1,721,115 research outputs found
Cytosolic carbonic anhydrase activity in chronic myeloid disorders with different clinical phenotype
No full textReversal of bone marrow angiogenesis in chronic lymphocytic leukaemia following fludarabine therapy
No full textPrognosis factors in low-grade Non-Hodgkin's lymphomas
No full textLow-grade non-Hodgkin lymphomas were once considered as a heterogenous group of lymphomas characterized by an indolent clinical course. Today, low-grade non-Hodgkin lymphomas are classified as a group of 10 distinct entities, each characterized by unique clinicobiologic features. Follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, lymphoplasmacytic lymphoma, and marginal zone lymphoma are the most-investigated subtypes. Several studies have been performed to identify prognostic factors specific for each subtype in an effort to help clinicians in treatment decisions. The field of biologically specific associated parameters holds great potential but requires more research and work to produce translational results
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Tryptase-positive mast cells predict clinical outcome of patients with early B-cell chronic lymphocytic leukemia
No full textIt has been recently demonstrated by different groups that angiogenesis is involved in the pathogenesis of B-cell chronic lymphocytic leukemia (CLL). As a matter of fact, low cellular levels and high serum concentrations of vascular endothelial growth factor (VEGF) as well as the extent of bone marrow (BM) angiogenesis closely correlate with clinical outcome of disease (1–2).
Most studies on neoplastic transformation have focused on events that occur within transformed cells. Recents works have addressed the microenviromnent of tumor cells and documented its importance in supporting tumor progression and metastasis (3).
Among host inflammatory cells secreting angiogenic cytokines, mast cells (MC) play a crucial role (4). MC are increased and reflect BM angiogenesis in B-cell CLL (5), however, clinico-prognostic implications of such a finding has not been assessed thus far.
With this background, correlations between tryptase-positive MC and either different clinico-biologic features or disease progression risk were sought in a series based on 33 previously untreated Binet stage A patients. Briefly, two murine monoclonal antibodies (MAbs) against the endothelial cell marker CD31 (MAb 1A10) and tryptase (MAb AA1; Dako, Glostrup, Denmark) were utilized. Briefly, 4-mm-thick sections were collected on 3-amino-propyl-triethoxysilane-coated slides, deparaffinized with the xylene–ethanol sequence, rehydrated in a graded ethanol scale and in Tris-buffered saline (TBS, pH 7.6), and incubated overnight at 4°C with 1A10 (1 : 25 in TBS) and AA1 (1 : 1500 in TBS), after prior antigen retrieval by enzymatic digestion with Ficin (Sigma, St Louis, MO, USA), in a pressure cooker for 90 s in ethylenediaminetetraacetic acid buffer, pH 8 for CD31, and for 30 min at room temperature for tryptase. The immunoreaction was performed with the streptavidin-peroxidase complex (LSAB2; Dako) and with alkakine phosphatase anti-alkaline phosphatase (APAAP; Dako) and Fast Red as chromogen for tryptase, and 3,3' diaminobenzidine tetrahydrochloride (Dako) 5% as chromogen for CD31, followed by hematoxylin counterstaining. An unrelated monoclonal IgG1 produced by the P3X63/Ag8 mouse secretory myeloma replacing the MAbs served as the negative control (6).
Pearson and Spearman correlations, Kruskall–Wallis rank-sum test and the corrected chi-square analysis were applied to compare groups. Progression-free survival (PFS) curves were plotted according to Kaplan–Meier, and compared with the log-rank test.
This study was conducted in accordance to the Declaration of Helsinki.
The number of tryptase-positive MC did not reflect findings representative of tumor mass such as Rai substage (P = 0.231), absolute peripheral blood lymphocytosis (P = 0.699), β2-microglobulin (P = 0.334), and disease progression such as lymphocyte doubling time (P = 0.148). Similar results were obtained when correlations were attempted with serum levels of VEGF (P = 0.388, Fig. 1A), fibroblast growth factor-2 (FGF-2; P = 0.627, Fig. 1B) and matrix metalloproteinase-9 (MMP-9, P = 0.670).
As genomic aberrations are independent predictors of disease progression in early B-cell CLL, their correlation with the number of tryptase-positive MC was sought. Results dealing with 20 patients available for such a comparison are shown in the Fig. 1C. The stratification carried out according to the major cytogenetic categories (normal karyotype, 13q as a sole aberration, 12q trisomy, 11q or 17p deletion) made it possible to find a correlation with MC number (P = 0.03; Kruskall–Wallis analysis). Interestingly, the two patients with the worst prognostic genomic aberrations (i.e. 11q and 17p) displayed the highest number of MCs in BM.
Finally, when the 75th percentile of tryptase-positive MC was set as an arbitrary cut-off (i.e. 10), two different pattern of disease progression were obtained. Patients whose number of tryptase-positive MC was equal or higher than the 75th percentile had a median PFS time of 19 months, while the median PFS was 40 months for patients displaying a number of tryptase-positive MC lower than the 75th percentile [P = 0.03, Fig. 1D; hazard ratio (HR) 0.330; 95% confidence interval (CI) 0.07–0.923].
We have previously demonstrated in three haematological malignancies, namely multiple myeloma, B-cell non-Hodgkin's lymphoma and myelodysplastic syndromes, that there is a striking association between MC and microvessel counts and that both increase in function of tumor progression, as defined by its increasing malignancy grades (6–9). Results of the present study, although based on a relatively small patient cohort, confirm the prognostic value of increased MC of the BM also in B-cell CLL. The angiogenic potential of CLL B-cells is revealead by their capacity to produce pro- and anti-angiogenic factors. As a consquence of such an attitude, CLL B-cells produce more anti-angiogenic factors (i.e. thrombospondin-1) and less VEGF in early stage in comparison with late stage (10). The angiogenic switching previously observed in several solid tumors and leading to disease progression seems to be present also in B-cell CLL. The exact mechanisms for these biologic features is not clear, but the changes of host inflammatory cells secreting angiogenic cytokines such as MC is crucial. Potential therapeutic implications of our findings as well as the capacity to interfere with angiogenic processes, thus delaying the time of progression in early B-cell CLL, represent an interesting field of scientific speculation
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
- …
