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Z-FA-FMK as a novel potent inhibitor of reovirus pathogenesis and oncolysis in vivo.
Kim, Manbok,Hansen, Kristina K,Davis, Lesley,van Marle, Guido,Gill, Michael John,Fox, Julie D,Hollenberg, Morley D,Rancourt, Derrick E,Lee, Patrick W K,Yun, Chae-Ok,Johnston, Randal N International Medical Press 2010 ANTIVIRAL THERAPY Vol.15 No.6
<P>BACKGROUND: Respiratory enteric orphan (reo)virus is a promising oncolytic viral candidate. Reoviral anticancer therapy is currently undergoing multiple clinical trials targeting various human cancers; however, there is no effective reoviral inhibitor that can be used to block unwanted reovirus replication during reoviral anticancer therapy. METHODS: Studies were conducted with transformed or normal cells in vitro and in vivo to characterize viral replication in the presence or absence of chemical inhibitors. RESULTS: We have identified a protease inhibitor that is very effective in the inhibition of viral replication. The dipeptide benzyloxycarbonyl-Phe-Ala-fluoromethyl ketone (Z-FA-FMK) effectively inhibited reovirus replication in a susceptible host and cured cells of a persistent infection with reovirus in vitro. Electron microscopic analysis of Z-FA-FMK-treated cells revealed that internalized reovirus virions, retained in a perinuclear localization, no longer undergo further processing into viral factories following Z-FA-FMK treatment, suggesting that Z-FA-FMK specifically affects a reovirus virion maturation step. Animal studies showed that reovirus infection of Ras oncogenic tumours and host heart tissues is completely blocked by Z-FA-FMK treatment in severe combined immunodeficiency mice. CONCLUSIONS: Z-FA-FMK is a very effective viral inhibitor that can prevent reovirus replication in vitro and reovirus-mediated myocarditis, as well as reovirus-mediated oncolysis, in vivo. A potential application of this drug for inhibition of reovirus infection is suggested.</P>
National narrative, ethnology, and academia in post-Soviet Uzbekistan
Marlène Laruelle 한양대학교 아태지역연구센터 2010 Journal of Eurasian Studies Vol.1 No.2
Since the disintegration of the Soviet Union, the new states of Central Asia have been obliged to adjust their institutions to new symbolic frontiers and to take into account the independence they achieved in 1991. Both universities and Academies of Sciences have been called to reconsider their research policies and to orient them in order to respond to emerging national issues. The building of national narratives is a particularly relevant object of study in observing the various modes of legitimization of the Central Asian states and the scientific instruments they deem necessary for their political validation. The aim of this paper is to overcome the apparent, albeit actual, character of a number of changes that have taken place in Uzbekistan since 1991, in order to demonstrate the continuity of personal, institutional, and intellectual lines uniting contemporary research to that conducted during Soviet period. The preference accorded to ancient history, the praise of the originality and long heritage of the people, and an obsession with ethnogenesis, all are rooted in the contemporary narrative of the previous regime. They invite a reconsideration of the past two decades in a more nuanced manner and a rereading of the Soviet past in order to understand the process of building the nation-state, which has now been underway for more than half a century.
Jérôme Mounier,Geneviève Héry-Arnaud,Audrey Gouëllo,Marlène Keravec,Solène Le Gal,Grégory Pacini,Stella Debaets,Gilles Nevez,Gilles Rault,Georges Barbier 한국미생물학회 2014 The journal of microbiology Vol.52 No.4
The aim of this study was to evaluate the use of denaturinghigh-performance liquid chromatography (DHPLC) to characterizecystic fibrosis (CF) airway microbiota includingboth bacteria and fungi. DHPLC conditions were first optimizedusing a mixture of V6, V7 and V8 region 16S rRNAgene PCR amplicons from 18 bacterial species commonlyfound in CF patients. Then, the microbial diversity of 4 sputumsamples from 4 CF patients was analyzed using culturalmethods, cloning/sequencing (for bacteria only) and DHPLCpeak fraction collection/sequencing. DHPLC analysis allowedidentifying more bacterial and fungal species than the classicalculture methods, including well-recognized pathogenssuch as Pseudomonas aeruginosa. Even if a lower number ofbacterial Operational Taxonomic Units (OTUs) was identifiedby DHPLC, it allowed to find OTUs unidentified bycloning/sequencing. The combination of both techniquespermitted to correlate the majority of DHPLC peaks to definedOTUs. Finally, although Aspergillus fumigatus detectionusing DHPLC can still be improved, this techniqueclearly allowed to identify a higher number of fungal speciesversus classical culture-based methods. To conclude, DHPLCprovided meaningful additional data concerning pathogenicbacteria and fungi as well as fastidious microorganisms presentwithin the CF respiratory tract. DHPLC can be consideredas a complementary technique to culture-dependentanalyses in routine microbiological laboratories.
Loredana Amoroso,Giovanni Erminio,Guy Makin,Andrew D. J. Pearson,Penelope Brock,Dominique Valteau-Couanet,Victoria Castel,Marlène Pasquet,Genevieve Laureys,Caroline Thomas,Roberto Luksch,Ruth Ladenste 대한암학회 2018 Cancer Research and Treatment Vol.50 No.1
Purpose Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with " three abnormal skeletal areas on iodine 123-metaiodobenzylguanidine ([123I]mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate. Materials and Methods Patients with metastatic high-risk neuroblastoma who had not achieved the SIOPEN criteria for HDT after induction received two courses of topotecan 1.5 mg/m2/day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m2, and doxorubicin, 45 mg/m2. Results Sixty-three patients were eligible and evaluable. Following two courses of TVD, four (6.4%) patients had an overall CR, while 28 (44.4%) had a PR with a combined response rate of 50.8% (95% confidence interval [CI], 37.9 to 63.6). Of these, 23 patients achieved a metastatic CR or a PR with " 3 mIBG skeletal areas and no bone marrow disease (36.5%; 95% CI, 24.7 to 49.6) and were eligible to receive HDT. Toxicity was mostly haematological, affecting 106 of the 126 courses (84.1%; 95% CI, 76.5 to 90.0), and dose reduction was necessary in six patients. Stomatitis was the second most common nonhematological toxicity, occurring in 20 patients (31.7%). Conclusion TVD was effective in improving the response rate of high-risk neuroblastoma patients after induction with COJEC enabling them to proceed to HDT. However, the long-term benefits of TVD needs to be determined in randomized clinical trials.
Alfand Marl F. Dy Closas,Shen-Yang LIM 대한파킨슨병및이상운동질환학회 2023 Journal Of Movement Disorders Vol.16 No.1
KMT2B-linked dystonia (DYT-KMT2B) is a childhood-onset dystonia syndrome typically beginning in the lower limbs and progressing caudocranially to affect the upper limbs with eventual prominent craniocervical involvement. Despite its recent recognition, it now appears to be one of the more common monogenic causes of dystonia syndromes. Here, we present an atypical case of DYT-KMT2B with oromandibular dystonia as the presenting feature, which remained restricted to this region three decades after symptom onset. This appears to be the first reported case of DYT-KMT2B from Southeast Asia and provides further supporting evidence for the pathogenic impact of the KMT2B c.6210_6213delTGAG variant.