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Dentritic cells and interleukin-2:cytochemical and ultrastructural study.
The aim of the present study was to verify
the effect of IL-2 on dendritic cell (DC) differentiation.
Various cytokines have been indicated as factors
inducing DC differentiation, but no data about the
interleukin-2 (IL-2) effect on DC differentiation have
been reported. Monocytes isolated from peripheral blood
were treated in vitro with the following factors: IL-2, IL-
4, GM-CSF and G-CSF alone or in combination.
Morphological (also ultrastructural) and cytochemical
observations were carried out starting from 3 to 21 days
of treatment. The results indicate that the differentiation
of cells showing dendritic pattern is related to the
presence of IL-2. Moreover a synergic effect of IL-2 and
GM-CSF was observed. The enzymatic features changed
with the culture time: before the differentiation into DC,
the stimulated cells expressed the typical pattern of
monocytes. On the contrary, at advanced stage of
differentiation, some enzyme activities changed and in
terminally differentiated dendritic cells the reactions for
peroxidase and serine esterase were negative.
Considering the morphological features, the ability
to interact with lymphocytes and the enzymatic pattern
observed, we suppose that IL-2 may act as a maturative
factor rather than as a growth factor in the DC
differentiation
Cytochemical demonstration of nitric oxide synthase and 5' nucleotidase in human glioblastoma.
Citarinostat and Momelotinib co-target HDAC6 and JAK2/STAT3 in lymphoid malignant cell lines: a potential new therapeutic combination
Histone deacetylase (HDAC) inhibitors represent an encouraging class of antitumor drugs. HDAC inhibitors induce a series of molecular and biological responses and minimal toxicity to normal cells. Citarinostat (Acy-241) is a second generation, orally administered, HDAC6-selective inhibitor. Momelotinib (CYT387) is an orally administered inhibitor of Janus kinase/signal transducer of transcription-3 (JAK/STAT3) signaling. Momelotinib showed efficacy in patients with myelofibrosis. We hypothesized that both HDAC and JAK/STAT pathways were important in lymphoproliferative disorders, and that inhibiting JAK/STAT3 and HDAC simultaneously might enhance the efficacy of momelotinib and citarinostat without increasing toxicity. Accordingly, we tested the citarinostat + momelotinib combination in lymphoid cell lines. Citarinostat + momelotinib showed strong cytotoxicity; it significantly reduced mitochondrial membrane potential, down-regulated Bcl-2 and Bcl-xL, and activated caspases 9 and 3. Caspase-8 was upregulated in only two lymphoid cell lines, which indicated activation of the extrinsic apoptotic pathway. We identified a lymphoid cell line that was only slightly sensitive to the combination treatment. We knocked down thioredoxin expression by transfecting with small interfering RNA that targeted thioredoxin. This knockdown increased cell sensitivity to the combination-induced cell death. The combination treatment reduced Bcl-2 expression, activated caspase 3, and significantly inhibited cell viability and clonogenic survival
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
Sudden onset of colitis after ablation of secretin-expressing lymphocytes in transgenic mice
Variations on the Author
“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
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