Edema e enfisema pulmonar agudo em bovinos no Sul do Brasil: doença espontânea e reprodução experimental

Descrevem-se os dados epidemiológicos, os sinais clínicos e as lesões de quatro surtos da doença do edema e enfisema pulmonar agudo em bovinos (EEPAB) nos estados de Santa Catarina e Paraná e sua reprodução experimental. A doença espontânea ocorreu após transferência de bovinos de pastagem madura e seca para outra jovem e viçosa. Todos os bovinos afetados eram vacas das raças holandês e pardo suíço. Os principais sinais clínicos foram dispneia e respiração abdominal dificultosa com o pescoço estendido e a boca aberta. Apresentaram, também, enfisema subcutâneo, queda na produção de leite e recuperação lenta ou morte. Os achados de necropsia foram restritos ao pulmão o qual tinha coloração vermelho escuro, não colabado, de aspecto brilhante e hipercriptante com enfisema interlobular acentuado. As lesões histológicas no pulmão consistiam principalmente de enfisema alveolar e interlobular intercalado por áreas de congestão e edema, degeneração hialina da parede dos alvéolos e infiltrado de macrófagos e eosinófilos, moderado, difuso. A reprodução experimental da doença foi realizada em um bovino, com administração de 0,7mg/kg de peso corporal de L-triptofano por via oral em dose única. O animal morreu no sétimo dia de experimento. Os sinais clínicos e lesões foram idênticos aos observados na doença espontânea.</jats:p

Dasatinib impairs long-term expansion of leukemic progenitors in a subset of acute myeloid leukemia cases

A number of signaling pathways might be frequently disrupted in acute myeloid leukemia (AML). We questioned whether the dual SRC/ABL kinase inhibitor dasatinib can affect AML cells and whether differences can be observed with normal CD34+ cells. First, we demonstrated that normal cord blood (CB) CD34+ cells were unaffected by dasatinib at a low concentration (0.5 nM) in the long-term culture on MS5 stromal cells. No changes were observed in proliferation, differentiation, and colony formation. In a subset of AML cases (3/15), a distinct reduction in cell proliferation was observed, ranging from 48% to 91% inhibition at 0.5 nM of dasatinib, in particular, those characterized by BCR–ABL or KIT mutations. Moreover, the inhibitory effects of dasatinib were cytokine specific. Stem cell factor-mediated proliferation was significantly impaired, associated with a reduced phosphorylation of ERK1/2 and STAT5, whereas no effect was observed on interleukin-3 and thrombopoietin-mediated signaling despite SRC activation. In conclusion, this study demonstrates that dasatinib is a potential inhibitor in a subgroup of AML, especially those that express BCR–ABL or KIT mutations

Transverse-momentum and pseudorapidity distributions of charged hadrons in pp collisions at √s=7 TeV

This is the pre-print version of the Published Article which can be accessed from the link below.Charged-hadron transverse-momentum and pseudorapidity distributions in proton-proton collisions at √s=7  TeV are measured with the inner tracking system of the CMS detector at the LHC. The charged-hadron yield is obtained by counting the number of reconstructed hits, hit pairs, and fully reconstructed charged-particle tracks. The combination of the three methods gives a charged-particle multiplicity per unit of pseudorapidity dNch/dη||η|<0.5=5.78±0.01(stat)±0.23(syst) for non-single-diffractive events, higher than predicted by commonly used models. The relative increase in charged-particle multiplicity from √s=0.9 to 7 TeV is [66.1±1.0(stat)±4.2(syst)]%. The mean transverse momentum is measured to be 0.545±0.005(stat)±0.015(syst)  GeV/c. The results are compared with similar measurements at lower energies

Adaptor protein Lnk binds to PDGF receptor and inhibits PDGF-dependent signaling

10.1016/j.exphem.2011.02.001Experimental Hematology395591-600EXHE

Adaptor Protein Lnk Inhibits C-Fms Mediated Macrophage Function

Abstract The macrophage colony-stimulating factor receptor (c-Fms) plays an important role in proliferation, differentiation and survival of macrophages and is involved in the regulation of distinct macrophage functions. Interaction with the ligand M-CSF results in activation of the intracellular tyrosine kinase domain and phosphorylation of tyrosine residues, thereby creating binding sites for several molecules containing Src homology 2 (SH2) domains. One such protein is the adaptor Lnk that negatively regulates several hematopoietic cytokine receptors including MPL, EpoR and c-Kit. Lnk belongs to a family of proteins sharing several structural motifs including a SH2 domain and a pleckstrin homology domain. The SH2 domain is known to be essential for its inhibitory effect which can be abolished by the point mutation R392E. In this study, we investigated the ability of Lnk to interact and modulate the function of c-Fms. In order to determine if Lnk can bind to c-Fms, immunoprecipitation was performed with lysates from 293T cells co-transfected with the cDNAs for c-Fms and Lnk. Only after exposure to M-CSF, Lnk bound to c-Fms, and binding was dependent on an intact SH2 domain. To elucidate further if Lnk exhibits biological and functional effects on macrophages, we examined both in-vitro differentiated macrophages derived from the bone marrow and also macrophages harvested from peritoneum from Lnk deleted (KO) and wild type (WT) mice. These cells appeared to be at a similar stage of differentiation because expression levels of myeloid and macrophage surface markers such as F4/80, CD11b and CD11c were the same in both bone marrow-derived and peritoneum-derived macrophages from Lnk KO and WT mice. Clonogenic assays demonstrated that the number of M-CFUs in the bone marrow were elevated in Lnk KO as compared to WT mice. Furthermore, the M-CSF-induced phosphorylation of AKT in these Lnk KO macrophages was increased and prolonged compared to WT macrophages. This was associated with prominent up-regulation of c-Fms in macrophages from Lnk KO mice. We found that Lnk additionally had several functional effects on bone marrow-derived macrophages. Production of reactive oxygen species (ROS) was dramatically increased in a M-CSF-dependent manner in Lnk KO macrophages upon stimulation with zymosan. In addition, knock-out of Lnk led to altered cytokine production of macrophages: Stimulation with zymosan caused increased levels of TNFalpha and IL-6 in the KO cells, while bacterial lipoproteins (Pam3CSK4) decreased levels of TNFalpha in KO compared to WT macrophages. Last, Lnk inhibited M-CSF-induced migration of macrophages in the Boyden chamber as Lnk KO macrophages showed a significantly higher migration capacity than WT macrophages. In summary, we show for the first time that Lnk can bind to c-Fms and can blunt the stimulation of M-CSF. Modulation of levels of Lnk in macrophages may provide a unique therapeutic approach to increase innate host defenses.</jats:p

Molecular investigation of lymph nodes in patients with colon cancer: a new road to better staging

Objective: Small nodal tumor infiltrates are identified by applying multilevel sectioning and immunohistochemistry (IHC) in addition to H&amp;E (hematoxylin and eosin) stains of resected lymph nodes. However, the use of multilevel sectioning and IHC is very time-consuming and costly. The current standard analysis of lymph nodes in colon cancer patients is based on one slide per lymph node stained by H&amp;E. A new molecular diagnostic system called ''One tep Nucleic Acid Amplification'' (OSNA) was designed for a more accurate detection of lymph node metastases. The objective of the present investigation was to compare the performance ofOSNAto current standard histology (H&amp;E). We hypothesize that OSNA provides a better staging than the routine use of one slide H&amp;E per lymph node.Methods: From 22 colon cancer patients 307 frozen lymph nodes were used to compare OSNA with H&amp;E. The lymph nodes were cut into halves. One half of the lymph node was analyzed by OSNA. The semi-automated OSNA uses amplification of reverse-transcribed cytokeratin19 (CK19) mRNA directly from the homogenate. The remaining tissue was dedicated to histology, with 5 levels of H&amp;E and IHC staining (CK19).Results: On routine evaluation of oneH&amp;Eslide 7 patients were nodal positive (macro-metastases). All these patients were recognized by OSNA analysis as being positive (sensitivity 100%). Two of the remaining 15 patients had lymph node micro-metastases and 9 isolated tumor cells. For the patients with micrometastases both H&amp;E and OSNA were positive in 1 of the 2 patients. For patients with isolated tumor cells, H&amp;E was positive in 1/9 cases whereas OSNA was positive in 3/9 patients (IHC as a reference). There was only one case to be described as IHC negative/OSNA positive. On the basis of single lymph nodes the sensitivity of OSNA and the 5 levels of H&amp;E and IHC was 94・5%.Conclusion: OSNA is a novel molecular tool for the detection of lymph node metastases in colon cancer patients which provides better staging compared to the current standard evaluation of one slide H&amp;E stain. Since the use of OSNA allows the analysis of the whole lymph node, sampling bias and undetected tumor deposits due to uninvestigated material will be overcome. OSNA improves staging in colon cancer patients and may replace the current standard of H&amp;E staining in the future