• Title/Summary/Keyword: degeneration

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Denaturation and Inactivation of Antioxidative Enzymes due to Repeated Exposure to UV-B and Inhibitory Effect of RGP Lens (UV-B 반복노출에 따른 항산화효소의 변성 및 활성저하와 RGP렌즈의 차단효과)

  • Byun, Hyun Young;Lee, Eun Jung;Oh, Dae Hwan;Kim, So Ra;Park, Mijung
    • Journal of Korean Ophthalmic Optics Society
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    • v.20 no.2
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    • pp.237-246
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    • 2015
  • Purpose: The present study was conducted to reveal the correlation of structural denaturation and decrease of enzyme activity when the antioxidative enzymes, superoxide dismutase (SOD) and catalase (CAT) were repeatedly exposed to UV-B, and further investigate whether the denaturation and inactivation of those enzymes can be effectively blocked by using UV-inhibitory RGP lens. Methods: Each enzyme solution was prepared from the standardized SOD and CAT, and repeatedly exposed to UV-B of 312 nm for 30 minutes, 1 hour and 2 hours a day over 1, 2, 3, 4 and 5 days. Structural denaturation of SOD and CAT induced by repeat UV-B irradiation was confirmed by the electrophoretic analysis, and their enzyme activity was determined by the colorimetric assay using the proper assay kit. At that time, the change in structure and activity of the antioxidant enzymes directly exposed to UV-B was compared to the case that UV-B was blocked by UV-inhibitory RGP lens. Results: SOD exposed repeatedly to UV-B showed the polymerization pattern in the electrophoretic analysis when it repeatedly exposed for 30 min a day, however, the change of its activity was less than 10%. On the other hand, CAT repeatedly exposed to UV-B reduced size and density of the electrophoretic band which indicated a structure denaturation, and its activity was significantly decreased. In the case that the repeat exposure time was longer, CAT activity was completely lost even though some enzyme band occurred in the electrphoretic analysis. In addition, the degeneration of CAT due to UV-B irradiation was inhibited to some extent by using RGP lens with a UV-B blocking of 63.7%, however, it was not completely inhibited. Conclusions: From these results, it was revealed that the structural denaturation of antioxidative enzymes was not perfectly correlated with the reduction in enzyme activity according to the type of enzyme. It is recommended to minimize the exposure time to UV when wearing contact lens, or wear the contact lenses having UV blocking rate of the FDA Class I blocker or the sunglasses having equivalent UV-blocking rate for reducing the damage of antioxidative enzymes induced by UV.

The Result of Bone Grafting for Fibrous Dysplasia (섬유성 골 이형성증에서 시행한 골 이식술의 결과 분석)

  • Jeong, Won-Ju;Kim, Tae-Seong;Cho, Hwan-Seong;Yoon, Jong-Pil;Park, Il-Hyung
    • The Journal of the Korean bone and joint tumor society
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    • v.20 no.2
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    • pp.74-79
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    • 2014
  • Purpose: Fibrous dysplasia is related to the mutation of gene encoding the alpha-subunit of a signal-transducing G-protein and has variable clinical course. Operation can be performed to prevent functional disorder or structural deformity. After curettage, autologous bone graft were used to fill the defects after curettage. The aim of this study is to compare the result of autogenous cancellous bone grafting and allogenic bone grafting for fibrous dysplasia. Materials and Methods: Among the patients who visit our hospital during the period of April, 1997 to October, 2013, we selected 34 patients who diagnosed fibrous dysplasia and visited our clinic over 1 year. There were 13 males and 21 females. Average age was 26.4 (range 2 to 57) years old. Autogenous bone graft (group I) in 5 cases, Non-autogenous bone graft (group II) in 30 cases. Iliac bone is used in all cases of autogenous bone graft. There were no significant difference in age, follow-up period, preoperational laboratory finding between two groups. Radiographic image was done to evaluate the recurrence of fibrous dysplasia or secondary degeneration. Results: There were four cases in recurrence (group I: 1 case, group II: 3 cases, p=0.554). In all recurrent cases, reoperations were done using curettage and autogenous iliac bone graft. There was no re-recurrence after reoperation. One case of secondary aneurysmal bone cyst was confirmed (group II) and 1 cases of pathologic fractures had developed (group I: 0 case, group II: 1 cases, p=0.559). No malignant change occurred. Conclusion: There were no significant difference between autogenous bone graft group and non-autogenous bone graft group. Our result suggested that autogenous bone graft seems to be good method to treat fibrous dysplasia, in the case of small volume of tumor lesion or non-weight bearing portion.

HISTOLOGICAL CHANGES AND EXPRESSION OF MATRIX METALLOPROTEINASE-2 AND TISSUE INHIBITOR OF MATRIX METALLOPROTEINASE-2 IN THE CANINE MANDIBULAR CONDYLE AFTER DISTRACTION OSTEOGENESIS (성견에서 하악골 신장술 후 하악과두 연골의 조직학적 변화와 Matrix Metalloproteinase-2 (MMP-2)와 Tissue Inhibitor of Matrix Metalloproteinase-2 (TIMP-2)의 발현)

  • Byun, June-Ho;Park, Bong-Wook;Cho, Yeong-Cheol;Sung, Iel-Yong;Son, Jae-Hee;Kim, Jong-Ryoul
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.28 no.5
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    • pp.404-416
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    • 2006
  • Purpose : This study was to clarify the changes in mandibular condyle after unilateral mandibular distraction osteogenesis throughout histological changes and expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2). Materials & Methods : Intraoral distractors were placed via submandibular incision in 8 dogs. Two unoperated animals served as controls. Distraction was performed five days after osteotomy as a rate of 0.5 mm twice per day for 10 days. Two animals were sacrificed on 7, 14, 28, and 56 days after completion of distraction, respectively. Ipsilateral condyles were harvested and processed for histological and immunohistochemical examinations. Results : The condyle cartilage is separated into four layers: fibrous layer, proliferative layer, hypertrophic layer, and calcified layer. At 7 days and 14 days after distraction, the condylar cartilage showed the decreased thickness of the articular cartilage and reduced cellularity. At 28 days after distraction, there was an increase in cellularity of fibrous, proliferative, and hypertrophic layer. However, it demonstrated reduced cellularity compared to the control. At 56 days of after distraction, the articular cartilage was an almost normal histologic structure. Positive Safranin-O staining, indicative of sulfated proteoglycans, was examined in the condylar cartilge of nonloaded control. At 7 days and 14 days after distraction, the sulfated proteoglycans is almost completely depleted from the noncalcified part of the condylar cartilage. At 28 days after distraction, there was an increase in Safranin-O staining intensity. However, the staining intensity of the experimental condyle was weaker than that of the control. At 56 days of after distraction, the condylar cartilage showed almost normal Safranin-O staining pattern. In control condyle, MMP-2 immunostaining was seen in fibrous, proliferative, and hypertrophic layer of condylar cartilage, however, it demonstrated lack of staining in fibrous and proliferative layer. At 7 days and 14 days after distraction, strong MMP-2 immunoreactivity was seen in the fibrous, proliferative and hypertrophic layer of the condylar cartilage. At 28 days after distraction, MMP-2 immunostaining was seen in the fibrous and hypertrophic layer of condylar cartilage, however, their immunoactivity was reduced. At 56 days after distraction, MMP-2 immunoreactivity showed almost normal immunostaining pattern. In control condyle, TIMP-2 immunostaining was primarily seen in fibrous and hypertrophic layer of condylar cartilage, however, it demonstrated lack of staining in proliferative layer. At 7 days after distraction, very weak TIMP-2 immunoreactivity appeared in fibrous, proliferative and hypertrophic layer of the condylar cartilage. At 14 days after distraction, weak TIMP-2 immunoreactivity was seen in the fibrous, proliferative and hypertrophic layer of the condylar cartilage. At 28 days after distraction, TIMP-2 immunoreactivity was increased in the fibrous and hypertrophic layer of condylar cartilage. At 56 days after completion of distraction, TIMP-2 immunoreactivity showed almost normal immunostaining pattern. Conclusions : The results show that short-term outcome of physiologic distraction osteogenesis may lead to degenerative changes in the condylar cartilage. These alterations in the condylar cartilage may be considered as a pressure-related degeneration of the cartilage tissue. However, the long-term results suggest that the condylar cartilage display repair activity after mandibular distraction osteogenesis.

Changes in Volatile Components and Capsaicin of Oleoresin Red Pepper during Cooking (고추 Oleoresin의 가열조리중 휘발성 성분 및 Capsaicin의 변화)

  • 최옥수;하봉석
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.23 no.2
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    • pp.232-237
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    • 1994
  • Changes of volatile components in modified oleoresin red pepper during cooking at high temperature were investigated. Dried red pepper was milled to 100mesh of size particle and oily compounds were extracted by reduced pressure steam distrillation. The rest part was reextracted and concentrated. The extracts were combined. The same volume of water and 4% of polyglycerol condensed ricinoleate (PGDR) were added to the combined extract, and emulsified to make oleoresin red pepper 119 volatile compounds were separated from the dried red pepper and oleoresin and 35 components were identified in both samples. The major flavor compounds were identified to be 2-methoxy-phenol, 2, 6-bis(1, 1-dimethylethyl)-4-methyl-phenol, 1, 4-dimethylbenzene, thylbenzene, 1, 2-benzenedicarboxylic acid, 2-methoxyl-4-methylphenol, 4-ethyl-2-methoxy-phenol, and 5- methyl-2-furancarboxyaldehyde, and their transferal from raw red pepper to oleresin was low. 93 voltilie compounds were isolated after 3 hours cooking at 100 and 82 volitile compounds were separated after that at $150^{\circ}C$. Degeneration of volatile compounds was peculiarly proportional to the temperature of cooling. Capsaicin was relatively stable during cooking and remaining ratio after cooking at 100 and $150^{\circ}C$ was 84.7% and 73.3%. respectively. Oleoresin from red pepper had a little antioxidation effect at $100^{\circ}C$ cooking, but, antioxidation effect at $150^{\circ}C$ cooking was not shown due to degradation of capsaicin.

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Anti-diabetic effect and mechanism of Korean red ginseng extract in C57BL/KsJ db/db mice

  • Yuan, Hai-Dan;Shin, Eun-Jung;Chung, Sung-Hyun
    • Proceedings of the Ginseng society Conference
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    • 2007.12a
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    • pp.57-58
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    • 2007
  • Purpose: Ginseng is a well-known medical plant used in traditional Oriental medicine. Korean red ginseng (KRG) has been known to have potent biological activities such as radical scavenging, vasodilating, anti-tumor and anti-diabetic activities. However, the mechanism of the beneficial effects of KRG on diabetes is yet to be elucidated. The present study was designed to investigate the anti-diabetic effect and mechanism of KRG extract in C57BL/KsJ db/db mice. Methods: The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. During the experiment, body weight and blood glucose levels were measured once every week. At the end of treatment, we measured Hemoglobin A1c (HbA1c), blood glucose, insulin, triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). Morphological analyses of liver, pancreas and white adipose tissue were done by histological observation through hematoxylin-eosin staining. Pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. To elucidate an action of mechanism of KRG, DNA microarray analyses were performed, and western blot and RT-PCR were conducted for validation. Results: Compared to the DC group mice, body weight gain of PIO treated group mice showed 15.2% increase, but the other group mice did not showed significant differences. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in RGL, 18.3% in RGH, 67.7% in MET, 52.3% in GPZ, 56.9% in PIO-treated group. With decreased plasma glucose levels, the insulin resistance index of the RGL-treated group was reduced by 27.7% compared to the DC group. Insulin resistance values for positive drugs were all markedly decreased by 80.8%, 41.1% and 68.9%, compared to that of DC group. HbA1c levels in RGL, RGH, MET, GPZ and PIO-treated groups were also decreased by 11.0%, 6.4%, 18.9%, 16.1% and 27.9% compared to that of DC group, and these figure revealed a similar trend shown in plasma glucose levels. Plasma TG and NEFA levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the RGL-treated group compared to those in DC group. Histological analysis of the liver of mice treated with KRG revealed a significantly decreased number of lipid droplets compared to the DC group. The control mice exhibited definitive loss and degeneration of islet, whereas mice treated with KRG preserved islet architecture. Compared to the DC group mice, KRG resulted in significant reduction of adipocytes. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin production, but decreased glucagon production. KRG treatment resulted in stimulation of AMP-activated protein kinase (AMPK) phosphorylation in the db/db mice liver. To elucidate mechanism of action of KRG extract, microarray analysis was conducted in the liver tissue of mice treated with KRG extract, and results suggest that red ginseng affects on hepatic expression of genes responsible for glycolysis, gluconeogenesis and fatty acid oxidation. In summary, multiple administration of KRG showed the hypoglycemic activity and improved glucose tolerance. In addition, KRG increased glucose utilization and improved insulin sensitivity through inhibition of lipogenesis and activation of fatty acid $\beta$-oxidation in the liver tissue. In view of our present data, we may suggest that KRG could provide a solid basis for the development of new anti-diabetic drug.

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Effects of Follicle Cells on the Chymotrypsin Resistance of Mouse Oocytes (난포세포가 생쥐 난자의 Chymotrypsin에 대한 내성에 미치는 영향)

  • Kim, Seong-Im;Bae, In-Ha;Kim, Hae-Kwon;Kim, Sung-Rye
    • Clinical and Experimental Reproductive Medicine
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    • v.26 no.3
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    • pp.407-417
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    • 1999
  • Objective: Mammalian follicle cells are the most important somatic cells which help oocytes grow, mature and ovulate and thus are believed to provide oocytes with various functional and structural components. In the present study we have examined whether cumulus or granulosa cells might playa role in establishing the plasma membrane structure of mouse oocytes during meiotic maturation. Design: In particular the differential resistances of mouse oocytes against chymotrypsin treatment were examined following culture with or without cumulus or granulosa cells, or in these cell-conditioned media. Results: When mouse denuded oocytes, freed from their surrounding cumulus cells, were cultured in vitro for $17{\sim}18hr$ and then treated with 1% chymotrypsin, half of the oocytes underwent degeneration within 37.5 min ($t_{50}=37.5{\pm}7.5min$) after the treatment. In contrast cumulus-enclosed oocytes showed $t_{50}=207.0$. Similarly, when oocytes were co-cultured with cumulus cells which were not associated with the oocytes but present in the same medium, the $t_{50}$ of co-cultured oocytes was $177.5{\pm}13.1min$. Furthermore, when oocytes were cultured in the cumulus cell-conditioned medium, $t_{50}$ of these oocytes was $190.0{\pm}10.8min$ whereas $t_{50}$ of the oocytes cultured in M16 alone was $25.5{\pm}2.9min$. Granulosa cell-conditioned medium also increased the resistance of oocytes against chymotrypsin treatment such that $t_{50}$ of oocytes cultured in granulosa cell-conditioned medium was $152.5{\pm}19.0min$ while that of oocytes cultured in M16 alone was $70.0{\pm}8.2min$. To see what molecular components of follicle cell-conditioned medium are involved in the above effects, the granulosa cell-conditioned medium was separated into two fractions by using Microcon-10 membrane filter having a 10 kDa cut-off range. When denuded oocytes were cultured in medium containing the retentate, $t_{50}$ of the oocytes was $70.0{\pm}10.5min$. In contrast, $t_{50}$ of the denuded oocytes cultured in medium containing the filtrate was $142.0{\pm}26.5min$. $T_{50}$ of denuded oocytes cultured in medium containing both retentate and filtrate was $188.0{\pm}13.6min$. However, $t_{50}$ of denuded oocytes cultured in M16 alone was $70.0{\pm}11.0min$ and that of oocytes cultured in whole granulosa cell-conditioned medium was $156.0{\pm}27.9min$. When surface membrane proteins of oocytes were electrophoretically analyzed, no difference was found between the protein profiles of oocytes cultured in M16 alone and of those cultured in the filtrate. Conclusions: Based upon these results, it is concluded that mouse follicle cells secrete a factor(s) which enhance the resistance of mouse oocytes against a proteolytic enzyme treatment. The factor appears to be a small molecules having a molecular weight less than 10 kDa.

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STUDIES ON THE DIMORPHISM AND TRANSITION OF BISEXUALITY OF HETEROSTYLOUS POLYGONACEAE (여뀌과 이형경식물의 Dinorphism과 Bisexuality의 변화)

  • Harn, Chang-Yawl
    • Journal of Plant Biology
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    • v.3 no.2
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    • pp.6-18
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    • 1960
  • The present experiments were designed in order to clarify the differences between the long and short styled plants and the transgressive gradition in the degree of dimorphism among the three heterostylous species of the Polygonus, P. japonica, F. esculentum, and P. senticosa, based on investigations regarding the floral structure, ecological and physiological traits, the results of which are summarized as follows: (1) P. japonica, although it exhibits typical dimorphism, has undergone so high a differentiation between long and short styled that its long styled individuals behave as if they were female; and short styled individuals as if male. In long-styled individuals, filament, anther, and pollen grains show signs of degeneration, most of the pollen being abortive. On the other hand, in short styled individuals, the filament, anther, and pollen grains have attained remarkable development; the pollen grians are large and fertile. In short-plant the fertilized flowers readily drop off in every stage of their embryo development. This species has completely lost the self-fertile property, which is characteristic of the non-dimorphic Polygonum genus. Although this specsei typically exhibits the physiological characteristics of the non-dimorphic Polygonum genus. Although this specisei typically exhibits the physiological characteristics of dimorphism in controlled pollination, the short-styled individuals bear no seed in nature, thus misleading taxonomists to idenfity the short-styled plant as male. 2) The morphological feature of the flower organ of P. senticosa obviously indicates definite dimorphism. Physiologically, however, no differentiation towards dimorphism was observed, the species still retaining, both in long and short-individuals, the self-fertile property common to the Polygonum genus. Elaborate examinations revealed that regardless of the modes of pollination, both fertiization and seed setting flourish, no differentiation betwen legitimate and illegitimate unions being recognizable. This sort of physiological property has not been observed in the investigations of other heterostylous plants. It is assumed that this species is differentiated structurally into dimorphism, but not yet physiologically. In nature, however, this plant would have more opportunities to be cross-pollinated, i.e., legitimately combined, than self-pollinated because of the development of two forms of flowers. 3) In terms of heterostylism, the F. esculentum just occupies the intermediate position between P. japonica and P. senticosa structurally, ecologically, and physiologically. Doescription of some of the physiological behavior of the plant will suffice to demonstrate the above facts. While P. japonica has completely lost its self-fertile property, P. senticosa still retains it wolly. In F. esculentum 2-6% of self-fertility is the result in illegitimate combination. There occur occasionally hereditary self fertile individuals among some of the F. or 20 min. irradiation plot, when they reach any stage of the same bacterial population. In addition to this increase of total population in the plots with the more dose of UV light irradiation, it seems that the more dose of UV light irradiation is the more shortened the generation time of Azotobacter. Therefore, it is clear that variation of reproductive rate must be, mere or less, due to the genetic effects induced by UV light irradiation. On the other hand, the lag phase or logarithmic growth phase in nonirradiated culture is shortened prominently, and this must be due to the difference in bacterial number of the original inoculm. The generation time of Azotobacter is shortened by exogeneous treatment of nuclei acid derivatives, and the degree is greater in case of DNA derivatives than RNA dervatives. W.H. Price reported that the rate of ribose nucleic acid to protein in Staphylococcus muscae is proportional to the generation time: that is the faster the cell can form ribose nucleic acid, the more rapid its growth. This explains the shortening of generation time by exogeneous RNA derivatives in this work reasonably. On the other hand, it is well known that the desoxyribose nuclic acid content per cell is constant and independent of the generation time. A.D. Laren and W.N. Takahashi reported that the infectious RNA from TMV is 6 times as sensitive to inactivation by UV as it is in the form of intact virus, and that inactivation of infectious TMV involves onlu a local change on RNA chain. But, the effect of exogeneous DNA in this work suggests that irradiated living cell which cotain DNA bring about some change on DNA moleculs as well as RNA molecules. And if the mutagenic effects of UV take into consideration, it is very reasonable. Therefore, it is clear that the variation of the generation time by UV irradiation is, more or less, due to the genetic effects. Therefore, it seems that the shortness of the average lifewpan of Azotobacter by UV irradiation is resulted not only from the influence of the environmental conditions, but also from the variation of genetic factor of the individual.

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Influence of the Food Intake Ability and the Number of Remaining Teeth on Oral Health Related Quality of Life in Some Elderly People (일부 노인의 저작강도별 음식섭취능력과 잔존치아수가 구강건강관련 삶의 질에 미치는 영향)

  • Kim, Da-Hye;Hwang, Soo-Jeong
    • Journal of dental hygiene science
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    • v.16 no.1
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    • pp.53-61
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    • 2016
  • Eating supports to gain energy and nutrition and improves quality of life. Ageing affects the food intake ability due to loss of natural teeth and the progressive muscle degeneration. Our objective was to investigate how the food intake ability (FIA) and the remaining teeth could influence on oral health related quality of life in the elderly. This study was performed with 503 elderly subjects living in Daejeon, Korea. The questionnaire with the FIA with 30 Korean food and Oral Health Impact Profile 14 (OHIP-14) and oral examination were surveyed. The five groups according to cluster analysis of FIA had the different numbers of remaining teeth and functional posterior teeth with opposing teeth or prosthesis significantly: group 1, $21.78{\pm}8.27$ and $2.80{\pm}2.63$; group 2, $16.75{\pm}7.87$ and $2.16{\pm}2.44$; group 3, $14.68{\pm}9.77$ and $1.73{\pm}2.30$; group 4, $9.93{\pm}8.13$ and $0.78{\pm}1.68$; group 5, $10.18{\pm}8.37$ and $0.51{\pm}1.22$. The more foods the subjects could masticate, the better oral health related quality of life they had. The medium FIA, soft FIA and the number of remaining teeth could explain 46% of OHIP-14, but hard FIA could not in the multiple regression model. We suggested to develop the oral health program for the elderly to be able to eat the food with medium physical property at least be helpful to improve oral health related quality of life.

Establishment of the expression system of human HtrA2 in the zebrafish (Zebrafish 동물모델에서 human HtrA2의 expression system 정립에 관한 연구)

  • Cho, Sung-Won;Park, Hyo-Jin;Kim, Goo-Young;Nam, Min-Kyung;Kim, Ho-Young;Ko, In-Ho;Kim, Cheol-Hee;Rhim, Hyang-Shuk
    • Journal of Life Science
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    • v.16 no.4
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    • pp.571-578
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    • 2006
  • HtrA2/Omi, a mitochondrial trypsin-like serine protease, is pivotal in regulating apoptotic cell death. Several lines of recent evidence suggest that HtrA2 is associated with the pathogenesis of neurodegenerative disorders; however, the physiological function of HtrA2 still remains elusive. For studying physiological function of HtrA2 in depth, it is necessary to develop a suitable expression system in the model animal. We therefore utilized the zebrafish as a model animal to establish expression of human HtrA2 (hHtrA2) in vivo. For expression of mature HtrA2 as GFP fusion in zebrafish embryos, the HtrA2 (WT) or (S306A) cDNAs with the C-terminal GFP tag were inserted into the pCS2+ plasmid. Expression patterns of HtrA2 in HEK293 cells were first monitored by immunofluorescence staining and immunoblot assays, showing approximately 64 kDa of the HtrA2-GFP fusion proteins. Subsequently, the hHtrA2 plasmid DNA or in vitro transcribed mRNA was microinjected into zebrafish embryos. The expression patterns of HtrA2 in Zebrafish embryos were monitored by GFP fluorescence in 24 hours-post-fertilization (hpf). Although expression patterns of HtrA2-GFP in developing embryos were different between the injected DNA and mRNA, both nucleic acids revealed good expression levels to further study the physiological role of HtrA2 in vivo. This study provides a suitable condition for expressing hHtrA2 in the zebrafish embryos as well as a method for generating useful system to investigate physiological properties of the specific human genes.

Adrenomedullin Deficiency Increases the Susceptibility of Liver Fibrosis Induced by CCl4 (아드레노메둘린 결핍은 사염화탄소로 유도된 간경화 감수성을 상승시킴)

  • Ji, Ae-Ri;Hwang, Meeyul;Kim, Ah-Young;Lee, Eun-Mi;Lee, Eun-Joo;Lee, Myeong-Mi;Sung, Soo-Eun;Kim, Sang-Hyeob;Park, Jin-Kyu;Jeong, Kyu-Shik
    • Journal of Life Science
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    • v.25 no.4
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    • pp.463-472
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    • 2015
  • Adrenomedullin (AM) is a peptide expressed in all body tissues, and its related receptors are increased in liver fibrosis. In this study, we evaluated the effect of AM deficiency on liver fibrogenesis induced by $CCl_4$ using AM heterozygous (HT) mice. The animals received a single injection of $CCl_4$ or olive oil for the acute experiment, and received $CCl_4$ or olive oil three times a week for 6 weeks for the chronic experiment. Fibrosis was accessed using histopathological analysis and the western blot. The AM HT mice showed mild pericentrilobular degeneration when compared to the AM wild type (WT) mice. In the acute experiment, there was no significant difference between the AM WT and AM HT mice. However, in the chronic experiment, the $CCl_4$-treated AM HT mice showed more severe liver fibrosis than that of the CCl4-treated AM WT mice. The AST and ALT levels of the AM HT $CCl_4$ group were higher than those of the AM WT CCl4 group. Additionally, the collagen deposition, $\alpha$- SMA protein and TGF-$\beta$ protein were increased in the AM HT $CCl_4$ group when compared to the AM WT $CCl_4$ group. The AM HT mice also exhibited severe lipid peroxidation through the GSH decrement. Taken together, our data suggest that AM deficiency increases the susceptibility to liver fibrosis induced by $CCl_4$, indicating a novel therapeutic target for patients with liver fibrosis.