The Nordic Arthroplasty Register Association: A unique collaboration between 3 national hip arthroplasty registries with 280,201 THRs

Background and purpose The possibility of comparing results and of pooling the data has been limited for the Nordic arthroplasty registries, because of different registration systems and questionnaires. We have established a common Nordic database, in order to compare demographics and the results of total hip replacement surgery between countries. In addition, we plan to study results in patient groups in which the numbers are too small to be studied in the individual countries

Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy

Radiotherapy is one of the most successful cancer therapies. Here the effect of irradiation on antigen presentation by MHC class I molecules was studied. Cell surface expression of MHC class I molecules was increased for many days in a radiation dose-dependent manner as a consequence of three responses. Initially, enhanced degradation of existing proteins occurred which resulted in an increased intracellular peptide pool. Subsequently, enhanced translation due to activation of the mammalian target of rapamycin pathway resulted in increased peptide production, antigen presentation, as well as cytotoxic T lymphocyte recognition of irradiated cells. In addition, novel proteins were made in response to γ-irradiation, resulting in new peptides presented by MHC class I molecules, which were recognized by cytotoxic T cells. We show that immunotherapy is successful in eradicating a murine colon adenocarcinoma only when preceded by radiotherapy of the tumor tissue. Our findings indicate that directed radiotherapy can improve the efficacy of tumor immunotherapy

A Detailed Analysis of the Murine TAP Transporter Substrate Specificity

The transporter associated with antigen processing (TAP) supplies cytosolic peptides into the endoplasmic reticulum for binding to major histocompatibility complex (MHC) class I molecules. Its specificity therefore influences the repertoire of peptides presented by MHC molecules. Compared to human TAP, murine TAP's binding specificity has not been characterized as well, even though murine systems are widely used for basic studies of antigen processing and presentation.We performed a detailed experimental analysis of murine TAP binding specificity by measuring the binding affinities of 323 peptides. Based on this experimental data, a computational model of murine TAP specificity was constructed. The model was compared to previously generated data on human and murine TAP specificities. In addition, the murine TAP specificities for known epitopes and random peptides were predicted and compared to assess the impact of murine TAP selectivity on epitope selection.Comparisons to a previously constructed model of human TAP specificity confirms the well-established differences for peptide substrates with positively charged C-termini. In addition these comparisons show that several residues at the N-terminus of peptides which strongly influence binding to human TAP showed little effect on binding to murine TAP, and that the overall influence of the aminoterminal residues on peptide affinity for murine TAP is much lower than for the human transporter. Murine TAP also partly prefers different hydrophobic amino acids than human TAP in the carboxyterminal position. These species-dependent differences in specificity determined in vitro are shown to correlate with the epitope repertoire recognized in vivo. The quantitative model of binding specificity of murine TAP developed herein should be useful for interpreting epitope mapping and immunogenicity data obtained in humanized mouse models

Standardized incidence rates of total hip replacement for primary hip osteoarthritis in the 5 Nordic countries: similarities and differences

Background The national hip registers of the Nordic countries provide an opportunity to compare age- and sex-standardized annual incidence of primary total hip replacement (THR) and types of implants used for primary hip osteoarthritis (OA) in Denmark, Finland, Iceland, Norway and Sweden. Methods The data on THR were from the national total hip replacement registries, and population data were from the national statistics agencies. Annual incidence density per 100,000 was calculated for each 5-year age group and it was age- standardized using the WHO European standard population. Results Crude country-specific annual incidence (all ages) for 1996-2000 varied between 73 and 90. WHO age- standardized annual incidence (all ages) varied between 61 (Finland) and 84 (Iceland). For the ages 50-89, comprising 94-98% of all THRs for OA, annual incidence varied between 217 (Finland) and 309 (Iceland). For Norway, the sex incidence ratio (women/men) was 2, and for the other countries it was between 1.1 and 1.3. The use of uncemented and hybrid replacements was considerably higher in Finland and Denmark than in the other countries. Interpretation We found overall similarity in THR incidence between the 5 Nordic countries, but substantial differences between women and men, and in the use of different types of implant. Population-based, age-standardized and disease-specific information on THR incidence is required in order to properly explore the causes of differences in provision and practice of THR in different countries, regions and groups, and it will aid in projecting future needs

Vigorous but Short-Term Gamma Interferon T-Cell Responses against a Dominant HLA-A*02-Restricted Measles Virus Epitope in Patients with Measles

The absolute and relative abundance of major histocompatibility complex class I-presented viral epitopes is important in the induction and maintenance of antiviral cytotoxic-T-lymphocyte (CTL) responses. We demonstrate that the supra-abundant HLA-A*0201-restricted peptide KLWESPQEI of the measles virus nonstructural C protein induces strong gamma interferon CD8(+)-T-cell responses in children with acute measles. However, longitudinal analysis indicates that these responses are only short-lived. Thus, some viral epitopes that can be immunodominant during primary infection may fail to establish memory CTL responses