1,583 research outputs found
Recovery of myocardial perfusion after percutaneous coronary intervention of chronic total occlusions is comparable to hemodynamically significant non-occlusive lesions.
BACKGROUND: The benefits of chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI) are being questioned. The aim of this study was to assess the effects of CTO PCI on absolute myocardial perfusion, as compared with PCI of hemodynamically significant non-CTO lesions. METHODS: Consecutive patients with a preserved left ventricular ejection fraction (â„50%) and a CTO or non-CTO lesion, in whom [15 O]H2 O positron emission tomography was performed prior and after successful PCI, were included. Change in quantitative (hyperemic) myocardial blood flow (MBF), coronary flow reserve (CFR) and perfusion defect size (in myocardial segments) were compared between CTOs and non-CTO lesions. RESULTS: In total 92 patients with a CTO and 31 patients with a non-CTO lesion were included. CTOs induced larger perfusion defect sizes (4.51 ± 1.69 vs. 3.23 ± 2.38 segments, P < 0.01) with lower hyperemic MBF (1.30 ± 0.37 vs. 1.58 ± 0.62 mL·min-1 ·g-1 , P < 0.01) and similarly impaired CFR (1.66 ± 0.75 vs. 1.89 ± 0.77, P = 0.17) compared with non-CTO lesions. After PCI both hyperemic MBF and CFR increased similarly between groups (P = 0.57 and 0.35) to normal ranges with higher hyperemic MBF values in non-CTO compared with CTO (2.89 ± 0.94 vs. 2.48 ± 0.73 mL·min-1 ·g-1 , P = 0.03). Perfusion defect sizes decreased similarly after CTO PCI and non-CTO PCI (P = 0.14), leading to small residual defect sizes in both groups (1.15 ± 1.44 vs. 0.61 ± 1.45 segments, P = 0.054). CONCLUSIONS: Myocardial perfusion findings are slightly more hampered in patients with a CTO before and after PCI. Percutaneous revascularization of CTOs, however, improves absolute myocardial perfusion similarly to PCI of hemodynamically significant non-CTO lesions, leading to satisfying results
Characterisation of the Cullin-3 mutation that causes a severe form of familial hypertension and hyperkalaemia
This is the final version of the article. Available from the publisher via the DOI in this record.Deletion of exon 9 from Cullinâ3 (CUL3, residues 403â459: CUL3Î403â459) causes pseudohypoaldosteronism type IIE (PHA2E), a severe form of familial hyperkalaemia and hypertension (FHHt). CUL3 binds the RING protein RBX1 and various substrate adaptors to form CullinâRINGâubiquitinâligase complexes. Bound to KLHL3, CUL3âRBX1 ubiquitylates WNK kinases, promoting their ubiquitinâmediated proteasomal degradation. Since WNK kinases activate Na/Cl coâtransporters to promote salt retention, CUL3 regulates blood pressure. Mutations in both KLHL3 and WNK kinases cause PHA2 by disrupting CullinâRINGâligase formation. We report here that the PHA2E mutant, CUL3Î403â459, is severely compromised in its ability to ubiquitylate WNKs, possibly due to altered structural flexibility. Instead, CUL3Î403â459 autoâubiquitylates and loses interaction with two important Cullin regulators: the COP9âsignalosome and CAND1. A novel knockâin mouse model of CUL3WT/Î403â459 closely recapitulates the human PHA2E phenotype. These mice also show changes in the arterial pulse waveform, suggesting a vascular contribution to their hypertension not reported in previous FHHt models. These findings may explain the severity of the FHHt phenotype caused by CUL3 mutations compared to those reported in KLHL3 or WNK kinases.This work was supported by the British Heart Foundation (a PhD studentship
to KS and PG 13 89 30577), Medical Research Council, and an ERC Starting
Investigator Grant (to TK), as well as the pharmaceutical companies supporting
the Division of Signal Transduction Therapy Unit (AstraZeneca, Boehringer
Ingelheim, GlaxoSmithKline, Merck, Janssen Pharmaceutica and Pfizer). The
Human Research Tissue Bank is supported by the NIHR Cambridge Biomedical
Research Centre
Moisture transport by Atlantic tropical cyclones onto the North American continent
Tropical Cyclones (TCs) are an important source of freshwater for the North American continent. Many studies have tried to estimate this contribution by identifying TC-induced precipitation events, but few have explicitly diagnosed the moisture fluxes across continental boundaries. We design a set of attribution schemes to isolate the column-integrated moisture fluxes that are directly associated with TCs and to quantify the flux onto the North American Continent due to TCs. Averaged over the 2004â2012 hurricane seasons and integrated over the western, southern and eastern coasts of North America, the seven schemes attribute 7 to 18 % (mean 14 %) of total net onshore flux to Atlantic TCs. A reduced contribution of 10 % (range 9 to 11 %) was found for the 1980â2003 period, though only two schemes could be applied to this earlier period. Over the whole 1980â2012 period, a further 8 % (range 6 to 9 % from two schemes) was attributed to East Pacific TCs, resulting in a total TC contribution of 19 % (range 17 to 22 %) to the ocean-to-land moisture transport onto the North American continent between May and November. Analysis of the attribution uncertainties suggests that incorporating details of individual TC size and shape adds limited value to a fixed radius approach and TC positional errors in the ERA-Interim reanalysis do not affect the results significantly, but biases in peak wind speeds and TC sizes may lead to underestimates of moisture transport. The interannual variability does not appear to be strongly related to the El Nino-Southern Oscillation phenomenon
Using honey to heal diabetic foot ulcers
Diabetic ulcers seem to be arrested in the inflammatory/proliferative stage of the healing process, allowing infection and inflammation to preclude healing. Antibiotic-resistant bacteria have become a major cause of infections, including diabetic foot infections. It is proposed here that the modern developments of an ancient and traditional treatment for wounds, dressing them with honey, provide the solution to the problem of getting diabetic ulcers to move on from the arrested state of healing. Honeys selected to have a high level of antibacterial activity have been shown to be very effective against antibiotic-resistant strains of bacteria in laboratory and clinical studies. The potent anti-inflammatory action of honey is also likely to play an important part in overcoming the impediment to healing that inflammation causes in diabetic ulcers, as is the antioxidant activity of honey. The action of honey in promotion of tissue regeneration through stimulation of angiogenesis and the growth of fibroblasts and epithelial cells, and its insulin-mimetic effect, would also be of benefit in stimulating the healing of diabetic ulcers. The availability of honey-impregnated dressings which conveniently hold honey in place on ulcers has provided a means of rapidly debriding ulcers and removing the bacterial burden so that good healing rates can be achieved with neuropathic ulcers. With ischemic ulcers, where healing cannot occur because of lack of tissue viability, these honey dressings keep the ulcers clean and prevent infection occurring
Genetic Editing of HBV DNA by Monodomain Human APOBEC3 Cytidine Deaminases and the Recombinant Nature of APOBEC3G
Hepatitis B virus (HBV) DNA is vulnerable to editing by human cytidine deaminases of the APOBEC3 (A3A-H) family albeit to much lower levels than HIV cDNA. We have analyzed and compared HBV editing by all seven enzymes in a quail cell line that does not produce any endogenous DNA cytidine deaminase activity. Using 3DPCR it was possible to show that all but A3DE were able to deaminate HBV DNA at levels from 10â2 to 10â5 in vitro, with A3A proving to be the most efficient editor. The amino terminal domain of A3G alone was completely devoid of deaminase activity to within the sensitivity of 3DPCR (âŒ10â4 to 10â5). Detailed analysis of the dinucleotide editing context showed that only A3G and A3H have strong preferences, notably CpC and TpC. A phylogenic analysis of A3 exons revealed that A3G is in fact a chimera with the first two exons being derived from the A3F gene. This might allow co-expression of the two genes that are able to restrict HIV-1Îvif efficiently
Organizing Effects of Sex Steroids on Brain Aromatase Activity in Quail
Preoptic/hypothalamic aromatase activity (AA) is sexually differentiated in birds and mammals but the mechanisms controlling this sex difference remain unclear. We determined here (1) brain sites where AA is sexually differentiated and (2) whether this sex difference results from organizing effects of estrogens during ontogeny or activating effects of testosterone in adulthood. In the first experiment we measured AA in brain regions micropunched in adult male and female Japanese quail utilizing the novel strategy of basing the microdissections on the distribution of aromatase-immunoreactive cells. The largest sex difference was found in the medial bed nucleus of the stria terminalis (mBST) followed by the medial preoptic nucleus (POM) and the tuberal hypothalamic region. A second experiment tested the effect of embryonic treatments known to sex-reverse male copulatory behavior (i.e., estradiol benzoate [EB] or the aromatase inhibitor, Vorozole) on brain AA in gonadectomized adult males and females chronically treated as adults with testosterone. Embryonic EB demasculinized male copulatory behavior, while vorozole blocked demasculinization of behavior in females as previously demonstrated in birds. Interestingly, these treatments did not affect a measure of appetitive sexual behavior. In parallel, embryonic vorozole increased, while EB decreased AA in pooled POM and mBST, but the same effect was observed in both sexes. Together, these data indicate that the early action of estrogens demasculinizes AA. However, this organizational action of estrogens on AA does not explain the behavioral sex difference in copulatory behavior since AA is similar in testosterone-treated males and females that were or were not exposed to embryonic treatments with estrogens
Observation of an Exotic Baryon in Exclusive Photoproduction from the Deuteron
In an exclusive measurement of the reaction , a
narrow peak that can be attributed to an exotic baryon with strangeness
is seen in the invariant mass spectrum. The peak is at
GeV/c with a measured width of 0.021 GeV/c FWHM, which is largely
determined by experimental mass resolution. The statistical significance of the
peak is . The mass and width of the observed peak are
consistent with recent reports of a narrow baryon by other experimental
groups.Comment: 5 pages, 5 figure
Measurement of Beam-Spin Asymmetries for Deep Inelastic Electroproduction
We report the first evidence for a non-zero beam-spin azimuthal asymmetry in
the electroproduction of positive pions in the deep-inelastic region. Data have
been obtained using a polarized electron beam of 4.3 GeV with the CLAS detector
at the Thomas Jefferson National Accelerator Facility (JLab). The amplitude of
the modulation increases with the momentum of the pion relative to
the virtual photon, , with an average amplitude of for range.Comment: 5 pages, RevTEX4, 3 figures, 2 table
Measurement of the Polarized Structure Function for in the Resonance Region
The polarized longitudinal-transverse structure function
has been measured in the resonance region at and 0.65
GeV. Data for the reaction were taken at Jefferson Lab
with the CEBAF Large Acceptance Spectrometer (CLAS) using longitudinally
polarized electrons at an energy of 1.515 GeV. For the first time a complete
angular distribution was measured, permitting the separation of different
non-resonant amplitudes using a partial wave analysis. Comparison with previous
beam asymmetry measurements at MAMI indicate a deviation from the predicted
dependence of using recent phenomenological
models.Comment: 5 pages, LaTex, 4 eps figures: to be published in PRC/Rapid
Communications. Version 2 has revised Q^2 analysi
Onset of asymptotic scaling in deuteron photodisintegration
We investigate the transition from the nucleon-meson to quark-gluon
description of the strong interaction using the photon energy dependence of the
differential cross section for photon energies above 0.5 GeV and
center-of-mass proton angles between and . A possible
signature for this transition is the onset of cross section scaling
with the total energy squared, , at some proton transverse momentum, .
The results show that the scaling has been reached for proton transverse
momentum above about 1.1 GeV/c. This may indicate that the quark-gluon regime
is reached above this momentum.Comment: Accepted by PRL; 5 pages, 2 figure
- âŠ