Allegoria dell’Occidente. Il patto col diavolo di Tawfiq al-Hakim

This paper aims to investigate the use and phenomenology of a Western myth – such as that of Faust – in the works of Tawfiq al-Hakim, considered to be one of the most famous and important Arab writers and dramatists, making particular reference to his tale, Ahd al-Shaytān (1938). This tale is analyzed starting from the legend of Faust and through its legacy within the thematic and iconographic world. Ahd al-Shaytān is a representative exemplum of the author’s literary idiosyncrasy given that in his works Tawfiq al-Hakim often recurs to a number of mythological themes and characters. His experience enables the exploration of this modern Western myth through the Arab tradition. At stake are the effects of an interaction between traditional and local elements and the full process of assimilation of this legacy. Tawfiq al-Hakim’s work offers an invaluable opportunity to investigate this interesting juxtaposition of Western myths and the author’s views on them. His familiarity with Western themes and patterns allows a reconsideration of Faust together with a new perspective on it.1. Scopo L’obiettivo di questo lavoro è quello di indagare le modalità e la fenomenologia della penetrazione di un mito profondamente occidentale — come quello di Faust — nella produzione di uno tra i più noti scrittori e drammaturghi arabi del Novecento: Tawfiq al-Hakim, concentrandosi in particolare su una sua novella del 1938, Ahd al-Shaytān (Il patto col diavolo). 2. Metodologia La novella, scelta in quanto exemplum rappresentativo di una pratica corrente nella produzione dell’autore, ovvero la rifunzionalizzazione di argomenti e personaggi mitologici di varia derivazione, viene analizzata nella prospettiva di una rivisitazione della leggenda di Faust e del suo patrimonio tematico e iconografico. La sua analisi permette di rilevare le tappe di un percorso assai interessante: quello della penetrazione e integrazione di un mito dell’Occidente moderno nella tradizione araba, considerato alla luce degli effetti che l’interazione con gli elementi tradizionali e autoctoni di quel patrimonio producono sul processo di assimilazione. 3. Risultati In quest’ottica, il corpus di Tawfiq al-Hakim appare fondante, non solo in virtù della sua familiarità con la trattazione di temi mitici provenienti anche dalla tradizione occidentale, ma per gli elementi di novità ed esclusività che da quella trattazione emergono. &nbsp

Tumor-associated and immunochemotherapy-dependent long-term alterations of the peripheral blood NK cell compartment in DLBCL patients

Natural Killer (NK) cells are a key component of tumor immunosurveillance and thus play an important role in rituximab-dependent killing of lymphoma cells via an antibody-dependent cellular cytotoxicity (ADCC) mechanism. We evaluated the phenotypic and functional assets of peripheral blood NK cell subsets in 32 newly-diagnosed diffuse large B-cell lymphoma (DLBCL) patients and in 27 healthy controls. We further monitored long-term modifications of patient NK cells for up to 12 months after rituximab-based immunochemotherapy. At diagnosis, patients showed a higher percentage of CD56dim and CD16C NK cells, and a higher frequency of GrzBC cells in CD56dim, CD56bright, and CD16C NK cell subsets than healthy controls. Conversely, DLBCL NK cell killing and interferon g (IFNg) production capability were comparable to those derived from healthy subjects. Notably, NK cells from refractory/relapsed patients exhibited a lower “natural” cytotoxicity. A marked and prolonged therapy-induced reduction of both “natural” and CD16- dependent NK cytotoxic activities was accompanied by the down-modulation of CD16 and NKG2D activating receptors, particularly in the CD56dim subset. However, reduced NK cell killing was not associated with defective lytic granule content or IFNg production capability. This study firstly describes tumor-associated and therapy-induced alterations of the systemic NK cell compartment in DLBCL patients. As these alterations may negatively impact rituximab-based therapy efficacy, our work may provide useful information for improving immunochemotherapeutic strategies

NKG2D/Ligand dysregulation and functional alteration of innate immunity cell populations in pediatric IBD

Background: Dysregulated innate immune responses play an important role in inflammatory bowel disease (IBD). NKG2D innate immunity receptor is a major sensor of tissue damage that, by recognizing multiple stress-induced, cell-associated ligands (MIC-A/B and ULBP1-5), potentiates the effector functions of innate-like (?/d TcR+, and natural killer receptor+ [NKR+]) T-cell populations. We analyzed the representivity, NKG2D/ligand expression pattern, and functional ability of the major innate immunity cell populations in pediatric IBD patients. Methods: We analyzed 41 Crohn's disease (CD) patients, 33 ulcerative colitis (UC) patients, and 51 age-matched non-IBD controls. The expression of NKG2D and its ligands, interferon-gamma (IFN-?) production, and cytotoxic granule release were assessed by immunostaining and multiparameter cytofluorimetric analysis on circulating and mucosal mononuclear subsets; the inflammatory infiltrate was also characterized by immunohistochemistry. Results: The expression pattern of NKG2D receptor and its ligands on mucosal and circulating innate immunity populations is severely disturbed in IBD; NKG2D and ligands are upregulated on immune infiltrate in both CD and UC active lesions; receptor/ligand upregulation also occurs on circulating leukocyte populations, where it depends on both disease activity and type (UC vs. CD). Finally, the frequency and effector capability of peripheral blood innate-like T-cell populations are also altered in IBD patients. Conclusions: The circulating and mucosal innate immunity compartment is phenotypically and functionally altered in pediatric IBD; some alterations may represent a distinctive feature of the pediatric disease condition. The disturbance of NKG2D/ligand pathway may play a role in sustaining immune activation which leads to chronic inflammatory tissue damage. (Inflamm Bowel Dis 2012

Alterations of NKG2D/ligands pathway in IBD

Background. The mucosal immune system balances the need of co-existing with commensal flora and food antigens while responding to pathogens. Inflammatory bowel disease (IBD), comprising Crohn disease (CD) and ulcerative colitis (UC), is a chronic inflam- matory condition of the gastrointestinal tract characterized by dysregulated innate and adaptive responses against commen- sal flora. The lectin-like NKG2D receptor is constitutively expressed on human NK cells, TCR , Natural Killer T (NKT, co-expressing the CD56 NK cell marker) and “clas- sical” CD8+ T cells and its expression can be positively or negatively regulated by cytokines and by chronic contact with its ligands. NKG2D engagement by its ligands triggers or potentiates lymphocyte cytotoxic activity and proinflamma- tory cytokine production. Human NKG2D ligands (MIC-A, MIC-B and the ULBP 1-4 family) are physiologically found only on mucosal and thymic epithelia in homeostatic con- ditions, but can be induced on several histotypes by stress factors as infections, neoplastic transformation and genotoxic damage. Inappropriate NKG2D-mediated lymphocyte activation, upon aberrant expression of NKG2D ligands, has been causally linked to autoimmune diseases such as rheumatoid arthritis, diabetes mellitus and celiac disease. Methods and aim. The aim of this study is to find whether alterations of the NKG2D/ligands pathway may play a role in pathogenetic mechanism leading to chronic inflammation in IBD paediatric patients. We analyzed peripheral blood monu- clear cells of 18 CD pts: 10 (with active disease, PCDAI score 10), and 8 in remission (PCDAI score 10), and 5 in remission (PUCAI score 10) and 26 age-matched non-IBD controls for the expression of NKG2D receptor, MIC-A and MIC-B molecules, by immuno-staining and FACS analysis. Results. The immunocytofluorimetric analysis of NKG2D receptor in distinct PBMC subset shows a significa- tive increase of the receptor in several T cell subpopulations, such as / TCR and NKT cells in IBD patients, as com- pared to age-matched controls. The augmented expression is selectively present in patients affected by UC (p 0.05 vs controls), while it is not shown in CD; moreover, the augmentation of NKG2D expression correlates with the activity of the disease (p 0.01 for / T cells, and p 0.05 for NK/T cells). Interestingly, constitutive expression of NKG2D on “classical” CD8+ T lymphocytes does not seem to be affected, and no induction is observed on CD4+ T lymphocytes, at variance with recent published data on adult IBD patients (Allez et al., 2007). We also assessed the expression of MIC-A/B ligands on lymphomononuclear cells. MIC-A/B expression was induced on a proportion of patients’ lymphocytes, where the induc- tion is more abundant on CD patients (p 0.05 vs controls) and correlates with the remission status (p 0.05 vs controls). Interestingly, NKG2D ligands are also induced on circulat- ing monocytes in IBD patients vs controls (p 0.05), where the induction is more pronounced in patients with the active disease (p 0.05 vs controls), and it is comparably observed both in CD and UC. Alterations in NKG2D/ligands expression pattern are also shown in patients’ mucosal samples. Conclusion. The results of this study provide a first evidence of a dysregulation in the expression of the immunoreceptor NKG2D and of its main ligands on selected mononuclear cell subsets in the peripheral blood of IBD paediatric patients. Interestingly, NKG2D expression in the periphery is augmented on innate-like T lymphocyte subpop- ulations (/ TCR, NKT), while “classical” T cell subsets (CD4+ and CD8+) display a normal phenotype; on the other hand, the induction of MIC-A/B ligands shows a distinct pattern on lymphocytes and on monocytes