437 research outputs found
Successful oxytocin-assisted nipple aspiration in women at increased risk for breast cancer
The high rate of interval malignancies urges for new screening methods for women at high risk for breast cancer. Nipple aspiration provides direct access to the breast tissue and its DNA, and therefore is a likely candidate, but clinical applications have been limited by the failure to obtain nipple aspiration fluid from most women. We performed oxytocin-assisted nipple aspiration in 90 women at increased risk for breast cancer based on family history or genetic test results (n = 63) and/or previous breast cancer (n = 34). Nipple fluid was obtained from 81/90 women (90%) and bilaterally in 77%. Mean discomfort rating was 0.6 (on a 0–10 scale), which was significantly lower than for mammography or MRI. These findings suggest that a new tool for biomarker detection in oxytocin-assisted nipple fluid of women at high risk for breast cancer is at hand
Henri Poincaré: The Status of Mechanical Explanations and the Foundations of Statistical Mechanics
The first goal of this paper is to show the evolution of Poincaré’s opinion on the mechanistic reduction of the principles of thermodynamics, placing it in the context of the science of his time. The second is to present some of his work in 1890 on the foundations of statistical mechanics. He became interested first in thermodynamics and its relation with mechanics, drawing on the work of Helm-holtz on monocyclic systems. After a period of skepticism concerning the kinetic theory, he read some of Maxwell’s memories and contributed to the foundations of statistical mechanics. I also show that Poincaré's contributions to the founda-tions of statistical mechanics are closely linked to his work in celestial mechanics and its interest in probability theory and its role in physics
Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC
We present the first results of meson production in the K^+K^- decay channel
from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by
the PHENIX detector at RHIC. Precision resonance centroid and width values are
extracted as a function of collision centrality. No significant variation from
the PDG accepted values is observed. The transverse mass spectra are fitted
with a linear exponential function for which the derived inverse slope
parameter is seen to be constant as a function of centrality. These data are
also fitted by a hydrodynamic model with the result that the freeze-out
temperature and the expansion velocity values are consistent with the values
previously derived from fitting single hadron inclusive data. As a function of
transverse momentum the collisions scaled peripheral.to.central yield ratio RCP
for the is comparable to that of pions rather than that of protons. This result
lends support to theoretical models which distinguish between baryons and
mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be
submitted to Physical Review C as a regular article. Plain text data tables
for the points plotted in figures for this and previous PHENIX publications
are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm
Neck circumference is associated with adipose tissue content in thigh skeletal muscle in overweight and obese premenopausal women
Neck circumference (NC) has been proposed as a simple and practical tool, independently associated
with cardiometabolic risk factors. However, the association of NC with inter-muscular adipose
tissue (IMAT) is still to be determined. We aimed to examine the association of NC with thigh IMAT,
and visceral adipose tissue (VAT) measured with computed tomography (CT) in overweight/obese
women. 142 premenopausal overweight and obese Caucasian women participated in this crosssectional study. NC was measured with an inextensible metallic tape above the thyroid cartilage
according to International Society for Advancement of Kinanthropometry protocol. Thigh IMAT and
VAT volumes were measured with a single cross-sectional CT. Regarding the covariates, fat mass (FM)
was assessed with dual-energy x-ray absorptiometry and physical activity was objectively measured
with accelerometry. NC was positively associated with thigh IMAT and VAT volumes (standardized
β coefcient: β=0.45, P-value= ≤0.001, β=0.60, P=≤0.001; respectively), which persisted after
adjusting for age, height, overall FM or moderate-to-vigorous physical activity. Our fndings show that
NC is associated with thigh IMAT volume in overweight and obese premenopausal Caucasian women,
regardless of the amount of lower-body fatness. These results suggest underscoring the relevance of NC
as a marker of adipose tissue content in thigh skeletal muscle.Portuguese Foundation for Science and Technology
Sapiens 358007/99Oeiras City CouncilBecel PortugalRoche Pharmaceuticals PortugalCompal PortugalUniversity of Granada Plan Propio de Investigacion 2016 -Excellence actions: Unit of Excellence on Exercise and Health (UCEES)Junta de AndaluciaEuropean Union (EU)
SOMM17/6107/UGRFundacion Carolina
C.201657496
Synergistic Inhibition of Endothelial Cell Proliferation, Tube Formation, and Sprouting by Cyclosporin A and Itraconazole
Pathological angiogenesis contributes to a number of diseases including cancer and macular degeneration. Although angiogenesis inhibitors are available in the clinic, their efficacy against most cancers is modest due in part to the existence of alternative and compensatory signaling pathways. Given that angiogenesis is dependent on multiple growth factors and a broad signaling network in vivo, we sought to explore the potential of multidrug cocktails for angiogenesis inhibition. We have screened 741 clinical drug combinations for the synergistic inhibition of endothelial cell proliferation. We focused specifically on existing clinical drugs since the re-purposing of clinical drugs allows for a more rapid and cost effective transition to clinical studies when compared to new drug entities. Our screen identified cyclosporin A (CsA), an immunosuppressant, and itraconazole, an antifungal drug, as a synergistic pair of inhibitors of endothelial cell proliferation. In combination, the IC50 dose of each drug is reduced by 3 to 9 fold. We also tested the ability of the combination to inhibit endothelial cell tube formation and sprouting, which are dependent on two essential processes in angiogenesis, endothelial cell migration and differentiation. We found that CsA and itraconazole synergistically inhibit tube network size and sprout formation. Lastly, we tested the combination on human foreskin fibroblast viability as well as Jurkat T cell and HeLa cell proliferation, and found that endothelial cells are selectively targeted. Thus, it is possible to combine existing clinical drugs to synergistically inhibit in vitro models of angiogenesis. This strategy may be useful in pursuing the next generation of antiangiogenesis therapy
Effective Rheology of Bubbles Moving in a Capillary Tube
We calculate the average volumetric flux versus pressure drop of bubbles
moving in a single capillary tube with varying diameter, finding a square-root
relation from mapping the flow equations onto that of a driven overdamped
pendulum. The calculation is based on a derivation of the equation of motion of
a bubble train from considering the capillary forces and the entropy production
associated with the viscous flow. We also calculate the configurational
probability of the positions of the bubbles.Comment: 4 pages, 1 figur
Centriole movements in mammalian epithelial cells during cytokinesis
<p>Abstract</p> <p>Background</p> <p>In cytokinesis, when the cleavage furrow has been formed, the two centrioles in each daughter cell separate. It has been suggested that the centrioles facilitate and regulate cytokinesis to some extent. It has been postulated that termination of cytokinesis (abscission) depends on the migration of a centriole to the intercellular bridge and then back to the cell center. To investigate the involvement of centrioles in cytokinesis, we monitored the movements of centrioles in three mammalian epithelial cell lines, HeLa, MCF 10A, and the p53-deficient mouse mammary tumor cell line KP-7.7, by time-lapse imaging. Centrin1-EGFP and α-Tubulin-mCherry were co-expressed in the cells to visualize respectively the centrioles and microtubules.</p> <p>Results</p> <p>Here we report that separated centrioles that migrate from the cell pole are very mobile during cytokinesis and their movements can be characterized as 1) along the nuclear envelope, 2) irregular, and 3) along microtubules forming the spindle axis. Centriole movement towards the intercellular bridge was only seen occasionally and was highly cell-line dependent.</p> <p>Conclusions</p> <p>These findings show that centrioles are highly mobile during cytokinesis and suggest that the repositioning of a centriole to the intercellular bridge is not essential for controlling abscission. We suggest that centriole movements are microtubule dependent and that abscission is more dependent on other mechanisms than positioning of centrioles.</p
Cyclophilin B Interacts with Sodium-Potassium ATPase and Is Required for Pump Activity in Proximal Tubule Cells of the Kidney
Cyclophilins (Cyps), the intracellular receptors for Cyclosporine A (CsA), are responsible for peptidyl-prolyl cis-trans isomerisation and for chaperoning several membrane proteins. Those functions are inhibited upon CsA binding. Albeit its great benefits as immunosuppressant, the use of CsA has been limited by undesirable nephrotoxic effects, including sodium retention, hypertension, hyperkalemia, interstial fibrosis and progressive renal failure in transplant recipients. In this report, we focused on the identification of novel CypB-interacting proteins to understand the role of CypB in kidney function and, in turn, to gain further insight into the molecular mechanisms of CsA-induced toxicity. By means of yeast two-hybrid screens with human kidney cDNA, we discovered a novel interaction between CypB and the membrane Na/K-ATPase β1 subunit protein (Na/K-β1) that was confirmed by pull-down, co-immunoprecipitation and confocal microscopy, in proximal tubule-derived HK-2 cells. The Na/K-ATPase pump, a key plasma membrane transporter, is responsible for maintenance of electrical Na+ and K+ gradients across the membrane. We showed that CypB silencing produced similar effects on Na/K-ATPase activity than CsA treatment in HK-2 cells. It was also observed an enrichment of both alpha and beta subunits in the ER, what suggested a possible failure on the maturation and routing of the pump from this compartment towards the plasma membrane. These data indicate that CypB through its interaction with Na/K-β1 might regulate maturation and trafficking of the pump through the secretory pathway, offering new insights into the relationship between cyclophilins and the nephrotoxic effects of CsA
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