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Chronic kidney disease is a significant health burden worldwide, with increasing incidence. Although several genome- wide association studies (GWAS) have investigated single nucleotide polymorphisms (SNP) associated with kidney trait, most studies were focused on European ancestry. Methods: We utilized clinical and genetic information collected from the Korean Genome and Epidemiology Study (KoGES). Results: More than five million SNPs from 58,406 participants were analyzed. After meta-GWAS, 1,360 loci associated with estimated glomerular filtration rate (eGFR) at a genome-wide significant level (p = 5 × 10–8) were identified. Among them, 399 loci were validated with at least one other biomarker (blood urea nitrogen [BUN] or eGFRcysC) and 149 loci were validated using both markers. Among them, 18 SNPs (nine known ones and nine novel ones) with 20 putative genes were found. The aggregated effect of genes estimated by MAGMA gene analysis showed that these significant genes were enriched in kidney-associated pathways, with the kidney and liver being the most enriched tissues. Conclusion: In this study, we conducted GWAS for more than 50,000 Korean individuals and identified several variants associated with kidney traits, including eGFR, BUN, and eGFRcysC. We also investigated functions of relevant genes using computational methods to define putative causal variants.
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BACKGROUND/OBJECTIVES@#Abeliophyllum distichum is a plant endemic to Korea, containing several beneficial natural compounds. This study investigated the effect of A. distichum leaf extract (ALE) on adipocyte differentiation.MATERIALS/METHODS: The cytotoxic effect of ALE was analyzed using cell viability assay.3T3-L1 preadipocytes were differentiated using induction media in the presence or absence of ALE. Lipid accumulation was confirmed using Oil Red O staining. The mRNA expression of adipogenic markers was measured using RT-PCR, and the protein expressions of mitogenactivated protein kinase (MAPK) and peroxisome proliferator-activated receptor gamma (PPARγ) were measured using western blot. Cell proliferation was measured by calculating the incorporation of Bromodeoxyuridine (BrdU) into DNA. @*RESULTS@#ALE reduced lipid accumulation in differentiated adipocytes, as indicated by Oil Red O staining and triglyceride assays. Treatment with ALE decreased the gene expression of adipogenic markers such as Pparγ, CCAAT/enhancer binding protein alpha (C/ebpα), lipoprotein lipase, adipocyte protein-2, acetyl-CoA carboxylase, and fatty acid synthase.Also, the protein expression of PPARγ was reduced by ALE. Treating the cells with ALE at different time points revealed that the inhibitory effect of ALE on adipogenesis is higher in the early period treatment than in the terminal period. Furthermore, ALE inhibited adipocyte differentiation by reducing the early phase of adipogenesis and mitotic clonal expansion. This was indicated by the lower number of cells in the Synthesis phase of the cell cycle (labeled using BrdU assay) and a decrease in the expression of early adipogenic transcription factors such as C/ebpβ and C/ebpδ. ALE suppressed the phosphorylation of MAPK, confirming that the effect of ALE was through the suppression of early phase of adipogenesis. @*CONCLUSIONS@#Altogether, the results of the present study revealed that ALE inhibits lipid accumulation and may be a potential agent for managing obesity.
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Purpose@#Forced expiratory flow between 25% and 75% (FEF 25%-75%) is known to sensitively reflect bronchial obstruction. Methacholine challenge test (MCT) has shown varying reduction levels of forced vital capacity (FVC) with the reduction in forced expiratory volume in 1 second (FEV1) in asthma. The aim of this study was to evaluate the clinical implication of provocative concentration causing a 20% fall in FEF 25%-75%(PC 20-FEF 25%-75%) and the percentage fall in FVC at the PC 20 dose of methacholine (△FVC). @*Methods@#A total of 194 children who visited the hospital due to respiratory symptoms and underwent MCT were analyzed retrospectively. The patients were divided into 3 groups. Group I had both PC 20-FEV1 and PC 20-FEF 25%-75% above 16 mg/mL; group II had a PC 20-FEF 25%-75% that fell below 16 mg/mL but PC 20-FEV1 was 16 mg/mL or above; group III had a PC 20-FEV1and a PC 20-FEF 25%-75% that both fell below 16 mg/mL. @*Results@#In group II, PC 20-FEV1 was lower (P = 0.026) and the rate of change in FEV1 and FEF 25%-75% from baseline to 16 mg/mL of methacholine concentration was greater than in group I (both P< 0.001). Levels of PC 20-FEF 25%-75% were higher in group II compared to group III (P < 0.001). △FVC showed a correlation with PC 20-FEV1 (P < 0.001) only in the whole group. @*Conclusion@#In asthmatic children, PC 20-FEF 25%-75% may be associated with bronchial hyperresponsiveness. △FVC was not associated with other parameters in either group. For subjects with a positive finding of PC 20-FEF 25%-75% and a negative finding of MCT, the progression to asthma can be suspected.
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BACKGROUND/OBJECTIVES@#Abeliophyllum distichum is a plant endemic to Korea, containing several beneficial natural compounds. This study investigated the effect of A. distichum leaf extract (ALE) on adipocyte differentiation.MATERIALS/METHODS: The cytotoxic effect of ALE was analyzed using cell viability assay.3T3-L1 preadipocytes were differentiated using induction media in the presence or absence of ALE. Lipid accumulation was confirmed using Oil Red O staining. The mRNA expression of adipogenic markers was measured using RT-PCR, and the protein expressions of mitogenactivated protein kinase (MAPK) and peroxisome proliferator-activated receptor gamma (PPARγ) were measured using western blot. Cell proliferation was measured by calculating the incorporation of Bromodeoxyuridine (BrdU) into DNA. @*RESULTS@#ALE reduced lipid accumulation in differentiated adipocytes, as indicated by Oil Red O staining and triglyceride assays. Treatment with ALE decreased the gene expression of adipogenic markers such as Pparγ, CCAAT/enhancer binding protein alpha (C/ebpα), lipoprotein lipase, adipocyte protein-2, acetyl-CoA carboxylase, and fatty acid synthase.Also, the protein expression of PPARγ was reduced by ALE. Treating the cells with ALE at different time points revealed that the inhibitory effect of ALE on adipogenesis is higher in the early period treatment than in the terminal period. Furthermore, ALE inhibited adipocyte differentiation by reducing the early phase of adipogenesis and mitotic clonal expansion. This was indicated by the lower number of cells in the Synthesis phase of the cell cycle (labeled using BrdU assay) and a decrease in the expression of early adipogenic transcription factors such as C/ebpβ and C/ebpδ. ALE suppressed the phosphorylation of MAPK, confirming that the effect of ALE was through the suppression of early phase of adipogenesis. @*CONCLUSIONS@#Altogether, the results of the present study revealed that ALE inhibits lipid accumulation and may be a potential agent for managing obesity.
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Purpose@#Induced sputum eosinophil count is useful for the evaluation and diagnosis of asthma and eosinophilic bronchitis (EB).The aim of this study was to evaluate the correlation of induced sputum eosinophil count with various allergic indicators, including the peripheral blood eosinophil count, in pediatric asthma and EB. @*Methods@#From May 2014 to July 2018, 126 children visited Kyungpook National University Children’s Hospital, and underwent methacholine bronchial challenge test and sputum induction. Peripheral blood eosinophil counts, serum eosinophil cationic protein (ECP), serum total IgE, immunoCAP for inhalant allergens, and skin prick test were performed in the study subjects. @*Results@#In the asthma group, the eosinophil count of induced sputum correlated with peripheral blood eosinophils (r=0.279, P=0.043).The concordance rates of sputum and peripheral blood eosinophil count in the asthma and EB groups were 64.1% and 25.7%, respectively. The number of eosinophils in the sputum also correlated with serum total IgE, ECP, and specific IgE to Dermatophagoides farinae, Dermatophagoides pteronyssinus, and Aspergillus in the asthma group. @*Conclusion@#The number of eosinophils in the induced sputum correlated with peripheral blood in the asthma group. However, a third of subjects were discordant. Therefore, we need to keep in mind the possibility of discordance when predicting the degree of airway eosinophilic inflammation using the peripheral blood eosinophils. In EB, the number of induced sputum eosinophils did not correlate with the number of peripheral blood eosinophils, which may be attributed to the difference in mechanism. Further studies are warranted.
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PURPOSE: This study examined the immunological activity and optimized the mixture conditions of Sargassum horneri (S. horneri) extracts in vitro and in vivo models.METHODS: S. horneri was extracted using three different methods: hot water extraction (HWE), 50% ethanol extraction (EE), and supercritical fluid extraction (SFE). Splenocyte proliferation and cytokine production (Interleukin-2 and Interferon-γ) were measured using a WST-1 assay and enzyme-linked immunosorbent assay, respectively. The levels of nitric oxide and T cell activation production were measured using a Griess assay and flow cytometry, respectively. The natural killer (NK) cell activity was determined using an EZ-LDH kit.RESULTS: Among the three different types of extracts, HWE showed the highest levels of splenocyte proliferation and cytokine production in vitro. In the animal model, three different types of extracts were administrated for 14 days (once/day) at 50 and 100 mg/kg body weight. HWE and SFE showed a high level of splenocyte proliferation and cytokine production in the with and without mitogen-treated groups, whereas EE administration did not induce the splenocyte activation. When RAW264.7 macrophage cells were treated with different mixtures (HWE with 5, 10, 15, 20% of SFE) to determine the optimal mixture ratio of HWE and SFE, the levels of nitric oxide and cytokine production increased strongly in the HWE with 5% and 10% of SFE containing group. In the animal model, HWE with 5% and 10% of SFE mixture administration increased the levels of splenocyte proliferation, cytokine production, and activated CD4⁺ cell population significantly, with the highest level observed in the HWE with 5% of SFE group. Moreover, the NK cell activity was increased significantly in the HWE with 5% of SFE mixture-treated group compared to the control group.CONCLUSION: The optimal mixture condition of S. horneri with immune-enhancing activity is the HWE with 5% of SFE mixture. These results confirmed that the extracts of S. horneri and its mixtures are potential candidate materials for immune enhancement.
Subject(s)
Body Weight , Chromatography, Supercritical Fluid , Enzyme-Linked Immunosorbent Assay , Ethanol , Flow Cytometry , In Vitro Techniques , Killer Cells, Natural , Macrophages , Models, Animal , Nitric Oxide , Sargassum , WaterABSTRACT
The safety and feasibility of simple coil embolization and stent deployment for the treatment of posterior inferior cerebellar artery (PICA) aneurysms, as well as their radiologic and clinical results, have not been adequately understood. Especially, if dissecting aneurysm of proximal PICA is associated with small caliber PICA and stenosis of ipsilateral vertebral artery orifice (VAO), endovascular coiling with saving of PICA is not always easy. This 64-year-old man presented with subarachnoid hemorrhage due to a ruptured dissecting aneurysm of left proximal PICA. The aneurysm was irregularly fusiform in nature with a shallow PICA orifice (1.4 mm) and narrow caliber (0.9–1.5 mm). Moreover, the ipsilateral VAO showed severe stenosis (1.8 mm). We performed bifemoral puncture and chose additional route from right vertebral artery to left vertebrobasilar junction for retrograde approach and deployment of LVIS Jr. intraluminal support at proximal PICA. And then, the antegrade approach and coiling of aneurysm was done. Despite of transient thrombus of PICA, the aneurysm was successfully secured with preservation of whole PICA course. For preservation of narrow PICA with ipsilateral VAO stenosis, the contralateral approach and deployment of LVIS Jr. intraluminal support may be considered.
Subject(s)
Humans , Middle Aged , Aneurysm , Aortic Dissection , Arteries , Constriction, Pathologic , Embolization, Therapeutic , Pica , Punctures , Stents , Subarachnoid Hemorrhage , Thrombosis , Vertebral ArteryABSTRACT
PURPOSE: Sargassum horneri (S. horneri) is a species of brown macroalgae that is common along the coast of Japan and Korea. The present study investigated the immuno-modulatory effects of different types of S. horneri extracts in RAW264.7 macrophages. METHODS: S. horneri was extracted by three different methods, hot water extraction, 50% ethanol extraction, and supercritical fluid extraction. Cell viability was then measured by MTT assay, while the production levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) were measured by enzyme-linked immunosorbent assay and Griess assay, respectively. The expression and activation levels of inducible NO synthase (iNOS), mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) were examined by western blot analysis. RESULTS: The three different S. horneri extracts were nontoxic against RAW 264.7 cells up to 50 µg/mL, among which treatment with hot water extract (HWE) of S. horneri significantly enhanced the production of TNF-α, IL-6, and NO in a dose-dependent manner. Hot water extract of S. horneri also increased the expression level of iNOS, suggesting that up-regulation of iNOS expression by HWE of S. horneri was responsible for the induction of NO production. In addition, treatment of RAW 264.7 macrophages with HWE of S. horneri increased the phosphorylation levels of ERK, p38 and JNK. Furthermore, the activation and subsequent nuclear translocation of NF-κB was enhanced upon treatment with HWE of S. horneri, indicating that HWE of S. horneri activates macrophages to secrete TNF-α, IL-6 and NO and induces iNOS expression via activation of the NF-κB and MAPKs signaling pathways. CONCLUSION: Taken together, these findings suggest that HWE of S. horneri possesses potential as a functional food with immunomodulatory activity.
Subject(s)
Blotting, Western , Cell Survival , Chromatography, Supercritical Fluid , Cytokines , Enzyme-Linked Immunosorbent Assay , Ethanol , Functional Food , Interleukin-6 , Japan , Korea , Macrophages , Necrosis , Nitric Oxide , Nitric Oxide Synthase , Phosphorylation , Protein Kinases , Sargassum , Seaweed , Up-Regulation , WaterABSTRACT
PURPOSE: Cytomegalovirus (CMV) infection is mostly asymptomatic but can be detrimental to certain hosts. We investigated changes of CMV seroprevalence in Koreans before and after the year 2000. METHODS: We reviewed laboratory values of patients who were tested for CMV immunoglobulin G (IgG) at Samsung Medical Center, Seoul, Korea, from January 1995 to December 2015. Changes in seroprevalence were analyzed by gender, age, region, and tested year period (period 1, 1995–2005 vs. period 2, 2006–2015). RESULTS: Overall CMV seropositivity was 94.1% (10,900/11,584). There was no significant difference for CMV seropositivity among the two periods (94.2% vs. 94.1%) (P=0.862). CMV seropositivity in the 11 to 20-year age group in period 2 (78.8%) was significantly lower than that of period 1 (89.9%) (P=0.001). The seropositivity of individuals aged 31–40 years (97.4%) was significantly higher than that of younger age groups (P < 0.001) and lower than that of older age groups (P < 0.001). Of 2,441 females of reproductive age (from 15 to 49), CMV seropositivity was 97% (2,467/2,441). The seropositivity in women aged 20–24-years was higher than that of men in the same age group (97.6% vs. 85.6%, P=0.003). No significant difference was observed among different regions. CONCLUSIONS: Overall CMV seropositivity of Koreans was estimated to be 94% and the average seropositivity of reproductive women was 97%. Monitoring of the changes in seroprevalence including the reproductive age group is needed in the future.
Subject(s)
Female , Humans , Male , Cytomegalovirus , Immunoglobulin G , Korea , Seoul , Seroepidemiologic StudiesABSTRACT
PURPOSE: A recent study analyzing several cytokines reported that long cardiopulmonary bypass (CPB) time and long aortic cross clamp (ACC) time were accompanied by enhanced postoperative inflammation, which contrasted with the modest influence of the degree of hypothermia. In this present study, we aimed to examine the effect of CPB temperature on the clinical outcome in infants undergoing repair of isolated ventricular septal defect (VSD). METHODS: Of the 212 infants with isolated VSD who underwent open heart surgery (OHS) between January 2001 and December 2010, 43 infants were enrolled. They were classified into 2 groups: group 1, infants undergoing hypothermic CPB (26degrees C-28degrees C; n=19) and group 2, infants undergoing near-normothermic CPB (34degrees C-36degrees C; n=24). RESULTS: The age at the time of the OHS, and number of infants aged<3 months showed no significant differences between the groups. The CPB time and ACC time in group 1 were longer than those in group 2 (88 minutes vs. 59 minutes, P=0.002, and 54 minutes vs. 37 minutes, P=0.006 respectively). The duration of postoperative mechanical ventilation was 1.6 days in group 1 and 1.8 days in group 2. None of the infants showed postoperative neurological and developmental abnormalities. Moreover, no postoperative differences in the white blood cell count and C-reactive protein levels were noted between two groups. CONCLUSION: This study revealed that hypothermic and near-normothermic CPB were associated with similar clinical outcomes and inflammatory reactions in neonates and infants treated for simple congenital heart disease.
Subject(s)
Humans , Infant , Infant, Newborn , C-Reactive Protein , Cardiopulmonary Bypass , Cytokines , Heart Defects, Congenital , Heart Septal Defects, Ventricular , Hypothermia , Inflammation , Leukocyte Count , Respiration, Artificial , Thoracic SurgeryABSTRACT
BACKGROUND: Immunoglobulin A nephropathy (IgAN) and thin glomerular basement membrane nephropathy (TBMN) are the most common causes of persistent hematuria during childhood. The objective of this study is to determine the difference in clinicl features and laboratory findings between pediatric patients with IgA deposited TBMN and IgAN alone. METHODS: Between January 2000 and March 2009, 95 children were diagnosed with IgAN by renal biopsy. Clinical features and laboratory findings of patients with isolated IgAN and with IgAN plus TBMN were compared; the children diagnosed with IgAN were compared to 127 children who had been diagnosed with TBMN alone during the same period. RESULTS: There were 71 (74.7%) of a total 95 patients that were diagnosed with isolated IgAN (Group 1); in 24 (25.3%) of the 95 patients IgAN was combined with TBMN (Group 2). There was marked difference in the gender distribution between Group 2 and isolated TBMN patients. The degree of proteinuria and pathologic severity was higher in Group 1 compared with Group 2. Gross hematuria was present in both groups. There were no distinguishing features in the other laboratory parameters. CONCLUSION: Patients with both IgAN and TBMN seem to have similar clinical features to patients with isolated IgAN; however, the latter tend to have better pathologic and laboratory findings, compared to the patients with IgAN alone.
Subject(s)
Child , Humans , Biopsy , Glomerular Basement Membrane , Glomerulonephritis, IGA , Hematuria , Immunoglobulin A , ProteinuriaABSTRACT
PURPOSE: This study was conducted to investigate the incidence of rotavirus infection and common rotavirus strains of newborn infants admitted to the NICU and elucidate association, between rotavirus infection and clinical symptoms, and the significance of rotavirus antigen test. METHODS: From July 2010 to June 2011, stools of 408 newborns admitted into the NICU were tested for rotavirus antigen by enzyme-linked fluorescent assay. Rotavirus positive stools were performed RT-PCR. RESULTS: A total of 408 stool samples were examined by VIDAS Rotavirus(R), and 128 specimens (31.4%) were proven positive. One hundred thirteen fecal specimens were eligible for RT-PCR and rotavirus was detected in 42 samples (10.3%). PCR (+) prevalence of antigen positive infants was significantly lower in 1-2 postnatal days group than infants older than three days after birth (P<0.001). Out of the 42 PCR positive infants, there were 26 (62%) symptomatic infants. Seventeen infants had fever, 15 had diarrhea, and 3 experienced vomiting. Rest of the 16 patients (38%) did not show any symptoms. The most common strain was G4P[6] (n=40, 95.2%), followed by G4P[8] (n=1, 2.4%), and G3P[3] (n=1, 2.4%). CONCLUSIONS: Rotavirus infection rate in the NICU was 31.4% in the antigen test and 11.7% in the PCR test. False positive rate of rotavirus antigen test was significantly higher in 1-2 postnatal days group. Thus, it should be considered to apply different RFV standards from adults when rotavirus antigen test result is evaluated in newborn infants. The most common strain of rotavirus was G4P[6].