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101.
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Sandi C Pinto RM Al-Mahdawi S Ezzatizadeh V Barnes G Jones S Rusche JR Gottesfeld JM Pook MA 《Neurobiology of disease》2011,42(3):496-505
Friedreich ataxia (FRDA) is an inherited neurodegenerative disorder caused by GAA repeat expansion within the FXN gene, leading to epigenetic changes and heterochromatin-mediated gene silencing that result in a frataxin protein deficit. Histone deacetylase (HDAC) inhibitors, including pimelic o-aminobenzamide compounds 106, 109 and 136, have previously been shown to reverse FXN gene silencing in short-term studies of FRDA patient cells and a knock-in mouse model, but the functional consequences of such therapeutic intervention have thus far not been described. We have now investigated the long-term therapeutic effects of 106, 109 and 136 in our GAA repeat expansion mutation-containing YG8R FRDA mouse model. We show that there is no overt toxicity up to 5 months of treatment and there is amelioration of the FRDA-like disease phenotype. Thus, while the neurological deficits of this model are mild, 109 and 106 both produced an improvement of motor coordination, whereas 109 and 136 produced increased locomotor activity. All three compounds increased global histone H3 and H4 acetylation of brain tissue, but only 109 significantly increased acetylation of specific histone residues at the FXN locus. Effects on FXN mRNA expression in CNS tissues were modest, but 109 significantly increased frataxin protein expression in brain tissue. 109 also produced significant increases in brain aconitase enzyme activity, together with reduction of neuronal pathology of the dorsal root ganglia (DRG). Overall, these results support further assessment of HDAC inhibitors for treatment of Friedreich ataxia. 相似文献
103.
Marcel F. Dvorak Peter C.Wing Michael G. Fehlings Alexander R. Vaccaro Eyal Itshayek Fin Biering-Sorensen Vanessa K. Noonan 《中国康复理论与实践》2014,20(2):196-200
收集脊柱损伤的信息对于脊髓损伤患者的诊断和治疗非常重要,设立脊髓损伤患者脊柱损伤基础数据集是为了规范脊柱损伤相关信息的收集方式和报告内容,学习并使用国际脊髓损伤脊柱损伤基础数据集,有助于规范和统一我国脊髓损伤患者脊柱损伤信息的收集,为相关治疗提供依据。本文将介绍国际脊髓损伤脊柱损伤基础数据集的研发过程,数据元素的内容以及数据编码的应用实例。 相似文献
104.
L-ascorbic acid is an essential dietary vitamin in humans, primates and certain mammals and is endogenously syn-thesised in some species. Epidemiological and ecological studies have shown that L-ascorbic acid has a protective effect against cancer, in particular non-hormone-dependent malignancies, such as oropharyngeal neoplasms. Experimental in vivo and in vitro studies, however, have yielded more controversial results, suggesting that the effects of L-ascorbic acid are dose- and perhaps, time-dependent with different effects depending on the species or organ studied. An update of the epidemiological and experimental evidence linking L-ascorbic acid to oral cancer and carcinogenesis is discussed together with a brief review of the possible mechanisms of action of L-ascorbic acid. 相似文献
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109.
Magnetic resonance (MR) imaging of jugular venous thrombosis was investigated in three patients who had symptoms suggestive of this condition; the diagnosis was later confirmed by computed tomography, by venography, and clinically. Bright intraluminal signal intensity was seen throughout the course of the affected jugular vein on MR images in all three patients, in sharp contrast to the lack of signal from the corresponding site in the uninvolved venous system. Temporal changes in signal intensity from the acute to subacute stage of thrombosis were evaluated for one patient. A relative increase in signal intensity for the subacute phase was believed to be related to a decrease in the T1 relaxation time. MR may be the imaging modality of choice in the investigation of venous thrombosis. 相似文献
110.
Clinical application of human egg cryopreservation 总被引:20,自引:17,他引:3
Tucker MJ; Morton PC; Wright G; Sweitzer CL; Massey JB 《Human reproduction (Oxford, England)》1998,13(11):3156-3159
Clinical egg cryopreservation has been applied during a 4-year period with
some limited success. Mostly mature and a few immature eggs were frozen
slowly and thawed rapidly in 1,2-propanediol and sucrose, and subsequently
inseminated by intracytoplasmic sperm injection (ICSI). Three studies were
performed in which: (i) it was established that 55% of aged unfertilized
mature eggs survive freezing; (ii) in 22 cycles of thawed donated eggs
cryosurvival was 24% with 15 cycles reaching transfer, and five pregnancies
were initiated, one of which went to term at 39 weeks with fraternal twin
boys, and one remains ongoing at 37 weeks; and (iii) in five cycles, where
in-vitro fertilization patients had some of their own eggs frozen/ thawed,
cryosurvival of mature eggs was poor at only 2.2%, although 44% sibling
germinal vesicle (GV) stage eggs survived. A normal female infant delivered
at 40 weeks arose from transfer of two embryos where GV eggs underwent in-
vitro maturation post-thaw and were fertilized by ICSI. Pregnancies
reported here and by others indicate a burgeoning awareness of the
potential benefits of egg cryopreservation, prompting cautious optimism for
the future of this technology.
相似文献