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61.
Aiuti A Slavin S Aker M Ficara F Deola S Mortellaro A Morecki S Andolfi G Tabucchi A Carlucci F Marinello E Cattaneo F Vai S Servida P Miniero R Roncarolo MG Bordignon C 《Science (New York, N.Y.)》2002,296(5577):2410-2413
Hematopoietic stem cell (HSC) gene therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) has shown limited clinical efficacy because of the small proportion of engrafted genetically corrected HSCs. We describe an improved protocol for gene transfer into HSCs associated with nonmyeloablative conditioning. This protocol was used in two patients for whom enzyme replacement therapy was not available, which allowed the effect of gene therapy alone to be evaluated. Sustained engraftment of engineered HSCs with differentiation into multiple lineages resulted in increased lymphocyte counts, improved immune functions (including antigen-specific responses), and lower toxic metabolites. Both patients are currently at home and clinically well, with normal growth and development. These results indicate the safety and efficacy of HSC gene therapy combined with nonmyeloablative conditioning for the treatment of SCID. 相似文献
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Sassone-Corsi P 《Science (New York, N.Y.)》2002,296(5576):2176-2178
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Kochendoerfer GG Chen SY Mao F Cressman S Traviglia S Shao H Hunter CL Low DW Cagle EN Carnevali M Gueriguian V Keogh PJ Porter H Stratton SM Wiedeke MC Wilken J Tang J Levy JJ Miranda LP Crnogorac MM Kalbag S Botti P Schindler-Horvat J Savatski L Adamson JW Kung A Kent SB Bradburne JA 《Science (New York, N.Y.)》2003,299(5608):884-887
We report the design and total chemical synthesis of "synthetic erythropoiesis protein" (SEP), a 51-kilodalton protein-polymer construct consisting of a 166-amino-acid polypeptide chain and two covalently attached, branched, and monodisperse polymer moieties that are negatively charged. The ability to control the chemistry allowed us to synthesize a macromolecule of precisely defined covalent structure. SEP was homogeneous as shown by high-resolution analytical techniques, with a mass of 50,825 +/-10 daltons by electrospray mass spectrometry, and with a pI of 5.0. In cell and animal assays for erythropoiesis, SEP displayed potent biological activity and had significantly prolonged duration of action in vivo. These chemical methods are a powerful tool in the rational design of protein constructs with potential therapeutic applications. 相似文献
65.
Polyansky OL Császár AG Shirin SV Zobov NF Barletta P Tennyson J Schwenke DW Knowles PJ 《Science (New York, N.Y.)》2003,299(5606):539-542
The spectrum of water vapor is of fundamental importance for a variety of processes, including the absorption and retention of sunlight in Earth's atmosphere. Therefore, there has long been an urgent need for a robust and accurate predictive model for this spectrum. In our work on the high-resolution spectrum of water, we report first-principles calculations that approach experimental accuracy. To achieve this, we performed exceptionally large electronic structure calculations and considered a variety of effects, including quantum electrodynamics, which have routinely been neglected in studies of small many-electron molecules. The high accuracy of the resulting ab initio procedure is demonstrated for the main isotopomers of water. 相似文献
66.
Colombo P 《Science (New York, N.Y.)》2008,322(5900):381-383
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HistoryA 2-year-old, entire female, Somali cat weighing 3.8 kg was admitted for a conjunctival graft on the right eye, for treatment of an acute descemetocele. Medetomidine 4.2 μg kg?1 and methadone 0.2 mg kg?1 were administered by intramuscular injection as preanaesthetic medication. Anaesthesia was induced using diazepam 0.26 mg kg?1 and propofol 4 mg kg?1 administered by intravenous (IV) injection. Following endotracheal intubation, anaesthesia was maintained with isoflurane delivered in oxygen (1 L minute?1) and nitrous oxide (2 L minute?1) via a non-rebreathing system. Twenty minutes after induction of anaesthesia, one drop of a 10% phenylephrine hydrochloride solution was administered topically to the right eye.Physical examinationAfter phenylephrine administration, a decrease in heart rate (from 95 to 80 beats minute?1) and an increase in arterial blood pressure occurred. The pulse then became difficult to palpate manually and multifocal ventricular premature contractions were observed on the electrocardiogram.ManagementNitrous oxide was discontinued and the isoflurane vaporizer setting was decreased from 1.5% to 0.5%. Lidocaine 1 mg kg?1 IV was administered, this resulted in ventricular bigeminy. The quality of the femoral pulse improved and was regular in rhythm and character. Surgery was completed as fast as possible. The bigeminy progressively disappeared and before disconnecting the cat from the breathing system, there was a normal sinus rhythm with a heart rate of 85 beats minute?1.Follow-upEchocardiography was performed during recovery and showed mitral and aortic valve insufficiency and dilation of the left ventricle, suggesting a reduction in systolic function. Echocardiography was repeated the following day and was normal.ConclusionsIn order to diminish the potential for cardiovascular sequelae associated with systemic absorption of ocular phenylephrine, less concentrated solutions, smaller drop size or different instillation techniques should be considered for topical use in small patients. 相似文献
70.
Giuliano Pisoni Patrizia D’Amelio Francesca Sassi Giovanni Manarolla Licia Scaccabarozzi Clara Locatelli Nausicaa Mazzocchi Mirko Baruscotti Dario DiFrancesco Paolo Moroni 《Veterinary journal (London, England : 1997)》2011,189(3):361-363
Formation of multinucleated giant cells (MGCs) by macrophage fusion is a typical cytopathic effect of lentiviral replication in caprine monocytes and MGC formation from cultured caprine peripheral blood mononuclear cells (PBMCs) has been considered to be diagnostic for small ruminant lentivirus (SRLV) infection. In this study, formation of MGCs was observed after 7–14 days when PBMCs were cultured from healthy goats free from SRLV infection. These MGCs expressed tartrate-resistant acid phosphatase, calcitonin receptor, integrin αVβ3, cathepsin K and matrix metalloproteinase 9 and were able to resorb bone in vitro in the absence of RANKL and macrophage colony stimulating factor, consistent with an osteoclast phenotype. 相似文献