2,362 research outputs found

    Expression of IL12 and IL23 receptors and cytokines in Chronic Lymphocytic Leukemia and normal B cells

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    The mechanisms of clonal expansion of CLL are only partially understood. Several interactions of neoplastic cells with accessory cells and cytokines potentially sustaining neoplastic B cell clone survival and proliferation have been described. Recently, a paracrine/autocrine loop has been reported, involving the upregulation of the IL23R complex and IL23 secretion by CLL cells. This loop drives CLL cell clonal expansion in vitro and in xenografted NSG mice. Furthermore, in situ observations on tissue sections demonstrate that infiltrating IL23 secreting CLL cells interact with macrophages and CD40L expressing T cells. Although inducible in vitro by co-culturing CLL cells with T cells or CD40L expressing cells, the IL23 loop is not observed following stimulation of CLL cells via surface Ig or contact with nurse like cells or bone marrow stromal cells. In this study, we investigated whether the IL23 loop could be induced following Toll-like receptor 9 (TLR9) engagement which influences leukemic cell survival, activation proliferation albeit in a heterogeneous manner. In addition, we explored the possible existence of an autocrine/paracrine loop mediated by IL12 which shares similarities and surface receptors with IL23 although with a likely opposite outcome in term of the possibility to sustain leukemic cell growth . IL23R and IL12R complexes (IL23R/IL12Rβ1, IL12β2/IL12Rβ1) expression were evaluated by flow-cytometry following stimulation with CpG oligodeoxynucleotide (ODN) that binds the TLR9 on CLL, showing that CLL cells are able to express the IL23R complex on membrane and, at lower extent, the IL12R complex. These receptors were assessed also in normal B cells by flow cytometry after 72h of stimulation with CpG and CpG+IL15. In this setting, normal B cells were less capable of IL23R complex expression compared to CLL cells. A further striking difference observed was related to the limited expression of IL12Rß2 receptor chain in stimulated CLL cells compared to normal B cells. Supernatants of CLL cells and normal B cells were both tested for the production of these cytokines after stimulation. The results showed a low level of IL23p19 secretion for both CLL cells and normal B cells, which is significant after CD40L stimulation (used as positive control), and a higher production of IL12p70 which is more pronounced in normal B cells compared to CLL. In another series of tests, CLL cells were stimulated with CpG for 72h, and subsequently exposed to IL12 or IL23. Exposure to IL12 and IL23 induced the expression of pSTAT1 and pSTAT3. Collectively our data corroborate the notion that IL23R complex act as a pro-survival factor for CLL cells. In contrast, the restricted IL12R complex expression in CLL cells compared to normal B cells indicated that the suppression of the expression of this receptor may favor the survival of the leukemic clones. The possibility of a reciprocal competition of the shared receptor chains is discussed

    Gruppo come spazio di transito e non luoghi

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    Nel lavoro viene descritto il concetto di non luogo, elaborato da M. Augé, in riferimento ad una esperienza di gruppo condotta con pazienti stanieri. Il non luogo, come spazio anonimo di transito, si pensi agli aeroporti, rappresenta bene la condizione sospesa del migrante. Attraverso la condivisione di vissuti di deterritorialità si possono ricercare elementi che accomunano e che rendono meno individualizzato il percorso migratorio

    Taphonomy of the Lower Permian Cardillo Quarry, Chama Basin, North-Central New Mexico

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    The Lower Permian Cardillo quarry is located near Arroyo del Agua, in the Chama Basin in north-central New Mexico. The quarry is stratigraphically high in the El Cobre Canyon Formation of the Cutler Group, which is Wolfcampian in age. During excavations in 1979, 1980 and 2002-2004, the remains of the labyrinthodont amphibian Eryops, the diadectamorph Diadectes, a captorhinid reptile, a varanopseid pelycosaur, and the pelycosaurs Sphenacodon and Ophiacodon were recovered from the Cardillo quarry. Taphonomic analysis reveals that this locality is an attritional fossil assemblage. The bones lie within a series of three distinct, pedogenically modified conglomerates that also include calcrete nodules, chert, quartzite and other siliceous pebbles. The skeletal material is mostly disarticulated, though two partially articulated pelycosaur skeletons were recovered from overbank sediments above the uppermost conglomerate. Isolated skeletal elements and bone fragments are in various stages of weathering and abrasion. The assemblage was not hydraulically sorted because all three Voorhies groups are well represented. The Cardillo quarry assemblage was formed by a series of crevasse splays that incorporated bones, bone fragments and basement clasts (siliceous pebbles). Thus, it is a classic example of a time-averaged vertebrate fossil assemblage

    Commentarii in quinque voces Porphirij autore Gasparo Cardillo Villalpandeo...

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    ColofónApostillas marginalesEnc. Perg.Sign.: A4, B-N8, O

    ROLE OF PHYSICAL ACTIVITY AND OXIDATIVE STRESS IN CACHEXIA

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    Cachexia is a muscle wasting syndrome leading to muscle atrophy and weakness associated to most chronic diseases, including cancer, acquired immune deficiency syndrome, rheumatoid arthritis, chronic obstructive pulmonary disease, renal failure. Cachexia is a critical issue in the comprehensive approach to chronic patients since it affects morbidity, mortality and quality of life. Physical exercise has important effects on secondary prevention or intervention against several diseases. Although there are good reasons to recommend regular physical activity in patient populations, recommending exercise is not a straightforward endeavor in patients with chronic diseases. Oxidative stress may be a pivotal etiological factor in the onset of cachexia. Expression of muscle specific ubiquitin ligase responsible for muscle wasting is increased by oxidative stress, whereas nitric oxide may protect against muscle atrophy. Also, endurance exercise causes oxidative stress. Thus the question arises whether to exercise or not to exercise in cachexia
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