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RISS 인기검색어
- 검색키워드
- 저자 : Tollefson, Ann E. (검색결과 2 건)
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Toth, Karoly,Lee, Sang R.,Ying, Baoling,Spencer, Jacqueline F.,Tollefson, Ann E.,Sagartz, John E.,Kong, Il-Keun,Wang, Zhongde,Wold, William S. M. Public Library of Science 2015 PLoS pathogens Vol.11 No.8
<▼1><P>Human adenoviruses have been studied extensively in cell culture and have been a model for studies in molecular, cellular, and medical biology. However, much less is known about adenovirus replication and pathogenesis <I>in vivo</I> in a permissive host because of the lack of an adequate animal model. Presently, the most frequently used permissive immunocompetent animal model for human adenovirus infection is the Syrian hamster. Species C human adenoviruses replicate in these animals and cause pathology that is similar to that seen with humans. Here, we report findings with a new Syrian hamster strain in which the STAT2 gene was functionally knocked out by site-specific gene targeting. Adenovirus-infected STAT2 knockout hamsters demonstrated an accentuated pathology compared to the wild-type control animals, and the virus load in the organs of STAT2 knockout animals was 100- to 1000-fold higher than that in wild-type hamsters. Notably, the adaptive immune response to adenovirus is not adversely affected in STAT2 knockout hamsters, and surviving hamsters cleared the infection by 7 to 10 days post challenge. We show that the Type I interferon pathway is disrupted in these hamsters, revealing the critical role of interferon-stimulated genes in controlling adenovirus infection. This is the first study to report findings with a genetically modified Syrian hamster infected with a virus. Further, this is the first study to show that the Type I interferon pathway plays a role in inhibiting human adenovirus replication in a permissive animal model. Besides providing an insight into adenovirus infection in humans, our results are also interesting from the perspective of the animal model: STAT2 knockout Syrian hamster may also be an important animal model for studying other viral infections, including Ebola-, hanta-, and dengue viruses, where Type I interferon-mediated innate immunity prevents wild type hamsters from being effectively infected to be used as animal models.</P></▼1><▼2><P><B>Author Summary</B></P><P>The biology of human adenoviruses has been studied extensively; however, much less is known about the replication and pathogenesis of the virus in a permissive host. Our laboratory pioneered the use of Syrian hamsters to study the pathogenesis of human adenoviruses. Syrian hamsters are permissive for species C human adenoviruses, which replicate in these animals and cause illness akin to that in humans. Hereby, we report findings with a new Syrian hamster strain (STAT2 KO hamsters), in which the Type I interferon pathway, an important part of the innate immune response to virus infection, is disrupted. This is the first genetically modified Syrian hamster strain ever reported. We show that these animals are very sensitive to infection with type 5 human adenovirus (Ad5). Ad5 replicates to 100- to 1000-fold higher titers in STAT2 KO hamsters than in wild-type ones, and this increased infection causes enhanced pathology. However, the adaptive immune response to the virus infection seems to be intact with the STAT2 KO hamsters, and surviving animals clear the virus effectively. The data reported here may be of interest to researchers focusing on adenoviruses, and also to those who utilize the Syrian hamster as their animal model for other purposes.</P></▼2>
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Sclerotherapy for Venous Malformations of Head and Neck: Systematic Review and Meta-Analysis
Lucio De Maria,Paolo De Sanctis,Karthik Balakrishnan,Megha Tollefson,Waleed Brinjikji 대한신경중재치료의학회 2020 Neurointervention Vol.15 No.1
We performed a systematic review and meta-analysis of studies performing sclerotherapy for treatment of venous malformations (VMs) of the face, head and neck. It is our hope that data from this study could be used to better inform providers and patients regarding the benefits and risks of percutaneous sclerotherapy for treatment of face, head and neck VMs. We searched PubMed, MEDLINE, and EMBASE from 2000–2018 for studies evaluating the safety and efficacy of percutaneous sclerotherapy of neck, face and head VMs. Two independent reviewers selected studies and abstracted data. The primary outcomes were complete and partial resolution of the VM. Data were analyzed using random-effects meta-analysis. Thirty-seven studies reporting on 2,067 patients were included. The overall rate of complete cure following percutaneous sclerotherapy with any agent was 64.7% (95% confidence interval [CI], 57.4–72.0%). Sodium tetradecyl sulfate had the lowest complete cure rate at 55.5% (95% CI, 36.1–74.9%) while pingyangmycin had the highest cure rate at 82.9% (95% CI, 71.1–94.7%). Overall patient satisfaction rates were 91.0% (95% CI, 86.1–95.9%). Overall quality of life improvement was 78.9% (95% CI, 67.0–90.8%). Overall permanent morbidity/mortality was 0.8% (95% CI, 0.3–1.3%) with no cases of mortality. Our systematic review and meta-analysis of 37 studies and over 2,000 patients found that percutaneous sclerotherapy is a very safe and effective treatment modality for treatment of VMs of the head, neck and face.
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