• Development and Reproduction
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• v.18 no.3
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• pp.161-166
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• 2014

Previously, we demonstrated that the shift and/or restriction of feeding time during relatively short-term period (4 weeks) could alter the pituitary gonadotropin expression and the weights of seminal vesicle and prostate in rats. We also found that the reverse feeding (RF) schedule (up to 8 weeks) might induce an adaptable metabolic stress and cause impairment of androgen-dependent reproductive tissues. In the present study, we extended the RF time regimen up to 12 weeks, and measured the reproductive tissue weights. After 4 and 8 weeks of RF, the weights of epididymis were not significantly different. After 12 weeks, however, epididymis weights of RF animals were significantly different (CON 12W : RF 12W = $48.26{\pm}0.62mg$ : $44.05{\pm}1.57mg$, p<0.05). After 4 and 12 weeks of feeding, seminal vesicle weights of RF animals were significantly decreased (CON 4W : RF 4W = $79.36{\pm}8.34mg$ : $46.28{\pm}2.43mg$, p<0.001; CON 12W : RF 12W = $72.04{\pm}3.76mg$ : $46.71{\pm}2.27mg$, p<0.001, respectively). Prostate weights were not changed by RF. Kidney and spleen weights of RF animals were significantly different on weeks 4 and 12 (Kidney, CON 4W : RF 4W = $249.72{\pm}4.20mg$ : $228.41{\pm}3.03mg$, p<0.001; CON 12W : RF 12W = $309.15{\pm}7.49mg$ : $250.72{\pm}6.13mg$, p<0.001, respectively, Spleen, CON 4W : RF 4W = $111.26{\pm}3.76mg$ : $96.88{\pm}4.69mg$, p<0.05; CON 12W : RF 12W = $123.93{\pm}10.72mg$ : $94.68{\pm}5.65mg$, p<0.05, respectively). Histology analysis of seminal vesicle revealed that the thinner epithelial cell layers, reduced complexities of swollen papilla folding in the exocrine glands on weeks 4 and 12 of RF. There was no histological difference between control and RF group on week 8. The present study indicates that up to 12 weeks RF induced differential changes in tissue weights of male mice. In particular, seminal vesicle, kidney and spleen seemed to temporarily adapted to the RF-induced metabolic stress on week 8 of feeding schedule. These results confirmed the our previous study that the RF might induce an adaptable metabolic stress and cause impairment of androgen-dependent reproductive tissues such as epididymis and seminal vesicle as well as non-reproductive tissues such as kidney and spleen. Further studies will be needed to achieve a better understanding of the how does mealtime shift affect the reproductive function and exact nature of adaptation.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.12
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• pp.1566-1577
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• 2010

Nandrolone, 19-nortestosterone, is a synthetic androgenic-anabolic steroid promoting muscle growth. Nandrolone is also present in pig meat and sera at non-negligible levels. A number of scientific reports have suggested a positive relationship between incidence of infertility and increased meat consumption in humans. The present study was designed to determine out the effect of feeding nandrolone on the testis of the male reproductive tract. Mixtures of food and nandrolone at different concentrations (0.005 ppm and 0.5 ppm) were supplied to pubertal male rats for 6 weeks. Body weight was recorded every week during the entire experimental period. At the end of the treatment, the testis, epididymis, and epididymal fat were collected and weighted. Sperm numbers in the caudal epididymis were counted. Differential gene or protein expression of steroidogenic enzymes in the testes among experimental groups was determined by semi-quantitative real-time PCR or western blotting analysis, respectively. Histological changes of the testis induced by nandrolone treatment were examined by hematoxylin and eosin staining. Immunohistochemical analysis was employed to detect changes in the localization of steroidogenic enzymes in the testes among experimental animals. There were no significant changes on body, testis, epididymis, and epididymal fat weights among experimental groups. A significant increase of caudal sperm number was found in the 0.5 ppm nandrolone-treated group. Histological examination of the testes noted a high frequency of germ cell sloughing in seminiferous tubules of 0.5 ppm nandrolone-treated rats. Even though transcript levels of $3{\beta}$-hydroxysteroid dehydrogenase (HSD) I, $17{\beta}$-HSD4, and $17{\alpha}$-hydroxylase were influenced by nandrolone treatments, protein levels of all molecules examined in the present study were not significantly affected. Immunohistochemical analysis showed no visible changes in the localization of steroidogenic enzymes in the testes among experimental groups. The current study showed that oral intake of nandrolone in male rats for 6 weeks did not cause significant damage to the testis. It is considered that a feeding effect of nandrolone on male fertility would not be remarkable.

• International Journal of Oral Biology
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• v.33 no.4
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• pp.205-211
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• 2008

Gingival overgrowth can cause dental occlusion and seriously interfere with mastication, speech, and dental hygiene. It is observed in 25 to 81% of renal transplant patients treated with cyclosporine A (CsA). CsA-induced gingival overgrowth (CIGO) is caused by quantitative alteration of the extracellular matrix components, particularly collagen. However, the molecular mechanisms involved in the pathogenesis of CIGO remain poorly understood, despite intense clinical and laboratory investigations. The aim of the present work is to identify differentially expressed genes closely associated with CIGO. Human gingival fibroblasts were isolated by primary explant culture of gingival tissues from five healthy subjects (HGFs) and two patients with the CIGO (CIGO-HGFs). The proliferative activity of CsA-treated HGFs and CIGO-HGFs was examined using the MTT assay. The identification of differentially expressed genes in CsA-treated CIGO-HGF was performed by differential display reverse transcriptase-polymerase chain reaction (RT-PCR) followed by DNA sequencing. CsA significantly increased the proliferation of two HGFs and two CIGO-HGFs, whereas three HGFs were not affected. Seven genes, including the beta subunit of prolyl 4-hydroxylase (P4HB) and testican 1, were upregulated by CsA in a highly proliferative CIGO-HGF. The increased P4HB and testican-1 mRNA levels were confirmed in CsA-treated CIGO-HGFs by semiquantitative RT-PCR. Furthermore, CsA increased type I collagen mRNA levels and suppressed MMP-2 mRNA levels, which are regulated by P4HB and testican-1, respectively. These results suggest that CsA may induce gingival overgrowth through the upregulation of P4HB and testican-1, resulting in the accumulation of extracellular matrix components.

• Journal of Animal Science and Technology
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• v.51 no.6
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• pp.459-470
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• 2009

The aim of this study was to analyze the proteome of proliferating bovine satellite cells from longissimus dorsi, deep pectoral and semitendinosus muscle depots which had been subjected to hormonal deprivation or addition in culture. For hormone deprivation or addition studies, the cells were either grown in 10% charcoal-dextran stripped fetal bovine serum (CD-FBS) or in 10% FBS supplemented medium. Further to analyze the effect of insulin like growth factor (IGF-1) and testosterone (TS), the cells were grown in 10% CD-FBS containing IGF-1 (10 ng/ml) or TS (10 nM). Results have shown that hormone deprivation had a negative impact on proliferation of the cells from each of the muscle depots. In case of IGF-1 and TS addition, the proliferation levels were low compared with that of the cells grown in 10% FBS. Hence, to gain the insights of the proteins that are involved in such divergent levels of proliferation, the proteome of such satellite cells proliferating under the above mentioned conditions were analyzed using 2D-DIGE and MALDI-ToF/ToF. Thirteen proteins during hormone deprivation and nine proteins from hormone addition were found to be differentially expressed in all the cultures of the cells from the three depots. Moreover, the results highlighted in this study offer a role for each differentially expressed protein with respect to its effect on positive or negative regulation of cell proliferation.

• Journal of Food Hygiene and Safety
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• v.22 no.1
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• pp.1-14
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• 2007

The term, "food safety", has traditionally been viewed as a practical science aimed at assuring the prevention acute illnesses caused by biological microorganisms, and only to a minor extent, chronic diseases cause by chronic low level exposures to natural and synthetic chemicals or pollutants. "food safety" meant to prevent microbiological agents/toxins in/on foods, due to contamination any where from "farm to Fork", from causing acute health effects, especially to the young, immune-compromised, genetically-predisposed and elderly. However, today a broader view must also include the fact that diet, perse (nutrients, vitamins/minerals, calories), as well as low level toxins and pollutant or supplemented synthetic chemicals, can alter gene expressions of stem/progenitor/terminally-differentiated cells, leading to chronic inflammation and other mal-functions that could lead to diseases such as cancer, diabetes, atherogenesis and possibly reproductive and neurological disorders. Understanding of the mechanisms by which natural or synthetic chemical toxins/toxicants, in/on food, interact with the pathogenesis of acute and chronic diseases, should lead to a "systems" approach to "food safety". Clearly, the interactions of diet/food with the genetic background, gender, and developmental state of the individual, together with (a) interactions of other endogenous/exogenous chemicals/drugs; (b) the specific biology of the cells being affected; (c) the mechanisms by which the presence or absence of toxins/toxicants and nutrients work to cause toxicities; and (d) how those mechanisms affect the pathogenesis of acute and/or chronic diseases, must be integrated into a "system" approach. Mechanisms of how toxins/toxicants cause cellular toxicities, such as mutagenesis; cytotoxicity and altered gene expression, must take into account (a) irreversible or reversal changes caused by these toxins or toxicants; (b)concepts of thresholds or no-thresholds of action; and (c) concepts of differential effects on stem cells, progenitor cells and terminally differentiated cells in different organs. This brief Commentary tries to illustrate this complex interaction between what is on/in foods with one disease, namely cancer. Since the understanding of cancer, while still incomplete, can shed light on the multiple ways that toxins/toxicants, as well as dietary modulation of nutrients/vitamins/metals/ calories, can either enhance or reduce the risk to cancer. In particular, diets that alter the embryo-fetal micro-environment might dramatically alter disease formation later in life. In effect "food safety" can not be assessed without understanding how food could be 'toxic', or how that mechanism of toxicity interacts with the pathogenesis of any disease.

• Radiation Oncology Journal
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• v.23 no.1
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• pp.43-50
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• 2005

Purpose : A number of genes and their products are Induced early or late following exposure of cells to ionizing radiation. These radiation-Induced genes have various effects on irradiated cells and tissues. Suppression subtractive hybridization (SSH) based on PCR was used to Identify the differentially expressed genes by radiation in cervix carcinoma cells. Materials and Methods : Total RNA and poly $(A)^+$ mRNA were Isolated from Irradiated and non-irradiated HeLa cells. Forward- and reverse-subtracted cDNA libraries were constructed using SSH. Eighty-eight clones of each were used to randomly select differentially expressed genes using reverse Northern blotting (dot blot analysis). Northern blotting was used to verify the screened genes. Results : Of the 17t clones, 10 genes in the forward-subtracted library and 9 genes In the reverse-subtracted library were identified as differentially expressed radiation-induced genes by PCR-select differential screening. Three clones from the forward-subtracted library were confirmed by Northern blotting, and showed increased expression in a dose-dependent manner, including a telomerase catalytic subunit and sodium channel-like protein gene, and an ESTs (expressed sequence tags) gene. Conclusion : We Identified differentially expressed radiation-induced genes with low-abundance genes with SSH, but further characterization of theses genes are necessary to clarify the biological functions of them.

• Journal of the Computational Structural Engineering Institute of Korea
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• v.25 no.5
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• pp.413-420
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• 2012

In this study, the Kernel integration scheme for 2D linear elastic direct boundary element method has been discussed on the basis of subparametric element. Usually, the isoparametric based boundary element uses same polynomial order in the both basis function and mapping function. On the other hand, the order of mapping function is lower than the order of basis function to define displacement field when the subparametric concept is used. While the logarithmic numerical integration is generally used to calculate Kernel integration as well as Cauchy principal value approach, new formulation has been derived to improve the accuracy of numerical solution by algebraic modification. The subparametric based direct boundary element has been applied to 2D elliptical partial differential equation, especially for plane stress/strain problems, to demonstrate whether the proposed algebraic expression for integration of singular Kernel function is robust and accurate. The problems including cantilever beam and square plate with a cutout have been tested since those are typical examples of simple connected and multi connected region cases. It is noted that the number of DOFs has been drastically reduced to keep same degree of accuracy in comparison with the conventional isoparametric based BEM. It is expected that the subparametric based BEM associated with singular Kernel function integration scheme may be extended to not only subparametric high order boundary element but also subparametric high order dual boundary element.

• IMMUNE NETWORK
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• v.7 no.3
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• pp.133-140
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• 2007

Background: It is well established that cross talk between natural killer (NK) cells and myeloid dendritic cells (DC) leads to NK cell activation and DC maturation. In the present study, we investigated whether type 1-polarized DC (DC1) matured in the presence of IFN-${\gamma}$ and type 2-polarized DC (DC2) matured in the presence of PGE2 can differentially activate NK cells. Methods: In order to generate DC, plastic adherent monocytes were cultured in RPMI 1640 containing GM-CSF and IL-4. At day 6, maturation was induced by culturing the cells for 2 days with cytokines or PGE2 in the presence or absence of LPS. Each population of DC was cocultured with NK cells for 24 h. The antigen expression on DC was analyzed by flow cytometry and cytokine production in culture supernatant was measured by ELISA or a bioassay for TNF-${\alpha}$ determination. NK cell-mediated lysis was determined using a standard 4h chromium release assay. Results: DC2, unlike DC1, had weak, if any, ability to induce NK cell activation as measured by IFN-${\gamma}$ production and cytolytic activity. DC2 were weakly stimulated by activated NK cells compared to DC1. In addition, IFN-${\gamma}$-primed mature DC appeared to be most resistant to active NK cell-mediated lysis even at a high NK cell/DC ratio. On the other hand, PGE2-primed DC were less resistant to feedback regulation by NK cells than IFN-${\gamma}$-primed mature DC. Finally, we showed that the differential effect of two types of DC population on NK cell activity is not due to differences in their ability to form conjugates with NK cells. Conclusion: These results suggest that different combinations of inflammatory mediators differentially affect the effector function of DC and, as a result, the function of NK cells, eventually leading to distinct levels of activation in adaptive immunity.

• Journal of Radiation Protection and Research
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• v.42 no.4
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• pp.189-196
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• 2017

Background: The effects of radiation on tissues vary depending on the radiation type. In this study, a minipig model was used to compare the effects of ${\beta}$-rays from $^{166}Ho$ and ${\gamma}$-rays from $^{60}Co$ on the skin. Materials and Methods: In this study, the detrimental effects of ${\beta}$- and ${\gamma}$-irradiation on the skin were assessed in minipigs. The histopathological changes in the skin from 1 to 12 weeks after exposure to 50 Gy of either ${\beta}$- (using $^{166}Ho$ patches) or ${\gamma}$- (using $^{60}Co$) irradiation were assessed. Results and Discussion: The skin irradiated by ${\beta}$-rays was shown to exhibit more severe skin injury than that irradiated by ${\gamma}$-rays at 1-3 weeks post-exposure; however, while the skin lesions caused by ${\beta}$-rays recovered after 8 weeks, the ${\gamma}$-irradiated skin lesions were not repaired after this time. The observed histopathological changes corresponded with gross appearance scores. Seven days post-irradiation, apoptotic cells in the basal layer were detected more frequently in ${\beta}$-irradiated skin than in ${\gamma}$-irradiated skin. The basal cell density and skin thickness gradually decreased until 4 weeks after ${\gamma}$- and ${\beta}$- irradiation. In ${\beta}$-irradiated skin lesions, and the density and thickness increased sharply back to control levels by 6-9 weeks. However, this was not the case in ${\gamma}$-irradiated skin lesions. In ${\gamma}$-irradiated skin, cyclooxygenase-2 (COX-2) was shown to be expressed in the epidermis, endothelial cells of vessels, and fibroblasts, while ${\beta}$-irradiated lesions exhibited COX-2 expression that was mostly limited to the epidermis. Conclusion: In this study, ${\beta}$-rays were shown to induce more severe skin injury than ${\gamma}$-rays; however, the ${\beta}$-rays-induced injury was largely repaired over time, while the ${\gamma}$-rays-induced injury was not repaired and instead progressed to necrosis. These findings reveal the differential effects of ${\gamma}$- and ${\beta}$-irradiation on skin and demonstrate the use of minipigs as a beneficial experimental model for studying irradiation-induced skin damage.

• Journal of Biomedical Engineering Research
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• v.23 no.5
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• pp.341-349
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• 2002

The target controlled infusion(TCI) pump system is a logical approach to the development of improved administration techniques of an intravenous anaesthetic agent. The principle of TCI system is based on an understanding of the pharmacokinetic properties, three or four compartment model. The TCI system is optimal and flexible control of the plasma drug concentration. But the clinical goal is always to achieve a therapeutic drug effect, not a therapeutic concentration. So we developed the algorithm to target the concentration at the site of drug effect rather than the concentration in the plasma. If impulse drug is inputted into body, the decline of plasma concentration with time is shown, resulting in the expression of the differential equation. Therefore, we must reformulate our three-compartment model as four-compartment model with the effect compartment. And we tested plasma targeting and effect targeting algorithm by computer simulation using four-compartment model. So we developed the TCI capable of applying all intravenous drugs by adjusting individual pharmacokinetic parameters independently.