Nonsense mutations, giving rise to UAA, UGA and UAG stop codons within the coding region of mRNAs, promote premature translational termination and are the leading cause of approx. 30% of inherited ...diseases, including cystic fibrosis, Duchenne muscular dystrophy and thalassaemia. For instance, in beta(0)39-thalassaemia the CAG (glutamine) codon is mutated to the UAG stop codon, leading to premature translation termination and to mRNA destabilization through the well-described NMD (nonsense-mediated mRNA decay). In order to develop an approach facilitating translation and, therefore, protection from NMD, aminoglycoside antibiotics have been tested on mRNAs carrying premature stop codons. These drugs decrease the accuracy in the codon-anticodon base-pairing, inducing a ribosomal read-through of the premature termination codons. Interestingly, recent papers have described drugs designed and produced for suppressing premature translational termination, inducing a ribosomal read-through of premature but not normal termination codons. These findings have introduced new hopes for the development of a pharmacological approach to the therapy of beta(0)39-thalassaemia. In this context, we started the development of a cellular model of the beta(0)39-thalassaemia mutation that could be used for the screening of a high number of aminoglycosides and analogous molecules. To this aim, we produced a lentiviral construct containing the beta(0)39-thalassaemia globin gene under a minimal LCR (locus control region) control and used this construct for the transduction of K562 cells, subsequently subcloned, with the purpose to obtain several K562 clones with different integration copies of the construct. These clones were then treated with Geneticin (also known as G418) and other aminoglycosides and the production of beta-globin was analysed by FACS analysis. The results obtained suggest that this experimental system is suitable for the characterization of correction of the beta(0)39-globin mutation causing beta-thalassaemia.
We report in this paper a novel thalassemia mutation (insertion of a single A nucleotide within the exon 1, at codon 18, of the beta-globin gene) associated with a deletion of the deltabeta-globin ...gene region, in a patient exhibiting high persistence of fetal hemoglobin. The novel mutation causes a frameshift with the generation of a UGA stop codon. Analysis of the parent's DNA demonstrates that the A insertion and frameshift mutation are inherited from the father, while the deltabeta-globin gene deletion is inherited from the mother. Gene dosage analysis and deletion-specific PCR demonstrate that the deletion is the (deltabeta)(0) Sicilian deletion, involving a 13.4-kb deltabeta-globin gene region.
Purpose:
To describe an extension of type B dissection into type A during endoluminal treatment of acute type B dissection.
Case Report:
A 57-year-old man with acute type B dissection underwent ...endovascular repair using 2 Excluder stent-grafts. Before releasing the second stent-graft, the patient complained of mild central chest pain, headache, and visual flashes, but no hemodynamic changes were noticed. An angiogram, performed soon afterwards, showed a retrograde extension of the dissection through the aortic arch involving both the left carotid artery and the ascending aorta. The procedure was completed, and the patient was transported to the operating room where the proximal ascending aorta was replaced. Spiral computed tomographic angiography performed 2 weeks after the procedure showed complete exclusion of the primary entry tear. At 6-month follow-up, the patient was asymptomatic; the left carotid artery dissection had disappeared.
Conclusions:
Endovascular repair of acute type B dissection is technically feasible, but longer experience will help prevent technical complications.
The effects of intramuscularly administrated vitamin E on total lipids, fatty acid profile, and lipid stability to oxidation was investigated in lamb liver. Twenty-four 5-day-old lambs were allotted ...to 4 groups of 6 each and given respectively 0 (control), 125, 200, 300 mg dl-alpha-tocopheryl acetate weekly from day 5 to 33. alpha-Tocopherol stored in lamb liver at the end of experiment showed linear correlation with the level of injected vitamin E. No effect on total lipids was found. A decrease in the level of liver thiobarbituric-acid reactive substances (TBARS), significantly correlated with liver alpha-tocopherol content, was found in vitamin E groups. The amount of linoleic and linolenic acids significantly increased in the vitamin E groups as compared to control group, and were correlated with the liver alpha-tocopherol content. TBARS were negatively correlated with the concentration of unsaturated fatty acids. Finally, in the liver of the treated groups, vitamin E concentrations in the range 30-50 micrograms/g showed adequate for an efficient protection from peroxidation of membrane lipids, and determined an increase in the unsaturated to saturated fatty acid ratio.
Flicker annoyance measurement, no matter if it is performed by processing the supplying voltage or by evaluating the light emitted by the lamp, relies on the assumption of a proper model of the ...behavior of the complex eye-brain system in presence of fluctuating light. The only experimental data available are the ones obtained, for a certain incandescent lamp, by asking several people to report their perception about flicker they were subjected to. In this paper, the possibility of achieving an "objective" evaluation of the flicker effects on human subject is investigated. In particular, the increment of the blood flow in a vessel at the optic nerve papilla is considered and taken as possible index of the annoyance due to flicker.
The response of the human eye to flicker depends on the type of lamp used. The standard flickermeter is based on the measurement of voltage and assumes the light source to be a 60 W incandescent ...lamp. When a different lamp is the source of light flicker, the standard flickermeter gives erroneous results. This paper presents a dynamic model of the eye-brain response to flicker. The model is based on the analysis of the light emitted by the lamp. A suitable measurement system has been developed and three different kinds of lamps have been considered. Experimental results show how the emitted light spectra and the human eye response to different colors determine the level of annoyance
The design of a dichroic mirror operating in S/X band for the Rosetta mission is described. In order to achieve the required performance, a trade-off between electrical and mechanical problems was ...necessary. So the shape of the holes in the dichroic plate was chosen according to good electrical performances in terms of cross-polar level and insertion losses and to acceptable mechanical deformations of the plate itself. Furthermore, a sample of the designed perforated mirror was manufactured and measured in an anechoic chamber. Software (GRASP8) simulations evaluated the impact of the dichroic plate on the electrical performances of the beam waveguide feeding the shaped Cassegrain antenna.
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