• Title/Summary/Keyword: Johns Hopkins University

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Recruitment for Phase I of the Trials of Hypertension Prevention

  • Satterfield Suzanne;Borhani Nemat O.;Whelton Paul;Goodwin Laretha;Brinkmann Connie;Charleston Jeanne;Corkery Beth Walker;Dolan Lee;Hataway Heidi;Hertert Stephanie;Lakatos Ed;Milas N. Carole;Morris Martha Clare
    • 대한예방의학회:학술대회논문집
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    • 1994.02b
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    • pp.313-319
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    • 1994
  • Phase I of the Trials of Hypertension Prevention was a multicenter, randomized, controlled trial designed to determine the efficacy of seven nonpharmacologic interventions in reducing blood pressure among persons with high-normal diastolic blood pressure. the initial goal for recruitment was to enroll 2,100 participants over a nine-month period. The yield from the first screening visit to randomization was 13% overall, with clinic-specific yields ranging from 4.5% to 31.7%. After five months of recruitment, approximately 60% of the goal for that point in the recruitment timetable had been randomized. Clinical centers falling short of their goals at that time altered their recruitment strategies and intensified their efforts, and centers that had exceeded their goals recruited additional participants. As a result, 2,182 participants, or 104\% of the goal for recruitment, were randomized over a 13-month period. Those clinics using a cohort, or wave, type of enrollment were most successful in achieving their recruitment goals within the prescribed timetable.

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Melatonin Rescues Mesenchymal Stem Cells from Senescence Induced by the Uremic Toxin p-Cresol via Inhibiting mTOR-Dependent Autophagy

  • Yun, Seung Pil;Han, Yong-Seok;Lee, Jun Hee;Kim, Sang Min;Lee, Sang Hun
    • Biomolecules & Therapeutics
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    • v.26 no.4
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    • pp.389-398
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    • 2018
  • p-Cresol, found at high concentrations in the serum of chronic kidney failure patients, is known to cause cell senescence and other complications in different parts of the body. p-Cresol is thought to mediate cytotoxic effects through the induction of autophagy response. However, toxic effects of p-cresol on mesenchymal stem cells have not been elucidated. Thus, we aimed to investigate whether p-cresol induces senescence of mesenchymal stem cells, and whether melatonin can ameliorate abnormal autophagy response caused by p-cresol. We found that p-cresol concentration-dependently reduced proliferation of mesenchymal stem cells. Pretreatment with melatonin prevented pro-senescence effects of p-cresol on mesenchymal stem cells. We found that by inducing phosphorylation of Akt and activating the Akt signaling pathway, melatonin enhanced catalase activity and thereby inhibited the accumulation of reactive oxygen species induced by p-cresol in mesenchymal stem cells, ultimately preventing abnormal activation of autophagy. Furthermore, preincubation with melatonin counteracted other pro-senescence changes caused by p-cresol, such as the increase in total 5'-AMP-activated protein kinase expression and decrease in the level of phosphorylated mechanistic target of rapamycin. Ultimately, we discovered that melatonin restored the expression of senescence marker protein 30, which is normally suppressed because of the induction of the autophagy pathway in chronic kidney failure patients by p-cresol. Our findings suggest that stem cell senescence in patients with chronic kidney failure could be potentially rescued by the administration of melatonin, which grants this hormone a novel therapeutic role.

Cripto Enhances Proliferation and Survival of Mesenchymal Stem Cells by Up-Regulating JAK2/STAT3 Pathway in a GRP78-Dependent Manner

  • Yun, SeungPil;Yun, Chul Won;Lee, Jun Hee;Kim, SangMin;Lee, Sang Hun
    • Biomolecules & Therapeutics
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    • v.26 no.5
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    • pp.464-473
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    • 2018
  • Cripto is a small glycosylphosphatidylinositol-anchored signaling protein that can detach from the anchored membrane and stimulate proliferation, migration, differentiation, vascularization, and angiogenesis. In the present study, we demonstrated that Cripto positively affected proliferation and survival of mesenchymal stem cells (MSCs) without affecting multipotency. Cripto also increased expression of phosphorylated janus kinase 2 (p-JAK2), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), 78 kDa glucose-regulated protein (GRP78), c-Myc, and cyclin D1. Notably, treatment with an anti-GRP78 antibody blocked these effects. In addition, pretreatment with STAT3 short interfering RNA (siRNA) inhibited the increase in p-JAK2, c-Myc, cyclin D1, and BCL3 levels caused by Cripto and attenuated the pro-survival action of Cripto on MSCs. We also found that incubation with Cripto protected MSCs from apoptosis caused by hypoxia or $H_2O_2$ exposure, and the level of caspase-3 decreased by the Cripto-induced expression of B-cell lymphoma 3-encoded protein (BCL3). These effects were sensitive to down-regulation of BCL3 expression by BCL3 siRNA. Finally, we showed that Cripto enhanced expression levels of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF). In summary, our results demonstrated that Cripto activated a novel biochemical cascade that potentiated MSC proliferation and survival. This cascade relied on phosphorylation of JAK2 and STAT3 and was regulated by GRP78. Our findings may facilitate clinical applications of MSCs, as these cells may benefit from positive effects of Cripto on their survival and biological properties.

Role for Social Media in Pediatric Liver Disease: Caregiver and Provider Perspectives

  • Mogul, Douglas B.;Bowring, Mary Grace;Lau, Jennifer;Babin, Erin;Bridges, John F.P.;Harpavat, Sanjiv;Miloh, Tamir
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.23 no.6
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    • pp.548-557
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    • 2020
  • Purpose: To better understand the benefits and harms of engagement with online pediatric liver disease communities within social media. Methods: We conducted a survey of caregivers of children with liver disease participating in online pediatric liver disease communities within social media, as well as a survey of healthcare providers (e.g., physicians, surgeons, nurse coordinators) from this field to better understand the perceived benefits and harms of participation. Results: Among 138 caregivers of children with liver disease that completed the survey, 97.8% agreed social media was a good place to learn about patient experiences and 88% agreed it was a good source of general information. Among caregivers, 84.8% agreed social media helps them to better advocate for their child. While 18% agreed that the information over social media was equal to the information from their healthcare team and 19% neither agreed/disagreed, only 3% indicated they would use this information to change care without telling their provider; in contrast, among 217 healthcare providers, 55% believed social media may lead caregivers to change management without telling their team. Conclusion: Engagement with online disease-specific communities in social media yields several benefits for caregivers and, in contrast to healthcare providers' concerns, participation is unlikely to lead to problems including caregivers changing the treatment plan without first discussing these plans with their team. Openness between caregivers and medical teams about the role for social media can help to improve trust and maximize the potential benefits of engagement with these groups.

Barrett's Esophagus and β-carotene Therapy: Symptomatic Improvement in GERD and Enhanced HSP70 Expression in Esophageal Mucosa

  • Dutta, Sudhir K.;Agrawal, Kireet;Girotra, Mohit;Fleisher, A. Steven;Motevalli, Mahnaz;Mah'moud, Mitchell A.;Nair, Padmanabhan P.
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6011-6016
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    • 2012
  • Introduction: Epidemiological studies suggest a protective role for ${\beta}$-carotene with several malignancies. Esophageal adenocarcinoma frequently arises from Barrett's esophagus (BE). We postulated that ${\beta}$-carotene therapy maybe protective in BE. Materials and Method: We conducted a prospective study in which 25 mg of ${\beta}$-carotene was administered daily for six-months to six patients. Each patient underwent upper endoscopy before and after therapy and multiple mucosal biopsies were obtained. Additionally, patients completed a gastroesophageal reflux disease (GERD) symptoms questionnaire before and after therapy and severity score was calculated. To study the effect of ${\beta}$-carotene at molecular level, tissue extracts of the esophageal mucosal biopsy were subjected to assessment of heat-shock protein 70 (HSP70). Results: A significant (p<0.05) reduction in mean GERD symptoms severity score from $7.0{\pm}2.4$ to $2.7{\pm}1.7$ following ${\beta}$-carotene therapy was noted. Measurement of Barrett's segment also revealed a significant reduction in mean length after therapy. In fact, two patients had complete disappearance of intestinal metaplasia. Furthermore, marked enhancement of HSP70 expression was demonstrated in biopsy specimens from Barrett's epithelium in four cases that were tested. Conclusions: Long-term ${\beta}$-carotene therapy realizes amelioration of GERD symptoms along with restitution of the histological and molecular changes in esophageal mucosa of patients with BE, associated with concurrent increase in mucosal HSP70 expression.

Socio-economic disparity in food consumption among young children in eight South Asian and Southeast Asian countries

  • Kang, Yunhee;Park, Chulwoo;Young, Anna Marie Pacheco;Kim, Jihye
    • Nutrition Research and Practice
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    • v.16 no.4
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    • pp.489-504
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    • 2022
  • BACKGROUND/OBJECTIVES: This study examined socio-economic differences in diverse food consumption among children 6-23 months of age in South Asia and Southeast Asian countries. SUBJECTS/METHODS: Data from Demographic and Health Surveys in four countries in South Asia (n = 15,749) and four countries in Southeast Asia (n = 10,789) were used. Survey-design adjusted proportions were estimated for the following 10 food items: grains, legumes, dark green leafy vegetables (DGLV), vitamin A-rich fruits, vitamin A-rich vegetables, other fruits and vegetables (OFV), fish, meat, dairy, and eggs. An equity gap was defined as an arithmetic difference in the proportion of each food item consumed in the past 24-hours between the wealthiest and lowest quintiles and between rural and urban areas, denoted by percentage points (pp). RESULTS: The consumption of most of the 10 food items was higher in the wealthiest quintiles and urban areas across eight countries. The size of equity gaps was greater in Southeast Asia than in South Asia, particularly for vitamin A-rich fruits (3.3-30.0 pp vs. 0.3-19.6 pp), vitamin A-rich vegetables (12.1-26.7 pp vs. 2.4-5.9 pp), meat (17.7-33.4 pp vs. 3.4-13.4 pp), and dairy (14.7-32.5 pp vs. 3.3-11.4 pp). However, the size of equity gap in egg consumption was greater in Southeast Asia than South Asia (11.2-19.8 pp vs. 11.0-26.7 pp). Relatively narrower gaps were seen in the consumption of grains (0.3-12.9 pp), DGLV (0.6-12.4 pp), and fish (0.1-16.8 pp) across all countries. CONCLUSIONS: Equity gaps in food consumption differed by socio-economic status and region. Reducing equity gaps in nutrient-rich foods and utilizing regionally available food resources may increase child dietary quality.

Reviews Value-in-Use of Specific Proteins Induced from Biological Resources (생물자원 유래 특이적 단백질의 이용가치에 관한 고찰)

  • Hyun, Dong-Yun;Kim, Ok-Tae;Bang, Kyong-Hwan;Kim, Young-Chang;Kang, Seung-Weon;Cha, Seon-Woo;Kim, Se-Yun
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2010.05a
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    • pp.3-3
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    • 2010
  • 소나무에서 추출해낸 천연유기유황(Natural Sulfur)의 의학적 가치는 1972년 Jacob 박사와 Herschler 박사가 오래곤 과학대학에서 천연식이유황(Natural Sulfur/MSM)을 가지고 표피조직에 미치는 영향을 구명하면서 keratin 단백질에 대한 연구가 활성화 되기 시작하였다. 세포내 골격물질은 크게 형태와 조성에 따라서 actin microfilament, microtubule, 그리고 intermediate filament(IF)로 구분된다. keratin의 특성은 keratin intermediate family중에서 K17 IF가 새로운 기능을 나타내는데 피부세포의 성장에 핵심적인 조절 역할을 한다는 사실이 밝혀 지면서 Dr. Pierre A. Coulombe(The Johns Hopkins University School of Medicine)연구실은 브로컬리와 같은 십자화과 식물 등에 과량 존재하는 항산화 및 항암물질인 sulforaphane이 K17의 발현을 특이적으로 증가시킨다는 것을 알아내어 피부박리와 같은 피부손상을 기능적으로 복구시킬수 있음을 확인하였다. 현재는 수포성 표피박리증 환자군의 많은 부분을 차지하는 K14 돌연변이와 동일한 유전적 변형을 일으킨 생쥐모델을 이용한 약물 효과 검증과 전 임상단계의 인체실험을 함께 진행중에 있다. Mark E. Van Dyke 박사(Wake Forest Institute for Regenerative Medicine Medical Center)는 인간의 머리털에서 유래된 keratin으로 외상에 의한 신경 절단이나 압좌(압박손상)는 현재 다른 부위의 신경을 잘라 이식하거나 절단된 신경 양끝을 인공도관(conduit)으로 연결해 신경재생을 유도하는 미세수술을 시행하게 되는데, 신경재생을 유도하는 도관에 keratin을 주입하면 신경이식과 맞먹는 신경재생 성공률을 기대할 수 있다고 하였다. 앞으로는 동물성 keratin뿐만 아니라 식물성 keratin도 함께 연구할 필요가 있다. 동물성 keratin의 농업적 이용은 가금류 깃털의 keratin을 축출하여 친환경 육묘용 용기를 만드는데 있다. 이 용기는 자연조건에서 생분해될 수 있는 특성을 갖고 있다.

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Nonmigrating tidal characteristics in the thermospheric neutral mass density

  • Kwak, Young-Sil;Kil, Hyosub;Lee, Woo-Kyoung;Oh, Seung-Jun;Yang, Tae-Yong
    • The Bulletin of The Korean Astronomical Society
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    • v.37 no.2
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    • pp.125.1-125.1
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    • 2012
  • The wave number 4 (wave-4) and wave number 3 (wave-3) longitudinal structures in the thermospheric neutral mass density are understood as tidal structures driven by diurnal eastward-propagating zonal wave number 3 (DE3) and wave number 2 (DE2) tides, respectively. However, those structures have been identified using data from limited time periods, and the consistency and recurrence of those structures have not yet been examined using long-term observation data. We examine the persistence of those structures by analyzing the neutral mass density data for the years 2001-2008 taken by the CHAllenging Minisatellite Payload (CHAMP) satellite. During years of low solar activity, the amplitude of the wave-4 structure is pronounced during August and September, and the wave-4 phase shows a consistent eastward phase progression of $90^{\circ}$ within 24 h local time in different months and years. During years of high solar activity, the wave-4 amplitude is small and does not show a distinctive annual pattern, but the tendency of the eastward phase shift at a rate of $90^{\circ}$/24 h exists. Thus the DE3 signature in the wave-4 structure is considered as a persistent feature. The wave-3 structure is a weak feature in most months and years. The amplitude and phase of the wave-3 structure do not show a notable solar cycle dependence. Among the contributing tidal modes to the wave-3 structure, the DE2 amplitude is most pronounced. This result may suggest that the DE2 signature, although it is a weak signature, is a perceivable persistent feature in the thermosphere.

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