Endogenous Presentation of CD8+ T Cell Epitopes from Epstein-Barr Virus–encoded Nuclear Antigen 1

Epstein-Barr virus (EBV)-encoded nuclear antigen (EBNA)1 is thought to escape cytotoxic T lymphocyte (CTL) recognition through either self-inhibition of synthesis or by blockade of proteasomal degradation by the glycine-alanine repeat (GAr) domain. Here we show that EBNA1 has a remarkably varied cell type-dependent stability. However, these different degradation rates do not correspond to the level of major histocompatibility complex class I-restricted presentation of EBNA1 epitopes. In spite of the highly stable expression of EBNA1 in B cells, CTL epitopes derived from this protein are efficiently processed and presented to CD8(+) T cells. Furthermore, we show that EBV-infected B cells can readily activate EBNA1-specific memory T cell responses from healthy virus carriers. Functional assays revealed that processing of these EBNA1 epitopes is proteasome and transporter associated with antigen processing dependent. We also show that the endogenous presentation of these epitopes is dependent on the newly synthesized protein rather than the long-lived stable EBNA1. Based on these observations, we propose that defective ribosomal products, not the full-length antigen, are the primary source of endogenously processed CD8(+) T cell epitopes front EBNA1.

Classification and analysis of integrating frameworks in multiscale modelling

Chemical engineers are turning to multiscale modelling to extend traditional modelling approaches into new application areas and to achieve higher levels of detail and accuracy. There is, however, little advice available on the best strategy to use in constructing a multiscale model. This paper presents a starting point for the systematic analysis of multiscale models by defining several integrating frameworks for linking models at different scales. It briefly explores how the nature of the information flow between the models at the different scales is influenced by the choice of framework, and presents some restrictions on model-framework compatibility. The concepts are illustrated with reference to the modelling of a catalytic packed bed reactor. (C) 2004 Elsevier Ltd. All rights reserved.

Impaired Antigen Presentation and Effectiveness of Combined Active/Passive Immunotherapy for Epithelial Tumors

Background: Although immunization with tumor antigens can eliminate many transplantable tumors in animal models, immune effector mechanisms associated with successful immunotherapy of epithelial cancers remain undefined. Methods: Skin from transgenic mice expressing the cervical cancer-associated tumor antigen human papillornavirus type 16 (HPV16) E6 or E7 proteins from a keratin 14 promoter was grafted onto syngeneic, non-transgenic mice. Skin graft rejection was measured after active immunization with HPV16 E7 and adoptive transfer of antigen-specific T cells. Cytokine secretion of lymphocytes from mice receiving skin grafts and immunotherapy was detected by enzyme-linked immunosorbent assay, and HPV16 E7-specific memory CD8(+) T cells were detected by flow cytometry and ELISPOT. Results: Skin grafts containing HPV16 E6- or E7-expressing keratinocytes were not rejected spontaneously or following immunization with E7 protein and adjuvant. Adoptive transfer of E7-specific T-cell receptor transgenic CD8(+) T cells combined with immunization resulted in induction of antigen-specific interferon gamma-secreting CD8(+) T cells and rejection of HPV16 E7-expressing grafts. Specific memory CD8(+) T cells were generated by immunotherapy. However, a further HPV16 E7 graft was rejected from animals with memory T cells only after a second E7 immunization. Conclusions: Antigen-specific CD8(+) T cells can destroy epithelium expressing HPV16 E7 tumor antigen, but presentation of E7 antigen from skin is insufficient to reactivate memory CD8(+) T cells induced by immunotherapy. Thus, effective cancer immunotherapy in humans may need to invoke sufficient effector as well as memory T cells.

The HIPASS catalogue - I. Data presentation

The H I Parkes All-Sky Survey (HIPASS) catalogue forms the largest uniform catalogue of H I sources compiled to date, with 4315 sources identified purely by their H I content. The catalogue data comprise the southern region delta < + 2&DEG; of HIPASS, the first blind H I survey to cover the entire southern sky. The rms noise for this survey is 13 mJy beam(-1) and the velocity range is -1280 to 12 700 km s(-1). Data search, verification and parametrization methods are discussed along with a description of measured quantities. Full catalogue data are made available to the astronomical community including positions, velocities, velocity widths, integrated fluxes and peak flux densities. Also available are on-sky moment maps, position-velocity moment maps and spectra of catalogue sources. A number of local large-scale features are observed in the space distribution of sources, including the super-Galactic plane and the Local Void. Notably, large-scale structure is seen at low Galactic latitudes, a region normally obscured at optical wavelengths.

Theoretical frameworks for analysing turn-based computer strategy games

This paper argues for a more specific formal methodology for the textual analysis of individual game genres. In doing so, it advances a set of formal analytical tools and a theoretical framework for the analysis of turn-based computer strategy games. The analytical tools extend the useful work of Steven Poole, who suggests a Peircian semiotic approach to the study of games as formal systems. The theoretical framework draws upon postmodern cultural theory to analyse and explain the representation of space and the organisation of knowledge in these games. The methodology and theoretical framework is supported by a textual analysis of Civilization II, a significant and influential turn-based computer strategy game. Finally, this paper suggests possibilities for future extensions of this work.

Regulation of antigen processing and presentation molecules in West Nile virus-infected human skin fibroblasts

Infection of humans with the West Nile flavivirus principally occurs via tick and mosquito bites. Here, we document the expression of antigen processing and presentation molecules in West Nile virus (WNV)-infected human skin fibroblast (HFF) cells. Using a new Flavivirus-specific antibody, 4G4, we have analyzed cell surface human leukocyte antigen (HLA) expression on virus-infected cells at a single cell level. Using this approach, we show that West Nile Virus infection alters surface HLA expression on both infected HFF and neighboring uninfected HFF cells. Interestingly, increased surface HLA evident on infected HFF cultures is almost entirely due to virus-induced interferon (IFN)alpha/beta because IFNalpha/beta-neutralizing antibodies completely prevent increased surface HLA expression. In contrast, RT-PCR analysis indicates that WNV infection results in increased mRNAs for HLA-A, -B, and -C genes, and HLA-associated molecules low molecular weight polypeptide-2 (LMP-2) and transporter associated with antigen presentation-1 (TAP-1), but induction of these mRNAs is not diminished in HFF cells cultured with IFNalpha/beta-neutralizing antibodies. Taken together, these data support the idea that that both cytokine-dependent and cytokine-independent mechanisms account for WNV-induced HLA expression in human skin fibroblasts. (C) 2004 Elsevier Inc. All rights reserved.

Case report: unusual presentation of Fasciolopsis buski in a Viet Namese child

A Viet Namese child presented with a history of abdominal pain. Shortly afterwards, he vomited eight live trematode flukes that were collected and morphologically identified as Fasciolopsis buski. The identification was confirmed by DNA analysis. Adult worms of F buski from humans are very rarely seen except at autopsy, and this is the first such report from Viet Nam. (C) 2003 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Clinical presentation of metabolic alkalosis in an adult patient with cystic fibrosis

In subtropical and tropical climates, dehydration is common in cystic fibrosis patients with respiratory exacerbations. This may lead to a clinical presentation of metabolic alkalosis with associated hyponatraemia and hypochloraemia. An adult cystic fibrosis patient who presented with a severe respiratory exacerbation accompanied by metabolic alkalosis is presented and the effects of volume correction are reported.

Conceptualizing special interest tourism - frameworks for analysis

To advance understanding of Special Interest Tourism (SIT), this paper will explore the complexities of this phenomenon in the early 21st century. First, a look at what is out there, both from a supply and demand perspective, will serve to paint a broad picture at macro-level. The paper will present a discussion of the SIT phenomenon at the macro-level within a triangular relationship of supply, demand and media. Then, a more specific look at SIT attempts to clarify the ambiguity of the term. Finally, a look at micro-level from the consumer's perspective will introduce the concepts of enduring and situational involvement, and the nature of the product. Proposed frameworks are presented to provide structure and possible directions for future research and as a means of progressing conceptual development. (c) 2004 Elsevier Ltd. All rights reserved.