• Journal of Life Science
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• v.24 no.4
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• pp.343-351
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• 2014

Phosphoinositide 3-kinase (PI3K) plays a central role in cell signaling and leads to cell proliferation, survival, motility, exocytosis, and cytoskeletal rearrangements, as well as specialized cell responses, superoxide production, and cardiac myocyte growth. PI3K is divided into three classes; type I PI3K is preferentially expressed in leukocytes and activated by ${\beta}{\gamma}$ subunits of heterotrimeric G-proteins. In this study, the cDNAs encoding the $PI3K{\gamma}$ gene were isolated from a brain cDNA library constructed using the flounder (Paralichthys olivaceus). The sequence of the isolated $PI3K{\gamma}$ was 1341 bp, encoding 447 amino acids. The nucleotide sequence of the $PI3K{\gamma}$ gene was analyzed with that of other species, including Oreochromis niloticus and Danio rerio, and it turned out to be well conserved during evolution. The $PI3K{\gamma}$ gene was subcloned into the expression vector pET-44a(+), and expressed in the E. coli BL21 (DE3) codon plus cell. The resulting protein was expressed as a fusion protein of approximately 49 kDa containing a C-terminal six-histidine extension that was derived from the expression vector. The expressed protein was purified to homogeneity by His-tag affinity chromatography and showed enzymatic activity corresponding to $PI3K{\gamma}$. The binding of wortmannin to $PI3K{\gamma}$, as detected by anti-wortmannin antisera, closely followed the inhibition of the kinase activities. The results obtained from this study will provide a wider base of knowledge on the primary structure and characterization of the $PI3K{\gamma}$ at the molecular level.

• Journal of Life Science
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• v.29 no.12
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• pp.1371-1377
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• 2019

Oxidative stress induced by the over-production of reactive oxygen species (ROS) in the brain is the most common cause of neurodegenerative diseases such as Alzheimer's. In the present study, we investigated the protective effects of flavonoids and their glycosides, namely kaempferol, kaempferol-3-O-glucoside, quercetin, and quercetin-3-β-D-glucoside, against H₂O₂-induced oxidative stress in the C6 glial cells. The H₂O₂-treated glial cells exhibited decreased cell viability and increased ROS production when compared with normal cells. However, cells treated with each of the four flavonoids/glycosides demonstrated significantly increased viability and suppressed ROS production when compared with the H₂O₂-treated control group. These results indicate that flavonoids/glycosides attenuate oxidative stress induced by H₂O₂ in C6 glial cells. To confirm the protective molecular mechanisms, we measured pro-inflammatory factors such as inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-1β. H₂O₂ treatment was seen to elevate these factors and decrease IκB-α in the C6 glial cells, while the flavonoids/glycosides induced a down-regulation of the pro-inflammatory factors and increased IκB-α, indicating a neuroprotective effects through attenuation of the inflammation. In particular, quercetin and its glycoside showed a higher neuroprotective effect than the kaempferol treatments. These results suggest that these flavonoids and their glycosides could be promising therapeutic agents for neurodegenerative diseases via the attenuation of oxidative stress.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.1
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• pp.23-34
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• 2012

Purpose: Acute symptomatic seizures are caused by structural changes, inflammation or metabolic changes of brain, such as tumor, stroke, meningitis, encephalitis and metabolic disorders. Inherited metabolic disorders that can cause seizures are organic acidopathies, lysosomal storage disorders, peroxisomal disorders and mineral disorders. We have done this study to find out the importance of organic acidopathies causing seizure disorders in Korean childhood and adolescent patients. Method: Retrograde analysis for 1,306 patients with seizure disorders whose clinical informations are available and have done urine organic acid analysis for 5 years period, between Jan. 1st 2007 to Dec. 31th 2011. Statistical analysis was done with Student's t test using SPSS. Result: Out of 1,306 patients, 665 patients (51%) showed abnormalities on urine organic acid analysis. The most frequent disease was mitochondrial respiratory chain disorders (394, 30.1%), followed by mandelic aciduria (127, 9.7%), ketolytic defects (81, 6.2%), 3-hydroxyisobutyric aciduria (19, 1.4%), glutaric aciduria type II (10, 0.8%), ethylmalonic aciduria (4), propionic aciduria (4), methylmalonic aciduria (3), glutaric aciduria type I (3), pyruvate dehydrogenase deficiency (3), pyruvate carboxylase deficiency (3), isovaleric aciduria (2), HMG-CoA lyase deficiency (2), 3-methylcrotonylglycinuria (2), fatty acid oxidation disorders (2), fumaric aciduria (1), citrullinemia (1), CPS deficiency (1), MCAD deficiency (1). Conclusion: On neonatal period, mandelic aciduria due to infection was found relatively frequently. Mitochondrial disorders are most frequent etiologic disease on all age group, followed by ketolytic defects and various organic acidopathies. The number and diversities of organic acidopathies emphasize meticulous evaluation of basic routine laboratory examinations and organic acid analysis with initial sample on every seizure patient.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.1
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• pp.14-22
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• 2012

Objectives: This study was performed to review clinical manifestations of hyperphenylalaninemia patients in Korean. Methods: 178 cases of hyperphenyalaninemia were diagnosed at department of pediatrics, Soonchunhyang University Hospital from January, 1983 to August. We reviewed DNA analysis, MR imaging, EEG, radiography of the left hand and wrist, bone densitometry (BMD), IQ test of hyperphenyalaninemia patients. Results: Out of 178 cases, 161 cases were diagnosed classic phenylketonuria and 17 cases were diagnosed BH4 deficiency. 122 cases performed DNA analysis. R243Q (10.3%), Y204C (9.9%), and IVS4-1G>A (8.1%) mutations were predominant. 22 cases underwent MR imaging. Varying degrees of symmetrical high signal intensity were noted on T2-weighted sequences in the periventricular deep white matter of 15 cases. 23 cases were performed EEG. 12 cases (52.3%) showed abnormal pattern. EEG abnormalities showed in 11 cases. On lumbar BMD four of 11 cases (36%) showed reduced bone density of more than 1 S.D. in four of 11 cases, bone age was less than chronological age by at least one year. 18 cases were performed IQ test. Mean IQ scores was $84{\pm}21.6$. Among older than 15 years (9 cases), Mean IQ scores was $72{\pm}21.2$. PTPS deficiency was 14 cases, DHPR deficiency was 2 cases, and GTPCH deficiency was 1 case. Conclusion: We confirmed there were varieties of DNA mutations. And MR imaging and EEG were nonspecific in PKU patients. Older children showed lower IQ score. Low phenylalanine diet prevents brain damage in PKU patient. Not only first few years of life but also lifetime, Keeping low phenylalanine diet is important.

• Journal of Food Hygiene and Safety
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• v.24 no.4
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• pp.391-397
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• 2009

Carnosine is a dipeptide ($\beta$-alanyl-L-histidine) found in mammalian brain, eye, olfactory bulb and skeletal muscle at high concentrations. Its biological functions include antioxidant and anti-glycation activities. The objectives of this study were to investigate anti-diabetic effects of carnosine as determined by blood glucose levels in glucose tolerance test (GTT) and insulin tolerance test (ITT), insulin level and serum biochemical and lipid levels in male C57BL/6J db/db mice. There were five experimental groups including normal (C57BL/6J), control (vehicle), and three groups of carnosine at doses of 6, 30, and 150 mg/kg b.w. Carnosine was orally administered to the diabetic mice everyday for 8 weeks. There was no significant difference in body weight changes in carnosine-treated groups compared to the control. The treatments of carnosine significantly decreased the blood glucose level in the diabetic mice compared with the control (p < 0.05) after 5 weeks. The treatments of carnosine also significantly decreased the blood glucose levels in GTT and ITT and glycosylated hemoglobin (HbA1c), compared with the control (p < 0.05). Carnosine at the dose of 6 mg/kg significantly decreased the serum insulin level compared to the control (p < 0.05). Carnosine significantly increased total proteins but significantly decreased lactate dehydrogenase and blood urea nitrogen compared with the control (p < 0.05). Carnosine also significantly decreased glucose, LDL, and triglyceride in the serum of diabetic mice compared to the control (p < 0.05). These results suggest that carnosine has a hypoglycermic effect resulting from reduction of glucose and lipid levels and that high carnosine-containing diets or drugs may give a benefit for controlling diabetes mellitus in humans.

• Journal of Korean Society of Transportation
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• v.24 no.2 s.88
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• pp.91-100
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• 2006

This paper examines the situation and tasks of UK rail privatization, especially focusing on after the Hatfield rail accident. Earlier research which focused on the UK's Privatization had little knowledge of the explanations for recent changes. Moreover they had difficulty making a direct comparison between national rail and the privatized rail. Therefore we aye left without a good explanation which has a comprehensive perspective. I attempt to show the change in the rail privatization Process and its outcome, focusing on after the Hatfield rail accident. This Paper argues that the UK's vail privatization process has a regulatory framework which is too complicated with overlapping responsibilities that brought about inefficiency, increasing costs and a superficial safety regime. Especially the planning of rail and infrastructure maintenance did not come to play an appropriate role. However after 2000, the government took charge of setting the strategy for railways, and the Office of Rail Regulation covered safety performance and cost. explain that these changes present a good opportunity to solve the problem of passing the buck for poor performance. Through the analysis, I find that the passenger rail network is well-suited to deliver long distance business and commuters and that the subsidy from the government is decreasing. However, performance, for example punctuality and reliability. should be improved. Especially the Hatfield rail accident caused a reduction in the satisfaction of passengers. In future. the problems of rising costs and monopoly franchise system should be addressed.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.287-296
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• 1997

Purpose : This is study of whether 3-D conformal radiotherapy for carcino-mas of the ethmoid sinus were better than those treated with conventional 2-D plan, Materials and Methods : The 3-D conformal treatment Plans were compared with conventional 2-D plans in 4 patients with malignancy of the ethmoid sinus. Isodose distribution, dose statistics, and dose volume histogram of the planning target volume were used to evaluate differences between 2-D and 3-D plans. In addition. the risk of radiation exposure of surrounding normal critical organs are evaluated by means of point dose calculation and dose volume histogram. Results : 3-D conformal treatment plans for each patient that the better tumor coverages by the planning target volume with improved dose homo-geneity, compared to 2-D conventional treatment Plans in the same Patient. On the other hand, the radiation dose distributions to the surrounding nor-mal tissue organs, such as the orbit and optic nerves are not significantly reduced with our technique, but a substantial sparing in the brain stem and optic chiasm for each patient. Conclusion : Our findings represented the potential advantage of 3-D treatment planning for dose homogeniety as well as sparing of the normal tissue surrounding the tumor. However, further investigational studies are required to define the clinical benefit.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.249-258
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• 1993

Between March 1983 and December 1989, ninety-six patients with intracranial glioma were treated in the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, Catholic University Medical College. We retrospectively reviewed each case to evaluate variable factors influencing the treatment results and to develop an optimal therapy Policy. Median follow-up is 57 months (range: 31~133 months). Of the 96 patients, 60 $(63\%)$ were males and 36 $(37\%)$ were females. Ages ranged from 3 to 69 years (median 42 years). The most common presenting symtoms were headeche $(67\%)$ followed by cerebral motor and sensory discrepancy $(54\%),$ nausea and vomiting $(34\%),$ seizure $(19\%),$ mental change $(10\%)$ and memory and calculation impairment $(8\%).$ Eighty five $(88.5\%)$ patients all, except 11 $(11.5\%)$ brain stem lesions, were biopsy proven intracranial glioma. The distribution by histologic type was 64 astrocytomas $(75\%),$ 4 mixed oligoastrocytomas $(5\%),$ and 17 oligodendrogliomas $(20\%).$ Fourty nine patients $(58\%$ were grade I, II histology and 36 $(42\%)$ patients were grade III, IV histology. Of the 96 patients, 64 $(67\%)$ recieved postoperative RT and 32 $(33\%)$ were treated with primary radiotherapy. Gross total resection was peformed in 14 $(16\%)$ patients, subtotal resection En 29 $(34\%),$ partial resection in 21 $(25\%),$ and biopsy only in 21 $(25\%).$ Median survival time was 53 months (range 2~ 133 months), and 2- and, 5-year survival rate were $69\%,49\%$ respectively. 5-year survival rate by histologic grade was grade I, $70\%,$ grade II, $58\%,$ grade III, $28\%,$ and grade IV, $15\%.$ Multivariated analysis demonstrate that age at diagnosis (p=0.0121), Karnofsky performance Status (KPS) (p=0.0002), histologic grade (p=0.0001), postoperative radiation therapy (p=0.0278), surgical extent (p =0.024), cerebellar location of tumor (p=0.0095) were significant prognostic factors influencing on survival.

• Journal of the Korean Society of Radiology
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• v.1 no.1
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• pp.17-23
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• 2007

Background: Cerebrovascular diseases are known to show different patterns of incidence among regions and races. Therefore, it is very important to determine the incidence pattern of a specific area in order to diagnose, treat and prevent cerebrovascular diseases. The objective of the present study is to analyze quantitatively the incidence ratios of hemorrhagic and ischemic cerebrovascular diseases by season, by gender and by age. Methods: The subjects of this study were 1603 patients hospitalized for hemorrhagic or ischemic cerebrovascular diseases at the Department of Neurosurgery or the Department of Neurology of a University Hospital. Statistical analysis of data used Excel 2003 of Microsoft, and t-test was conducted using ORIGIN 6.0 of MICROCAL. Results: In the subjects, the incidence ratios of hemorrhagic and ischemic cerebrovascular diseases for four years, the period of this research, were 38.55% and 61.45%, respectively. The mean and standard deviation of age when hemorrhagic cerebrovascular diseases occurred were 58.20 and 12.60, respectively, and the percentages of subjects in their 40s, 50s, 60s and 70s were all around 20%. On the contrary, the mean and standard deviation of age when ischemic cerebrovascular diseases occurred were 65.01 and 13.59, respectively. The average age of patients with ischemic cerebrovascular diseases was older than that of patients with hemorrhagic brain diseases, and the percentages of those in their 60s, 70s and 80s were 15.53%, 37.06% and 27.72%, respectively. The season when hemorrhagic cerebrovascular diseases appeared most frequently was winter, which was followed by summer, spring and autumn. The season when hemorrhagic cerebrovascular diseases appeared most frequently was spring, which was followed by summer, winter and autumn. Conclusions: In this study, the incidence rates of hemorrhagic and ischemic cerebrovascular diseases were 38.55% and 61.45%, showing the rising percentage of ischemic cerebrovascular diseases. For making adequate prevention and disease control plans, it is considered necessary to make a long-term epidemiological investigation of cerebrovascular diseases.

• Korean Journal of Veterinary Research
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• v.34 no.2
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• pp.361-368
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• 1994

Teratogenic and embryotoxic effects of mercury have been reported, however, there is little information about possible antidotes against mercury exposure during gestation. In order to evaluate therapeutic effects of selenium as an antidote against mercury poisoning, pregnant CD-1 mice were exposed to methylmercury chloride(20ppm) through the drinking water with treatment of sodium selenite (1.0mg, 2.0mg or 3.0mg/kg b.w., subcutaneously) or BAL(5.0mg/kg b.w., subcutaneously) under the single or combination base as the therapeutic agents from day 6 to 15 of gestation. Fetal growth parameters such as body weight and crown-rump length in the mice exposed to mercury, were reduced as was placental weight compared to those in the control. Treatment of selenium(alone, combination with BAL) reduced the harmful effects induced by mercury on the fetal growth parameters even though no specific relationship between dose and therapeutic effect. The incidence of dead fetuses/resorptions and malformed fetuses(especially cleft palate) was also increased in the mercury only treated group. Selenium treatment demonostrated reduced the incidence of abnormal fetuses under the exposure of mercury. Relative maternal organ weights(liver, kidney, spleen) were increased significantly but relative brain weight was decreased as evidenced by decreased in the mercury treated mice compared to that in the control. A subtle indication of maternal mercury toxicity evidenced by changes of relative maternal organ weights, decreased water and feed consumption were also prevented efficiently by selenium treatment. The present study suggests that methylmercuric chloride is embrytoxic and teratogenic in CD-1 mice when exposured during organogenesis and that selenium administration may have therapeutic application for the treatment of mercury poisoning although more applicable study in human should be performed with caution in the future.