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排序方式: 共有66条查询结果,搜索用时 31 毫秒
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Deepika S. Darbari Zhengyuan Wang Minjung Kwak Mariana Hildesheim James Nichols Darlene Allen Catherine Seamon Marlene Peters-Lawrence Anna Conrey Mary K. Hall Gregory J. Kato James G. Taylor VI 《PloS one》2013,8(11)
Background
Frequent painful vaso-occlusive crises (VOCs) were associated with mortality in the Cooperative Study of Sickle Cell Disease (CSSCD) over twenty years ago. Modern therapies for sickle cell anemia (SCA) like hydroxyurea are believed to have improved overall patient survival. The current study sought to determine the relevance of the association between more frequent VOCs and death and its relative impact upon overall mortality compared to other known risk factors in a contemporary adult SCA cohort.Methods
Two hundred sixty four SCA adults were assigned into two groups based on patient reported outcomes for emergency department (ED) visits or hospitalizations for painful VOC treatment during the 12 months prior to evaluation.Results
Higher baseline hematocrit (p = 0.0008), ferritin (p = 0.005), and HDL cholesterol (p = 0.01) were independently associated with 1 or more painful VOCs requiring an ED visit or hospitalization for acute pain. During a median follow-up of 5 years, mortality was higher in the ED visit/hospitalization group (relative risk [RR] 2.68, 95% CI 1.1-6.5, p = 0.03). Higher tricuspid regurgitatant jet velocity (TRV) (RR 2.41, 95% CI 1.5-3.9, p < 0.0001), elevated ferritin (RR 4.00, 95% CI 1.8-9.0, p = 0.001) and lower glomerular filtration rate (RR=2.73, 95% CI 1.6-4.6, p < 0.0001) were also independent risk factors for mortality.Conclusions
Severe painful VOCs remain a marker for SCA disease severity and premature mortality in a modern cohort along with other known risk factors for death including high TRV, high ferritin and lower renal function. The number of patient reported pain crises requiring healthcare utilization is an easily obtained outcome that could help to identify high risk patients for disease modifying therapies.Trial Registration
ClinicalTrials.gov NCT00011648 http://clinicaltrials.gov/ 相似文献4.
Kiselev A. V. Ostapenko O. V. Rogozhkina E. V. Kholod N. S. Seit-Nebi A. S. Baranov A. N. Lesina E. A. Ivashchenko T. E. Sabetskii V. A. Shavlovskii M. M. Rechinsky V. O. Kisselev L. L. Baranov V. S. 《Molecular Biology》2002,36(1):30-33
Nonsense mutations in the dystrophin gene are the cause of Duchenne muscular dystrophy (DMD) in 10–15% of patients. In such an event, one approach to gene therapy for DMD is the use of suppressor tRNAs to overcome the premature termination of translation of the mutant mRNA. We have carried out cotransfection of the HeLa cell culture with constructs containing a suptRNA gene (pcDNA3suptRNA) and a marker LacZ gene (pNTLacZhis) using their polymer VSST-525 complexes. It was found that the number of cells producing -galactosidase depends inversely on the dose of the suptRNA gene. A single in vivo injection of the construct providing for expression of the suptRNAochre gene into mdx mouse muscle resulted in the production of dystrophin in 2.5% of fibers. This suggests that suppressor tRNAs are applicable in gene therapy for hereditary diseases caused by nonsense mutations. 相似文献
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The BCL-xL and ACR-1 genes promote differentiation and reduce apoptosis in muscle fibers of mdx mice
Mikhaĭlov VM Kropotov AV Zelenin AV Krutilina RI Kolesnikov VA Zelenina IA Baranov AN Shteĭn GI Ostapenko OV Tomilin NV Baranov VS 《Genetika》2002,38(11):1445-1450
The effects of the human BCL-xL and ACR-1 genes on dystrophin expression in cross-striated muscle fibers (CSMF) and on CSMF viability were studied in mdx mice after ballistic cotransfection with the human dystrophin minigene. In control mice, the proportion of dystrophin-positive (D(+)) and dying CSMF were 2.1 +/- 0.1 and 2.1 +/- 0.3%, respectively. Introduction of the dystrophin minigene (20 micrograms of the pSG5dys plasmid) increased the proportions of D(+) and dying CSMF to 5.6 +/- 1.4% and 4.5 +/- 0.9%, respectively. When pSG5dys was introduced along with the pSFFV-Neo plasmid carrying the BCL-xL gene (10 micrograms of each plasmid per shot), the death of CSMF decreased to 3.7 +/- 1% and the proportion of D(+) CSMF significantly (P < 0.05) increased to 12.2 +/- 2.2%. Contransfection with the dystrophin minigene and the BCL-xL gene at 20 micrograms of each plasmid per shot did not stimulate generation of D(+) CSMF, but did reduce the CSMF death to 1.5 +/- 0.3%. Introduction of pSG5dys along with the pRc-CMV-10.1 plasmid containing the ACR-1 gene (10 micrograms of each plasmid per shot) reduced the proportion of D(+) CSMF to 1.1 +/- 0.5% and significantly reduced the proportion of dying CSMF to 0.9 +/- 0.3% as compared with the proportions observed in intact mice or in mice subjected to transfection with pSG5dys. Introduction of the pSG5dys plasmid substantially reduced the proportion of CSMF with peripheral nuclei, suggesting disturbed CSMF differentiation. After cotransfection with the human-dystrophin minigene, the BCL-xL and ACR-1 genes did not affect the extent of CSMF differentiation as compared with that observed in the case of the dystrophin minigene alone. Thus, ballistic transfection of mdx mice with the human dystrophin gene used along with the BCL-xL or ACR-1 gene was shown to suppress the death of muscle fibers and to expedite dystrophin synthesis and cell differentiation. 相似文献
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Ostrovskaia SS Ostapenko VV Waĭnson AA 《Radiatsionnaia biologiia, radioecologiia / Rossi?skaia akademiia nauk》2000,40(6):662-667
The breathing of gas mixtures containing 8-9% O2 during irradiation of tumors has been tested at several cancer clinics (in Russia and abroad) with the purpose of decreasing the morbidity of normal issues, thus providing the possibility to increase the dose of radiation. Previous experiments have demonstrated a broad spectrum of dose modification factors (DMF) for different normal tissues as well as for different transplanted tumors, with in general larger protection of normal tissues. The present study was designed to assess the radioprotective effect for mouse kidney of breathing a gas mixture containing 8% O2 by morphometry of histological specimens. Both kidneys were locally irradiated using single fractions (11-19 Gy in air and 13-19 Gy in hypoxia) or 5 fractions separated by 24 h intervals (25-35 Gy in air and 30-40 Gy in hypoxia). Histological examination was performed 8 and 10 months after treatment. The DMF for glomeruli damage (glomerulosclerosis, ecstatic capillaries, hemorrhage) was in the range 1.25-1.29. Tubular damage showed a DMF of 1.28-1.37. Using the endpoint of development of interstitial tissue in the cortex a DMF of 1.32-1.37 was found after a single treatment, and 1.48 after fractionated irradiation. The radioprotective effect for arteriolar lesions was lower than measured using the above endpoints, namely 1.13-1.15 after single and 1.16-1.18 after fractionated irradiation. It was shown previously on groups of animals treated in the same manner that the DMF was between 1.24-1.26 when renal damage was assessed by hematocrit measurements, between 1.32-1.28 when it was evaluated by urination frequency, and 1.23-1.27 when kidney wet and dry weights were used as end-points. All these data witness that breathing 8% oxygen increases the tolerance of kidney function with a DMF above 1.2. The impact of low protection of arterioli on renal function in the late period after radiotherapy needs additional study. 相似文献
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Effects of medium viscosity on kinetic parameters of poly(U) hydrolysis catalyzed by RNase from Bac. intermedius 7P (binase) were studied in solutions of sucrose (4-50 wt. %) and glycerol (35-62 wt. %) in Tris--sodium acetate buffer (pH 7.5) at 25 degreesC. The rate constant of reaction kcat was practically unchanged over a wide range of viscosities (1-15 cP for sucrose and 2.5-3 cP for glycerol). In glycerol solutions, kcat slightly increased with viscosity increase from 4 to 10 cP. Addition of NaCl to the buffer medium resulted in an inhibitory effect of Na+ on kcat, prevented by 50% sucrose or 60% glycerol. It is concluded that binase-catalyzed poly(U) cleavage occurs through a "tense"-substrate mechanism, similarly to reactions catalyzed by alpha-chymotrypsin, trypsin, and laccase. 相似文献
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Pasquier CM; Promponas VI; Varvayannis NJ; Hamodrakas SJ 《Bioinformatics (Oxford, England)》1998,14(8):749-750
Summary : FT is a tool written in C++, which implements the Fourier
analysis method to locate periodicities in aminoacid or DNA sequences. It
is provided for free public use on a WWW server with a Java interface.
Availability : The server address is http://o2.db. uoa.gr/FT Contact :
shamodr@atlas.uoa.gr
相似文献
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