1.Association of CYP2C19*2 and *3 Genetic Variants with Essential Hypertension in Koreans.
Dong Jik SHIN ; Jisun KWON ; Ah Ram PARK ; Yousun BAE ; Eun Soon SHIN ; Sungha PARK ; Yangsoo JANG
Yonsei Medical Journal 2012;53(6):1113-1119
PURPOSE: The cytochrome P450 2C19 (CYP2C19) metabolizes arachidonic acid to produce epoxyicosanoid acids, which are involved in vascular tone and regulation of blood pressure. Recent findings suggest that CYP2C19 gene might be considered as a novel candidate gene for treatment of cardiovascular disease. The aim of the present study was to evaluate the association between two variants, CYP2C19*2 (681G>A) and CYP2C19*3 (636G>A) and the development of essential hypertension (EH) in Koreans. MATERIALS AND METHODS: We carried out an association study in a total of 1190 individuals (527 hypertensive subjects and 663 unrelated healthy controls). The CYP2C19 polymorphisms were genotyped using the SNaPShot(TM) assay. RESULTS: The distribution of alleles and genotypes of CYP2C19*3 showed significant difference between hypertensive patients and normal controls (p=0.011 and p=0.013, respectively). Logistic regression analysis indicated that the CYP2C19*3 (636A) allele carriers were significantly associated with EH [odds ratio, 0.691; 95% confidence interval (CI), 0.512-0.932, p=0.016], in comparison to wild type homozygotes (CYP2C19*1/*1). Neither genotype nor allele distribution of CYP2C19*2 polymorphism showed significant differences between hypertensive and control groups (p>0.05). CONCLUSION: Our present findings strengthen the evidence of an association between CYP2C19 gene polymorphism and EH prevalence. In particular, the CYP2C19*3 defective allele may contribute to reduced risk for the development of EH.
Adult
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Alleles
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Aryl Hydrocarbon Hydroxylases/*genetics
;
Asian Continental Ancestry Group/genetics
;
Female
;
Genotype
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Homozygote
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Humans
;
Hypertension/epidemiology/*genetics
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Logistic Models
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Male
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Middle Aged
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Polymorphism, Genetic/*genetics
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Young Adult
2.Ischemic brain injury decreases dynamin-like protein 1 expression in a middle cerebral artery occlusion animal model and glutamate-exposed HT22 cells.
Laboratory Animal Research 2016;32(4):194-199
Dynamin-like protein I (DLP-1) is an important mitochondrial fission and fusion protein that is associated with apoptotic cell death in neurodegenerative diseases. In this study, we investigated DLP-1 expression in a focal cerebral ischemia animal model and glutamate-exposed hippocampal-derived cell line. Middle cerebral artery occlusion (MCAO) was surgically induced in adult male rats to induce focal cerebral ischemic injury. Brain tissues were collected 24 hours after the onset of MCAO. MCAO induces an increase in infarct volume and histopathological changes in the cerebral cortex. We identified a decrease in DLP-1 in the cerebral cortices of MCAO-injured animals using a proteomic approach and Western blot analysis. Moreover, glutamate treatment significantly decreased DLP-1 expression in a hippocampal-derived cell line. The decrease in DLP-1 indicates mitochondrial dysfunction. Thus, these results suggest that neuronal cell injury induces a decrease in DLP-1 levels and consequently leads to neuronal cell death.
Adult
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Animals
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Blotting, Western
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Brain Injuries*
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Brain Ischemia
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Brain*
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Cell Death
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Cell Line
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Cerebral Cortex
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Glutamic Acid
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Humans
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Infarction, Middle Cerebral Artery*
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Male
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Middle Cerebral Artery*
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Mitochondrial Dynamics
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Models, Animal
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Neurodegenerative Diseases
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Neurons
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Rats
3.Efficacy of the Phosphorylated tau 181 in Differential Diagnosis of the Alzheimer's Disease: A Systematic Review and Meta-Analysis.
Jin A MO ; Jae Won JANG ; Ju Hee LIM ; Min LEE ; Ah Ram SUL ; Hee Jin KIM ; Young Chul YOUN
Dementia and Neurocognitive Disorders 2014;13(4):129-138
BACKGROUND: The purpose of this study was to evaluate the value of phosphorylated tau with epitopes threonine 181(p-tau181) in cerebrospinal fluid (CSF) for the differential diagnosis of Alzheimer's disease typed dementia from other type of dementia. METHODS: A systematic literature search was performed to identify studies on p-tau181. Two evaluators independently evaluated the quality of the ten studies using the Scottish Intercollegiate Guidelines Network (SIGN) tool. The literature review covered from October 27, 1946 to October 22, 2013, and eight domestic databases including KoreaMed and international databases including Ovid-MEDLINE, EMBASE, and Cochrane Library were used. Tau concentrations were compared to healthy controls and to subjects with Alzheimer's disease (AD) using random effect meta-analysis. Outcome measures were Cohen's delta, sensitivity and specificity. RESULTS: Finally, 8 studies (8 diagnostic evaluation studies) were identified to evaluate CSF p-tau181. The effectiveness of this test was evaluated based on diagnostic accuracy. The diagnostic accuracy for identifying AD by ELISA was high which revealed pooled sensitivity as 0.843 (95% CI 0.818-0.867), pooled specificity as 0.799(95% CI 0.768-0.828) and summary receiver operating characteristic area under the curve 0.9082+/-0.0236. CONCLUSIONS: CSF p-tau181 concentrations in other type of dementia are intermediate between controls and AD patients. Overlap between both controls and AD patients results in insufficient diagnostic accuracy, and the development of more specific biomarkers for these disorders is needed.
Alzheimer Disease*
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Biomarkers
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Cerebrospinal Fluid
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Dementia
;
Diagnosis, Differential*
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Enzyme-Linked Immunosorbent Assay
;
Epitopes
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Humans
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Outcome Assessment (Health Care)
;
ROC Curve
;
Sensitivity and Specificity
;
tau Proteins
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Threonine
4.Anticancer effects of Ulva compressa extracts on FaDu human hypopharangeal squamous carcinoma cells in vitro
Ji Yun JANG ; Seo Yun JUNG ; Bo-Ram PARK ; Seul Ah LEE ; Chun Sung KIM
International Journal of Oral Biology 2022;47(3):41-48
Ulva compressa Linnaeus (UCL) is a green algae seaweed that performs photosynthesis and is used as a food material in some Asian regions including Korea. It is known to be the dominant species in copper ion-contaminated seas, and many studies on copper ion resistant mechanisms have been reported. UCL is known to have an excellent antioxidant effect, but limited information is available regarding its other physiological activities. In this study, we investigated the anticancer activity of 30% prethanol extracts of Ulva compressa Linnaeus (30% PeUCL) and the underlying mechanisms of its activity on human FaDu hypopharyngeal squamous carcinoma cells. The 30% PeUCL extracts suppressed FaDu cell viability without affecting normal cells (L929), as determined by MTT and viability assays. Furthermore, the 30% PeUCL extracts induced apoptosis, as determined by DAPI staining. The 30% PeUCL extracts inhibited colony formation effectively as well as wound-healing of FaDu cells, even at noncytotoxic concentrations. In addition, 30% PeUCL extracts induced apoptosis significantly through proteolytic cleavage of caspase-3, -7, and -9, and poly (ADP-ribose) polymerase, and by downregulation of Bcl-2 and upregulation of Bax in FaDu cells, as determined by Western blot analysis. Collectively, these results suggest that the inhibitory effect of 30% PeUCL extracts on the growth of oral cancer cells, colony formation and wound-healing may be mediated by caspase- and mitochondrial-dependent apoptotic pathways in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, 30% PeUCL extracts can be administered as a natural chemotherapeutic drug for the treatment of human oral cancers.
5.Methanol extracts of Humulus japonicus induced apoptosis in human FaDu hypopharynx squamous carcinoma cells
Ji Yeon JANG ; Bo-Ram PARK ; Seul Ah LEE ; Mi Suk CHOI ; Chun Sung KIM
International Journal of Oral Biology 2022;47(1):9-15
Humulus japonicus (HJ) is a widely used herbal medicine for pulmonary tuberculosis, hypertension, leprosy, and venomous wounds in Asia, particularly in China. Although HJ has certain physiological activities, such as longitudinal bone growth, antioxidation and alleviation of rheumatism, its anticancer activities, other than in colorectal and ovarian cancer, are yet to be studied. In this study, we investigated the anti-cancer activity and mechanism of methanol extracts of HJ (MeHJ) against human FaDu hypopharyngeal squamous carcinoma cells. MeHJ suppressed FaDu cell viability without affecting normal cells (L929), which was demonstrated using the MTT and Live & Dead assays.Furthermore, MeHJ effectively inhibited colony formation of FaDu cells, even at non-cytotoxic concentrations, and significantly induced apoptosis through the proteolytic cleavage of caspase-9, -3, -7, poly (ADP-ribose) polymerase and through the downregulation of BCL-2 and upregulation of BAX in FaDu cells, as determined by DAPI staining, flow cytometry, and western blot analyses. Collectively, these findings suggest that the inhibitory effects of MeHJ on the growth and colony formation of oral cancer cells may be mediated by caspase- and mitochondrial-dependent apoptotic pathways in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, MeHJ has the potential to be used as a natural chemotherapeutic drug against human oral cancer.
6.A Systematic Review of Studies Using Video-recording to Capture Interactions between Staff and Persons with Dementia in Long-term Care Facilities
Da Eun KIM ; Hae SAGONG ; Eunjoo KIM ; Ah Ram JANG ; Ju Young YOON
Journal of Korean Academy of Community Health Nursing 2019;30(4):400-413
PURPOSE: The use of video-recording offers important advantages in observing and assessing the relationship between specific behaviors in health care settings. The purpose of this systematic review is to investigate and synthesize the methodological characteristics of studies using video-technology for measuring interactions with the older persons with dementia and staff in long-term care facilities.METHODS: We searched Medline, Embase and CINHAL databases for published articles in English using a video-recording method for both staff and the residents with dementia. Quantitative research design studies (e.g., descriptive or experimental studies) were included.RESULTS: Among 5,605 searched papers, a total of 20 studies were selected for this review. Situations of video-recording were providing personal care (n=12), mealtime (n=6), and conversation (n=3). Concepts measured by video-recording were classified into two groups: 1) Staff [care practice by staff (n=13) and communication by staff (n=11)] and 2) residents [communication by resident (n=4), activities of daily life function of resident (n=8), and behavioral and psychological symptoms of dementia (n=10)].CONCLUSION: This review demonstrates that video technologies are actively used to evaluate the relationship between quality of care and health outcomes of the elderly with dementia in many international nursing studies. This study provides the foundation for a future research using video-recording technologies to examine the interactions and relationships between staff and the residents in Korean long-term care settings.
8.Survey on Value Elements Provided by Artificial Intelligence and Their Eligibility for Insurance Coverage With an Emphasis on Patient-Centered Outcomes
Hoyol JHANG ; So Jin PARK ; Ah-Ram SUL ; Hye Young JANG ; Seong Ho PARK
Korean Journal of Radiology 2024;25(5):414-425
Objective:
This study aims to explore the opinions on the insurance coverage of artificial intelligence (AI), as categorized based on the distinct value elements offered by AI, with a specific focus on patient-centered outcomes (PCOs). PCOs are distinguished from traditional clinical outcomes and focus on patient-reported experiences and values such as quality of life, functionality, well-being, physical or emotional status, and convenience.
Materials and Methods:
We classified the value elements provided by AI into four dimensions: clinical outcomes, economic aspects, organizational aspects, and non-clinical PCOs. The survey comprised three sections: 1) experiences with PCOs in evaluating AI, 2) opinions on the coverage of AI by the National Health Insurance of the Republic of Korea when AI demonstrated benefits across the four value elements, and 3) respondent characteristics. The opinions regarding AI insurance coverage were assessed dichotomously and semi-quantitatively: non-approval (0) vs. approval (on a 1–10 weight scale, with 10 indicating the strongest approval). The survey was conducted from July 4 to 26, 2023, using a web-based method. Responses to PCOs and other value elements were compared.
Results:
Among 200 respondents, 44 (22%) were patients/patient representatives, 64 (32%) were industry/developers, 60 (30%) were medical practitioners/doctors, and 32 (16%) were government health personnel. The level of experience with PCOs regarding AI was low, with only 7% (14/200) having direct experience and 10% (20/200) having any experience (either direct or indirect). The approval rate for insurance coverage for PCOs was 74% (148/200), significantly lower than the corresponding rates for other value elements (82.5%–93.5%; P ≤ 0.034). The approval strength was significantly lower for PCOs, with a mean weight ± standard deviation of 5.1 ± 3.5, compared to other value elements (P ≤ 0.036).
Conclusion
There is currently limited demand for insurance coverage for AI that demonstrates benefits in terms of nonclinical PCOs.
9.Quantification of Vestibulospinal Reflex Under the Stress Condition on Both Soleus Muscles
Mi Joo KIM ; Seo Jin JANG ; Eun Ji LEE ; Ah Ram YU ; Jong Hyun HWANG ; Gyu Cheol HAN ; Ju Kang LEE
Journal of the Korean Balance Society 2012;11(1):14-22
BACKGROUND AND OBJECTIVES: Vestibulospinal reflex (VSR), which is measured in static state, tends to be compensated prior to vestibule-ocular reflex. Therefore, by establishing method that enables to track and observe quantified VSR, the reliability of experiment is attempted to be increased. MATERIALS AND METHODS: On five SD Rats to measure electromyogram (EMG), electrodes, in the form of stranded cables composed of seven wires, are chronically implanted on both sides of the soleus muscles. Pre and post operative condition of sitting still, standing, and ladder step walking was compared before, and six and twenty four hours after a unilateral labyrinthectomy with quantified muscle activity in maximal voluntary activity. Simultaneously by using multi modality electric potential plus package, the muscle activity between the two legs was tracked and compared. RESULTS: In the sitting still position, the left/right soleus muscle activities were 25.7/26.0 microV before a unilateral labyrinthectomy which was changed after the surgery with the value of 23.1/8.1 microV and 23.4/14.3 microV when six and twenty four hours passed respectively. In the standing position, 92.8/124.0 microV of preoperative value was changed to 89.6/37.3 microV six hours after the unilateral labyrinthectomy, and it was 97.0/54.7 microV 24 hours after. The preoperative value in ladder step walking test was 56.2/86.0 microV, and postoperative ones were 54.9/21.2 microV and 55.7/38.0 microV after six and twenty four hours respectively. CONCLUSION: VSR assessment method by using quantitative EMG well reflects the process of vestibular compensation, and to maintain the tension of extensor muscles, ladder step walking test is shown to be useful.
Animals
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Compensation and Redress
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Electrodes
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Leg
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Muscle, Skeletal
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Muscles
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Rats
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Reflex
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Track and Field
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Walking
10.Association of Insulin, Metformin, and Statin with Mortality in Breast Cancer Patients
Mihong CHOI ; Jiyeon HAN ; Bo Ram YANG ; Myoung-jin JANG ; Miso KIM ; Dae-Won LEE ; Tae-Yong KIM ; Seock-Ah IM ; Han-Byoel LEE ; Hyeong-Gon MOON ; Wonshik HAN ; Dong-Young NOH ; Kyung-Hun LEE
Cancer Research and Treatment 2021;53(1):65-76
Purpose:
This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer.
Materials and Methods:
We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer.
Results:
Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)–negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05).
Conclusion
Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.