• 제목/요약/키워드: Johns Hopkins University

검색결과 241건 처리시간 0.035초

Cell-Based Screen Using Amyloid Mimic β23 Expression Identifies Peucedanocoumarin III as a Novel Inhibitor of α-Synuclein and Huntingtin Aggregates

  • Ham, Sangwoo;Kim, Hyojung;Hwang, Seojin;Kang, Hyunook;Yun, Seung Pil;Kim, Sangjune;Kim, Donghoon;Kwon, Hyun Sook;Lee, Yun-Song;Cho, MyoungLae;Shin, Heung-Mook;Choi, Heejung;Chung, Ka Young;Ko, Han Seok;Lee, Gum Hwa;Lee, Yunjong
    • Molecules and Cells
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    • 제42권6호
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    • pp.480-494
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    • 2019
  • Aggregates of disease-causing proteins dysregulate cellular functions, thereby causing neuronal cell loss in diverse neurodegenerative diseases. Although many in vitro or in vivo studies of protein aggregate inhibitors have been performed, a therapeutic strategy to control aggregate toxicity has not been earnestly pursued, partly due to the limitations of available aggregate models. In this study, we established a tetracycline (Tet)-inducible nuclear aggregate (${\beta}23$) expression model to screen potential lead compounds inhibiting ${\beta}23$-induced toxicity. High-throughput screening identified several natural compounds as nuclear ${\beta}23$ inhibitors, including peucedanocoumarin III (PCIII). Interestingly, PCIII accelerates disaggregation and proteasomal clearance of both nuclear and cytosolic ${\beta}23$ aggregates and protects SH-SY5Y cells from toxicity induced by ${\beta}23$ expression. Of translational relevance, PCIII disassembled fibrils and enhanced clearance of cytosolic and nuclear protein aggregates in cellular models of huntingtin and ${\alpha}$-synuclein aggregation. Moreover, cellular toxicity was diminished with PCIII treatment for polyglutamine (PolyQ)-huntingtin expression and ${\alpha}$-synuclein expression in conjunction with 6-hydroxydopamine (6-OHDA) treatment. Importantly, PCIII not only inhibited ${\alpha}$-synuclein aggregation but also disaggregated preformed ${\alpha}$-synuclein fibrils in vitro. Taken together, our results suggest that a Tet-Off ${\beta}23$ cell model could serve as a robust platform for screening effective lead compounds inhibiting nuclear or cytosolic protein aggregates. Brain-permeable PCIII or its derivatives could be beneficial for eliminating established protein aggregates.

Evidence for Enhanced Telomerase Activity in Barrett's Esophagus with Dysplasia and Adenocarcinoma

  • Merchant, Nipun B.;Dutta, Sudhir K.;Girotra, Mohit;Arora, Manish;Meltzer, Stephen J.
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권2호
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    • pp.679-683
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    • 2013
  • Background: Dysplasia and adenocarcinoma developing in Barrett's esophagus (BE) are not always endoscopically identifiable. Molecular markers are needed for early recognition of these focal lesions and to identify patients at increased risk of developing adenocarcinoma. The aim of the current study was to correlate increased telomerase activity (TA) with dysplasia and adenocarcinoma occurring in the setting of BE. Materials and Methods: Esophageal mucosal biopsies were obtained from patients (N=62) who had pathologically verified BE at esophagogastroduodenoscopy (EGD). Mucosal biopsies were also obtained from the gastric fundus as controls. Based on histopathology, patients were divided into three groups: 1) BE without dysplasia (n=24); 2) BE with dysplasia (both high grade and low grade, n=13); and 3) BE with adenocarcinoma (n=25). TA was measured by a PCR-based assay (TRAPeze$^{(R)}$ ELISA Telomerase Detection Kit). Statistical analyses were performed using one-way ANOVA and post-hoc Bonferroni testing. Results: TA was significantly higher in biopsies of BE with dyplasia and BE with adenocarcinoma than in BE without dysplasia. Subgroup analyses did not reveal any significant correlations between TA and patient age, length of BE, or presence of gastritis. Conclusions: Telomerase activity in esophageal mucosal biopsies of BE may constitute a useful biomarker for the early detection of esophageal dysplasia and adenocarcinoma.

소뇌 운동실조 이상 환자를 위한 운동상상 기반의 뇌-컴퓨터 인터페이스 (Motor Imagery based Brain-Computer Interface for Cerebellar Ataxia)

  • 최영석;신현출
    • 한국지능시스템학회논문지
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    • 제24권6호
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    • pp.609-614
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    • 2014
  • 소뇌 운동실조는 점차 진행되는 신경퇴행질병이며 운동 조절을 위한 기능의 상실을 동반하기에 환자의 삶을 심각하게 저하시킨다. 소뇌 운동실조 환자는 운동제어 과정에서 부적절한 폐회로 소뇌 반응으로 인해 운동 명령이 제한된다. 본 논문에서는 최근 뇌-컴퓨터 인터페이스 기술을 이용하여 소뇌의 이상으로 인한 운동실조 환자들이 외부기기를 제어할 수 있도록 운동상상 기반의 뇌파의 특성을 분석하고 이를 이용한 뇌-컴퓨터 인터페이스 기법을 제안한다. 뇌파 기반의 뇌-컴퓨터 인터페이스의 효용성을 검증하기 위하여 소뇌 운동실조 환자와 정상인 그룹에서 운동상상에 따른 뮤밴드 파워를 조절하는 능력을 비교하였다. 이를 통하여 소뇌 운동실조 환자에의 뇌-컴퓨터 인터페이스의 가능성을 보여준다.

Epidural Lysis of Adhesions

  • Lee, Frank;Jamison, David E.;Hurley, Robert W.;Cohen, Steven P.
    • The Korean Journal of Pain
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    • 제27권1호
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    • pp.3-15
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    • 2014
  • As our population ages and the rate of spine surgery continues to rise, the use epidural lysis of adhesions (LOA) has emerged as a popular treatment to treat spinal stenosis and failed back surgery syndrome. There is moderate evidence that percutaneous LOA is more effective than conventional ESI for both failed back surgery syndrome, spinal stenosis, and lumbar radiculopathy. For cervical HNP, cervical stenosis and mechanical pain not associated with nerve root involvement, the evidence is anecdotal. The benefits of LOA stem from a combination of factors to include the high volumes administered and the use of hypertonic saline. Hyaluronidase has been shown in most, but not all studies to improve treatment outcomes. Although infrequent, complications are more likely to occur after epidural LOA than after conventional epidural steroid injections.

중국내 북한이탈주민을 통해 본 북한의료이용 만족도 (Satisfaction with Health Care in North Korea: A Study of North Korean Refugees in China)

  • 김개영;정우진;이윤환;박종연;;이명근;이옥철
    • 보건행정학회지
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    • 제16권4호
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    • pp.48-67
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    • 2006
  • The aim of the study was to examine levels of satisfaction with health care in North Korea and to identify factors associated with it using a convenience sample of North Korean refugees in China. Data from the 2004 Survey of Health Seeking Behavior of North Korean Households conducted by the Center for Refugee and Disaster Response, Johns Hopkins Bloomberg School of Public Health were used. The study subjects were 273 North Korean refugees whose length of stay in China was less than 3 months. Factor analysis was used to extract factor dimensions from the 12 satisfaction items. Bivariate (t test and ANOVA) and multiple regression analyses were used in examining factors associated with satisfaction with health care use in North Korea Overall, satisfaction level was low ($2.36{\pm}0.36$, score range: 1-5). Of the three-factor dimensions, physician skills scored the highest $(2.93{\pm}0.36)$, followed by drug availability $(2.51{\pm}0.07)$ and general cleanliness $(1.66{\pm}0.55)$. In the multiple regression analysis, having a usual source of care was significantly associated with patient satisfaction. Respondents who identified primary care (section) doctors as their usual source of care tended to be less satisfied than those with the city or county hospital as their usual source of care. County residents tended to report a lower degree of satisfaction with general cleanliness than city residents. Among socioeconomic characteristics, the number of household assets positively predicted satisfaction with drug availability. North Korean residents appear to be dissatisfied with their medical care. It may reflect some inadequacies in the North's universal health care system to meet the healthcare needs of its people.