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Major Subset (major + subset)
Selected AbstractsConstitutive activation of the neuregulin-1/ErbB receptor signaling pathway is essential for the proliferation of a neoplastic Schwann cell lineGLIA, Issue 2 2003Paul W. Frohnert Abstract Neuregulin-1 (NRG-1) proteins promote Schwann cell survival, differentiation and proliferation during development. High levels of an NRG-like activity are also present in some human peripheral nerve sheath tumors, suggesting that NRG-1 isoforms may be involved in the development of these neoplasms. We examined the expression of NRG-1 and its receptors, the erbB membrane tyrosine kinases, in JS1 cells, a rapidly proliferating line derived from a chemically induced rat malignant peripheral nerve sheath tumor (MPNST). Relative to nontransformed Schwann cells, JS1 cells overexpress the NRG-1 receptor erbB3 and its erbB2 coreceptor; JS1 erbB2 transcripts show no evidence of the activating mutation commonly found in N-ethyl-N-nitrosourea-induced neoplasms. JS1 cells do not express the epidermal growth factor receptor (EGFR), a kinase implicated in the pathogenesis of a major subset of MPNSTs. JS1 cells also express mRNAs encoding multiple , and , isoforms from the glial growth factor and sensory and motor neuron-derived factor NRG-1 subfamilies. Stimulation with NRG-1, in the presence of forskolin produces a dose-dependent increase in JS1 DNA synthesis. Even in unstimulated JS1 cells, however, erbB2 and erbB3 are constitutively tyrosine phosphorylated. Reducing this constitutive phosphorylation with the specific erbB inhibitor PD158780 markedly impairs JS1 DNA synthesis. These observations support the hypothesis that NRG-1 isoforms and erbB kinases act in an autocrine and/or paracrine fashion to promote mitogenesis in JS1 cells. The absence of EGFR expression in JS1 cells suggests that constitutive activation of the NRG-1/erbB signaling pathway is an alternative means of inducing Schwann cell neoplasia. © 2003 Wiley-Liss, Inc. [source] Cross-presentation, dendritic cell subsets, and the generation of immunity to cellular antigensIMMUNOLOGICAL REVIEWS, Issue 1 2004William R. Heath Summary:, Cross-presentation involves the uptake and processing of exogenous antigens within the major histocompatibility complex (MHC) class I pathway. This process is primarily performed by dendritic cells (DCs), which are not a single cell type but may be divided into several distinct subsets. Those expressing CD8, together with CD205, found primarily in the T-cell areas of the spleen and lymph nodes, are the major subset responsible for cross-presenting cellular antigens. This ability is likely to be important for the generation of cytotoxic T-cell immunity to a variety of antigens, particularly those associated with viral infection, tumorigenesis, and DNA vaccination. At present, it is unclear whether the CD8,-expressing DC subset captures antigen directly from target cells or obtains it indirectly from intermediary DCs that traffic from peripheral sites. In this review, we examine the molecular basis for cross-presentation, discuss the role of DC subsets, and examine the contribution of this process to immunity, with some emphasis on DNA vaccination. [source] A new mesalazine foam enema (Claversal Foam) compared with a standard liquid enema in patients with active distal ulcerative colitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2002H. Malchow Background: Rectally administered mesalazine (5-aminosalicylic acid) is a recognized therapy for distal ulcerative colitis. It is frequently applied as a liquid enema. However, there are reasons (acceptability to the patient, more uniform topical dispersion and effective adhesion) to prefer a foam-based enema. Aim: This study compared a foam enema (2 g mesalazine per day, Claversal Foam) with a standard liquid enema (4 g mesalazine per day, Salofalk enema). Methods: Patients with active distal ulcerative colitis, diagnosed according to standardized criteria, were treated for 4 weeks. The primary goal was clinical remission; endoscopic remission, histological changes, global assessment and standard safety measures were also analysed. A major subset of the patients also provided quality-of-life data. Results: Both foam and liquid enema gave good rates of clinical and endoscopic remission. The foam enema was shown to be as efficacious as the reference, even though the daily dose in the foam treatment contained only half as much active drug as in the reference treatment. Minor regional differences in efficacy were seen. The tolerabilities of the two formulations were comparable. Conclusions: The foam enema offers a safe, efficacious and acceptable treatment for distal ulcerative colitis. [source] Bone marrow cells from myelodysplastic syndromes show altered immunophenotypic profiles that may contribute to the diagnosis and prognostic stratification of the disease: A pilot study on a series of 56 patients,CYTOMETRY, Issue 3 2010Sergio Matarraz Abstract A heterogeneous spectrum of immunophenotypic abnormalities have been reported in myelodysplastic syndromes (MDS). However, most studies are restricted to the analysis of CD34+ cells and/or other major subsets of CD34, cells, frequently not exploring the diagnostic and prognostic impact of immunophenotyping. Methods: We propose for the first time an immunophenotypic score (IS) based on the altered distribution and immunophenotypic features of maturing/mature compartments of bone marrow (BM) hematopoietic cells in 56 patients with MDS that could contribute to a refined diagnosis and prognostic evaluation of the disease. Results: Although MDS-associated phenotypes were detected in reactive BM, the overall immunophenotypic profile of BM cells allowed an efficient discrimination between MDS and both normal and reactive BM, once the number and degree of severity of the abnormalities detected per patient were simultaneously considered in the proposed IS. Interestingly, increasingly higher IS were found among patients with MDS showing adverse prognostic factors and in low- versus high-grade cases. The most informative prognostic factors included the number of CD34+ cells, presence of aberrant CD34,/CD117+ precursors, decreased mature neutrophils and CD34, erythroid precursors, and increased numbers of CD36,/lo erythroid precursors; in addition, the IS was an independent prognostic factor for overall survival. Conclusions: Assessment of immunophenotypic abnormalities of maturing/mature BM cells allows an efficient discrimination between MDS and both normal and reactive BM, once the number and degree of severity of the abnormalities detected are simultaneously scored. Interestingly, progressively higher IS were found among patients with MDS with adverse prognostic features and shorter overall survival. © 2010 Clinical Cytometry Society [source] CD56bright natural killer (NK) cells: an important NK cell subsetIMMUNOLOGY, Issue 4 2009Aurélie Poli Summary Human natural killer (NK) cells can be subdivided into different populations based on the relative expression of the surface markers CD16 and CD56. The two major subsets are CD56bright CD16dim/, and CD56dim CD16+, respectively. In this review, we will focus on the CD56bright NK cell subset. These cells are numerically in the minority in peripheral blood but constitute the majority of NK cells in secondary lymphoid tissues. They are abundant cytokine producers but are only weakly cytotoxic before activation. Recent data suggest that under certain conditions, they have immunoregulatory properties, and that they are probably immediate precursors of CD56dim NK cells. CD56bright NK cell percentages are expanded or reduced in a certain number of diseases, but the significance of these variations is not yet clear. [source] Regulatory T cells and asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2009D. S. Robinson Airway inflammation in asthma is characterized by activation of T helper type-2 (Th2) T cells, IgE production and eosinophilia. In many cases, this process is related to an inappropriate T cell response to environmental allergens, and other T cell-dependent pathways may also be involved (such as Th17). Regulatory T cells (Tregs) are T cells that suppress potentially harmful immune responses. Two major subsets of Treg are CD25hi, Foxp3+Tregs and IL-10-producing Tregs. There is evidence that the numbers or function of both subsets may be deficient in patients with atopic allergic disease. Recent work has extended these findings into the airway in asthma where Foxp3 expression was reduced and CD25hi Treg-suppressive function was deficient. In animal models of allergic airways disease, Tregs can suppress established airway inflammation and airway hyperresponsiveness, and protocols to enhance the development, recruitment and function of Tregs have been described. Together with studies of patients and in vitro studies of human T cells, these investigations are defining potential interventions to enhance Treg function in the airway in asthma. Existing therapies including corticosteroids and allergen immunotherapy act on Tregs, in part to increase IL-10 production, while vitamin D3 and long-acting ,-agonists enhance IL-10 Treg function. Other possibilities may be enhancement of Treg function via histamine or prostanoid receptors, or by blocking pro-inflammatory pathways that prevent suppression by Tregs (activation of Toll-like receptors, or production of cytokines such as IL-6 and TNF-,). As Tregs can also suppress the potentially beneficial immune response important for controlling infections and cancer, a therapeutic intervention should target allergen- or site-specific regulation. [source] | |||||||||||||