The Prognostic Impact of Protein Expression of E-Cadherin-Catenin Complexes Differs between Rectal and Colon Carcinoma

The E-cadherin-catenin complex provides cell-cell adhesion. In order for a carcinoma to metastasize, cancer cells must let go of their hold of neighboring cells in the primary tumor. The presence of components of the E-cadherin-catenin complex in 246 rectal adenocarcinomas was examined by immunohistochemistry and compared to their presence in 219 colon carcinomas. The expression data were correlated to clinical information from the patients' records. There were statistically significant differences in protein expression between the rectal and the colon carcinomas regarding membranous β-catenin, γ-catenin, p120-catenin, and E-cadherin, as well as nuclear β-catenin. In the rectal carcinomas, there was a significant inverse association between the expression of p120-catenin in cell membranes of the primary tumors and the occurrence of local recurrence, while membranous protein expression of β-catenin was inversely related to distant metastases

Differences in Protein Expression and Gene Amplification of Cyclins between Colon and Rectal Adenocarcinomas

Adenocarcinomas of rectum and colon may be different with regard to the cellular biological basis for cancer development. A material of 246 rectal cancers removed surgically at Akershus University Hospital in the years 1992–2000 was investigated and was compared to a material of 219 colon cancers operated on at Akershus University Hospital during the years 1988, 1990 and 1997–2000. There were highly significant differences between the rectal and the colon cancers in the protein expression of cyclin D1, cyclin D3, cyclin E, nuclear β-catenin, and c-Myc and in gene amplification of cyclin A2, cyclin B1, cyclin D1, and cyclin E. Gene amplification and protein expression in the rectal cancers correlated significantly for the cyclins B1, D3, and E. A statistically significant relation was observed between overexpression of cyclin A2 and local relapse of rectal carcinomas, as higher expression of cyclin A2 was associated with lower local recurrence rate

Immunological changes and increased expression of myxovirus resistance protein a in thyroid tissue of patients with recent onset and untreated Graves' disease

Background: Few studies have systematically examined the immune cells that infiltrate thyroid tissue at the time of the onset of Graves&#39; disease (GD). The role of viruses in the pathogenesis of autoimmune thyroid diseases is controversial. The present study analyzed inflammatory responses with respect to signs of virus infection. Methods: Thyroid tissue was obtained from 22 patients with newly diagnosed and untreated GD, 24 patients with chronic GD, and 24 controls. Inflammation was assessed by immunostaining for CD4+ and CD8+ T cells, plasma cells (CD138+), and plasmacytoid dendritic cells (PDCs). The production of interferon-inducible myxovirus resistance protein A (MxA) was analyzed as a sign of virus infection. Results: The degree of thyroid inflammation and fibrosis was significantly higher in both patient groups compared with that in controls. The number of CD4+ T cells and plasma cells (activated B cells) was significantly higher in both patient groups. CD8+ cells were only present in patients with chronic disease. MxA expression and the number of PDCs increased only in patients with newly diagnosed GD. There was a strong positive correlation between the number of PDCs and the number of MxA+ leucocytes. Conclusion: The increase in CD8+ T cells during the chronic stage of GD suggests that they may play a role in progression of the autoimmune process from early to chronic thyroiditis. Upregulation of MxA expression during the early stages of the disease, and the positive correlation between the number of PDCs and the number of MxA+ leucocytes, suggests that activated PDCs secrete type I IFNs at the lesion site, possibly in response to viral infection. &nbsp;</p

SLIM Ultrahigh Resolution Ion Mobility Spectrometry Separations of Isotopologues and Isotopomers Reveal Mobility Shifts due to Mass Distribution Changes

We report on separations of ion isotopologues and isotopomers using ultrahigh-resolution traveling wave-based Structures for Lossless Ion Manipulations with serpentine ultralong path and extended routing ion mobility spectrometry coupled to mass spectrometry (SLIM SUPER IMS-MS). Mobility separations of ions from the naturally occurring ion isotopic envelopes (e.g., [M], [M+1], [M+2], ... ions) showed the first and second isotopic peaks (i.e., [M+1] and [M+2]) for various tetraalkylammonium ions could be resolved from their respective monoisotopic ion peak ([M]) after SLIM SUPER IMS with resolving powers of ∼400–600. Similar separations were obtained for other compounds (e.g., tetrapeptide ions). Greater separation was obtained using argon versus helium drift gas, as expected from the greater reduced mass contribution to ion mobility described by the Mason–Schamp relationship. To more directly explore the role of isotopic substitutions, we studied a mixture of specific isotopically substituted (15N, 13C, and 2H) protonated arginine isotopologues. While the separations in nitrogen were primarily due to their reduced mass differences, similar to the naturally occurring isotopologues, their separations in helium, where higher resolving powers could also be achieved, revealed distinct additional relative mobility shifts. These shifts appeared correlated, after correction for the reduced mass contribution, with changes in the ion center of mass due to the different locations of heavy atom substitutions. The origin of these apparent mass distribution-induced mobility shifts was then further explored using a mixture of Iodoacetyl Tandem Mass Tag (iodoTMT) isotopomers (i.e., each having the same exact mass, but with different isotopic substitution sites). Again, the observed mobility shifts appeared correlated with changes in the ion center of mass leading to multiple monoisotopic mobilities being observed for some isotopomers (up to a ∼0.04% difference in mobility). These mobility shifts thus appear to reflect details of the ion structure, derived from the changes due to ion rotation impacting collision frequency or momentum transfer, and highlight the potential for new approaches for ion structural characterization

Organic selenium supplementation increased selenium concentrations in ewe and newborn lamb blood and in slaughter lamb meat compared to inorganic selenium supplementation

Background Selenium is part of the antioxidant defence system in animals and humans. The available selenium concentration in soil is low in many regions of the world. The purpose of this study was to evaluate the effect of organic versus inorganic selenium supplementation on selenium status of ewes, their lambs, and slaughter lambs. Methods Ewes on four organic farms were allocated five or six to 18 pens. The ewes were given either 20 mg/kg inorganic selenium as sodium selenite or organic selenium as selenized nonviable yeast supplementation for the two last months of pregnancy. Stipulated selenium concentrations in the rations were below 0.40 mg/kg dry matter. In addition 20 male lambs were given supplements from November until they were slaughtered in March. Silage, hay, concentrates, and individual ewe blood samples were taken before and after the mineral supplementation period, and blood samples were taken from the newborn lambs. Blood samples from ewes and lambs in the same pens were pooled. Muscle samples were taken from slaughter lambs in March. Selenium concentrations were determined by atomic absorption spectrometry with a hydride generator system. In the ANOVA model, selenium concentration was the continuous response variable, and selenium source and farm were the nominal effect variables. Two-sample t-test was used to compare selenium concentrations in muscle samples from the slaughtered lambs that received either organic or inorganic selenium supplements. Results In all ewe pens the whole blood selenium concentrations increased during the experimental period. In addition, ewe pens that received organic selenium had significantly higher whole blood selenium concentrations (mean 0.28 μg/g) than ewe pens that received inorganic selenium (mean 0.24 μg/g). Most prominent, however, was the difference in their lambs; whole blood mean selenium concentration in lambs from mothers that received organic selenium (mean 0.27 μg/g) was 30% higher than in lambs from mothers that received inorganic selenium (mean 0.21 μg/g). Slaughter lambs that received organic selenium had 50% higher meat selenium concentrations (mean 0.12 mg/kg wet weight) than lambs that received inorganic selenium (mean 0.08 mg/kg wet weight). Conclusion Organic selenium supplementation gave higher selenium concentration in ewe and newborn lamb blood and slaughter lamb meat than inorganic selenium supplementation

Evidence-informed capacity building for setting health priorities in low- and middle-income countries: : A framework and recommendations for further research

Priority-setting in health is risky and challenging, particularly in resource-constrained settings. It is not simply a narrow technical exercise, and involves the mobilisation of a wide range of capacities among stakeholders – not only the technical capacity to “do” research in economic evaluations. Using the Individuals, Nodes, Networks and Environment (INNE) framework, we identify those stakeholders, whose capacity needs will vary along the evidence-to-policy continuum. Policymakers and healthcare managers require the capacity to commission and use relevant evidence (including evidence of clinical and cost-effectiveness, and of social values); academics need to understand and respond to decision-makers’ needs to produce relevant research. The health system at all levels will need institutional capacity building to incentivise routine generation and use of evidence. Knowledge brokers, including priority-setting agencies (such as England’s National Institute for Health and Care Excellence, and Health Interventions and Technology Assessment Program, Thailand) and the media can play an important role in facilitating engagement and knowledge transfer between the various actors. Especially at the outset but at every step, it is critical that patients and the public understand that trade-offs are inherent in priority-setting, and careful efforts should be made to engage them, and to hear their views throughout the process. There is thus no single approach to capacity building; rather a spectrum of activities that recognises the roles and skills of all stakeholders. A range of methods, including formal and informal training, networking and engagement, and support through collaboration on projects, should be flexibly employed (and tailored to specific needs of each country) to support institutionalisation of evidence-informed priority-setting. Finally, capacity building should be a two-way process; those who build capacity should also attend to their own capacity development in order to sustain and improve impact