• Korean Journal of Veterinary Research
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• v.43 no.2
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• pp.181-188
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• 2003

Cordyceps has a reputation for its broad biological activities and as a tonic which replenishs vital function in Chinese traditional medicines. As an attempt to obtain fundamental data for the development of new type Cordyceps, the effects of the fruiting bodies of cultivated fungus of Paecilomyces japonica grown on silkworm larvae on radiationinduced damages were investigated. We performed this study to determine the effect of Dongchongxiacao (Paecilomyces japonica) on jejunal crypt survival, endogenous spleen colony formation, and apoptosis in jejunal crypt cells and hair follicles of mice irradiated with high and low dose of gamma-radiation. Treatment with Dongchongxiacao showed no significant modifying effects on the jejunal crypt survival and endogenous spleen colony formation. The frequency of radiationinduced apoptosis was reduced by pretreatment of Dongchongxiacao (i.p.: 50 mg/kg of body weight, at 12 and 36 hours before irradiation, p<0.01). The spontaneous levels of apoptotic cells are $0.082{\pm}0.041$ in intestinal crypts and $0.231{\pm}0.084$ per hair follicle section of skin. Pretreatment of Dongchongxiacao was associated with decreases of 26.86% in intestinal crypt and 66.36% in hair follicle decrease in the number of cells with nuclei positively stained for apoptosis compared with the irradiation control group. We demonstrated for the first time that Dongchongxiacao administration could reduce the extent of apoptosis produced by radiation in the hair follicle. The results presented herein that Dongchongxiacao given before irradiation is capable of reducing the severity of cell loss as a result of apoptosis.

• YAKHAK HOEJI
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• v.46 no.6
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• pp.426-432
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• 2002

Cervical cancer is one of the leading causes of female death from cancer worldwide with about 500,000 deaths per year. A strong association between certain human papilloma viruses (HPV type 16 and 18) and cervical cancer has been well known. An extract of Saururus chinensis, named as PE-46, has been used to investigate whether this agent has the ability of inhibiting the oncogenes E6 and E7 of HPV type 16. PE-46 inhibited the proliferation of human cervical cancer cell lines in a dose response manner. PE-46 also inhibited the in vitro binding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53. In addition, PE-46 inhibited the in vitro binding of E7 and Rb which is essential tumor suppressor for the control of cell cycle. The levels of mRNA for E6 and E7 were also decreased by PE-46. SiHa cells treated with PE-46 induced G0/G1 arrest, resulting in inhibition of growth. Our study showed that the PE-46 can inhibit the cervical carcinomas via both inhibition of bindings between oncogenes and tumor suppressors, and inhibition of G1longrightarrowS transition. PE-46 inhibited the oncogenecity of E6 and E7 of HPV 16 type, thus could be used as a putative modulating agent for the treatment of cervical carcinomas caused by HPV.

• The Korean Journal of Applied Statistics
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• v.31 no.1
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• pp.123-137
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• 2018

A nonlinear mixed effects model is mainly used to analyze repeated measurement data in various fields. A nonlinear mixed effects model consists of two stages: the first-stage individual-level model considers intra-individual variation and the second-stage population model considers inter-individual variation. The individual-level model, which is the first stage of the nonlinear mixed effects model, estimates the parameters of the nonlinear regression model. It is the same as the general nonlinear regression model, and usually estimates parameters using the least squares estimation method. However, the least squares estimation method may have a problem that the estimated value of the parameters and standard errors become extremely large if the assumed nonlinear function is not explicitly revealed by the data. In this paper, a new estimation method is proposed to solve this problem by introducing the ridge regression method recently proposed in the nonlinear regression model into the first-stage individual-level model of the nonlinear mixed effects model. The performance of the proposed estimator is compared with the performance with the standard estimator through a simulation study. The proposed methodology is also illustrated using quantitative high throughput screening data obtained from the US National Toxicology Program.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.3
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• pp.177-183
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• 2010

Tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthase (NOS) activity, is known to play important roles in modulating both NO and superoxide production during vascular diseases such as atherosclerosis. However, the role of BH4 in functions of vascular smooth muscle cells is not fully known. In this study, we tested the effects of BH4 and dihydrobiopterin (BH2), a BH4 precursor, on migration and proliferation in response to platelet-derived growth factor-BB (PDGF-BB) in rat aortic smooth muscle cells (RASMCs). Cell migration and proliferation were measured using a Boyden chamber and a 5-bromo-2'-deoxyuridine incorporation assay, respectively, and these results were confirmed with an ex vivo aortic sprout assay. Cell viability was examined by 2,3-bis [2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide assays. BH4 and BH2 decreased PDGF-BBinduced cell migration and proliferation in a dose-dependent manner. The inhibition of cell migration and proliferation by BH4 and BH2 was not affected by pretreatment with $N^G$-nitro-L-arginine methyl ester, a NOS inhibitor. Moreover, the sprout outgrowth formation of aortic rings induced by PDGF-BB was inhibited by BH4 and BH2. Cell viability was not inhibited by BH4 and BH2 treatment. The present results suggest that BH4 and BH2 may inhibit PDGF-stimulated RASMC migration and proliferation via the NOS-independent pathway. Therefore, BH4 and its derivative could be useful for the development of a candidate molecule with an NO-independent anti-atherosclerotic function.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.2
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• pp.111-117
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• 2006

An area of current research is investigating the app1ication of human mesenchymal stem cells or hMSCs as a cell-based regenerative therapy. In order to achieve effective bone regeneration, appropriate matrices functioning as cell-carriers must be identified and optimized in terms of function, efficacy and biocompatibility. Two methods of approaching optimization of matrices are to facilitate adhesion of the donor hMSCs and furthermore to facilitate recruitment of host progenitor cells to osteoblastic differentiation. Pleiotrophin is an extracellular matrix protein that was first identified in developing rat brains and believed to be associated with developing neuronal pathways. A recent publication by Imai and colleagues demonstrated that transgenic mice with upregulated pleiotrophin expression developed a greater volume of cortical as well as cancellous bone. The proposed mechanism of action of pleiotrophin is demonstrated here. Through either environmental stresses and/or intracellular regulation, there is an increase in pleiotrophin production. The pleiotrophin is released extracellularly into areas requiring bone deposition. A receptor-mediated process recruits host osteoprogenitor cells into these areas. Therefore, the aim of our study was to investigate the osteoconductive properties of pleiotrophin. We wanted to determine if pleiotrophin coating facilitates cellular adhesion and furthermore if this has any effect on hMSCs derived bone formation in an animal model. The results showed a dose dependent response of cellular adhesion in fibronectin samples, and cellular adhesion was facilitated with increasing pleiotrophin concentrations. Histologic findings taken after 5 weeks implantation in SCID mouse showed no presence of bone formation with only a dense fibrous connective tissue. Possible explanations for the results of the osteogenesis assay include inappropriate cell loading.

• Journal of Life Science
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• v.11 no.2
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• pp.181-189
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• 2001

Cytokines are hormone-like proteins which mediate and regulast inflammatory and immune responses. Transforming growth factor -$\beta$1(TGF-$\beta$) plays an important role in the control of the immune response and wound healing, and in the development o various tissues and organs, Nitric oxide(NO) is major messenger molecule regulating immune function and blood vessel dilation and serving as a neurotransmitter in the brain and peripheral nervous system. Also, NO is to be a potent mutagen that cause mutation in the p53 tumor suppressor gene in early phases of human gastric carcinogenesis. The purpose of this study was to investigate the effect of Helicobacter phlori lystes, lipopolysaccharide (LPS), and Staphylococcus enterotoxin B(SEB) on production of TGF-$\beta$1 and NO by human fibroblasts. Primary cultured human fibroblasts were incubated with H. pylori lysates(Hp), LPs, SEB, Hp+LPS, Hp+SEB, Hp+LPS+SEB. Cultured supernatants that were collected at 24, 48 and 72 hr were assessed for TGF-$\beta$1 by enzyme-linked immunosorbent assay and NO production by quantification of nitrite ion. TGF-$\beta$1 production in fibroblasts exposed with Hp, LPS or SEB for 48 hrs was enhanced, but for 72 hrs inhibited. Its production by doble exposure such as Hp+LPS, Hp+SEB, Hp+LPS+SEB was lowered in comparison with single exposure of Hp in cases of 24 and 48 hrs incubation, but for 72 hrs decreased in Hp vaculoating toxin(+), increased in Hp vacuolating toxin(-). No production in fibroblasts increaed at all doses of LPS. But its production by exposure of SEB increased or decreased according to dose and incubation time. Also, NO production by Hp vacuolating toxin(+) increased at all doses, but its production by Hp vacuolating toxin(-) decreased. Its production by doble exposure such as Hp+LPS, Hp+SEB, Hp+LPS+SEB decreased in comparison with single exposure Hp Therefore, quantities pf TGB-$\beta$1 and NO released by human fibroblasts shows differences according to kinds of stimulants. Also, in care stimulated with same kinds of stimulants, its productions exhibit quantitative differences according to exposure times. These results suggest that the decreased of TGF-$\beta$1 in fibroblasts by mixed exposure with Hp producing vacuolating toxin and bacterial toxins such as LPS and SEB may effect negatively in healing of host tissue and increased of NO by infection oh H. pylori may related to the increased susceptibility for human gastric carcinogenesis.

• Journal of agricultural medicine and community health
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• v.16 no.2
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• pp.165-171
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• 1991

Two patients with confirmed cerebral cysticercosis were treated with Albendazole(Zentel$^{(R)}$) at a daily dose of 1.200mg t.i.d. for 14 consecutive days and evaluated for tolerance and therapeutic effects. First case was 29 year old male, who had experience of 4 times of grand mal seizures during 1 year period before administration in Korea University Hospital. His chief complaints were seizure and moderate degree headache. He also had 4 subcutaneous nodules on the thorax, right and left upper arms. Among them one nodule was biopsied and confirmed microscopically as Cysticercus cellulosae hominis. Computed tomography of the brain showed four round low density lesions in right postero-frontal area, sylvian area, intra-occipital area and left parietal area. Second case was 48 year old male, who also had experience of seizures at 3 years, 5 months and 3 months before administration. In this case, no subcutaneous nodules and no headaches were noted. Brain CT showed four round low density lesions in right postero-parietal area and temporo-parietal area, and left temporo-parietal and parietal area. Serum antibody against cystic fluid antigen was detected by ELISA in both cases. The efficacy of the treatment of cerebral cysticercosis was assessed by the frequency of convulsions after treatment for 22 months follow-up. by the disappearance of the densities in cystic lesions at brain CT for 6 months follow-up, and disappearance of subcutaneous nodules, headache and so on. As the results, all low density lesions in both cases were disappeared in films of brain CT, and 4 nodules in first case were also disappeared. No more seizure and complain of headache occurred during the last 22 months after treatment in both cases. Post-treatment complete blood count and liver function test revealed no remarkable change compared to pre-treatment test. In the nations of Latin America, the physicians do not initially recommended the simultaneous administrations of steroids, reserving them only for patients whom the adverse reactions such as severe headache and/or seizures are occurred. According to them, in most patients these symptoms are controlled with aspirin and symptomatic drugs. But our experience using praziquantel is different, and most cerebral cysticercosis patients who takes PZQ had complaint of severe headache and sometimes seizure. So we simultaneously used dexamethasone as 6mg q.i.d. for 14 consecutive days and 6 days tapering thereafter in both cases for prevention of reactions produced by the host in response to the deaths of the parasites. As the conclusion, albendazole is effective in patients who presented cerebral cysticercosis and albendazole may help in the control of cysticercosis.

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.12
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• pp.1760-1764
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• 2002

In order to elucidate the physiological function of circulating IGF-I on muscle protein synthesis in the chicken under malnutritional conditions, we administrated recombinant chicken IGF-I using a osmotic mini pump to fasted young chickens and measured the rate of muscle protein synthesis and plasma metabolite. The pumps delivered IGF-I at the rate of $22{\mu}g/d\{300{\mu}g{\cdot}(kg\;body\;weight{\cdot}d)^{-1}\}$. Fractional rate of protein synthesis in the muscle was measured using a large dose injection of L-[$2,6-^3H$]phenylalanine. Constant infusion of chicken IGF-I did not affect plasma glucose level. Significant interaction between dietary treatment and IGF-I infusion was observed in plasma NEFA and total cholesterol concentrations. When chicks were fasted, IGF-I infusion decreased plasma NEFA and total cholesterol concentrations. On the other hand, IGF-I administration did not affect plasma levels of both metabolites. Fasting reduced plasma triglyceride concentration significantly. IGF-I infusion also decreased the level of plasma triglyceride. Plasma IGF-I concentration of young chickens was halved by fasting for 1 d. IGF-I infusion using an osmotic minipump for 1 d increased plasma IGF-I concentration in fasted chicks to the level of fed chicks. Fasting decreased body weight and the loss of body weight was significantly ameliorated by IGF-I infusion. There was a significant interaction between dietary treatment and IGF-I infusion in the fractional rate of breast muscle protein synthesis. There was no effect of IGF-I infusion on muscle protein synthesis in fed chicks. Muscle protein synthesis reduced by fasting was ameliorated by IGF-I infusion, but did not reach to the level of fed control. Muscle weight of fasted chicks infused with IGF-I was similar to fasted birds without IGF-I infusion, which suggests that muscle protein degradation would be increased by IGF-I infusion as well as protein synthesis in fasted chicks.

• Development and Reproduction
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• v.13 no.4
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• pp.321-327
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• 2009

This study aimed to examine the testis toxicities of metal compound, manganese (Mn), which may be generated as mist or fume in the industrial sites. As well as serum prolactin (PRL) concentration was analyzed because Mn accumulation in basal ganglia up-regulates serum PRL and hyperprolactinemia consecutively induces the testis toxicity. Male F344 rats were divided into the 4 groups (2 controls and 2 Mn treated groups, n=10) on the basis of the test condition (inhalation, Mn $1.5mg/m^3$ or not) and treatment period (for 4-weeks and 13-weeks). The treatment time was 6 hr. a day, 5 days a week for the whole body. Basic tests including changes in body weight, feed rate were observed. Blood and testis Mn concentration, and testis toxicity test such as the number and deformity test of sperm were also observed. Serum PRL level was analyzed by ELISA to certify the relationship between the Mn induced increase of the serum PRL level and sperm production. Blood and testis Mn concentrations were significantly and dose-dependently increased. Sperm count was decreased in Mn-treatment groups than control in a treatment time dependent manner. Morphological analysis of cauda epidydimal sperm showed that the frequencies of morphologically abnormal sperms such as bent tail and small head were increased in the both Mn-treatment groups than control. A significant increase in serum PRL levels was found in response to Mn treatment but it was not hyperprolactinemia range. These results suggest that treatment of Mn up-regulates the serum PRL concentration and induces the testis toxicity. The No Aversed Effect Level (NOAEL) of inhaled Mn on the male rat testis may be under the $1.5mg/m^3$.

• Korean Journal of Food Science and Technology
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• v.53 no.5
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• pp.657-668
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• 2021

We prepared the growth and survival models of enterohemorrhagic Escherichia coli (EHEC) and Campylobacter jejuni in milk as a function of temperature and assessed the microbiological risks associated with the consumption of whole milk. EHEC and C. jejuni were not detected in whole milk (n=195) in the retail market. The minimum growth temperature of EHEC in milk was 7℃. The lag time of EHEC in whole milk was longer than that in skim milk. The survival ability of C. jejuni in milk was better at 4℃ than at 10℃. Lower delta values were observed in whole milk than in skim milk, indicating that C. jejuni survived better in skim milk. The probability of foodborne illness from whole milk consumption was 5.70×10^-5 for EHEC and 9.86×10^-9 for C. jejuni. Sensitivity analysis results show that the market temperature of EHEC and the dose-response model of C. jejuni are correlated with the probability of foodborne illness.