1,613 research outputs found
Cardiopulmonary bypass via common carotid artery cannulation in redo sternotomy
There are certain situations in redo cardiac surgery in adults where it may not be possible to use alternate arterial cannulation sites like the common femoral artery and axillary artery. We report a case where we established safe cardiopulmonary bypass with common carotid artery cannulation in an adult patient. The patient underwent aortic valve replacement for severe aortic regurgitation 8 months after repair of type A aortic dissection plus aortic valve resuspension
Cytotoxic activity of the novel Akt inhibitor, MK-2206, in T-cell acute lymphoblastic leukemia.
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive neoplastic disorder arising from T-cell progenitors. T-ALL accounts for
15% of newly diagnosed ALL cases in children and 25% in adults. Although the prognosis of T-ALL has improved, due to the use of
polychemotherapy schemes, the outcome of relapsed/chemoresistant T-ALL cases is still poor. A signaling pathway that is
frequently upregulated in T-ALL, is the phosphatidylinositol 3-kinase/Akt/mTOR network. To explore whether Akt could represent a
target for therapeutic intervention in T-ALL, we evaluated the effects of the novel allosteric Akt inhibitor, MK-2206, on a panel of
human T-ALL cell lines and primary cells from T-ALL patients. MK-2206 decreased T-ALL cell line viability by blocking leukemic cells
in the G0/G1 phase of the cell cycle and inducing apoptosis. MK-2206 also induced autophagy, as demonstrated by an increase in
the 14-kDa form of LC3A/B. Western blotting analysis documented a concentration-dependent dephosphorylation of Akt and its
downstream targets, GSK-3a/b and FOXO3A, in response to MK-2206. MK-2206 was cytotoxic to primary T-ALL cells and induced
apoptosis in a T-ALL patient cell subset (CD34þ/CD4/CD7), which is enriched in leukemia-initiating cells. Taken together, our
findings indicate that Akt inhibition may represent a potential therapeutic strategy in T-ALL
Maternal neurofascin-specific autoantibodies bind to structures of the fetal nervous system during pregnancy, but have no long term effect on development in the rat
Neurofascin was recently reported as a target for axopathic autoantibodies in patients with multiple sclerosis (MS), a response that will exacerbate axonal pathology and disease severity in an animal model of multiple sclerosis. As transplacental transfer of maternal autoantibodies can permanently damage the developing nervous system we investigated whether intrauterine exposure to this neurofascin-specific response had any detrimental effect on white matter tract development. To address this question we intravenously injected pregnant rats with either a pathogenic anti-neurofascin monoclonal antibody or an appropriate isotype control on days 15 and 18 of pregnancy, respectively, to mimic the physiological concentration of maternal antibodies in the circulation of the fetus towards the end of pregnancy. Pups were monitored daily with respect to litter size, birth weight, growth and motor development. Histological studies were performed on E20 embryos and pups sacrificed on days 2, 10, 21, 32 and 45 days post partum. Results: Immunohistochemistry for light and confocal microscopy confirmed passively transferred anti-neurofascin antibody had crossed the placenta to bind to distinct structures in the developing cortex and cerebellum. However, this did not result in any significant differences in litter size, birth weight, or general physical development between litters from control mothers or those treated with the neurofascin-specific antibody. Histological analysis also failed to identify any neuronal or white matter tract abnormalities induced by the neurofascin-specific antibody. Conclusions: We show that transplacental transfer of circulating anti-neurofascin antibodies can occur and targets specific structures in the CNS of the developing fetus. However, this did not result in any pre- or post-natal abnormalities in the offspring of the treated mothers. These results assure that even if anti-neurofascin responses are detected in pregnant women with multiple sclerosis these are unlikely to have a negative effect on their children
Intragenic DNA methylation prevents spurious transcription initiation.
In mammals, DNA methylation occurs mainly at CpG dinucleotides. Methylation of the promoter suppresses gene expression, but the functional role of gene-body DNA methylation in highly expressed genes has yet to be clarified. Here we show that, in mouse embryonic stem cells, Dnmt3b-dependent intragenic DNA methylation protects the gene body from spurious RNA polymerase II entry and cryptic transcription initiation. Using different genome-wide approaches, we demonstrate that this Dnmt3b function is dependent on its enzymatic activity and recruitment to the gene body by H3K36me3. Furthermore, the spurious transcripts can either be degraded by the RNA exosome complex or capped, polyadenylated, and delivered to the ribosome to produce aberrant proteins. Elongating RNA polymerase II therefore triggers an epigenetic crosstalk mechanism that involves SetD2, H3K36me3, Dnmt3b and DNA methylation to ensure the fidelity of gene transcription initiation, with implications for intragenic hypomethylation in cance
The Observation of Up-going Charged Particles Produced by High Energy Muons in Underground Detectors
An experimental study of the production of up-going charged particles in
inelastic interactions of down-going underground muons is reported, using data
obtained from the MACRO detector at the Gran Sasso Laboratory. In a sample of
12.2 10^6 single muons, corresponding to a detector livetime of 1.55 y, 243
events are observed having an up-going particle associated with a down-going
muon. These events are analysed to determine the range and emission angle
distributions of the up-going particle, corrected for detection and
reconstruction efficiency. Measurements of the muon neutrino flux by
underground detectors are often based on the observation of through-going and
stopping muons produced in interactions in the rock below the
detector. Up-going particles produced by an undetected down-going muon are a
potential background source in these measurements. The implications of this
background for neutrino studies using MACRO are discussed.Comment: 18 pages, 9 figures. Accepted by Astrop. Physic
A search for the decay modes B+/- to h+/- tau l
We present a search for the lepton flavor violating decay modes B+/- to h+/-
tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472
million BBbar pairs. The search uses events where one B meson is fully
reconstructed in one of several hadronic final states. Using the momenta of the
reconstructed B, h, and l candidates, we are able to fully determine the tau
four-momentum. The resulting tau candidate mass is our main discriminant
against combinatorial background. We see no evidence for B+/- to h+/- tau l
decays and set a 90% confidence level upper limit on each branching fraction at
the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.
Evidence for an excess of B -> D(*) Tau Nu decays
Based on the full BaBar data sample, we report improved measurements of the
ratios R(D(*)) = B(B -> D(*) Tau Nu)/B(B -> D(*) l Nu), where l is either e or
mu. These ratios are sensitive to new physics contributions in the form of a
charged Higgs boson. We measure R(D) = 0.440 +- 0.058 +- 0.042 and R(D*) =
0.332 +- 0.024 +- 0.018, which exceed the Standard Model expectations by 2.0
sigma and 2.7 sigma, respectively. Taken together, our results disagree with
these expectations at the 3.4 sigma level. This excess cannot be explained by a
charged Higgs boson in the type II two-Higgs-doublet model. We also report the
observation of the decay B -> D Tau Nu, with a significance of 6.8 sigma.Comment: Expanded section on systematics, text corrections, improved the
format of Figure 2 and included the effect of the change of the Tau
polarization due to the charged Higg
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