• Journal of Korean Neurosurgical Society
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• v.29 no.11
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• pp.1421-1428
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• 2000

Objectives : The aim of this study is to evaluate the sequential metabolic changes in experimental hydrocephalus and the clinical applicability to the diagnosis and prognosis of hydrocephalus using proton MR spectroscopy. Methods : Hydrocephalus was experimentally induced in 30 cats(2-3kg body weight) by injecting 1ml of sterile kaolin suspension(250mg/ml) into the cisterna magna. Proton MRS was performed with a 1.5 T MRI/MRS unit (Vision Plus, Siemens) at pre-treatment and at 1, 3, 7, 14, 21, and 28 days after the kaolin injection. PRESS(TR/TE＝1500/270msec) technique was employed. The major metabolites which include N-acetyl aspartate (NAA), creatine(Cr), choline(Cho), and lactate(Lac) were quantitatively analyzed and the relative concentrations ratios were evaluated. Multislice $T_2$-weighted images were also obtained using fast spin echo sequence(TR/TE＝ 2500/96msec) to monitor the morphologic changes along with progression of hydrocephalus. Results : Hydrocephalus was successfully induced in all 30 cats. Twenty five cats died within 3 days and one at the end of the second week. In all animals, the NAA/Cr ratios initially decreased during the acute stage. In 4 surviving cats, the NAA/Cr ratios initially decreased during the acute stage(<14 days) and then gradually increased to the prekaolin level as follows : pre-kaolin($1.49{\pm}0.04$), day 1($1.11{\pm}0.07$), day 7($1.17{\pm}0.04$), day 14($1.40{\pm}0.03$), day 21 ($1.46{\pm}0.06$), day 28($1.43{\pm}0.03$). These levels were relatively well correlated with the symptomatologic improvement. Lactate peak, which reflects the evidence of ischemia, did not appear throughout the entire period except in one case which expired at the end of the second week. Conclusions : The NAA/Cr ratio of the sequential proton MRS in kaolin-induced hydrocephalic cats reflects a metabolic aspect of the hydrocephalus at each stage. A decreased NAA level at the early stage is from both neuronal and axonal damage which may provide diagnostic information in the acute stage of hydrocephalus. In addition, the initial fall of NAA/Cr ratio and recovery in the late stage, when no lactate peak emerges, may suggest that the main insult of the parenchyma is not to the neuron itself but to the axon, which may be related to a good prognosis. However, emergence of the lactate peak and unrecoverable NAA/Cr at the end of the acute phase may be a poor prognostic factor. In the chronic stage, recovery of NAA/Cr ratio may provide a diagnostic clue for the differentiation between hydrocephalus and cortical atrophy.

• Journal of Chest Surgery
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• v.32 no.8
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• pp.726-731
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• 1999

Background: The distinction between non-invasive and invasive or thymic carcinoma has been severely compromised by lack of objective morphological criteria. A reliable biological marker of tumor aggressiveness is, therefore, mandatory for predicting tumor behavior. Material and Method: Thirty thymic epithelial tumors, including 7 non-invasive thymoma, 10 invasive thymoma, and 13 thymic carcinoma of the Rosai's classification; and 5 stage I, 7 stage II, 2 stage III, and 3 stage IVa of the Masaoka stage of thymoma were investigated for expression of bcl-2 and p53 proteins by immunohistochemistry. Result: The thymic epithelial cells showed positive immunostain for bcl-2 in 0 (0%), 3 (30%), 8 (61.5%) of categories in the Rosai's classification respectively and in 0 (0%), 1 (14.3%), 2 (100%), 0 (0%) of stage I, II, III, IVa of the Masaoka stage respectively. Thymic carcinoma, and high stage thymoma had significantly higher proportion of bcl-2 expression than thymoma (p=0.021) and low stage thymoma (p=0.011). However, p53 showed no correlation with the histological subtypes nor with clinical aggressiveness. Bcl-2 expression appeared to be positively correlated with p53 immunoactivity (p=0.007, kappa=0.525). Conclusion: These date indicate that bcl-2 expression correlates with aggressiveness in thymic epithelial tumors, but further studies on mutation of p53 protein is necessary because bcl-2 expression appeared to be positively correlated with p53 immunoactivity.

• Development and Reproduction
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• v.12 no.1
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• pp.19-30
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• 2008

Proper development of fertilized oocyte to blastocyst is a key step in mammalian development to implantation. During development of preimplantation embryos, the mammalian embryo needs supply the energy substrate for keep viability. Usually mammalian oocyte get substrate especially energy substrate from oviduct and uterus, because it does not store much substrate into cytoplasm during oogenesis. Carbohydrates are known as a main energy substrate for preimplantation stage embryos. Glucose, lactate and pyruvate are essential component in preimplantation embryo culture media and there are stage specific preferences to them. Glucose transporter and $H^+$-monocarboxylate cotransporter are a main mediator for carbohydrate transport and those expression levels are primarily under the control of intrinsic or extrinsic factors like insulin and glucose. Other organic substances, amino acids, lipids and nucleotides are used as energy substance and cellular regulation factor. Though since 1960s, successful development of fertilized embryo to blastocyst has been accomplished with chemically defined medium for example BWW and give rise to normal offspring in mammals, the role of metabolites and the regulation of intermediary metabolism are still poorly understood. Glucose may permit expression of metabolic enzymes and transporters in compacting morula, capable of generating the energy required for blastocyst formation. In addition, it has been suggested that the cytokines can modulate the metabolic rate of carbohydrate in embryos and regulate the preimplantation embryonic development through control the metabolic rate. Recently we showed that lactate can be used as a mediator for preimplantation embryonic development. Those observations indicate that metabolites of carbohydrate are required by the early embryo, not only as an energy source, but also as a key substrate for other regulatory and biosynthetic pathways. In addition metabolites of carbohydrate may involve in cellular activity during development of preimplantation embryos. It is suggested that through these regulation and with other regulation mechanisms, embryo and uterus can prepare the embryo implantation and further development, properly.

• Journal of Animal Science and Technology
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• v.52 no.4
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• pp.337-346
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• 2010

We report non-specific immune responses and disease resistance against Vibrio anguillarum, Streptococcus iniae and Edwardsiella tarda by dietary supplementation of fermented garlic powder (FGP) in olive flounder for the first time. Four isonitrogenous (45% crude protein) and isocaloric (17.1 MJ/kg) diets were formulated to have 0%, 0.5%, 1% and 2% of the FGP (G-0, G-0.5, G-1 and G-2). The experimental diets were fed to juvenile olive flounder averaging 23.4 g in triplicate groups (90 fish/group) in a flow-through system. After a five-week feeding trial, healthy fish with similar sizes from each tank were selected and injected with 1 ml of three bacteria each to evaluate disease resistance of the fish. During the 5-week feeding trial, the weight gain, specific growth rate, feed conversion ratio, protein efficiency ratio, and survival of the fish were not significantly affected by the experimental diets. However, feed intake was significantly lower (P<0.05) in the fish fed the G-2 diet compared with the control group. Hemoglobin, myeloperoxidase activity, cholesterol and HDL-cholesterol were not different between the dietary groups. However, hematocrit, nitroblue tetrazolium (NBT) activity, and lysozyme activity were increased (P<0.05) with an increment of dietary FGP. Plasma triglyceride of the fish fed the G-0.5 diet was significantly lower than that of fish fed the control diet. The cumulative mortality was lower in the fish fed diets containing FGP compared with the control group in the challenge test except for the bacteria Edwardsiella tarda. The results in this study indicate that dietary supplementation of FGP can enhance the non-specific immune responses and disease resistance of olive flounder against V. anguillarum and S. iniae.

• Clinical and Experimental Pediatrics
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• v.49 no.4
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• pp.417-423
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• 2006

Purpose : The objectives of this study were to assess ventricular function by tissue Doppler imaging in children who were receiving chemotherapy or who had received chemotherapy, and to apply repeated tissue Doppler imaging to make an early assessment in cardiac toxicity studies. Methods : This study was conducted on 23 oncology patients on-treatment or off-treatment from April 2005 to July 2005 at Dongsan Medical Center, Keimyung University. All patients(group 1) were divided into two groups, fractional shortening(FS) over 29 percent(group 2) and FS under 28 percent (group 3) in the first category. These same patients were also divided into the following groups : group treated with anthracyclin(group 4) and group treated without anthracyclin(group 5). Deceleration time(DT), isovolumic relaxation time(IVRT), FS, peak early diastolic(E), and peak late diastolic (A) velocity of transmitral flow were measured by M-mode and pulsed wave Doppler. Systolic(Sm), peak early diastolic(Em), and peak late diastolic(Am) velocity in apical 4-chamber and 2-chamber views were measured by tissue Doppler imaging. The author calculated a modified Tei index, E/A, E/Em ratio by using measured values. Results : Twenty three patients were enrolled : 12 boys and 11 girls. The average age of patients was 8 years and 4 months. Thirteen out of 23 patients were in the group treated with anthracyclin (group 4) and 6 had FS under 28 percent(group 3). E/Em ratio showed a significant difference between group 1 and control group($6.46{\pm}1.85$ vs $7.06{\pm}1.64$, P<0.05). Other parameters had no difference statistically. Conclusion : This study showed that the change of cardiac function developed earlier in diastolic function than in systolic function, as E/Em ratio reflecting the mean LV diastolic pressure showed a significant difference between the control group and chemotherapy groups. Echocardiography using tissue Doppler imaging is a non-invasive, comfortable and reliable method for post-chemotherapy follow up.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.1
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• pp.78-83
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• 2011

The flower of Chrysanthemum morifolium Ramat. with antioxidant, anticancer, and anti-inflammatory functions has been a widely used traditional herb as a healthy beverage and medicine. The aim of the present study was to investigate a herb tea consisting of C. morifolium Ramat., Corni fructus and Schizandra chinensis Baillon for its hepatoprotective activity against $CCl_4$-induced toxicity in freshly isolated rat hepatocytes and antigenotoxic effect against oxidative stress induced DNA damage in human leukocytes. Three different compositions of the herb tea (Mix I, II, and III) were prepared by extracting with water at $90^{\circ}C$. Freshly isolated rat hepatocytes were exposed to $CCl_4$ along with/without various concentrations of each tea. Protection of rat primary cells against $CCl_4$-induced damage was determined by the MTT assay. The significant antihepatotoxic effect of the tea was shown in Mix I and II. The increased transaminase (AST and/or ALT) release in media of $CCl_4$ treated hepatocytes was significantly lowered by all the teas tested. The effect of the tea on DNA damage in human leukocytes was evaluated by Comet assay. All teas showed a protective effect against $H_2O_2$-induced DNA damage. From these results, it is assumed that herb tea based on C. morifolium Ramat., Corni fructus and Schizandra chinensis Baillon exerted antihepatotoxic and antigenotoxic effects.

• IMMUNE NETWORK
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• v.3 no.2
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• pp.150-155
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• 2003

Background: We investigated the effect of donor marrow T cell depletion, administration of FK506, cyclosporin A (CSA), and 3-deazaadenosine (DZA) on graft versus host disease (GVHD) after allogeneic murine hematopoietic stem cell transplantation (HSCT). Methods: We used 4 to 6 week old Balb/c ($H-2^d$, recipient), and C3H/He ($H-2^k$, donor) mice. Total body irradiated recipients received $1{\times}10^7$ bone marrow cells (BM) and $0.5{\times}10^7$ splenocytes of donor under FK506 (36 mg/kg/day), CSA (5 mg/kg/day, 20 mg/kg/day), and DZA (45 mg/kg/day), which were injected intraperitoneally from day 1 to day 14 daily and then three times a week for another 2 weeks. To prevent the GVHD, irradiated Balb/c mice were transplanted with $1{\times}10^7$ rotor-off (R/O) cells of donor BM. The severity of GVHD was assessed daily by clinical scoring method. Results: All experimental groups were well grafted after HSCT. Mice in experimental group showed higher GVHD score and more rapid progression of GVHD than the mice with R/O cells (R/O group) (p<0.01). There were relatively low GVHD scores and slow progressions in FK506 and low dose CSAgroups than high dose CSA group (p<0.01). The survival was better in FK506 group than low dose CSA group. All mice treated with CSA died within 12 days after HSCT. The GVHD score in DZA group was low and slow in comparison with control group (p<0.05), but severity and progression were similar with low dose CSA group (p=0.11). All mice without immunosuppressive treatment died within 8 days, but all survived in R/O group (p<0.01). Survival in low dose CSA group was longer than in control group (p<0.05), but in high dose CSA group, survival was similar to control group. The survival benefit in DZA group was similar with low dose CSA group. FK506 group has the best survival benefit than other groups (p<0.01), comparable with R/O group (p=0.18), although probability of survival was 60%. Conclusion: We developed lethal GVHD model after allogeneic murine HSCT. In this model, immunosuppressive agents showed survival benefits in prevention of GVHD. DZA showed similar survival benefits to low dose CSA. We propose that DZA can be used as a new immunosuppressive agent to prevent GVHD after allogeneic HSCT.

• Journal of Gastric Cancer
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• v.5 no.4 s.20
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• pp.273-280
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• 2005

Purpose: Cyclin G2 has been reported to be a negative cell-cycle regulator in various cancer tissues. However, the pattern of cyclin G2 expression in gastric cancer is relatively unknown. We investigated the expression of cyclin G2 in gastric cancer tissues and evaluated the clinical significance of its expression. Materials and Methods: Well-preserved gastric cancer tissues were consecutively obtained from 172 patients who underwent gastric cancer operations at Samsung Medical Center between November 1994 and December 1997. Cyclin G2 expression in the tissues was examined immunohistochemically, and the clinicopathological features and prognostic significance according to the expression were analyzed. Results: Of the 172 gastric cancer tissues, cyclin G2 expression was positive in 43 tissues (25.0%). According to the stage, cyclin G2 expression was lower in more advanced stages (P<0.001). Negative expression of cyclin G2 was positively correlated with more advanced depth of tumor invasion (P<0.05), presence of lymph-node metastasis (P<0.05) and presence of lymphatic invasion (P<0.05). The prognosis of the cyclin G2(+) group was significantly better than that of the cyclin G2(-) group (P<0.001). Multivariate analysis revealed that T stage, lymph-node metastasis, distant metastasis, and lymphatic invasion were independent prognostic factors, but the expression of cyclin G2 was not. Conclusion: Cyclin G2 was expressed in 25% of the gastric cancer tissues, and negative expression of cyclin G2 was associated with more advanced tumor progression. Cyclin G2 may be a negative cell-cycle regulator in gastric cancer, and further studies are necessary to elucidate its exact role in the mechanism of carcinogenesis.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.265-272
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• 2004

Background : RASSF1A, which is one of tumor suppressor genes, is frequently inactivated by hypermethylation of the promoter region in a variety of human cancers, including lung cancer. This study was performed to investigate the association between RASSF1A methylation and the clinicopathological factors in patients with squamous cell carcinoma of the lung. Methods : Eighty-one samples from the patients with squamous cell carcinoma of lung were examined. The promoter methyation of RASSF1A was analyzed by methylation specific PCR and sequencing. Statistical analysis was made to examine the association between RASSF1A methylation and the clinicopathological parameters. Results : RASSF1A methylation was observed in 37.0 % (30 of 81) of the patients with squamous cell carcinoma of the lung. RASSF1A methylation was found to be associated with cellular differentiation(p=0.0097) and the overall survival(p=0.0635). However, there was no association between RASSF1A methylation and the other clinicopathological parameters, such as the pathological TNM stage, the recurrence rate, lymph node invasion and the amount of cigarettes smoked. Conclusion : RASSF1A methylation might be associated with a poor prognosis in patients with squamous carcinoma of the lung. A larger scale study is needed.

• Journal of Life Science
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• v.30 no.8
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• pp.701-707
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• 2020

Gene editing technology using the clustered regularly interspaced short palindromic repeat (CRISPR) and the CRISPR associated protein (Cas)9 has been highly anticipated in developing breeding techniques. In this study, we discuss gene scissors as a tool for silkworm molecular breeding through analysis of Bombyx mori Kynurenine 3-Monooxygenase (BmKMO) gene editing using the CRISPR/Cas9 system and analysis of generational transmission through mutagenesis and selective crossing. The nucleotide sequence of the BmKMO gene was analyzed, and three guide RNAs (gRNAs) were prepared. Each synthesized gRNA was combined with Cas9 protein and then analyzed by T7 endonuclease I after introduction into the BM-N silkworm cell line. To edit the silkworm gene, K1P gRNA and Cas9 complexes were subsequently microinjected into the silkworm embryos; the hatching rate was 18% and the incidence of mutation was 60%. The gene mutation was verified in the heterozygous G0 generation, but no phenotypic change was observed. In homozygotes generated by self-crossing, a mutant phenotype was observed. These results suggest that silkworm molecular breeding using the CRISPR/Cas9 system is possible and could be an effective way of shortening the time required.