170,062 research outputs found
<i>Ift140<sup>cauli/cauli</sup></i> embryos exhibit skeletal, somite and neural tube defects.
No full text<p>Morphological and expression analysis of <i>Ift140<sup>+/+</sup></i> and <i>Ift140<sup>cauli/cauli</sup></i> embryos. Lateral view of E16.5 skull in <i>Ift140<sup>+/+</sup></i> (A) and <i>Ift140<sup>cauli/cauli</sup></i> (B) embryos. <i>Ift140<sup>cauli/cauli</sup></i> embryos exhibit fusion of the exoccipital bone and C1/C2 vertebrae (arrow in B). Ventral view of skull base in <i>Ift140<sup>+/+</sup></i> (C) and <i>Ift140<sup>cauli/cauli</sup></i> (D) embryos. <i>Ift140<sup>+/+</sup></i> (E) and <i>Ift140<sup>cauli/cauli</sup></i> (F) mandibles. The normal organisation of the ribs seen in E16.5 <i>Ift140<sup>+/+</sup></i> embryos (G) is severely disrupted in <i>Ift140<sup>cauli/cauli</sup></i> (H) with lateral branching (asterisk), thickened ossified nodules (red arrow) and abnormal costovertebral articulations (red arrowhead). (I–P) <i>In situ</i> hybridisation of gene expression patterns of <i>myogenin</i> (I–L), <i>Msx1</i> (M,N) and <i>Sox9</i> (O,P). <i>Myogenin</i> staining at E11.5 reveals the highly ordered segmental structure of a <i>Ift140<sup>+/+</sup></i> embryo (I) while in the <i>Ift140<sup>cauli/cauli</sup></i> embryo (J) <i>myogenin</i> staining reveals the presence of disorganised and branched somite-derived structures (myotome; arrow). (K,L) Sections of wholemount embryos at the level indicated by the horizontal line in I and J, illustrating the loss of segmental <i>myogenin</i> staining and the accumulation of blood within distorted and irregular intersomitic vessels (arrowheads) in <i>Ift140<sup>cauli/cauli</sup></i> embryos. (M,N) <i>Msx1</i> expression delineates the dorsal margin of the neural tube in an E11.5 <i>Ift140<sup>+/+</sup></i> embryo (M) but highlights the disrupted neural tube structure in an <i>Ift140<sup>cauli/cauli</sup></i> embryo (arrowhead in N). In addition, the neural tube is convoluted and irregular in appearance, as shown in E12.5 embryos stained for <i>Sox9</i> (arrow in P). PMX, premaxilla; MD, mandible; MX, maxilla; P, palatine; PP, palatal process; AL, alisphenoid; BS, basisphenoid; TR, tympanic ring; BO, basioccipital; EX, exoccipital; C1/C2, fused 1<sup>st</sup> and 2<sup>nd</sup> cervical vertebrae.</p
<i>Ift140<sup>cauli/caul</sup></i> mutants show palate defects, hydrops fetalis and malformation of the lungs and heart.
No full text<p>Coronal sections of E13.5 <i>Ift140<sup>+/+</sup></i> (A) and <i>Ift140<sup>cauli/cauli</sup></i> (B) palates, highlighting hypoplastic palatal shelves in <i>Ift140<sup>cauli/cauli</sup></i> embryos. Transverse sections of E13.5 <i>Ift140<sup>+/+</sup></i> (C and E) and <i>Ift140<sup>cauli/cauli</sup></i> (D and F) embryos at the level of the kidneys (C and D) and heart (E and F). <i>Ift140<sup>cauli/cauli</sup></i> mutant embryos have grossly normal kidneys but show accumulation of fluid around the kidneys and lungs (asterisks in D and F), which is not evident in <i>Ift140<sup>+/+</sup></i> controls (C and E). The lungs of <i>Ift140<sup>cauli/cauli</sup></i> embryos are also abnormal in shape (F), unlike the cone-shaped lobes seen in <i>Ift140<sup>+/+</sup></i> controls (E). The atrioventricular valves of the heart are well formed in <i>Ift140<sup>+/+</sup></i> embryos (E), but both the tricuspid and mitral valves are abnormal in <i>Ift140<sup>cauli/cauli</sup></i> mutants (F). <i>Ift140<sup>cauli/cauli</sup></i> embryos appear to have ventricular hypotrophy and the interventricular septum is not well formed (depicted by dashed line in F). An irregular accumulation of blood can also be seen in the atria and ventricles of <i>Ift140<sup>cauli/cauli</sup></i> mutants (F). T, tongue; PS, palatal shelf; K, kidneys; L, lung; RA, right atrium; RV, right ventricle; TV, tricuspid valve; MV, mitral valve.</p
An <i>Ift140</i> mutation is responsible for the ciliopathic phenotype observed in <i>cauli</i>.
No full text<p>Representative E13.5 wildtype (A) and mutant (B) embryos showing exencephaly (black arrowhead), open mouth (white arrowhead), polydactyly (asterisks) and caudal neural tube closure defects (arrow) in mutants. Chromatogram of <i>cauli</i> mutant showing the homozygous missense mutation (c.2564T>A) in the Intraflagellar Transport Protein 140 (<i>Ift140</i>) gene (C). IFT140 protein alignment showing the isoleucine to lysine substitution at position 855 of the protein in <i>cauli</i> and the corresponding amino acid across several species (D). Schematic of the IFT140 protein detailing protein domains, location of <i>Ift140<sup>cauli/cauli</sup></i> mutation and reported human mutations (E). Mainzer-Saldino (black), Jeune asphyxiating thoracic dystrophy (red), <sup>+</sup>compound heterozygous, <sup>#</sup>homozygous <sup>∧</sup>no second mutation identified. Black box represents mutation reported in this paper. Primary cilia from E10.5 <i>Ift140<sup>+/+</sup></i> (F) and <i>Ift140<sup>cauli/cauli</sup></i> (G) limb buds show a severely altered cilia morphology in the mutant.</p
Molecular signalling is disturbed in <i>Ift140<sup>cauli/cauli</sup></i> embryos.
No full text<p>WISH analysis of the forelimbs and hindlimbs of <i>Ift140<sup>+/+</sup></i> and <i>Ift140<sup>cauli/cauli</sup></i> embryos. Dorsal view of fore- and hindlimb buds (A–J′), where anterior is always to the top of the image. Distal view of forelimb buds (K′–M′), where dorsal side is facing to the right of the image. Arrowhead in (C) indicates ectopic <i>Shh</i> expression domain. Bars in (J,L and M′,N′) indicate anterior-posterior extent of <i>Grem1</i> expression. Arrowhead in (K) indicates disruption in <i>Grem1</i> expression in mutant forelimb. Asterisk in (W and X) indicates elevated anterior <i>Dusp6</i> expression. Arrow, arrowhead and asterisk in J′ indicate a single ectopic digit, bifid ectopic digit and proximal syndactyly respectively. A, anterior; P, posterior; D, dorsal; V, ventral; FL, forelimb; HL, hindlimb. All embryos are E11.5 except G′–J′ which are E13.5.</p
Epithelial cellular architecture and levels of Ift140 are altered in <i>Ift140<sup>cauli/caul</sup></i> mutants.
No full text<p>Scanning electron micrographs and immunohistochemistry of epithelia from E10.5 <i>Ift140<sup>+/+</sup></i> (A and C) and <i>Ift140<sup>cauli/cauli</sup></i> (B and D) limb buds. The rigid cellular architecture seen in wildtype limbs is highly disrupted in the mutant, as evidenced by the lack of cilia (compare arrows in A), the presence of thick, disorganised cell junctions (arrows in D) and the more diffuse E-cadherin staining in the mutant (D). Overlay of E-cad (green) and phalloidin (red) in <i>Ift140<sup>+/+</sup></i> (C) and <i>Ift140<sup>cauli/cauli</sup></i> (D) epithelium. Cilia counts identify a significant decrease in cilia (***p = 2.05×10<sup>−7</sup>) in limb buds of <i>Ift140<sup>cauli/cauli</sup></i> when compared to <i>Ift140<sup>+/+</sup></i> controls (E). Ift140 can be detected at the base and tip of wildtype limb bud cilia (F) but it undetectable in the majority of mutant cilia (G). Western blot analysis shows a reduction of Ift140 protein levels in <i>Ift140<sup>cauli/cauli</sup></i> tissue when compared to control and heterozygous samples (H), and a significant reduction of <i>Ift140</i> transcript levels (***p = 0.0026) in <i>Ift140<sup>cauli/cauli</sup></i> mutant embryos (I). Embryos harbouring a homozygous <i>Ift140</i> null allele show a complete lack of Ift140 protein by western blot (J) and exhibit identical phenotypes to those identified in <i>Ift140<sup>cauli/cauli</sup></i> embryos (K,L), including exencephaly (white arrow), open mouth (white arrowhead) and an expanded hindlimb field (asterisk). Scale bar; 2 µM (A and B), 30 µM (C and D).</p
Treatment of chronic hepatitis C in patients with glucose-6-phosphate dehydrogenase deficiency: is ribavirin harmful?
No full textTreatment for chronic hepatitis C is based on combination therapy
with pegylated interferon and ribavirin (RBV).1,2 One of the most
important side effects of RBV is hemolytic anemia, which may
require RBV dose reduction or discontinuation3 with a significant
decrease in the rate of sustained virologic response (SVR).4 Little
is known about the safety of RBV treatment in patients with
concomitant glucose-6-phosphate dehydrogenase (G6PD) deficiency,
who are inherently prone to hemolysis.
Thyroid, hemostasis and thrombosis
No full textThe aim of this paper is to briefly review
some practical aspects of the relationship
between thyroid function and several disorders
of the hemostatic system in terms of bleeding
and thrombosis. Thrombocytopenia, acquired
hemophilia, hypercoagulability, cardioembolism
and other biochemical coagulative and fibrinolytic
abnormalities have been described in the
past years both in hyper- and hypothyroidism.
Since most of hyper- and hypothyroid conditions
are the consequence of autoimmune thyroid
disease (1), either deranged immune function,
altered circulating thyroid hormone concentration,
or both may concur in the pathogenesis of
hemostatic disorders of potential crucial clinical
impact. These aspects will be outlined and discussed
in an attempt to give answers to some
questions, often arising in the clinical approach
Oral anticoagulant therapy in the primary and secondary prophylaxis of stroke
No full textAbstract
Stroke is the first cause of disability and the second cause of mortality in the world. Oral anticoagulants have been proved to be effective in the primary and secondary prophylaxis of stroke not only in cardiac conditions but also in other pathologies such as the antiphospholipid syndrome. Though the efficacy of oral anticoagulants in the prevention of stroke has been consolidated in several conditions such as mechanical prosthesis, atrial fibrillation, and the antiphospholipid syndrome, their role is less clear in patent foramen ovale, interatrial septal aneurysm, dilated cardiomyopathy, and aortic plaques. Nevertheless, oral anticoagulants have recently been re-evaluated in large clinical trials and have been shown to be effective in the secondary prevention of myocardial infarction and stroke. This review considers both the established and controversial aspects and the role of anticoagulation clinics in the practical approach to these patients, as well as their education and quality of life
Severe autoimmune hemolytic anemia in a patient with chronic hepatitis C during treatment with peginterferon alfa-2a and ribavirin
No full textPeginterferon (Peg-IFN) alfa in combination with ribavirin represents the gold standard treatment for chronic hepatitis C, but is associated with various side effects, especially hematological abnormalities. We report here a case of severe autoimmune hemolytic anemia (AIHA) complicated by symptomatic myocardial ischemia in a patient with chronic hepatitis C during combination therapy. The worsening hemolysis after ribavirin withdrawal and exclusion of other causes implicated Peg-IFN alfa as the cause of AIHA. Our study demonstrates that in patients without preexisting immunological abnormalities Peg-IFN can de novo induce autoimmune complications that, albeit rarely, may be life-threatenin
Lower-thermosphere response to solar activity: an empirical-mode-decomposition analysis of GOCE 2009–2012 data
No full textForecasting the thermosphere (the atmosphere's uppermost layer, from about 90 to 800 km altitude) is crucial to space-related applications, from space mission design to re-entry operations, space surveillance and more. Thermospheric dynamics is directly linked to the solar dynamics through the solar UV (ultraviolet) input, which is highly variable, and through the solar wind and plasma fluxes impacting Earth's magnetosphere. The solar input is non-periodic and non-stationary, with long-term modulations from the solar rotation and the solar cycle and impulsive components, due to magnetic storms. Proxies of the solar input exist and may be used to forecast the thermosphere, such as the F10.7 radio flux and the Mg II EUV (extreme-ultraviolet) flux. They relate to physical processes of the solar atmosphere. Other indices, such as the Ap geomagnetic index, connect with Earth's geomagnetic environment.
We analyse the proxies' time series comparing them with in situ density data from the ESA (European Space Agency) GOCE (Gravity Field and Steady-State Ocean Circulation Explorer) gravity mission, operational from March 2009 to November 2013, therefore covering the full rising phase of solar cycle 24, exposing the entire dynamic range of the solar input. We use empirical mode decomposition (EMD), an analysis technique appropriate to non-periodic, multi-scale signals. Data are taken at an altitude of 260 km, exceptionally low for a low-Earth-orbit (LEO) satellite, where density variations are the single most important perturbation to satellite dynamics.
We show that the synthesized signal from optimally selected combinations of proxy basis functions, notably Mg II for the solar flux and Ap for the plasma component, shows a very good agreement with thermospheric data obtained by GOCE, during periods of low and medium solar activity. In periods of maximum solar activity, density enhancements are also well represented. The Mg II index proves to be, in general, a better proxy than the F10.7 index for modelling the solar flux because of its specific response to the UV spectrum, whose variations have the largest impact over thermospheric density
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