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MHC class I molecules regulate brain development and plasticity in mice and HLA class I molecules are associated with brain disorders in humans. We investigated the relationship between plasma‐derived soluble human HLA class I molecules (sHLA class I), HLA class I serotypes and dementia. A cohort of HLA class I serotyped elderly subjects with no dementia/pre‐dementia (NpD, n = 28), or with dementia (D, n = 28) was studied. Multivariate analysis was used to examine the influence of dementia and HLA class I serotype on sHLA class I levels, and to compare sHLA class I within four groups according to the presence or absence of HLA‐A23/A24 and dementia. HLA‐A23/A24 and dementia, but not age, significantly influenced the level of sHLA class I. Importantly, the concurrent presence of HLA‐A23/A24 and dementia was associated with higher levels of sHLA class I (p < 0.001). This study has shown that the simultaneous presence of HLA‐A23/HLA‐A24 and dementia is associated with high levels of serum sHLA class I molecules. Thus, sHLA class I could be considered a biomarker of neurodegeneration in certain HLA class I carriers. [ABSTRACT FROM AUTHOR]

This essay considers ceremonial features represented during Christian diplomatic receptions held at the court of Cordoba, under the rule of Caliphs ʿAbd al-Raḥmān III (912‒961) and al-Ḥakam II (961‒976), in a comparative perspective. The declaration of the Umayyad Caliphate of the West by ʿAbd al-Raḥmān III marked the institutionalization of a carefully elaborated court ceremonial, reaching its greatest development under the rule of al-Ḥakam II. Detailed official ambassadorial ceremonies will be addressed, such as receptions of ambassadors from Emperor Constantine VII Porphyrogennetos, and King Otto I, or the reception and submission of Ordoño IV, deposed king of Leon, accounted by both Muslim and Christian sources. Such ceremonies will be compared with ʿAbbasid and Byzantine similar receptions, analyzing furthermore the origin and symbology of those rituals within the framework of diplomatic and cultural exchanges and encounters. [ABSTRACT FROM AUTHOR]

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by overproduction of red blood cells. We have performed a comprehensive characterization of blood immune cells for expression of naïve and memory receptors as well as β2m-associated and β2m-free MHC class I heavy chains, also known as closed and open conformers, respectively, in PV patients and age-matched controls (CTR). We show that the peripheral CD3+CD8+ T cell pool in PV patients is clearly divided into two discrete populations, a more granular CD3+CD8high T cell population enriched in effector-memory CD45RA+ T cells (CD8+ TEMRA) when compared to CTR (P < 0.001), and a less granular CD3+CD8int T cell population that is completely absent in the CTR group (78 vs. 0%, P < 0.001) and is a mixture of naïve (CD8+ TN) and CD8+ TEMRA cells expressing intermediate levels of CD28, i.e., CD3+CD8intCD28int. While the percentage of CD3+CD8int TN cells correlated positively with the number of erythrocytes, the percentage of CD3+CD8int TEMRA correlated negatively with the number of platelets. Finally, we report that PV patients' lymphocytes and monocytes display lower levels of closed (W6/32+) MHC-I conformers at the cell surface while exhibiting increased amounts of open (HC-10+) MHC-I conformers. The implications of this distinctive immune signature are discussed. [ABSTRACT FROM AUTHOR]

In the year of 839/840 (225 of the Hijrah) the first Byzantine embassy carrying a letter from Emperor Teophilus arrives at the capital of al-Andalus, Cordoba, under the rule of Emir 'Abd ar-Rahman II. The dispatch of this embassy clearly falls within the process of the oriental influence of al-Andalus as well as within the undergoing shift of supremacy in the Mediterranean of that time. Through the historical accounts in the sources al-Muqtabis II-1 by Ibn Hayyan and Nafh at-tib min ghosn al-Andalus ar-ratib wa Tarikh Lisan Addin bin Al-Khatib by al-Makkari, I shall discuss the aims of the embassy and the motivation of its dispatch in 839/840 in the framework of the historical and political circumstances of the Mediterranean. This article must be read as an essay which attempts to appreciate the meaning of this embassy, as it is part of the undergoing research thesis project of its author2. [ABSTRACT FROM AUTHOR]

Background/Aims: Host factors that may influence progression of hepatitis C infection to chronic hepatitis include T-cell responses and iron accumulation. We evaluated the hepatic expression of immunological markers relevant for a cytotoxic response in relation to viral and HFE genotype.Methods: Frozen liver biopsies were obtained at diagnosis from 28 HFE genotyped patients. Sections stained for CD8, MHC-I, β2m, HFE and CD68 were analyzed blind by morphometry. Response to therapy was available in 12 cases.Results: A negative correlation was found between the number of CD8+ cells and fibrosis. CD8+ cells localized as clusters in portal tracts and sinusoids and were seen interacting with MHC-I positive lining cells. MHC-I and β2m were expressed mainly in the endothelial and Kupffer cells. HFE was expressed in most, but not all, round and dendritic CD68+ cells. Patients with virus genotype 3a had higher hepatic MHC-I and HFE expression, and a better-sustained response to IFN therapy than other patients.Conclusions: In chronic hepatitis C virus infection MHC-I expression in the liver seems to relate to viral-genotype. In addition, the expression of MHC-I molecules by Kupffer cells places them as probable important players in the host response to HCV. [Copyright &y& Elsevier]

Although a number of inflammatory cytokines have been shown to be associated with periodontal pathogenesis, it is important to investigate further whether these biomarkers are associated with the degree of success in nonsurgical treatment of chronic periodontitis. The aim of the present study was to quantify the total levels of interleukin (IL)-1α, -1β, -6, -10 and tumour necrosis factor (TNF)-α in gingival crevicular fluid (GCF) of chronic periodontitis patients prior to and following nonsurgical periodontal therapy. In total, 52 GCF samples from disease sites of patients with chronic periodontitis, prior to and following periodontal therapy, and ten non-disease sites from non-periodontitis subjects, were collected and cytokine concentrations were determined using a multiplex method. Periodontal parameters, including bleeding on probing, probing pocket depth and the clinical attachment level, in all the sites were recorded. Untreated disease sites exhibited higher cytokine levels in the GCF when compared with the non-disease sites. Nonsurgical periodontal therapy resulted in a statistically significant decrease in the total levels of IL-1α, -1β and -6 in the GCF, but not in IL-10 or TNF-α. The results support the hypothesis that proinflammatory cytokines, including IL-1α, IL-1β and IL-6, are likely to be involved in the pathogenesis of periodontitis and are good markers to evaluate the success of nonsurgical therapy in disease sites of patients with periodontitis. [ABSTRACT FROM AUTHOR]

Abstract: During the last years several authors have described a small population of CD8+ T cells expressing NK receptors (NKRs). Although their origin remains largely unknown, we have recently demonstrated that IL-15 is capable of inducing NKR expression in purified human CD8+CD56− T cells. In this study we show that IL-15-driven NKR induction in CD8+ T cells was linked with CD56 de novo acquisition, consistent with an effector-memory phenotype, increased anti-apoptotic levels, high granzyme B/perforin expression and with the ability of displaying in vitro NK-like cytotoxicity. Interestingly, dissection of NKR functional outcome in IL-15-cultured CD8+ T cells revealed: (i) that NKG2D cross-linking was able per se to upregulate degranulation levels and (ii) that KIR and NKG2A cross-linking upregulated secretion of cytokines such as IFN-γ, TNF-α, IL-1β and IL-10. These results suggest that IL-15 is capable of differentiating CD8+ T cells into NK-like T cells displaying a regulatory phenotype. [Copyright &y& Elsevier]

Iron overload in the liver may occur in clinical conditions such as hemochromatosis and nonalcoholic steatohepatitis, and may lead to the deterioration of the normal liver architecture by mechanisms not well understood. Although a relationship between the expression of ICAM-1, and classical major histocompatibility complex (MHC) class I molecules, and iron overload has been reported, no relationship has been identified between iron overload and the expression of unconventional MHC class I molecules. Herein, we report that parameters of iron metabolism were regulated in a coordinated-fashion in a human hepatoma cell line (HepG2 cells) after iron loading, leading to increased cellular oxidative stress and growth retardation. Iron loading of HepG2 cells resulted in increased expression of Nor3.2-reactive CD1d molecules at the plasma membrane. Expression of classical MHC class I and II molecules, ICAM-1 and the epithelial CD8 ligand, gp180 was not significantly affected by iron. Considering that intracellular lipids regulate expression of CD1d at the cell surface, we examined parameters of lipid metabolism in iron-loaded HepG2 cells. Interestingly, increased expression of CD1d molecules by iron-loaded HepG2 cells was associated with increased phosphatidylserine expression in the outer leaflet of the plasma membrane and the presence of many intracellular lipid droplets. These data describe a new relationship between iron loading, lipid accumulation and altered expression of CD1d, an unconventional MHC class I molecule reported to monitor intracellular and plasma membrane lipid metabolism, in the human hepatoma cell line HepG2. [ABSTRACT FROM AUTHOR]

β2-microglobulin knockout (β2m-/-) mice represent an instructive model of spontaneous iron overload resembling genetic hemochromatosis. The mechanism of iron accumulation in this mouse model may be more complex than involving the MHC class I-like protein HFE. We report that β2m-deficient mice, like Hfe-/- mice, lack the adaptive hepatic hepcidin mRNA increase to iron overload. The inverse correlation of hepatic iron levels and hepcidin mRNA expression in six β2m-/- mice underlines the importance of hepcidin in regulating body iron stores. In contrast to Hfe-/- mice, β2m-deficient mice display increased expression of the duodenal iron transporters DMT1 and ferroportin 1. This result implicates a broader role of β2m in mammalian iron metabolism, suggesting that (an) additional β2m-interacting protein(s) could be involved in controlling iron homeostasis, and highlighting the emerging connection of iron metabolism with the immune system. [Copyright &y& Elsevier]

Studies carried out during the last few decades have consistently shown that cell surface MHC class I (MHC-I) molecules are endowed with functions unrelated with antigen presentation. These include cis–trans-interactions with inhibitory and activating KIR and LILR, and cis-interactions with receptors for hormones, growth factors, cytokines, and neurotransmitters. The mounting body of evidence indicates that these non-immunological MHC-I functions impact clinical and biomedical settings, including autoimmune responses, tumor escape, transplantation, and neuronal development. Notably, most of these functions appear to rely on the presence in hematopoietic and non-hematopoietic cells of heavy chains not associated with β2m and the peptide at the plasma membrane; these are known as open MHC-I conformers. Nowadays, open conformers are viewed as functional cis-trans structures capable of establishing physical associations with themselves, with other surface receptors, and being shed into the extracellular milieu. We review past and recent developments, strengthening the view that open conformers are multifunctional structures capable of fine-tuning cell signaling, growth, differentiation, and cell communication. [ABSTRACT FROM AUTHOR]

Background Drowning is the third leading cause of death worldwide (WHO, 2010). According to Brenner et al (2009) participating in swimming lessons (SL) can reduce by 88% the risk of drowning in children 1-4 years old, despite some controversy regarding the most appropriate swimming programs (Ward, 2009). On the other hand no studies tested the skills acquired in SL in drowning prevention. So we proposed a test to evaluate the survivability of a child that accidentally falls into the water. Methods Twenty two children (4.68±0.82yrs) who practice SL (2.01±0.91yrs/practice) were subjected to two tests: aquatic readiness (AR) (Stallman et al, 2008); and survival test (ST), which consisted of an inflatable boat ride (unknown pool; presence of the usual swim teacher; wearing t-shirt) which 'accidentally' turns. Recorded images were later observed by 6 field experts whose observations obtained an overall index of concordance (IC) of 89%. Results In ST 15 children had positive responses (n=10, 100% IC; n=1, 66% IC; n=1, 83% IC; n=3, 50% IC) and 7 (n=6, 100% IC; n=1, 66% IC) would be in danger. Conclusions Through this test, we found that not all children whose result was positive in AR had a positive performance in the ST. This brings us to observe according to Langendörfer (2011) that the positive or negative response of the subject depends on the interaction of various constraints such as individual characteristics, the environment conditions, and the state in which the swimmer is. The application of ST suggests that the inclusion of safety and prevention activities in swimming lessons, aiming to develop attitudes and motor skills as a defense to drowning, must be taken into account. More studies are necessary to provide valid information to assist pediatricians in advising parents regarding what type of SL are more appropriate to reduce drowning. [ABSTRACT FROM AUTHOR]