facilitate the study of primary murine PMN in vitro and in vivo

The retinoid anticancer signal: mechanisms of target gene regulation

Retinoids induce growth arrest, differentiation, and cell death in many cancer cell types. One factor determining the sensitivity or resistance to the retinoid anticancer signal is the transcriptional response of retinoid-regulated target genes in cancer cells. We used cDNA microarray to identify 31 retinoid-regulated target genes shared by two retinoid-sensitive neuroblastoma cell lines, and then sought to determine the relevance of the target gene responses to the retinoid anticancer signal. The pattern of retinoid responsiveness for six of 13 target genes (RARβ2, CYP26A1, CRBP1, RGS16, DUSP6, EGR1) correlated with phenotypic retinoid sensitivity, across a panel of retinoid-sensitive or -resistant lung and breast cancer cell lines. Retinoid treatment of MYCN transgenic mice bearing neuroblastoma altered the expression of five of nine target genes examined (RARβ2, CYP26A1, CRBP1, DUSP6, PLAT) in neuroblastoma tumour tissue in vivo. In retinoid-sensitive neuroblastoma, lung and breast cancer cell lines, direct inhibition of retinoid-induced RARβ2 expression blocked induction of only one of eight retinoid target genes (CYP26A1). DNA demethylation, histone acetylation, and exogenous overexpression of RARβ2 partially restored retinoid-responsive CYP26A1 expression in RA-resistant MDA-MB-231 breast, but not SK-MES-1 lung, cancer cells. Combined, rather than individual, inhibition of DUSP6 and RGS16 was required to block retinoid-induced growth inhibition in neuroblastoma cells, through phosphorylation of extracellular-signal-regulated kinase. In conclusion, sensitivity to the retinoid anticancer signal is determined in part by the transcriptional response of key retinoid-regulated target genes, such as RARβ2, DUSP6, and RGS16

Thymidine Phosphorylase/β-tubulin III expressions predict the response in Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel

<p>Abstract</p> <p>Background</p> <p>To assess the role of Thymidine Phosphorylase and β-tubulin III in clinical outcome of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel.</p> <p>Methods</p> <p>The clinical data and tumor biopsies prior treatment from 33 advanced gastric cancer patients receiving capecitabine plus paclitaxel (cohort 1, experimental group) and 18 patients receiving capecitabine plus cisplatin (cohort 2, control group) in Beijing Cancer Hospital from July 2003 to December 2008 were retrospectively collected and analyzed for Thymidine Phosphorylase and β-tubulin III expressions by immunohistochemistry. The relationships between expressions of biomarkers and response or survival were determined by statistical analysis.</p> <p>Results</p> <p>The median age of 51 patients was 57 years (range, 27-75) with male 34 and female 17, and the response rate, median progression-free survival and overall survival were 43.1%, 120d and 265d. Among cohort 1, the response rate, median progression-free survival and overall survival in β-tubulin III positive (n = 22) and negative patients (n = 11) were 36.4%/72.7% (positive vs negative, <it>P </it>= 0.049), 86d/237d (<it>P </it>= 0.046) and 201d/388d (<it>P </it>= 0.029), respectively; the response rate (87.5% vs 14.3%, <it>P </it>= 0.01) and median progression-free survival (251d vs 84d, <it>P </it>= 0.003) in Thymidine Phosphorylase positive & β-tubulin III negative patients (n = 8) were also significantly higher than those in Thymidine Phosphorylase negative & β-tubulin III positive patients (n = 7). There was no correlation between β-tubulin III expression and response or survival among cohort 2 (n = 18).</p> <p>Conclusions</p> <p>In Chinese advanced gastric cancer, Thymidine Phosphorylase positive & β-tubulin III negative might predict response and prognosis to capecitabine plus paclitaxel chemotherapy. Further prospective evaluation in large samples should be performed to confirm these preliminary findings.</p