Róza Ádány

Tumor-infiltrating myeloid-derived suppressor cells are pleiotropic-inflamed monocytes/macrophages that bear M1- and M2-type characteristics

Here, tumor‐infiltrating CD11b+ myelomonocytoid cells in murine colon adenocarcinoma‐38 and GL261 murine glioma were phenotypically characterized. Over 90% were of the CD11b+F4/80+ monocyte/macrophage lineage. They also had a myeloid‐derived suppressor cell (MDSC) phenotype, as they suppressed the proliferation of activated splenic CD8+ T cells and had a CD11b+CD11c+Gr‐1lowIL‐4Rα+ phenotype. In addition, the cells expressed CX3CR1 and CCR2 simultaneously, which are the markers of an inflammatory monocyte. The MDSCs expressed CD206, CXCL10, IL‐1β, and TNF‐α mRNAs. They also simultaneously expressed CXCL10 and CD206 proteins, which are typical, classical (M1) and alternative (M2) macrophage activation markers, respectively. Peritoneal exudate cells (PECs) strongly expressed CD36, CD206, and TGF‐β mRNA, which is characteristic of deactivated monocytes. The MDSCs also secreted TGF‐β, and in vitro culture of MDSCs and PECs with anti‐TGF‐β antibody recovered their ability to secrete NO. However, as a result of secretion of proinflammatory cytokines, MDSCs could not be categorized into deactivated monocyte/macrophages. Thus, tumor‐infiltrating MDSCs bear pleiotropic characteristics of M1 and M2 monocytes/macrophages. Furthermore, CD206 expression by tumor‐infiltrating MDSCs appears to be regulated by an autocrine mechanism that involves TGF‐β.

Factor XIII of blood coagulation in human monocytes

The presence of Factor XIII subunit a was demonstrated in human monocytes by immunoperoxidase staining using specific antisera against Factor XIII and its subunits. This finding was verified by immunobiochemical techniques, as well. In an immunoblotting system after SDS polyacrylamide gel electrophoresis of denatured monocyte homogenate a protein band comigrating with Factor XIII subunit a showed positive reaction with antibodies against this subunit or whole Factor XIII. In contrast, no subunit b of Factor XIII could be detected by either of these methods in monocytes. Activity measurements were carried out by the dansylcadaverine incorporation assay in the absence and presence of anti-Factor XIII antibody with and without thrombin activation. The expression of transglutaminase activity required thrombin and was completely abolished in presence of anti- Factor XIII antibody, which clearly indicate that practically all the transglutaminase activity measured in monocytes comes from Factor XIII. Factor XIII of monocytes and macrophages might have a role in formation of focal fibrin thrombi as well as in organization of stable, fibrinolysis resistant fibrin clot at the site of inflammation or around tumor cells.

A comparative health survey of the inhabitants of Roma settlements in Hungary.

OBJECTIVES We compared the health of people living in Roma settlements with that of the general population in Hungary. METHODS We performed comparative health interview surveys in 2003 to 2004 in representative samples of the Hungarian population and inhabitants of Roma settlements. RESULTS In persons older than 44 years, 10% more of those living in Roma settlements reported their health as bad or very bad than did those in the lowest income quartile of the general population. Of those who used any health services, 35% of the Roma inhabitants and 4.4% of the general population experienced some discrimination. In Roma settlements, the proportion of persons who thought that they could do much for their own health was 13% to 15% lower, and heavy smoking and unhealthy diet were 1.5 to 3 times more prevalent, than in the lowest income quartile of the general population. CONCLUSIONS People living in Roma settlements experience severe social exclusion, which profoundly affects their health. Besides tackling the socioeconomic roots of the poor health of Roma people, specific public health interventions, including health education and health promotion programs, are needed.

Identification of factor XIII-A as a marker of alternative macrophage activation

Abstract.Factor XIII subunit A of blood coagulation (FXIII-A) is known to be synthesized but not secreted by the monocyte/macrophage cell line. On the basis of its intracellular localization and substrate profile, FXIII-A is thought to be involved in certain intracellular processes. Our present study was designed to monitor the changes in FXIII-A gene expression and protein production in long-term culture of human monocytes during their differentiation into macrophages in the presence of activating agents (interleukin-4, interferon-γ, Mycobacterium bovis BCG) inducing classical and alternative activation pathways. By using quantitative RT-PCR and fluorescent image analysis at the single-cell level we demonstrated that the expression of FXIII-A both at the mRNA as well as at the protein level is inversely regulated during the two activation programmes. Here we conclude that FXIII-A expression is an intracellular marker for alternatively activated macrophages, while its absence in monocyte-derived macrophages indicates their classically activated state.

Factor XIII subunit A as an intracellular transglutaminase

Abstract: Over the last 2 decades there has been increasing evidence that the role of factor XIII (FXIII) is not restricted to the area of hemostasis and that its subunit A functions as an intracellular enzyme in platelets and monocytes/macrophages. FXIII is already expressed during compartmentalisation of the precursors of megakaryocyte/platelet and monocyte/macrophage cell lines in the bone marrow. FXIII-A, produced by megakaryocytes, is packaged into budding platelets and is present in huge quantity in circulating ones. It seems very likely that it plays an important role in the cytoskeletal remodelling associated with the activation stages of platelets. FXIII-A can also be detected in blood monocytes and in all subsets of monocyte-derived macrophages throughout the body. FXIII-A is mainly localised in the cytoplasm, in association with cytoskeletal filaments, but at a relatively early stage of macrophage differentiation it also appears transiently in the nucleus. Cytoplasmic expression has a very close relationship with phagocytic activities. Further research is needed to understand the biological significance of its nuclear presentation.

Does socioeconomic status fully mediate the effect of ethnicity on the health of Roma people in Hungary

Background: Several models have been proposed to explain the association between ethnicity and health. It was investigated whether the association between Roma ethnicity and health is fully mediated by socioeconomic status in Hungary. Methods: Comparative health interview surveys were performed in 2003–04 on representative samples of the Hungarian population and inhabitants of Roma settlements. Logistic regression models were applied to study whether the relationship between Roma ethnicity and health is fully mediated by socioeconomic status, and whether Roma ethnicity modifies the association between socioeconomic status and health. Results: The health status of people living in Roma settlements was poorer than that of the general population (odds ratio of severe functional limitation after adjustment for age and gender 1.8 (95% confidence interval 1.4 to 2.3)). The difference in self-reported health and in functionality was fully explained by the socioeconomic status. The less healthy behaviours of people living in Roma settlements was also related very strongly to their socioeconomic status, but remained significantly different from the general population when differences in the socioeconomic status were taken into account, (eg odds ratio of daily smoking 1.6 (95% confidence interval 1.3 to 2.0) after adjustment for age, gender, education, income and employment). Conclusion: Socioeconomic status is a strong determinant of health of people living in Roma settlements in Hungary. It fully explains their worse health status but only partially determines their less healthy behaviours. Efforts to improve the health of Roma people should include a focus on socioeconomic status, but it is important to note that cultural differences must be taken into account in developing public health interventions.

IL23R in the Swedish, Finnish, Hungarian and Italian populations: association with IBD and psoriasis, and linkage to celiac disease

BackgroundAssociation of the interleukin-23 receptor (IL23R) with inflammatory bowel disease (IBD) has been confirmed in several populations. IL23R also associates with psoriasis, suggesting that the gene may be an important candidate for many chronic inflammatory diseases.MethodsWe studied association of single-nucleotide variants in IL23R with IBD in Swedish patients, in both Crohns disease (CD) and ulcerative colitis (UC) subsets. The same genetic variants were also studied in Finnish patients with psoriasis or celiac disease, and in Hungarian and Italian patients with celiac disease.ResultsAssociation of IL23R with IBD was replicated in our Swedish patients, and linkage and association of the IL23R region with psoriasis was found in the Finnish population. The IL23R region was also linked to celiac disease in Finnish families, but no association of IL23R variants with celiac disease was found in the Finnish, Hungarian or Italian samples.ConclusionOur study is the first to demonstrate association of IL23R with CD and UC in Swedish patients with IBD. It is also the first study to report linkage and association of the IL23R region with psoriasis in the Finnish population. Importantly, this is the first report of linkage of the IL23R region to celiac disease, a chronic inflammatory condition in which IL23R has not been previously implicated.

Sustainable prevention of obesity through integrated strategies: The SPOTLIGHT project’s conceptual framework and design

BackgroundThe prevalence of overweight and obesity in Europe is high. It is a major cause of the overall rates of many of the main chronic (or non communicable) diseases in this region and is characterized by an unequal socio-economic distribution within the population. Obesity is largely determined by modifiable lifestyle behaviours such as low physical activity levels, sedentary behaviour and consumption of energy dense diets. It is increasingly being recognised that effective responses must go beyond interventions that only focus on a specific individual, social or environmental level and instead embrace system-based multi-level intervention approaches that address both the individual and environment. The EU-funded project “sustainable prevention of obesity through integrated strategies” (SPOTLIGHT) aims to increase and combine knowledge on the wide range of determinants of obesity in a systematic way, and to identify multi-level intervention approaches that are strong in terms of Reach, Efficacy, Adoption, Implementation and Maintenance (RE-AIM).Methods/DesignSPOTLIGHT comprises a series of systematic reviews on: individual-level predictors of success in behaviour change obesity interventions; social and physical environmental determinants of obesity; and on the RE-AIM of multi-level interventions. An interactive web-atlas of currently running multi-level interventions will be developed, and enhancing and impeding factors for implementation will be described. At the neighbourhood level, these elements will inform the development of methods to assess obesogenicity of diverse environments, using remote imaging techniques linked to geographic information systems. The validity of these methods will be evaluated using data from surveys of health and lifestyles of adults residing in the neighbourhoods surveyed. At both the micro- and macro-levels (national and international) the different physical, economical, political and socio-cultural elements will be assessed.DiscussionSPOTLIGHT offers the potential to develop approaches that combine an understanding of the obesogenicity of environments in Europe, and thus how they can be improved, with an appreciation of the individual factors that explain why people respond differently to such environments. Its findings will inform governmental authorities and professionals, academics, NGOs and private sector stakeholders engaged in the development and implementation of policies to tackle the obesity epidemic in Europe.

EGFR gene copy number alterations in primary cutaneous malignant melanomas are associated with poor prognosis

Copy number alterations of the epidermal growth factor receptor (EGFR) gene have been extensively analyzed in different cancers, but no data are available for primary malignant melanoma. The aim of the present study was to simultaneously investigate the EGFR gene and chromosome 7 copy number alterations in 81 cutaneous malignant melanomas by interphase FISH and correlate the data with clinicopathological parameters of patients. EGFR mRNA levels were detected by Affymetrix GeneChip Human Genome U133 Plus 2.0 expression arrays for 16 lesions. Both increased gene dosage and chromosome 7 alterations were found in 70% of tumors. Extra EGFR copies were detected in an additional 10% of samples. Polysomy 7 was associated with EGFR gene amplification. Significant correlation was found between EGFR alterations and histological subtypes, tumor thickness, ulceration and metastases formation. Amplification was significantly higher in lesions that developed metastases within 2 years after surgical excision of the primary tumor. Gene copy alterations were associated with elevated mRNA expression in 77% of lesions when compared to tumors with disomic EGFR status, the correlation was not directly proportional to gene copy number. Associations between protein expression and mRNA levels were even less prominent. In conclusion, our study indicates that amplification of the EGFR gene and polysomy 7 are frequent alterations in primary melanomas and are associated with bad prognosis. Further studies are required to clarify whether melanoma patients with EGFR alterations can benefit from anti‐EGFR therapy.

Characterisation of connective tissue cells containing factor XIII subunit a.

Paraffin embedded sections of human liver, lymph node, and placenta showed that certain connective tissue cells were positive for factor XIII subunit a. These cells were further characterised by double immunofluorescence labelling and by combined immunofluorescence and enzyme cytochemical staining on frozen sections. They were labelled by the monoclonal antibodies RFD7 and anti-Leu M3 (markers of the macrophage cell line) but gave a negative reaction for the fibroblast marker IIG10 and showed no alkaline phosphatase activity. Immunoblotting detected factor XIII subunit a in macrophages isolated from placenta but not in human fibroblasts. At lower dilutions, the commercially available antibody against the b subunit of factor XIII also positively reacted with the same cell population. The facts that immunoblotting showed that the antiserum crossreacted with the a subunit and that placental macrophages did not stain strongly for the b subunit also indicate that this antigen is not present in adult connective tissue cells.