Fas ligand and tumour counter-attack in colorectal cancer stratified according to microsatellite instability status

Expression of membrane-bound Fas ligand (FasL) by colorectal cancer cells may allow the development of an immune-privileged site by eliminating incoming tumour-infiltrating lymphocytes (TILs) in a Fas-mediated counter-attack. Sporadic colorectal cancer can be subdivided into three groups based on the level of DNA microsatellite instability (NISI). High-level NISI (NISI-High) is characterized by the presence of TILs and a favourable prognosis, while microsatellite-stable (MSS) cancers are TIL-deficient and low-level MSI (MSI-Low) is associated with an intermediate TIL density. The purpose of this study was to establish the relationship between MSI status and FasL expression in primary colorectal adenocarcinoma. Using immunohistochemistry and a selected series of 101 cancers previously classified as 31 MSI-High, 30 NISI-Low, and 40 MISS, the present study sought to confirm the hypothesis that increased TIL density in MSI-High cancers is associated with low or absent membrane-bound FasL expression, while increased FasL in MSS cancers allows the killing of host TILs. TUNEL/CD3 double staining was also used to determine whether MSS cancers contain higher numbers of apoptotic TILs in vivo than MSI-High or MSI-Low cancers. Contrary to the initial hypothesis, it was found that MSI-High cancers were associated with higher FasL expression (p = 0.04) and a stronger intensity of FasL staining (p = 0.007). In addition, mucinous carcinomas were independently characterized by increased FasL expression (p = 0.03) and staining intensity (p = 0.0005). Higher FasL expression and staining intensity did not correlate with reduced TIL density or increased numbers of apoptotic TILs. However, consistent with the hypothesis that curtailment of the host anti-tumour immune response contributes to the poor prognosis in MSS cancers, it was found that apoptotic TILs were most abundant in MSS carcinomas and metastatic Dukes' stage C or D tumours (p = 0.004; p = 0.046 respectively). This study therefore suggests that MSS colorectal cancers are killing incoming TILs in an effective tumour counter-attack, but apparently not via membrane-bound FasL. Copyright (C) 2003 John Wiley Sons, Ltd.

Sources of Brazil's Counter-Hegemony

There have been two key initiatives taken in the last two decades in Brazil to create a counter-hegemonic project for the country. One initiative resulted from Brazil's business community and high-level State bureaucracy and aimed at forming a regional economic and political bloc that would guarantee and enlarge a relative independence from the hegemonic powers. The other resulted from the emergence of the new unionist movement in São Paulo and from the formation of Partido dos Trabalhadores and aimed at promoting radical democratization and reducing social exclusion. Both initiatives have created policies and changes that have converged to enhance Brazil's counter-hegemonic position as a regional and emerging power.

STRATEGIES FOR SUPERIOR PERFORMANCE IN RECESSIONS: PRO OR COUNTER-CYCLICAL?

Recessions are recurring events in which most firms suffer severe impacts while others are less affected or may even prosper. Strategic management has made little progress in understanding such performance differences. In a scenario of decreased demand, intensified competition, and higher uncertainty, most firms try to survive by pro-cyclically cutting costs and investments. But firms could take advantage of undervalued resources in the market to counter-cyclically invest in new business opportunities to overtake competitors. We survey Brazilian firms in various industries about the 2008-2009 recession and analyze data using PLS-SEM. We find that while most firms pro-cyclically reduce costs and investments in recessions, a counter-cyclical strategy of investing in opportunities created by changes in the market enables superior performance. Most successful are firms with a propensity to recognize opportunities, an entrepreneurial orientation to invest, and the flexibility to efficiently implement investments.

Comparison between the HemoCue® and an automated counter for measuring hemoglobin

To determine the precision and agreement of the hemoglobin (Hb) measurements in capillary and venous blood samples by the HemoCue® and an automated counter. Hb was determined by both equipaments in blood samples of 29 pregnant women. The HemoCue® showed low repeatability of Hb measurements in duplicate in capillary (CR=0.53 g/dL, CV=13.6%) and venous blood (CR=0.53 g/dL, CV=13.6%). Hb measurements in capillary blood were higher than those in venous blood (12.4 and 11.7 g/dL, respectively; p<0.05). There was high agreement between Hb in capillary blood by the HemoCue® and in venous blood by the counter (r icc=0.86; p<0.01), and also between the diagnosis of anemia by both equipments (k=0.81; p<0.01). The HemoCue® seems to be more appropriate for capillary blood and require training of the measurers.

Economic crisis and counter-reform of universal health care systems: Spanish case

The economic crisis that has been affecting Europe in the 21st century has modified social protection systems in the countries that adopted, in the 20th century, universal health care system models, such as Spain. This communication presents some recent transformations, which were caused by changes in Spanish law. Those changes relate to the access to health care services, mainly in regards to the provision of care to foreigners, to financial contribution from users for health care services, and to pharmaceutical assistance. In crisis situations, reforms are observed to follow a trend which restricts rights and deepens social inequalities.

Detection of circulating polysaccharide antigen of Schistosoma mansoni in hamster sera by crossed immunoelectrophoresis

Crossed immunoelectrophoresis (IEC) was used for detection of free and complexed circulating polisaccharide anodic antigen (AgCA) of Schistosoma mansoni in sera of infected hamsters. An attempt was also done to detect AgCA in human sera from patients infected with S. mansoni. The conditions for isolation and detection of complexed AgCA were established. The sensitivity of IEC was increased by incorporation of 2% polyethylene glicol (PEG) to the agarose and by maintaining the system at 4°C during the electrophoretic run. Free AgCA was detected in 12 and the complexed in 30 of the 37 hamsters sera analysed. Correlation between AgCA (free and complexed) and the parasite load was observed. AgCA was not detected, under the experimental conditions used, in human sera from 7 patients in the acute and 23 in the chronic phase of infection.

Mapping Mediterranean Portugal: Pastoral and Counter-pastoral

This article focuses on the different images of Mediterranean Portugal developed by three important Portuguese social scientists of the 20th century: the geographer Orlando Ribeiro, the ethnologist Jorge Dias and the social anthropologist José Cutileiro. The article argues that these different images stem from different ideological attitudes towards the countryside, ranging from pastoral to counter-pastoral, and are also related to different ways of addressing the links between the countryside and national identity.

The patent expiry as a major inflection point in a branded Rx drug's life and strategies to counter generic competition - exemplified at Pfizer's blockbuster drug Lipitor in the USA

A large number of expensive, but highly profitable branded prescription drugs will go off-patent in the USA between 2011 and 2015. Their revenues are crucial to fund the immense costs associated with the development of an innovative drug. The rising cost pressure on pharmaceutical stakeholders has increased the demand for more affordable medications, as provided by the branded drug's generic counterpart. Yet, research based incumbents are moving beyond the traditional late lifecycle strategies and deploy more aggressive tactics in order to protect their brands, as seen with Pfizer's Lipitor!. It is doubtful, whether these efforts will help the blockbuster business model to resist current market conditions.

External and internal dynamics in the EU's counter-terrorism policy: a political and legal analysis

Tese de Doutoramento em Ciência Política e Relações Internacionais

The word problem distinguishes counter languages

Counter automata are more powerful versions of finite state automata where addition and subtraction operations are permitted on a set of n integer registers, called counters. We show that the word problem of Zn is accepted by a nondeterministic m-counter automaton if and only if m &= n.

Macrophage migration inhibitory factor: a counter-regulator of glucocorticoid action and critical mediator of septic shock.

Recent studies have led to the discovery of a mediator that acts as an endogenous counter-regulator of glucocorticoid action within the immune system. Isolated as a product of anterior pituitary cells, this protein was found to have the sequence of macrophage migration inhibitory factor (MIF), one of the first cytokine activities to be described. Macrophages and T cells release MIF in response both to various inflammatory stimuli and upon incubation with low concentrations of glucocorticoids. The glucocorticoid-induced secretion of MIF is tightly regulated and decreases at high, anti-inflammatory steroid concentrations. Once secreted, MIF "overrides" the anti-inflammatory and immunosuppressive effects of steroids on macrophage and T-cell cytokine production. The physiological role of MIF thus appears to be to counter-balance steroid inhibition of the inflammatory response. Anti-MIF antibodies fully protect animals from experimentally induced gram-negative or gram-positive septic shock, an effect that may be the result of the increased anti-inflammatory effects of glucocorticoids after neutralization of endogenous MIF. Anti-MIF therapeutic strategies are presently under development and may prove to be a means to modulate cytokine production in septic shock as well as in other inflammatory disease states.

Accès sans prescription aux statines: bénéfique ou délétère. [Over-the-counter statins: benefit or harmful?]

Making statin available over the counter is one of the measures proposed to correct its underuse. Since May 2004, simvastatin 10 mg is sold over the counter in Great Britain. But uncertainties persist concerning the efficacy of statin in primary prevention and at a 10 mg dose. Finally, there is a risk of side effects and drug interactions. Beyond the correction of statin underuse and the hope of coronary heart disease mortality reduction, the British decision highlighted the will to give individuals a sense of responsibility concerning their health and its financial cost. Anyway, the benefit of switching statin from prescription to over the counter should be experimentally evaluated before its introduction.