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        Resident microglia die and infiltrated neutrophils and monocytes become major inflammatory cells in lipopolysaccharide-injected brain

        Ji, Kyung-Ae,Yang, Myung-Soon,Jeong, Hey-Kyeong,Min, Kyoung-Jin,Kang, Seung-Hee,Jou, Ilo,Joe, Eun-Hye John Wiley & Sons, Inc. 2007 Glia Vol.55 No.15

        <P>Generally, it has been accepted that microglia play important roles in brain inflammation. However, recently several studies suggested possible infiltration of blood neutrophils and monocytes into the brain. To understand contribution of microglia and blood inflammatory cells to brain inflammation, the behavior of microglia, neutrophils, and monocytes was investigated in LPS (lipopolysaccharide)-injected substantia nigra pars compacta, cortex, and hippocampus of normal and/or leukopenic rats using specific markers of neutrophils (myeloperoxidase, MPO), and microglia and monocytes (ionized calcium binding adaptor molecule-1, Iba-1), as well as a general marker for these inflammatory cells (CD11b). CD11b-immunopositive (CD11b<SUP>+</SUP>) cells and Iba-1<SUP>+</SUP> cells displayed similar behavior in intact and LPS-injected brain at 6 h after the injection. Interestingly, however, CD11b<SUP>+</SUP> cells and Iba-1<SUP>+</SUP> cells displayed significantly different behavior at 12 h: Iba-1<SUP>+</SUP> cells disappeared while CD11b<SUP>+</SUP> cells became round in shape. We found that CD11b/Iba-1-double positive (CD11b<SUP>+</SUP>/Iba-1<SUP>+</SUP>) ramified microglia died within 6 h after LPS injection. The round CD11b<SUP>+</SUP> cells detected at 12 h were MPO<SUP>+</SUP>. These CD11b<SUP>+</SUP>/MPO<SUP>+</SUP> cells were not found in leukopenic rats, suggestive of neutrophil infiltration. MPO<SUP>+</SUP> neutrophils expressed inducible nitric oxide synthase, interleukin-1β, cyclooxygenase-2, and monocyte chemoattractant protein-1, but died within 18 h. CD11b<SUP>+</SUP> cells detected at 24 h appeared to be infiltrated monocytes, since these cells were once labeled with Iba-1 and were not found in leukopenic rats. Furthermore, transplanted monocytes were detectable in LPS-injected brain. These results suggest that at least a part of neutrophils and monocytes could have been misinterpreted as activated microglia in inflamed brain. © 2007 Wiley-Liss, Inc.</P>

      • KCI등재

        Actual situation and prescribing patterns of opioids by pain physicians in South Korea

        Min Jung Kim,Ji Yeon Kim,Yun Hee Lim,Sung Jun Hong,Jae Hun Jeong,Hey Ran Choi,Sun Kyung Park,김정은,Min Ki Lee,Jae Hun Kim 대한통증학회 2022 The Korean Journal of Pain Vol.35 No.4

        Background: Use of opioids for chronic intractable pain is increasing globally, and their proper use can improve patients’ quality of life. In contrast, opioid use disorders, such as abuse or addiction, caused by prescribing opioids, are a worldwide issue. This study aimed to understand current opioid prescribing patterns and pain physicians’ experiences with opioid use in South Korea. Methods: Pain physicians in 42 university hospitals in South Korea were asked to complete anonymous questionnaires regarding opioid prescriptions. Results: A total of 69 surveys were completed. Most pain physicians started prescribing opioids at a pain score of 7/10 and aimed to reduce pain by 50%. Most physicians (73.1%) actively explained the prescribed medications and possible side effects, and 61.2% of physicians preferred the prescription interval of 4 weeks. Immediate-release opioids were the most popular treatment for breakthrough pain (92.6%). The most common side effect encountered by physicians was constipation (43.3%), followed by nausea/vomiting (34.3%). Of the physicians, 56.5% replied that addiction and misuse prevalences were less than 5%. However, the most concerning side effect was addiction (33.0%). Conclusions: The survey results showed that the prescribing patterns of pain physicians generally followed Korean guidelines. Physicians were most interested in the safety and effectiveness of opioid prescriptions. They were most concerned about respiratory depression and abuse or addiction. A significant number of physicians agreed that the NHIS regulations needed improvement for patient convenience and safe and effective treatment, though there were pros and cons of the NHIS restrictions on prescription conditions.

      • KCI등재

        Association between dyslipidemia and asthma in children: a systematic review and multicenter cohort study using a common data model

        Ji Eun Lim,Hye Min Kim,Ju Hee Kim,Hey-Sung Baek,Man Yong Han 대한소아청소년과학회 2023 Clinical and Experimental Pediatrics (CEP) Vol.66 No.8

        Background: The association between dyslipidemia and asthma in children remains unclear. Purpose: This study investigated the association between dyslipidemia and cholesterol levels in children. Methods: A systematic literature review was performed to identify studies investigating the association between dyslipidemia and asthma in children. The PubMed database was searched for articles published from January 2000–March 2022. Data from a cohort study using electronic health records from 5 hospitals, converted to the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM), were used to identify the association between total cholesterol (TC) levels and asthma in children. This cohort study used the Cox proportional hazards model to examine hazard ratio (HR) of asthma after propensity score matching, and included an aggregate meta-analysis of HR. Results: We examined 11 studies reporting an association between dyslipidemia and asthma in children. Most were cross-sectional; however, their results were inconsistent. In OMOP-CDM multicenter analysis, the high TC (>170 mg/dL) group included 29,038 children, while the normal TC (≤170 mg/dL) group included 88,823 children including all hospital datasets. In a meta-analysis of this multicenter cohort, a significant association was found between high TC levels and later development of asthma in children <15 years of age (pooled HR, 1.30; 95% confidence interval, 1.12–1.52). Conclusion: Elevated TC levels in children may be associated with asthma.

      • Poster Session : PS 0821 ; Upper GI Tract : Primary Malignant Melanoma of the Esophagus: A Case Report

        ( Ji Hyun Lee ),( Ki Nam Shim ),( Min Sun Ryu ),( Kwang Jin Woo ),( Jeon Mi Lee ),( Hey Won Yoon ),( Chung Hyun Tae ),( Chang Mo Moon ),( Seoung Eun Kim ),( Hye Kyung Jung ),( Sung Ae Jung ) 대한내과학회 2014 대한내과학회 추계학술발표논문집 Vol.2014 No.1

        Primary malignant melanoma of the esophagus is an extremely rare disease which counts for approximately 0.1-0.2% of all esophageal malignancies. It is also a very aggressive disease with a poor prognosis, with its 5yr survival rate ranging from 2.2% - 37.5%. Here we report a case of primary malignant melanoma of the esophagus in a patient whose diagnosis was made relatively early and thus total resection by an Ivor Lewis procedure was possible. A 51 year old Asian woman visited our hospital with epigastric discomfort. The patient had no noticeable medical history. She complained of mild nausea and dyspepsia, but there was no vomiting or weight loss. Physical examination showed no palpable lymph nodes in the head and neck region. There was no tenderness or rebound tenderness on the abdomen. For evaluation of her upper gastrointestinal symptoms, she had the upper endoscopy done. Endoscopy identifi ed a few dark pigmented, polypoid lesions scattered from 22cm to 30cm from the incisor tooth. The lesions were various in size, ranging from 0.2cm to 4-5cm and were fl at, slightly elevated with a irregular base. Biopsy done from two spots showed a well demarcated, slightly elevated and black pigmented tumor. For stage work-up, additional examinations were performed. The chest CT showed no abnormal thickening of the esophagus or any enlarged lymph nodes in the mediastinum. The PET-CT showed a mild focal abnormal uptake in the upper thoracic esophagus. The patient underwent an Ivor-Lewis procedure in June, 2013. Pathologic examination revealed spindle shaped malignant melanocytes with hyperchromated nucleis and black pigmentation. The lesion had invaded the submucosal layer. Thus the patient was diagnosed as esophageal malignant melanoma, stage T2N0M0. She is now under close observation at the out-patient department and has been disease free for 13 months.e

      • KCI등재

        Astrogliosis Is a Possible Player in Preventing Delayed Neuronal Death

        Jeong, Hey-Kyeong,Ji, Kyung-Min,Min, Kyoung-Jin,Choi, Insup,Choi, Dong-Joo,Jou, Ilo,Joe, Eun-Hye Korean Society for Molecular and Cellular Biology 2014 Molecules and cells Vol.37 No.4

        Mitigating secondary delayed neuronal injury has been a therapeutic strategy for minimizing neurological symptoms after several types of brain injury. Interestingly, secondary neuronal loss appeared to be closely related to functional loss and/or death of astrocytes. In the brain damage induced by agonists of two glutamate receptors, N-ethyl-D-aspartic acid (NMDA) and kainic acid (KA), NMDA induced neuronal death within 3 h, but did not increase further thereafter. However, in the KA-injected brain, neuronal death was not obviously detectable even at injection sites at 3 h, but extensively increased to encompass the entire hemisphere at 7 days. Brain inflammation, a possible cause of secondary neuronal damage, showed little differences between the two models. Importantly, however, astrocyte behavior was completely different. In the NMDA-injected cortex, the loss of glial fibrillary acidic protein-expressing ($GFAP^+$) astrocytes was confined to the injection site until 7 days after the injection, and astrocytes around the damage sites showed extensive gliosis and appeared to isolate the damage sites. In contrast, in the KA-injected brain, $GFAP^+$ astrocytes, like neurons, slowly, but progressively, disappeared across the entire hemisphere. Other markers of astrocytes, including $S100{\beta}$, glutamate transporter EAAT2, the potassium channel Kir4.1 and glutamine synthase, showed patterns similar to that of GFAP in both NMDA- and KA-injected cortexes. More importantly, astrocyte disappearance and/or functional loss preceded neuronal death in the KA-injected brain. Taken together, these results suggest that loss of astrocyte support to neurons may be a critical cause of delayed neuronal death in the injured brain.

      • Anti-Inflammatory Effect of Procyanidins from Wild Grape ( <i>Vitis amurensis</i> ) Seeds in LPS-Induced RAW 264.7 Cells

        Bak, Min-Ji,Truong, Van Long,Kang, Hey-Sook,Jun, Mira,Jeong, Woo-Sik Hindawi Publishing Corporation 2013 Oxidative medicine and cellular longevity Vol.2013 No.-

        <P>In the present study, the anti-inflammatory effect and underlying mechanisms of wild grape seeds procyanidins (WGP) were examined using lipopolysaccharide- (LPS-) stimulated RAW 264.7 cells. We used nitric oxide (NO) and prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>) and reactive oxygen species (ROS) assays to examine inhibitory effect of WGP and further investigated the mechanisms of WGP suppressed LPS-mediated genes and upstream expression by Western blot and confocal microscopy analysis. Our data indicate that WGP significantly reduced NO, PGE<SUB>2</SUB>, and ROS production and also inhibited the expression of proinflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions. Consistently, WGP significantly reduced LPS-stimulated expression of proinflammatory cytokines such as tumor necrosis factor <I><I>α</I></I> (TNF-<I><I>α</I></I>) and interleukin- (IL-) 1<I><I>β</I></I>. Moreover, WGP prevented nuclear translocation of nuclear factor-<I><I>κ</I></I>B (NF<I><I>κ</I></I>B) p65 subunit by reducing inhibitory <I><I>κ</I></I>B-<I><I>α</I></I> (I<I><I>κ</I></I>B<I><I>α</I></I>) and NF<I><I>κ</I></I>B phosphorylation. Furthermore, we found that WGP inhibited LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK). Taken together, our results demonstrated that WGP exerts potent anti-inflammatory activity through the inhibition of iNOS and COX-2 by regulating NF<I><I>κ</I></I>B and p38 MAPK pathway.</P>

      • KCI등재

        발효홍삼이 제2형 당뇨병 환자의 혈당 및 인슐린저항성에 미치는 영향

        김혜옥(Hey-Ok Kim),박민정(Min-Jung Park),한지숙(Ji-Sook Han) 한국식품영양과학회 2011 한국식품영양과학회지 Vol.40 No.5

        본 연구는 홍삼추출물을 Bifidobacterium longum H-1으로 발효시켜 인삼사포닌을 체내에서 흡수가 잘 되는 형태로 변화시킨 발효홍삼을 제2형 당뇨병환자에게 아침과 저녁 식전에 한 캡슐씩 하루 780 ㎎을 섭취하였다. 위약군은 동량의 cellulose를 실험군과 동일하게 제조한 후 같은 방법으로 섭취하도록 하였다. 연구대상자는 약물이나 식사로만 치료하는 총 38명의 제2형 당뇨병 환자로 발효홍삼군 20명(남자 12, 여자 8), 위약군 18명(남자 11, 여자 7)으로 구성되었으며, 두 군의 일반적 특성 및 생활습관은 유의적인 차이가 없었다. 연구결과 발효홍삼을 섭취한 군에서의 공복혈당은 136.29±16.45 ㎎/dL에서 127.71±17.74 ㎎/dL로 유의하게(p<0.05) 감소하였으며, 당화혈색소 역시 7.36±1.02%에서 6.96±0.93%로 감소하였다. 특히 당화혈색소가 8% 이상인 고당화혈색소군에서 유의적으로(p<0.05) 감소하는 것으로 나타났다. 인슐린 저항성은 대조군에서는 유의적 변화가 없는 반면, 발효홍삼군에서는 섭취 전 3.11±1.13 m㏖/L에서 섭취후 2.23±0.71 m㏖/L로 유의한(p<0.01) 감소를 나타내었다. 혈청지질 변화는 없었으며, LDL-콜레스테롤도 발효홍삼군에서 유의한 변화가 없었다. 간 기능 지표인 AST, ALT, γ-GTP와 신장기능 지표인 BUN, creatinine에서 유의적인 차이를 나타내지 않았으며, 정상범위에 속하여 발효홍삼의 안전성을 확인하였다. 이상의 연구 결과 한국인 제2형 당뇨병 환자에 있어 발효홍삼은 혈당 및 당화혈색소 감소와 인슐린 저항성 개선에 효과적인 것으로 나타났으며, 인체 안전성지표인 간 및 신장 기능도 정상으로 확인되었으므로 당뇨병 환자의 혈당 개선을 통해 합병증지연 또는 예방에 있어 효과를 기대할 수 있을 것으로 사료된다. We performed a randomized placebo-controlled trial to determine whether or not fermented red ginseng supplementation modulates blood glucose and insulin resistance in type 2 diabetic patients. A total of 38 patients were randomized to either a fermented red ginseng group or placebo group. The patients in the experimental or placebo group consumed 780 mg of fermented red ginseng or cellulose supplement per day for 12 weeks, respectively. Lifestyle factors and dietary intakes of the patients were not altered during the 12-weeks period. In the fermented red ginseng group after 12 weeks, the fasting blood glucose levels were significantly decreased (136.29±16.45 ㎎/dL to 127.71±17.74 ㎎/dL) and HbA₁c was also decreased. Especially, high HbA1c (HbA1c≥8%, 8.45±0.56% to 7.82±0.53%) was significantly decreased compared to low HbA1c (HbA1c <8%, 6.71±0.85% to 6.44±0.49%) in the fermented red ginseng group. Serum low-density lipoprotein was slightly decreased in the fermented red ginseng group compared to the placebo group. Homeostasis model assessment-insulin resistance was significantly reduced in the fermented red ginseng group compared to the placebo group. These results suggest that fermented red ginseng supplementation could be helpful to reduce blood glucose by improving insulin resistance in type 2 diabetic patients.

      • Anti‐fibrotic effect of chorionic plate‐derived mesenchymal stem cells isolated from human placenta in a rat model of CCl<sub>4</sub>‐injured liver: Potential application to the treatment of hepatic diseases

        Lee, Min,Jae,Jung, Jieun,Na, Kyu‐,Hwan,Moon, Ji Suk,Lee, Hey,Jin,Kim, Jae‐,Hwan,Kim, Gwang Il,Kwon, Sung‐,Won,Hwang, Seong‐,Gyu,Kim, Gi Jin Wiley Subscription Services, Inc., A Wiley Company 2010 Journal of cellular biochemistry Vol.111 No.6

        <P><B>Abstract</B></P><P>Translational studies have explored the therapeutic effects of stem cells, raising hopes for the treatment of numerous diseases. Here, we evaluated the therapeutic effect of chorionic plate‐derived mesenchymal stem cells (CP‐MSCs) isolated from human placenta and transplanted into rats with carbon tetrachloride (CCl<SUB>4</SUB>)‐injured livers. CP‐MSCs were analyzed for hepatocyte‐specific gene expression, indocyanine green (ICG) uptake, glycogen storage, and urea production following hepatogenic differentiation. PKH26‐labeled CP‐MSCs were directly transplanted into the livers of rats that had been exposed to CCl<SUB>4</SUB> (1.6 g/kg, twice per week for 9 weeks). Blood and liver tissue were analyzed at 1, 2, and 3 weeks post‐transplantation. The expression of type I collagen (Col I) and matrix metalloproteinases (MMPs) was analyzed in rat T‐HSC/Cl‐6 hepatic stellate cells co‐cultured with CP‐MSCs following exposure to TGF‐β. The expression levels of α‐smooth muscle actin (α‐SMA) and Col I were lower in transplanted (TP) rats than in non‐transplanted (Non‐TP) animals (<I>P</I> < 0.05), whereas the expression levels of albumin and MMP‐9 were increased. TP rats exhibited significantly higher uptake/excretion of ICG than non‐TP rats (<I>P</I> < 0.005). In addition, collagen synthesis in T‐HSC/Cl‐6 cells exposed to TGF‐β was decreased by co‐culture with CP‐MSCs, which triggered the activation of MMP‐2 and MMP‐9. These results contribute to our understanding of the potential pathophysiological roles of CP‐MSCs, including anti‐fibrotic effects in liver disease, and provide a foundation for the development of new cell therapy‐based strategies for the treatment of difficult‐to‐treat liver diseases. J. Cell. Biochem. 111: 1453–1463, 2010. © 2010 Wiley‐Liss, Inc.</P>

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