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1.  A co-twin study of the relative effect of birth weight and gestational age on retinopathy of prematurity 
Eye  2011;25(11):1478-1483.
To determine the relative effect of birth weight and gestational age on retinopathy of prematurity (ROP) using preterm twin pairs discordant for birth weight.
This study was a retrospective cohort study including 55 consecutive twin pairs of 110 preterm infants (gestational age ≤33 weeks). The outcomes of ROP including occurrence (any stage), severe ROP (stage 3 or more), and clinically significant ROP requiring laser treatment were compared between twins with the lower birth weight from each pair and their co-twins with the higher birth weight. Using twin pairs having different birth weight and identical gestational age, the independent effects of prematurity and intrauterine growth on ROP could be evaluated. Other perinatal morbidities related to prematurity were also compared between twin pairs.
No significant differences in ROP between larger and smaller infants were observed in the twin-paired analysis while analysis on individual infants showed strong association between small birth weight and ROP outcomes. However, in both the larger and smaller infant groups, gestational age of <28 weeks was significantly associated with ROP outcomes. No differences were found between twin pairs regarding other perinatal morbidities including bronchopulmonary dysplasia, respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage, and periventricular leukomalacia.
Birth weight is not associated with ROP, while gestational age is in the twin-paired study, suggesting that gestational age is a better predictor of ROP than birth weight. This indicates that maturity is more important in the pathogenesis of ROP than intrauterine growth.
PMCID: PMC3213664  PMID: 21869833
retinopathy of prematurity; gestational age; birth weight
2.  Effect of Lysine to Digestible Energy Ratio on Growth Performance and Carcass Characteristics in Finishing Pigs 
This experiment was performed to investigate the effects of lysine (Lys) to DE ratio on growth performance, and carcass characterics in finishing barrows. Ninety six cross-bred finishing barrows ((Landrace×Yorkshire) ×Duroc, average BW 58.25±0.48 kg) were assigned as a randomized complete block design by 2 energy levels and 4 Lys:DE ratios on the basis of BW to one of 8 treatments with 3 replications with 4 animals per pen. The levels of DE and Lys:DE ratio for each treatment were i) DE 3.35 Mcal/kg, 1.5 g Lys/Mcal DE, ii) DE 3.35 Mcal/kg, 1.8 g Lys/Mcal DE, iii) DE 3.35 Mcal/kg, 2.1 g Lys/Mcal DE, iv) DE 3.35 Mcal/kg, 2.4 g Lys/Mcal DE, v) DE 3.60 Mcal/kg, 1.5 g Lys/Mcal DE, vi) DE 3.60 Mcal/kg, 1.8 g Lys/Mcal DE, vii) DE 3.60 Mcal/kg, 2.1 g Lys/Mcal DE, viii) DE 3.60 Mcal/kg, 2.4 g Lys/Mcal DE. During finishing period from 58 kg to 103 kg of BW, increased energy density in the diet increased (p<0.05) ADG and gain:feed ratio, but did not influence ADFI. As Lys:DE ratio was increased, ADG, ADFI and gain:feed ratio were improved in finishing barrows (p<0.05). There were positive interactions (p<0.05) between carcass weight, grade, and backfat thickness and energy density and Lys level (p<0.05). In conclusion, data from our current study suggest that maximum yields including ADG, gain:feed ratio, carcass weight and grade can be achieved by administrating finishing pigs with an ideal Lys:DE ratio, Lys 2.1 g/DE Mcal.
PMCID: PMC4093041  PMID: 25049520
Barrows; Backfat; Lysine:DE Ratio; Carcass Characteristics
3.  Salvage chemotherapy with irinotecan, 5-fluorouracil and leucovorin for taxane- and cisplatin-refractory, metastatic gastric cancer 
British Journal of Cancer  2005;92(10):1850-1854.
We performed a phase II study of combination chemotherapy with irinotecan, 5-fluorouracil (5-FU) and leucovorin in metastatic gastric cancer patients who were previously treated with taxane and cisplatin, to evaluate the antitumour activity and toxicity of the combination chemotherapy. The metastatic gastric adenocarcinoma patients who were previously treated with taxane and cisplatin combination as first line, and had at least one measurable lesion, 0–2 ECOG performance status and adequate organ functions, were considered eligible. They received irinotecan (150 mg m−2, day 1) and leucovorin (100 mg m−2, day 1), followed by continuous infusion of 5-FU (1000 mg m−2 day−1, days 1 and 2) every 2 weeks. Treatment was continued until progression of disease was observed. In all, 64 patients were treated with this combination chemotherapy. The median age of the patients was 55 years (range, 33–74 years), and the median ECOG performance status was 1 (0–1, 61 (95%)). Out of 64 patients, 57 were assessable for response. Among 57 assessable patients, no complete response and 12 partial responses were observed (overall response rate, 21%; 95% confidence interval (CI), 10–32%). Stable disease was observed in 14 patients (25%) and progressive disease in 31 patients (54%). The median time to progression was 2.5 months (95% CI, 1.6–3.4) and the median overall survival since the start of the second-line modified FOLFIRI was 7.6 months (95% CI, 6.5–8.7). Grade 3–4 haematologic toxicities included neutropenia in seven patients (11%) and thrombocytopenia in five patients (8%). Grade 3–4 nonhaematologic toxicities included diarrhoea in two patients (3%) and vomiting in two patients (3%). There were no treatment-related deaths. The combination of irinotecan, 5-FU and leucovorin showed moderate activity and favourable toxicity profile as a second-line treatment in metastatic gastric cancer patients, who were previously treated with taxane and cisplatin.
PMCID: PMC2361777  PMID: 15870718
gastric carcinoma; irinotecan; 5-FU; salvage chemotherapy
4.  Nasal-type NK/T cell lymphoma: clinical features and treatment outcome 
British Journal of Cancer  2005;92(7):1226-1230.
Nasal-type NK/T cell lymphoma is an increasingly recognised disease entity of aggressive clinical behaviour. The objective of this study was to investigate clinical features and treatment outcomes in patients with nasal-type NK/T cell lymphoma. From January 1991 to December 2003, 26 patients diagnosed as nasal-type NK/T cell lymphoma were included in the analysis. One half of patients presented with poor performance status (ECOG ⩾2); 46% of patients were categorised as high intermediate or high-risk group according to IPI; and 46% of patients were diagnosed at advanced stage. The median survival for 26 patients with nasal-type NK/T cell lymphoma was 7.4 months (95% CI, 0.1, 16.9). The treatment outcome of primary anthracycline-based chemotherapy was poor: 60% CR rate in localised disease and 0% CR rate in advanced disease. After a median follow-up of 24.4 months (range 3.1–99.0) in patients with localised disease who had achieved a CR (range 29.6–165.7), three patients (50.0%) developed disease recurrence at 6.1, 21.8, and 52.1 months, respectively, and all patients presented with locoregional failure. The predictive factors for poor survival were of age greater than 60, advanced stage and poor performance in multivariate analysis. In conclusion, Nasal-type NK/T cell lymphomas showed a poor response to the conventional anthracycline-based chemotherapy, and thus an investigation for an innovative therapy is urgently needed to improve survival in these patients.
PMCID: PMC2361983  PMID: 15798768
extra-nasal; natural killer cell lymphoma; treatment
5.  Identification of two novel frame shift mutations of the NF1 gene in Korean patients with neurofibromatosis type 1. 
Journal of Korean Medical Science  2000;15(5):542-544.
Neurofibromatos is type 1 (NF1) is one of the most common inherited disorders and is characterized by abnormalities in multiple tissues derived from the neural crest. The NF-1 gene has been cloned and mapped to human chromosome 17q11.2. The NF-1 gene has an open reading frame that predicts a protein consisting of 2,818 amino acids, known as neurofibromin. Here, we report two kinds of novel frame shift mutations of the NF1 gene from 2 out of 56 unrelated Korean NF1 patients. These mutations were detected using polymerase chain reaction and single strand conformational polymorphism analysis. Sequencing analysis revealed four base pair insertion at codon 1270 of exon 22, and a base pair deletion at codon 1398 of exon 24. These mutations resulted in premature termination of the mutant alleles and may encode truncated forms of neurofibromin.
PMCID: PMC3054687  PMID: 11068991
6.  FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium 
Agarwal, D | Pineda, S | Michailidou, K | Herranz, J | Pita, G | Moreno, L T | Alonso, M R | Dennis, J | Wang, Q | Bolla, M K | Meyer, K B | Menéndez-Rodríguez, P | Hardisson, D | Mendiola, M | González-Neira, A | Lindblom, A | Margolin, S | Swerdlow, A | Ashworth, A | Orr, N | Jones, M | Matsuo, K | Ito, H | Iwata, H | Kondo, N | Hartman, M | Hui, M | Lim, W Y | T-C Iau, P | Sawyer, E | Tomlinson, I | Kerin, M | Miller, N | Kang, D | Choi, J-Y | Park, S K | Noh, D-Y | Hopper, J L | Schmidt, D F | Makalic, E | Southey, M C | Teo, S H | Yip, C H | Sivanandan, K | Tay, W-T | Brauch, H | Brüning, T | Hamann, U | Dunning, A M | Shah, M | Andrulis, I L | Knight, J A | Glendon, G | Tchatchou, S | Schmidt, M K | Broeks, A | Rosenberg, E H | van't Veer, L J | Fasching, P A | Renner, S P | Ekici, A B | Beckmann, M W | Shen, C-Y | Hsiung, C-N | Yu, J-C | Hou, M-F | Blot, W | Cai, Q | Wu, A H | Tseng, C-C | Van Den Berg, D | Stram, D O | Cox, A | Brock, I W | Reed, M W R | Muir, K | Lophatananon, A | Stewart-Brown, S | Siriwanarangsan, P | Zheng, W | Deming-Halverson, S | Shrubsole, M J | Long, J | Shu, X-O | Lu, W | Gao, Y-T | Zhang, B | Radice, P | Peterlongo, P | Manoukian, S | Mariette, F | Sangrajrang, S | McKay, J | Couch, F J | Toland, A E | Yannoukakos, D | Fletcher, O | Johnson, N | Silva, I dos Santos | Peto, J | Marme, F | Burwinkel, B | Guénel, P | Truong, T | Sanchez, M | Mulot, C | Bojesen, S E | Nordestgaard, B G | Flyer, H | Brenner, H | Dieffenbach, A K | Arndt, V | Stegmaier, C | Mannermaa, A | Kataja, V | Kosma, V-M | Hartikainen, J M | Lambrechts, D | Yesilyurt, B T | Floris, G | Leunen, K | Chang-Claude, J | Rudolph, A | Seibold, P | Flesch-Janys, D | Wang, X | Olson, J E | Vachon, C | Purrington, K | Giles, G G | Severi, G | Baglietto, L | Haiman, C A | Henderson, B E | Schumacher, F | Le Marchand, L | Simard, J | Dumont, M | Goldberg, M S | Labrèche, F | Winqvist, R | Pylkäs, K | Jukkola-Vuorinen, A | Grip, M | Devilee, P | Tollenaar, R A E M | Seynaeve, C | García-Closas, M | Chanock, S J | Lissowska, J | Figueroa, J D | Czene, K | Eriksson, M | Humphreys, K | Darabi, H | Hooning, M J | Kriege, M | Collée, J M | Tilanus-Linthorst, M | Li, J | Jakubowska, A | Lubinski, J | Jaworska-Bieniek, K | Durda, K | Nevanlinna, H | Muranen, T A | Aittomäki, K | Blomqvist, C | Bogdanova, N | Dörk, T | Hall, P | Chenevix-Trench, G | Easton, D F | Pharoah, P D P | Arias-Perez, J I | Zamora, P | Benítez, J | Milne, R L
British Journal of Cancer  2014;110(4):1088-1100.
Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium.
Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression.
Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02–1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2.
Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.
PMCID: PMC3929867  PMID: 24548884
breast cancer; SNP; FGF receptors; susceptibility; disease subtypes
7.  Ultra-thin strut cobalt chromium bare metal stent usage in a complex real-world setting. (SOLSTICE registry) 
Netherlands Heart Journal  2015;23(2):124-129.
To report clinical follow-up at 6 months after implantation of the ultra-thin strut cobalt chromium SolarFlex stent in a real-world setting.
Methods and results
Patients (n = 240) with single or multiple vessel coronary artery disease undergoing percutaneous coronary intervention (PCI) at four sites in Europe were enrolled in the SOLSTICE (SolarFlex Stent in Routine Clinical Practice) registry. Follow-up at 6 months was 100 %. Diabetes was present in 29 % of the patients, 30 % presented with acute myocardial infarction and 17 % had unstable angina. Of the patients, 27 % had previously undergone PCI or coronary artery bypass surgery. Lesion complexity was high (50 % B2 + C type lesions). Device success was achieved in 99.7 % of cases and the major adverse cardiac event (MACE) rate was 5.8 % at 6 months of follow-up. Target lesion revascularisation (TLR) was 5.0 % at 6 months.
The SOLSTICE registry showed that in a complex real-world setting the SolarFlex bare metal stent, with ultra-thin struts and customised scaffolding, provided low clinical MACE and TLR rates. These results provide support for the use of the latest generation bare metal stent in contemporary European practice.
PMCID: PMC4315800  PMID: 25563495
Bare metal stent; Cobalt chromium stent; Stent design
8.  Refractive errors in a rural Korean adult population: the Namil Study 
Eye  2013;27(12):1368-1375.
To assess the prevalence of refractive errors, including myopia, high myopia, hyperopia, astigmatism, and anisometropia, in rural adult Koreans.
We identified 2027 residents aged 40 years or older in Namil-myeon, a rural town in central South Korea. Of 1928 eligible residents, 1532 subjects (79.5%) participated. Each subject underwent screening examinations including autorefractometry, corneal curvature measurement, and best-corrected visual acuity.
Data from 1215 phakic right eyes were analyzed. The prevalence of myopia (spherical equivalent (SE) <−0.5 diopters (D)) was 20.5% (95% confidence interval (CI): 18.2−22.8%), of high myopia (SE <−6.0 D) was 1.0% (95% CI: 0.4−1.5%), of hyperopia (SE>+0.5 D) was 41.8% (95% CI: 38.9−44.4%), of astigmatism (cylinder <−0.5 D) was 63.7% (95% CI: 61.0−66.4%), and of anisometropia (difference in SE between eyes >1.0 D) was 13.8% (95% CI: 11.9−15.8%). Myopia prevalence decreased with age and tended to transition into hyperopia with age up to 60−69 years. In subjects older than this, the trend in SE refractive errors reversed with age. The prevalence of astigmatism and anisometropia increased consistently with age. The refractive status was not significantly different between males and females.
The prevalence of myopia and hyperopia in rural adult Koreans was similar to that of rural Chinese. The prevalence of high myopia was lower in this Korean sample than in other East Asian populations, and astigmatism was the most frequently occurring refractive error.
PMCID: PMC3869499  PMID: 24037232
refractive error; prevalence; myopia; hyperopia; astigmatism; anisometropia
9.  Utilization Trends of Anti-TNF Agents and Health Outcomes in Adults and Children with Inflammatory Bowel Diseases: A Single-center Experience 
Inflammatory bowel diseases  2014;20(7):1242-1249.
Utilization trends and health effects of infliximab and adalimumab in inflammatory bowel disease (IBD) are incompletely understood. We aimed to describe utilization trends of these 2 anti–tumor necrosis factor (TNF) agents, determine the correlation between utilization with rates of hospitalization and surgery and describe differences in use between adults and children.
Longitudinal data were analyzed for drug utilization, hospitalization, and abdominal surgery. Descriptive statistics were used to show trends, and utilization quotients were compared for standardization. Multivariate logistic regression analysis assessed the association between drug use and rates of hospitalization and surgery.
Four hundred thirty-eight pediatric and 2514 adult patients with IBD generated a total of 51,882 inpatient and outpatient encounters, representing 1185 Crohn’s disease, 1531 ulcerative colitis, and 236 indeterminate colitis patients. From 2007 through 2012, utilization quotients declined for hospitalization but remained unchanged for surgery; adalimumab saw a 3-fold increase, despite continued dominance of infliximab. Median band and mean fitted plots showed downward hospitalization trends from 2006 to 2012. Utilization of infliximab peaked in 2008, Q4 with gradual decline to 2012, Q2; and adalimumab showed moderate increased utilization since 2007, Q1. Use of infliximab (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.70–0.83) and adalimumab (OR, 0.79; 95% CI, 0.72–0.87) was associated with decreased hospitalization risk but not associated with reduced abdominal surgery risk. Children had increased hospitalization (OR, 2.68; 95% CI, 2.49–2.88) but decreased risk for abdominal surgery (OR, 0.57; 95% CI, 0.46–0.70).
Current infliximab use remains substantially greater than adalimumab use, despite recent increased use of adalimumab. Although trends for hospitalization for IBD are decreasing, it is not reflected in abdominal surgery rates in a tertiary IBD referral center.
PMCID: PMC4227810  PMID: 24846718
biologics; infliximab; adalimumab; Crohn’s disease; ulcerative colitis; inflammatory bowel disease
10.  Appropriateness of Emergency Department Use in Pediatric Inflammatory Bowel Disease: A Quality Improvement Opportunity 
We sought to characterize emergency department (ED) encounters for pediatric inflammatory bowel disease (IBD) to identify areas for prevention.
Retrospective chart review of 5 consecutive ED encounters at 7 centers was performed.
Of 35 unique encounters by 32 patients, 3 main factors contributed to ED utilization: disease severity or course, day or time of care, and physician instruction. Of the ED encounters, approximately one-fifth were judged medically unnecessary, and one-half avoidable in a more optimal health care system.
ED visits by pediatric patients with IBD may be reduced in a more optimal health care system.
PMCID: PMC4226338  PMID: 24918980
chronic care model; emergency department; inflammatory bowel disease; pediatrics; reducing cost
11.  Docosahexaenoic acid induces the degradation of HPV E6/E7 oncoproteins by activating the ubiquitin–proteasome system 
Cell Death & Disease  2014;5(11):e1524-.
The oncogenic human papillomavirus (HPV) E6/E7 proteins are essential for the onset and maintenance of HPV-associated malignancies. Here, we report that activation of the cellular ubiquitin–proteasome system (UPS) by the omega-3 fatty acid, docosahexaenoic acid (DHA), leads to proteasome-mediated degradation of E6/E7 viral proteins and the induction of apoptosis in HPV-infected cancer cells. The increases in UPS activity and degradation of E6/E7 oncoproteins were associated with DHA-induced overproduction of mitochondrial reactive oxygen species (ROS). Exogenous oxidative stress and pharmacological induction of mitochondrial ROS showed effects similar to those of DHA, and inhibition of ROS production abolished UPS activation, E6/E7 viral protein destabilization, and apoptosis. These findings identify a novel role for DHA in the regulation of UPS and viral proteins, and provide evidence for the use of DHA as a mechanistically unique anticancer agent for the chemoprevention and treatment of HPV-associated tumors.
PMCID: PMC4260735  PMID: 25393480
12.  A phase-1b study of everolimus plus paclitaxel in patients with small-cell lung cancer 
British Journal of Cancer  2013;109(6):1482-1487.
The mammalian target of rapamycin (mTOR) pathway is dysregulated in small-cell lung cancer (SCLC) and everolimus is an oral mTOR inhibitor.
This phase-1b study assessed everolimus safety at the levels of 2.5, 5, or 10 mg once daily in combination with paclitaxel (175 mg m−2) once every 3 weeks in previously treated SCLC patients. The primary end point was to determine the maximum tolerated dose of everolimus.
Among 21 enrolled patients, common drug-related adverse events were anaemia, neutropenia, thrombocytopenia, pain, hyperglycemia, and stomatitis. Out of 11 evaluable patients treated with everolimus at the level of 5 mg, 1 patient experienced dose-limiting toxicity (DLT) of grade 4 febrile neutropenia and grade 3 thrombocytopenia. The other two DLTs (grade 4 thrombocytopenia and grade 3 hyperglycemia) occurred in two out of three patients receiving everolimus 10 mg. The overall objective response rate was 28%.
Everolimus showed an acceptable safety profile and preliminary antitumour activity at the dose of 5 mg once daily when combined with 3-weekly paclitaxel 175 mg m−2 in patients with SCLC.
PMCID: PMC3776982  PMID: 23963141
everolimus; paclitaxel; phase-1b; small-cell lung cancer
13.  Prognostic implication of mucinous histology in colorectal cancer patients treated with adjuvant FOLFOX chemotherapy 
British Journal of Cancer  2013;108(10):1978-1984.
There have been controversies in prognostic impact of mucinous histology on colorectal cancer, and its implication in patients treated with adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is unclear.
Stage II and III colorectal cancer patients who underwent curative resection followed by adjuvant FOLFOX were included. Patients were grouped according to the mucinous content: >50%, mucinous adenocarcinoma (MAC); <50%, adenocarcinoma with intermediated mucinous component (AIM); and without any mucinous component, non-MAC (NMA). Clinicopathological features and disease-free survival (DFS) were compared.
Among a total of 521 patients, 27 patients (5.2%) had MAC, 41 patients (7.9%) had AIM, and 453 patients (86.9%) had NMA. Mucinous adenocarcinoma and AIM had higher frequency of proximal location and microsatellite instability, but lower frequency of angiolymphatic invasion. Disease-free survival was significantly worse in the MAC compared with NMA (3-year DFS 57% and 86%, respectively; P<0.001) and AIM (3-year DFS 87%, P=0.01 vs MAC). Multivariate analysis revealed MAC as an independent negative prognostic factor of DFS (adjusted hazard ratio 7.96, 95% confidence interval 3.76–16.8).
Adenocarcinoma with intermediated mucinous component and MAC have distinct clinicopathological features compared with NMA. Mucinous adenocarcinoma has an adverse prognostic impact on stage II or III colorectal cancer treated with adjuvant FOLFOX.
PMCID: PMC3670503  PMID: 23652310
colorectal cancer; mucinous adenocarcinoma; mucinous histology; adjuvant chemotherapy; oxaliplatin
14.  The beneficial effect of palliative resection in metastatic colorectal cancer 
British Journal of Cancer  2013;108(7):1425-1431.
We aimed to determine the role of palliative resection in metastatic colorectal cancer (mCRC) and ascertain which patient populations would benefit most from this treatment.
A total of 1015 patients diagnosed with mCRC at Seoul National University Hospital between 2000 and 2009 were retrospectively studied.
Of the 1015 patients, 168 patients with only liver and/or lung metastasis received curative resection. The remaining 847 patients were treated with palliative chemotherapy and/or palliative resection combined with best supportive care. Palliative resection was performed in 527 (62.2%) cases (complete resection with negative margin (R0) in 93, R1/2 in 434). Resected patients had a more prolonged median overall survival (OS) than unresected patients (21.3 vs 14.1 months; P<0.001). In multivariate analysis, R0 resection was found to be associated with a superior OS compared with R1/2 resection (51.3 vs 19.1 months; P<0.001) and no resection (51.3 vs 14.1 months; P<0.001). When we performed propensity score matching, palliative resection was found to be related to prolonged OS (hazard ratio=0.72, 95% confidence interval=0.59–0.89; P=0.003).
Palliative resection without residual disease and chemotherapy confers a longer-term survival outcome than palliative chemotherapy alone in mCRC patient subset.
PMCID: PMC3629435  PMID: 23481187
colonic neoplasms; resection; metastasectomy; chemotherapy
15.  P42 Ebp1 regulates the proteasomal degradation of the p85 regulatory subunit of PI3K by recruiting a chaperone-E3 ligase complex HSP70/CHIP 
Cell Death & Disease  2014;5(3):e1131-.
The short isoform of ErbB3-binding protein 1 (Ebp1), p42, is considered to be a potent tumor suppressor in a number of human cancers, although the mechanism by which it exerts this tumor-suppressive activity is unclear. Here, we report that p42 interacts with the cSH2 domain of the p85 subunit of phosphathidyl inositol 3-kinase (PI3K), leading to inhibition of its lipid kinase activity. Importantly, we found that p42 induces protein degradation of the p85 subunit and further identified HSP70/CHIP complex as a novel E3 ligase for p85 that is responsible for p85 ubiquitination and degradation. In this process, p42 couples p85 to the HSP70/CHIP-mediated ubiquitin–proteasomal system (UPS), thereby promoting a reduction of p85 levels both in vitro and in vivo. Thus, the tumor-suppressing effects of p42 in cancer cells are driven by negative regulation of the p85 subunit of PI3K.
PMCID: PMC3973206  PMID: 24651434
p42 Ebp1; p85 subunit; PI3K; HSP70/CHIP
16.  Data Build-up for the Construction of Korean Specific Greenhouse Gas Emission Inventory in Livestock Categories 
Many studies on methane (CH4) and nitrous oxide (N2O) emissions from livestock industries have revealed that livestock production directly contributes to greenhouse gas (GHG) emissions through enteric fermentation and manure management, which causes negative impacts on animal environment sustainability. In the present study, three essential values for GHG emission were measured; i.e., i) maximum CH4 producing capacity at mesophilic temperature (37°C) from anaerobically stored manure in livestock category (B0,KM, Korean livestock manure for B0), ii) EF3(s) value representing an emission factor for direct N2O emissions from manure management system S in the country, kg N2O-N kg N−1, at mesophilic (37°C) and thermophilic (55°C) temperatures, and iii) Nex(T) emissions showing annual N excretion for livestock category T, kg N animal−1 yr−1, from different livestock manure. Static incubation with and without aeration was performed to obtain the N2O and CH4 emissions from each sample, respectively. Chemical compositions of pre- and post-incubated manure were analyzed. Contents of total solids (% TS) and volatile solid (% VS), and the ratio of carbon to nitrogen (C/N) decrease significantly in all the samples by C-containing biogas generation, whereas moisture content (%) and pH increased after incubation. A big difference of total nitrogen content was not observed in pre- and post-incubation during CH4 and N2O emissions. CH4 emissions (g CH4 kg VS−1) from all the three manures (sows, layers and Korean cattle) were different and high C/N ratio resulted in high CH4 emission. Similarly, N2O emission was found to be affected by % VS, pH, and temperature. The B0,KM values for sows, layers, and Korean cattle obtained at 37°C are 0.0579, 0.0006, and 0.0828 m3 CH4 kg VS−1, respectively, which are much less than the default values in IPCC guideline (GL) except the value from Korean cattle. For sows and Korean cattle, Nex(T) values of 7.67 and 28.19 kg N yr−1, respectively, are 2.5 fold less than those values in IPCC GL as well. However, Nex(T) value of layers 0.63 kg N yr−1 is very similar to the default value of 0.6 kg N yr−1 in IPCC GLs for National greenhouse gas inventories for countries such as South Korea/Asia. The EF3(s) value obtained at 37°C and 55°C were found to be far less than the default value.
PMCID: PMC4093265  PMID: 25049972
Greenhouse Gases; Livestock; Manure; Methane; Nitrous Oxide
17.  Ensiling Characteristics and the In situ Nutrient Degradability of a By-product Feed-based Silage 
This study was conducted to evaluate the ensiling characteristics and the in situ degradability of a by-product feed (BF)-based silage. Before ensilation, the BF-based mixture was composed of 50% spent mushroom substrate, 21% recycled poultry bedding, 15% ryegrass straw, 10.8% rice bran, 2% molasses, 0.6% bentonite, and 0.6% microbial inoculant on a wet basis and ensiled for up to 4 weeks. The BF-based silage contained on average 39.3% moisture, 13.4% crude protein (CP), and 52.2% neutral detergent fiber (NDF), 49% total digestible nutrient, and 37.8% physically effective NDF1.18 on a dry matter (DM) basis. Ensiling the BF-based silage for up to 4 weeks affected (p<0.01) the chemical composition to a small extent, increased (p<0.05) the lactic acid and NH3-N content, and decreased (p<0.05) both the total bacterial and lactic acid bacterial counts from 109 to 108 cfu/g when compared to that before ensiling. These parameters indicated that the silage was fermented and stored well during the 4-week ensiling period. Compared with rice or ryegrass straws, the BF-based silage had a higher (p<0.05) water-soluble and filterable fraction, a lower insoluble degradable DM and CP fraction (p<0.05), a lower digestible NDF (p<0.05) fraction, a higher (p<0.05) DM and CP disappearance and degradability rate, and a lower (p<0.05) NDF disappearance and degradability rate. These results indicated that cheap, good-quality BF-based roughage could be produced by ensiling SMS, RPB, rice bran, and a minimal amount of straw.
PMCID: PMC4093216  PMID: 25049944
Spent Mushroom Substrate; By-product Feed; Silage; Degradability; Ruminant
18.  Effect of Dietary Supplementation of Procyanidin on Growth Performance and Immune Response in Pigs 
This study was performed to determine the effect of dietary supplementation of procyanidin on growth performance, blood characteristics, and immune function in growing pigs. In experiment 1 (Exp. 1), thirty-two crossbred pigs with an initial BW of 19.2±0.3 kg were allocated into 4 treatments for an 8-wk experiment: i) CON (basal diet), ii) MOS 0.1 (basal diet+0.1% mannanoligosaccharide), iii) Pro-1 (basal diet+0.01% procyanidin), and iv) Pro-2 (basal diet+0.02% procyanidin). Pigs fed Pro-1 and Pro-2 diets had greater (p<0.05) gain:feed ratio compared with those fed CON or MOS 0.1 diets. Serum creatinine concentration was less (p<0.05) in Pro-2 treatment than those in CON, MOS 0.1 and Pro-1 treatments. In Exp. 2, twelve pigs (BW 13.4±1.3 kg) received basal diet with i) 0 (CON), ii) 0.02% (Pro-0.02%), and iii) 0.04% procyanidin (Pro-0.04%) for 4 wk. Concentration of platelets was lower (p<0.05) in the Pro-0.04% group compared to CON at 24 h after lipopolysaccharide (LPS) challenge. In addition, secretion of cytokines from cultured peripheral blood mononuclear cells (PBMC) in the presence or absence of procyanidin was examined. The levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were lower (p<0.05) in Pro (LPS-stimulated PBMCs+procyanidin) than those in CON (LPS-stimulated PBMCs+PBS) at 4 h after LPS challenge. These data suggest that dietary addition of procyanidin improves feed efficiency and anti-inflammatory cytokines of pigs.
PMCID: PMC4093277  PMID: 25049935
Growth Performance; Immune Response; Lipopolysaccharide; Pigs; Procyanidin
20.  The effects of Helicobacter pylori infection on intraocular pressure in anterior uveitis 
Eye  2012;26(12):1503-1510.
We investigated the influence of H. pylori infection on intraocular pressure (IOP) in anterior uveitis patients to clarify whether H. pylori infection is related to high IOP in anterior uveitis.
In this prospective study, 165 Korean anterior uveitis patients were examined. All patients underwent serological analysis to identify the cause of uveitis, including the presence of H. pylori infection by enzyme-linked immunosorbent assay. Serological values were compared between patients with and without high IOP.
Seropositivity for H. pylori was 69.70% of patients with high IOP and 38.38% of patients with normal IOP (P<0.01).
This study suggests that H. pylori infection is associated with high IOP in anterior uveitis.
PMCID: PMC3522840  PMID: 23154495
anterior uveitis; Helicobacter pylori; Intraocular pressure
21.  Placenta-derived mesenchymal stem cells improve memory dysfunction in an Aβ1–42-infused mouse model of Alzheimer's disease 
Cell Death & Disease  2013;4(12):e958-.
Mesenchymal stem cells (MSCs) promote functional recoveries in pathological experimental models of central nervous system (CNS) and are currently being tested in clinical trials for neurological disorders, but preventive mechanisms of placenta-derived MSCs (PD-MSCs) for Alzheimer's disease are poorly understood. Herein, we investigated the inhibitory effect of PD-MSCs on neuronal cell death and memory impairment in Aβ1–42-infused mice. After intracerebroventrical (ICV) infusion of Aβ1–42 for 14 days, the cognitive function was assessed by the Morris water maze test and passive avoidance test. Our results showed that the transplantation of PD-MSCs into Aβ1–42-infused mice significantly improved cognitive impairment, and behavioral changes attenuated the expression of APP, BACE1, and Aβ, as well as the activity of β-secretase and γ-secretase. In addition, the activation of glia cells and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were inhibited by the transplantation of PD-MSCs. Furthermore, we also found that PD-MSCs downregulated the release of inflammatory cytokines as well as prevented neuronal cell death and promoted neuronal cell differentiation from neuronal progenitor cells in Aβ1–42-infused mice. These data indicate that PD-MSC mediates neuroprotection by regulating neuronal death, neurogenesis, glia cell activation in hippocampus, and altering cytokine expression, suggesting a close link between the therapeutic effects of MSCs and the damaged CNS in Alzheimer's disease.
PMCID: PMC3877561  PMID: 24336078
PD-MSC; Alzheimer's disease; amyloid-β; cytokines; neurogenesis
22.  Surgical strategy for an anomalous origin of the right coronary artery 
Park, C | Lee, J | Jun, Y | Choi, C | Son, K | Park, K
Journal of Cardiothoracic Surgery  2013;8(Suppl 1):O142.
PMCID: PMC3844575
25.  CT and MRI of fibrous dysplasia of the spine 
The British Journal of Radiology  2012;85(1015):996-1001.
The purpose of this study was to present the CT and MRI findings of patients with fibrous dysplasia (FD) of the spine.
Among the patients with pathologically proven skeletal FD, 12 (8 males and 4 females; mean age, 43 years) who were evaluated with either spine CT or MRI were included. The number and location of the involved vertebral segments, the presence of lytic lesions, ground-glass opacity (GGO), an expansile nature, cortical disruption, a sclerotic rim, a decrease in body height and contour deformity were examined on CT scans (n = 12), while signal intensity, enhancement patterns and the presence of a dark signal rim on the lesion were examined using MRI (n = 9).
Nine patients had polyostotic FD, including one with an isolated spinal localisation, while three had monostotic FD. An expansile nature (n = 3) and osteolytic lesions with GGO (n = 3) were seen. On CT images, GGO was noted in all patients. An expansile nature (n = 11) and presence of lytic lesions (n = 11) were noted. A decrease in body height (n = 9) and sclerotic rim formation (n = 9) were indicated. Contour deformities were visible in six patients. The MRI findings were non-specific. Dark signal rims were visible on MRI in seven patients.
Typical imaging findings of extraspinal FD were noted on spine CT scans. These characteristic CT imaging findings of spinal FD may be helpful in differentiating FD from other common spine diseases.
PMCID: PMC3474066  PMID: 22167510

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