Limitations of HLA-transgenic mice in presentation of HLA-restricted cytotoxic T-cell epitopes from endogenously processed human papillomavirus type 16 E7 protein

We investigated the use of mice transgenic for human leucocyte antigen (HLA) A*0201 antigen-binding domains to test vaccines composed of defined HLA A*0201-restricted cytotoxic T-lymphocyte (CTL) epitopes of human papillomavirus (HPV) type 16 E7 oncoprotein. HPV is detected in >90% of cervical carcinomas. HPV16 E7 oncoprotein transforms cells of the uterine cervix and functions as a tumour-associated antigen to which immunotherapeutic strategies may be directed. We report that although the HLA A*0201 E7 epitope peptides function both to prime for E7 CTL responses, and to sensitize target cells for E7-directed CTL killing in situations where antigen processing is not required, the epitopes are not processed out of either endogenously expressed or immunization-introduced E7, by the mouse antigen-processing and presentation machinery. Thus (1) CTL induced by HLA A*0201 peptide immunization killed E7 peptide-pulsed target cells, but did not kill target cells expressing whole E7; (2) immunization with whole E7 protein did not elicit CTL directed to HLA A*0201-restricted E7 CTL epitopes; (3) HLA A*0201-restricted CTL epitopes expressed in the context of a DNA polytope vaccine did not activate E7-specific T cells either in 'conventional' HLA A*0201 transgenic (A2.1K(b) ) mice, or in HHD transgenic mice in which expression of endogenous H-2 class 1 is precluded; and (4) HLA A*0201 E7 peptide epitope immunization was incapable of preventing the growth of an HLA A*0201- and E7-expressing tumour. There are generic implications for the universal applicability of HLA-class 1 transgenic mice for studies of human CTL epitope presentation in murine models of human infectious disease where recognition of endogenously processed antigen is necessary. There are also specific implications for the use of HLA A2 transgenic mice for the development of E7-based therapeutic vaccines for cervical cancer.

Identification of the enamelin (g.8344delG) mutation in a new kindred and presentation of a standardized ENAM nomenclature

The amelogenesis imperfectas (Al) area geneticatly heterogeneous group of diseases that result in defective development of tooth enamel. Although X-linked, autosomal. dominant and autosomal. recessive forms of Al have been clinically characterized, only two genes (AMELX and ENAM) have been associated with Al. To date, three enamelin (ENAM) mutations have been identified. These mutations cause phenotypically diverse forms of autosomal. dominant Al. Detailed phenotype-genotype correlations have not been performed for autosomal. dominant Al due to ENAM mutations. We identified a previously unreported kindred segregating for the ENAM mutation, g.8344delG. Light and electron microscopy analyses of unerupted permanent teeth show the enamel is markedly reduced in thickness, Lacks a prismatic structure and has a laminated appearance. Taken together these histological features support the enamelin protein as being critical for the development of a normal. enamel. thickness and that it Likely has a role in regulating c-axis crystallite growth. Because there is growing molecular and phenotypic diversity in the enamelin defects, it is critical to have a nomenclature and numbering system for characterizing these conditions. We present a standardized nomenclature for ENAM mutations that will allow consistent reporting and communication. (C) 2003 Elsevier Science Ltd. All rights reserved.

Induction of suppressor cells following mucosal presentation of Actinomyces viscosus in mice

Mucosal presentation of Actinomyces viscosus results in antigen-specific systemic immune suppression, known as oral tolerance. The aim of the present study was to determine the mechanism by which this oral tolerance is induced. DBA/2 mice were gastrically immunized with A. viscosus. Serum, Peyer's patch (PP) and spleen cells were transferred to syngeneic recipients which were then systemically challenged with the sameiA. viscosus strain. To determine antigen-specificity of cells from gastrically immunized mice, recipients which received immune spleen cells were also challenged with Porphyromonas gingivalis. One week after the last systemic challenge, the delayed type hypersensitivity (DTH) response was determined by footpad swelling and the level of serum IgG, IgA and IgM antibodies to A. viscosus or P. gingivalis measured by an ELISA. No suppression of DTH response or of specific serum antibodies was found in recipients which received serum from gastrically immunized mice. Systemic immune suppression to A. viscosus was observed in recipients which had been transferred with PP cells obtained 2 days but not 4 and 6 days after gastric immunization with A. viscosus. Conversely, suppressed immune response could be seen in recipients transferred with spleen cells obtained 6 days after gastric immunization. The immune response to P. gingivalis remained unaltered in mice transferred with A. viscosus-gastrically immunized cells. The results of the present study suggest that oral tolerance induced by A. viscosus may be mediated by antigen-specific suppressor cells which originate in the PP and then migrate to the spleen.

Ocular scanning and perceptual size distortion in hemispatial neglect: effects of prism adaptation and sequential stimulus presentation

When asked to compare two lateralized shapes for horizontal size, neglect patients often indicate the left stimulus to be smaller. Gainotti and Tiacci (1971) hypothesized that this phenomenon might be related to a rightward bias in the patients' gaze. This study aimed to assess the relation between this size underestimation and oculomotor asymmetries. Eye movements were recorded while three neglect patients judged the horizontal extent of two rectangles. Two experimental manipulations were performed to increase the likelihood of symmetrical scanning of the stimulus display. The first manipulation entailed a sequential, rather than simultaneous presentation of the two rectangles. The second required adaptation to rightward displacing prisms, which is known to reduce many manifestations of neglect. All patients consistently underestimated the left rectangle, but the pattern of verbal responses and eye movements suggested different underlying causes. These include a distortion of space perception without ocular asymmetry, a failure to view the full leftward extent of the left stimulus, and a high-level response bias. Sequential presentation of the rectangles and prism adaptation reduced ocular asymmetries without affecting size underestimation. Overall, the results suggest that leftward size underestimation in neglect can arise for a number of different reasons. Incomplete leftward scanning may perhaps be sufficient to induce perceptual size distortion, but it is not a necessary prerequisite.

Disclosure of Intangible Assets: an Empirical Study of Financial Corporations in the Iberian Peninsula

The purpose of this paper is to analyse, firstly, to what extent intangible assets in the consolidated accounts of seven Portuguese banks and seven Spanish banks between 2006 and 2009 are disclosed and, secondly, to analyse what the most influential factors are in the above mentioned disclosure. In order to do this, before reviewing the existing literature and on the basis of other studies on this topic, a disclosure index has been created based on the requirements related to the intangible assets as stated in IAS 38. Then, two statistical analyses have been made: a univariate one for each of the explanatory variables and a multivariate one, in which all variables have been analysed. Both analyses led to the conclusion that the disclosure index of intangible assets is 0.96, where the bank dimension and the internationalization degree are the variables that are considered explanatory of the variation of the disclosure index in the regression analysis.

The impact of size and age of the company on assessing financial risk

Textiles and tourism sectors are two important sectors in Portuguese economy. Its high exposure to both internal and international economy volatility transform the companies operating in these economic sectors especially vulnerable to recent economic crises in Portugal and European Union. The objective of this paper is to evaluate and understand the impact of size and age on the financial health of textile and tourism companies, measured by economic indices. An empirical based model is proposed. Its implications are derived and tested on a sample of 4061 Portuguese companies from textile and tourism sector, during the period 2005-2009. The results conclude that age has a stronger impact on the risk of failure than size. Whereas the effect of age is generally positive regarding the financial health of the company, the effect of size is less clear and depends on the age of the company.

Financial and economic analysis of prevention of needlesticks in the hospital sector

This paper discusses the financial and economic analysis of prevention of needlestick accidents related to Occupational Health and Safety projects and presents the application to a case study involving a Hospital.

Financial Risk Analysis of Portuguese Textile and Tourism Companies

Textile and tourism sectors are two important industries in the Portuguese economy. However, its high exposure to both internal and international economic volatility make the companies operating in these economic sectors particularly vulnerable to economic crises, such as the ones which have been impacting Portugal and the European Union. The objective of this paper is to evaluate and understand the impact of size and age on the financial health of textile and tourism companies, measured by economic indices. An empirical based model is proposed. Its implications are derived and tested on a sample of 4061 Portuguese companies from textile and tourism sectors, during the period 2005-2009. The findings suggest that age has a major impact on the risk of failure, rather than size. Whereas the effect of age is generally positive regarding the financial health of the company, the effect of size is less clear and ultimately depends on the age of the company.

Financial Risk Analysis of Portuguese Textile and Tourism Companies

Textile and tourism sectors are two important industries in the Portuguese economy. However, its high exposure to both internal and international economic volatility make the companies operating in these economic sectors particularly vulnerable to economic crises, such as the ones which have been impacting Portugal and the European Union. The objective of this paper is to evaluate and understand the impact of size and age on the financial health of textile and tourism companies, measured by economic indices. An empirical based model is proposed. Its implications are derived and tested on a sample of 4061 Portuguese companies from textile and tourism sectors, during the period 2005-2009. The findings suggest that age has a major impact on the risk of failure, rather than size. Whereas the effect of age is generally positive regarding the financial health of the company, the effect of size is less clear and ultimately depends on the age of the company.