• Title/Summary/Keyword: Johns Hopkins University

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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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    • v.42 no.6
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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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    • v.14 no.2
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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.

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

  • Choi, Young-Seok;Shin, Hyun-Chool;Ying, Sarah H.;Newman, Geoffrey I.;Thakor, Nitish
    • Journal of the Korean Institute of Intelligent Systems
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    • v.24 no.6
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    • pp.609-614
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    • 2014
  • Cerebellar ataxia is a steadily progressive neurodegenerative disease associated with loss of motor control, leaving patients unable to walk, talk, or perform activities of daily living. Direct motor instruction in cerebella ataxia patients has limited effectiveness, presumably because an inappropriate closed-loop cerebellar response to the inevitable observed error confounds motor learning mechanisms. Recent studies have validated the age-old technique of employing motor imagery training (mental rehearsal of a movement) to boost motor performance in athletes, much as a champion downhill skier visualizes the course prior to embarking on a run. Could the use of EEG based BCI provide advanced biofeedback to improve motor imagery and provide a "backdoor" to improving motor performance in ataxia patients? In order to determine the feasibility of using EEG-based BCI control in this population, we compare the ability to modulate mu-band power (8-12 Hz) by performing a cued motor imagery task in an ataxia patient and healthy control.

Epidural Lysis of Adhesions

  • Lee, Frank;Jamison, David E.;Hurley, Robert W.;Cohen, Steven P.
    • The Korean Journal of Pain
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    • v.27 no.1
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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.

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

  • Kim, Gae-Young;Chung Woo-Jin;Lee, Yun-Hwan;Park, Chong-Yon;Robinson W. Courtland;Lee, Myung-Ken;Lee, Og-Cheol;Burnham Gilbert M.
    • Health Policy and Management
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    • v.16 no.4
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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.