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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.
Purpose
To determine the relative effect of birth weight and gestational age on retinopathy of prematurity (ROP) using preterm twin pairs discordant for birth weight.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1038/eye.2011.208
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.
doi:10.5713/ajas.2012.12311
PMCID: PMC4093041
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.
doi:10.1038/sj.bjc.6602575
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.
doi:10.1038/sj.bjc.6602502
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.  Prognostic implication of mucinous histology in colorectal cancer patients treated with adjuvant FOLFOX chemotherapy 
British Journal of Cancer  2013;108(10):1978-1984.
Background:
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.
Methods:
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.
Results:
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).
Conclusion:
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.
doi:10.1038/bjc.2013.232
PMCID: PMC3670503  PMID: 23652310
colorectal cancer; mucinous adenocarcinoma; mucinous histology; adjuvant chemotherapy; oxaliplatin
7.  The beneficial effect of palliative resection in metastatic colorectal cancer 
British Journal of Cancer  2013;108(7):1425-1431.
Background:
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.
Methods:
A total of 1015 patients diagnosed with mCRC at Seoul National University Hospital between 2000 and 2009 were retrospectively studied.
Results:
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).
Conclusion:
Palliative resection without residual disease and chemotherapy confers a longer-term survival outcome than palliative chemotherapy alone in mCRC patient subset.
doi:10.1038/bjc.2013.94
PMCID: PMC3629435  PMID: 23481187
colonic neoplasms; resection; metastasectomy; chemotherapy
8.  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.
doi:10.1038/cddis.2014.79
PMCID: PMC3973206  PMID: 24651434
p42 Ebp1; p85 subunit; PI3K; HSP70/CHIP
9.  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.
doi:10.5713/ajas.2013.13401
PMCID: PMC4093265  PMID: 25049972
Greenhouse Gases; Livestock; Manure; Methane; Nitrous Oxide
10.  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.
doi:10.5713/ajas.2013.13448
PMCID: PMC4093216  PMID: 25049944
Spent Mushroom Substrate; By-product Feed; Silage; Degradability; Ruminant
11.  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.
doi:10.5713/ajas.2013.13359
PMCID: PMC4093277  PMID: 25049935
Growth Performance; Immune Response; Lipopolysaccharide; Pigs; Procyanidin
12.  The effects of Helicobacter pylori infection on intraocular pressure in anterior uveitis 
Eye  2012;26(12):1503-1510.
Purpose
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.
Methods
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.
Results
Seropositivity for H. pylori was 69.70% of patients with high IOP and 38.38% of patients with normal IOP (P<0.01).
Conclusion
This study suggests that H. pylori infection is associated with high IOP in anterior uveitis.
doi:10.1038/eye.2012.206
PMCID: PMC3522840  PMID: 23154495
anterior uveitis; Helicobacter pylori; Intraocular pressure
13.  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.
doi:10.1038/cddis.2013.490
PMCID: PMC3877561  PMID: 24336078
PD-MSC; Alzheimer's disease; amyloid-β; cytokines; neurogenesis
14.  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.
doi:10.1186/1749-8090-8-S1-O142
PMCID: PMC3844575
17.  CT and MRI of fibrous dysplasia of the spine 
The British Journal of Radiology  2012;85(1015):996-1001.
Objectives
The purpose of this study was to present the CT and MRI findings of patients with fibrous dysplasia (FD) of the spine.
Methods
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).
Results
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.
Conclusion
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.
doi:10.1259/bjr/81329736
PMCID: PMC3474066  PMID: 22167510
18.  Body mass, tobacco smoking, alcohol drinking and risk of cancer of the small intestine—a pooled analysis of over 500 000 subjects in the Asia Cohort Consortium 
Annals of Oncology  2011;23(7):1894-1898.
Background
The evidence for a role of tobacco smoking, alcohol drinking, and body mass index (BMI) in the etiology of small intestine cancer is based mainly on case–control studies from Europe and United States.
Subjects and methods
We harmonized the data across 12 cohort studies from mainland China, Japan, Korea, Singapore, and Taiwan, comprising over 500 000 subjects followed for an average of 10.6 years. We calculated hazard ratios (HRs) for BMI and (only among men) tobacco smoking and alcohol drinking.
Results
A total of 134 incident cases were observed (49 adenocarcinoma, 11 carcinoid, 46 other histologic types, and 28 of unknown histology). There was a statistically non-significant trend toward increased HR in subjects with high BMI [HR for BMI >27.5 kg/m2, compared with 22.6–25.0, 1.50; 95% confidence interval (CI) 0.76–2.96]. No association was suggested for tobacco smoking; men drinking >400 g of ethanol per week had an HR of 1.57 (95% CI 0.66–3.70), compared with abstainers.
Conclusions
Our study supports the hypothesis that elevated BMI may be a risk factor for small intestine cancer. An etiologic role of alcohol drinking was suggested. Our results reinforce the existing evidence that the epidemiology of small intestine cancer resembles that of colorectal cancer.
doi:10.1093/annonc/mdr562
PMCID: PMC3493138  PMID: 22147734
alcohol drinking; body mass index; prospective studies; small intestine cancer; tobacco smoking
20.  High throughput Screening to Identify Natural Human Monoamine Oxidase B Inhibitors 
Phytotherapy research : PTR  2012;27(6):818-828.
Age-related increase in monoamine oxidase B (MAO-B) may contribute to CNS neurodegenerative diseases. Moreover, MAO-B inhibitors are used in the treatment of idiopathic Parkinson disease as preliminary monotherapy or adjunct therapy with L-dopa. To date, meager natural sources of MAO-B inhibitors have been identified, and the relative strength, potency and rank of many plants relative to standard drugs such as Selegiline (L-deprenyl, Eldepryl) are not known. In this work, we developed and utilized a high throughput enzyme microarray format to screen and evaluate 905 natural product extracts (0.025–.7 mg/ml) to inhibit human MAO-B derived from BTI-TN-5B1-4 cells infected with recombinant baculovirus. The protein sequence of purified enzyme was confirmed using 1D gel electrophoresis-matrix assisted laser desorption ionization-time-of-flight-tandem mass spectroscopy, and enzyme activity was confirmed by [1] substrate conversion (3-mM benzylamine) to H202 and [2] benzaldehyde. Of the 905 natural extracts tested, the lowest IC50s [<0.07 mg/ml] were obtained with extracts of Amur Corktree (Phellodendron amurense), Bakuchi Seed(Cyamopsis psoralioides), Licorice Root (Glycyrrhiza glabra/uralensis), Babchi (Psoralea corylifolia seed). The data also show, albeit to a lesser extent, inhibitory properties of herbs originating from the mint family (Lamiaceae) and Turmeric, Comfrey, Bringraj, Skullcap, Kava-kava, Wild Indigo, Gentian and Green Tea. In conclusion, the data reflect relative potency information by rank of commonly used herbs and plants that contain human MAO-B inhibitory properties in their natural form.
doi:10.1002/ptr.4795
PMCID: PMC3521852  PMID: 22887993
monoamine oxidase; Parkinson’s; herbs; natural medicine; MPTP; dopamine
21.  Comparison of postoperative intraocular pressure changes between 23-gauge transconjunctival sutureless vitrectomy and conventional 20-gauge vitrectomy 
Eye  2012;26(6):796-802.
Purpose
To compare the intraocular pressure (IOP) after 23-gauge transconjunctival sutureless vitrectomy (TSV) and conventional 20-gauge vitrectomy for various vitreoretinal diseases.
Methods
This was a retrospective interventional case series including 338 cases of 23-gauge TSV and 476 cases of 20-gauge vitrectomy with minimum follow-up period of 1 month. Postoperative 1 day, 1 week and 1 month IOPs were compared. Multiple regression analysis to assess the actual effect of gauge of vitrectomy on postoperative IOP was performed including intraoperative and postoperative factors influencing postoperative IOP as covariates.
Results
The mean IOP of 20-gauge vitrectomy was significantly higher than that of 23-gauge TSV (20.6±8.02 mm Hg vs12.8±4.48 mm Hg, P<0.001) at postoperative day 1, but the differences were not significant at postoperative 1 week and 1 month. The IOP pattern of 23-gauge TSV demonstrated more stable course than that of 20-gauge vitrectomy. At 1 day post vitrectomy, the incidence of hypertony was higher in 20-gauge, whereas that of hypotony was higher in 23-gauge. Among risk factors, the 20-gauge vitrectomy showed the strongest association with postoperative 1 day IOP rise.
Conclusion
Twenty-three-gauge TSV has stable and lower IOP in the early postoperative period than the 20-gauge vitrectomy. In patients whose retina and optic nerves are vulnerable to higher or fluctuating IOP, 23-gauge TSV may be more beneficial.
doi:10.1038/eye.2012.23
PMCID: PMC3376279  PMID: 22388595
20-gauge; 23-gauge; hypotony; intraocular pressure; transconjunctival sutureless vitrectomy
22.  Antitumor activity of IL-32β through the activation of lymphocytes, and the inactivation of NF-κB and STAT3 signals 
Cell Death & Disease  2013;4(5):e640-.
Cytokine and activation of lymphocytes are critical for tumor growth. We investigated whether interleukin (IL)-32β overexpression changes other cytokine levels and activates cytotoxic lymphocyte, and thus modify tumor growth. Herein, IL-32β inhibited B16 melanoma growth in IL-32β-overexpressing transgenic mice (IL-32β mice), and downregulated the expressions of anti-apoptotic proteins (bcl-2, IAP, and XIAP) and cell growth regulatory proteins (Ki-67 antigen (Ki-67) and proliferating cell nuclear antigen (PCNA)), but upregulated the expressions of pro-apoptotic proteins (bax, cleaved caspase-3, and cleaved caspase-9). IL-32β also inhibited colon and prostate tumor growth in athymic nude mice inoculated with IL-32β-transfected SW620 colon or PC3 prostate cancer cells. The forced expression of IL-32β also inhibited cell growth in cultured colon and prostate cancer cells, and these inhibitory effects were abolished by IL-32 small interfering RNA (siRNA). IL-10 levels were elevated, but IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels were reduced in the tumor tissues and spleens of IL-32β mice, and athymic nude mice. The number of cytotoxic T (CD8+) and natural killer (NK) cells in tumor tissues, spleen, and blood was significantly elevated in IL-32β mice and athymic nude mice inoculated with IL-32β-transfected cancer cells. Constituted activated NF-κB and STAT3 levels were reduced in the tumor tissues of IL-32β mice and athymic nude mice, as well as in IL-32β-transfected cultured cancer cells. These findings suggest that IL-32β inhibits tumor growth by increasing cytotoxic lymphocyte numbers, and by inactivating the NF-κB and STAT3 pathways through changing of cytokine levels in tumor tissues.
doi:10.1038/cddis.2013.166
PMCID: PMC3674373  PMID: 23703385
IL-32β; lymphocytes; NF-κB; STAT3; tumor growth
23.  Dynamics of Air Temperature, Velocity and Ammonia Emissions in Enclosed and Conventional Pig Housing Systems 
This study aimed to compare the dynamics of air temperature and velocity under two different ventilation and housing systems during summer and winter in Korea. The NH3 concentration of both housing systems was also investigated in relation to the pig’s growth. The ventilation systems used were; negative pressure type for the enclosed pig house (EPH) and natural airflow for the conventional pig house (CPH). Against a highly fluctuating outdoor temperature, the EPH was able to maintain a stable temperature at 24.8 to 29.1°C during summer and 17.9 to 23.1°C during winter whilst the CPH had a wider temperature variance during summer at 24.7 to 32.3°C. However, the temperature fluctuation of the CPH during winter was almost the same with that of EPH at 14.5 to 18.2°C. The NH3 levels in the CPH ranged from 9.31 to 16.9 mg/L during summer and 5.1 to 19.7 mg/L during winter whilst that of the EPH pig house was 7.9 to 16.1 mg/L and 3.7 to 9.6 mg/L during summer and winter, respectively. These values were less than the critical ammonia level for pigs with the EPH maintaining a lower level than the CPH in both winter and summer. The air velocity at pig nose level in the EPH during summer was 0.23 m/s, enough to provide comfort because of the unique design of the inlet feature. However, no air movement was observed in almost all the lower portions of the CPH during winter because of the absence of an inlet feature. There was a significant improvement in weight gain and feed intake of pigs reared in the EPH compared to the CPH (p<0.05). These findings proved that despite the difference in the housing systems, a stable indoor temperature was necessary to minimize the impact of an avoidable and highly fluctuating outdoor temperature. The EPH consistently maintained an effective indoor airspeed irrespective of season; however the CPH had defective and stagnant air at pig nose level during winter. Characteristics of airflow direction and pattern were consistent relative to housing system during both summer and winter but not of airspeed. The ideal air velocity measurement favored the EPH and therefore can be appropriate for the Korean environment. Further emphasis on its cost effectiveness will be the subject of future investigations.
doi:10.5713/ajas.2011.11515
PMCID: PMC4093470
Conventional Pig Housing; Enclosed Pig Housing; Ammonia; Hydrogen Sulfide; Air Velocity
24.  Intra-arterial Tirofiban Infusion for Partial Recanalization with Stagnant Flow in Hyperacute Cerebral Ischemic Stroke 
Interventional Neuroradiology  2011;17(4):442-451.
Summary
Early reocclusion is a major concern associated with poor clinical outcomes in patients with an ischemic cerebral stroke. This occurs most frequently in patients with partial initial recanalization. This study focuses on partial recanalization with stagnant antegrade flow after intravenous (IV) tPA or spontaneously, treated with the administration of intra-arterial (IA) tirofiban. Three patients with initial M1 occlusion on diagnostic studies had an occluded segment that was recanalized with stagnant flow after IV tPA or spontaneously. In all cases, IA tirofiban was administrated. We evaluated the distal blood flow and the degree of vascular narrowing in the pre and post-procedure angiography and at follow-up in addition to the clinical status. In all patients, severe vascular narrowing with stagnation of blood flow was detected in the initial M1. After infusion of IA tirofiban, improvement of the distal blood flow was achieved rapidly within 40 minutes in all patients. The severe vascular narrowing resolved rapidly in two patients without residual stenosis. In one patient, moderate vascular narrowing was still present. The median baseline National Institutes of Health Stroke Scale (NIHSS) scores were 18 and the median post-procedural NIHSS scores were 2 at two weeks. No intracerebral hemorrhage occurred in any of the patients. Treatment with IA tirofiban was safe and effective in patients with partial initial recanalization. It can be suggested that detection of any partial recanalization is time for administration of glycoprotein IIb-IIIa receptor inhibitor in hyperacute ischemic stroke.
PMCID: PMC3296504  PMID: 22192548
acute ischemic stroke, reocclusion, endovascular treatment, tirofiban

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