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Role of Oxygen Free Radical in the Expression of Interleukin-8 and Interleukin-$1{\beta}$ Gene in Mononuclear Phagocytic Cells (내독소에 의한 말초혈액 단핵구의 IL-8 및 IL-$1{\beta}$ 유전자 발현에서 산소기 역할에 관한 연구)

  • Kang, Min-Jong;Kim, Jae-Yeol;Park, Jae-Seok;Lee, Seung-Joon;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.6
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    • pp.862-870
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    • 1995
  • Background: Oxygen free radicals have generally been considered as cytotoxic agents. On the other hand, recent results suggest that small nontoxic amounts of these radicals may act a role in intracellular signal transduction pathway and many efforts to reveal the role of these radicals as secondary messengers have been made. It is evident that the oxygen radicals are released by various cell types in response to extracellular stimuli including LPS, TNF, IL-1 and phorbol esters, all of which translocate the transcription factor $NF{\kappa}B$ from cytoplasm to nucleus by releasing an inhibitory protein subunit, $I{\kappa}B$. Activation of $NF{\kappa}B$ is mimicked by exposure to mild oxidant stress, and inhibited by agents that remove oxygen radicals. It means the cytoplasmic form of the inducible tanscription factor $NF{\kappa}B$ might provide a physiologically important target for oxygen radicals. At the same time, it is well known that LPS induces the release of oxygen radicals in neutrophil with the activation of $NF{\kappa}B$. From above facts, we can assume the expression of IL-8 and IL-$1{\beta}$ gene by LPS stimulation may occur through the activation of $NF{\kappa}B$, which is mediated through the release of $I{\kappa}B$ by increasing amounts of oxygen radicals. But definitive evidence is lacking about the role of oxygen free radicals in the expression of IL-8 and IL-$1{\beta}$ gene in mononuclear phagocytic cells. We conducted a study to determine whether oxygen radicals act a role in the expression of IL-8 and IL-$1{\beta}$ gene in mononuclear phagocytic cells. Method: Human peripheral blood monocytes were isolated from healthy volunteers. Time and dose relationship of $H_2O_2$-induced IL-8 and IL-$1{\beta}$ mRNA expression was observed by Northern blot analysis. To evaluate the role of oxygen radicals in the expression of IL-8 and IL-$1{\beta}$ mRNA by LPS stimulation, pretreatment of various antioxiants including PDTC, TMTU, NAC, ME, Desferrioxamine were done and Northern blot analysis for IL-8 and IL-$1{\beta}$ mRNA was performed. Results: In PBMC, dose and time dependent expression of IL-8 and IL-$1{\beta}$ mRNA by exogenous $H_2O_2$ was not observed. But various antioxidants suppressed the expression of LPS-induced IL-8 and IL-$1{\beta}$ mRNA expression of PBMC and the suppressive activity was most prominant when the pretreatment was done with TMTU. Conclusion: Oxygen free radical may have some role in the expression of IL-8 and IL-$1{\beta}$ mRNA of PBMC but that radical might not be $H_2O_2$.

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The Influence of Aging on Pulmonary Function Tests in Elderly Korean Population (한국에서 노화에 따른 폐기능지표의 변화양상)

  • Lee, Jae-Myung;Kim, Eun-Jung;Kang, Min-Jong;Son, Jee-Woong;Lee, Seung-Joon;Kim, Dong-Gyu;Park, Myung-Jae;Lee, Myung-Goo;Hyun, In-Gyu;Jung, Ki-Suck
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.6
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    • pp.752-759
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    • 2000
  • Background : Many studies have shown that pulmonary function differs widely among race, age and geographical residency. By virtue of the improvement of nutrition and environment, the elderly population in Korea is markedly increasing and so are the ages of patients complaining respiratory symptoms. However, we do not have our own data on the pulmonary functional reserve of elderly persons in Korea. We evaluate the deterioration of pulmonary functional reserve and standardize the predictive values of pulmonary function in the elderly population. Method : Pulmonary function tests were conducted in 100 men and 100 women over the age of 65. We analyzed changes of FVC and $FEV_1$ according to age and height by linear regression. We compared our new multiple linear regression equation with other equations currently used in Korea. Results : In men, the mean age was $71.5{\pm}5.2$(mean${\pm}$SD) years and the mean height was $163.6{\pm}6.2$cm. The mean FVC was $3.42{\pm}0.49{\ell}$ and the mean $FEV_1, $2.72{\pm}v$. In women, the mean age was $72.0{\pm}5.1$ years and the mean height was $149.1{\pm}5.9$cm. The mean FVC was $2.22{\pm}0.42{\ell}$ and the mean $FEV_1$ $1.83{\pm}0.34{\ell}$. Multiple linear regression equation using age and height as an independent factors was as follows : FVC(${\ell}$)=1.857-0.0356$\times$age(year)+0.02517$\times$height(cm) (p<0.01, $R^2$=0.279), $FEV_1(${\ell}$)=1.340-0.02698$\times$age(year)+0.02021$\times$height(cm) (p<0.01, $R^2$=0.255) in men, FVC(${\ell}$) =-0.09765-0.03332$\times$age(year)+0.03164$\times$height(cm) (p<0.01, $R^2$=0.435), $FEV_1(${\ell}$)=-0.l69-0.02469$\times$age(year)+0.02539$\times$height(cm) (p<0.01, $R^2$=0.41) in women. Conclusion : We established prediction regressions for pulmonary functional tests in the elderly Korean population. We also confirmed that currently adopted equations do not exactly anticipate the expected pulmonary functional reserve in the aged person over 65 years old. We suggest that our new equations from this study should be applied to interpret the pulmonary function tests in the elderly population in Korea.

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A Multicenter, Randomized, Open, Comparative Study for the Efficacy and Safety of Oral Moxifloxacin 400 mg Once a Day and Clarithromycin 500 mg Twice Daily in Korean Patients with Acute Exacerbations of Chronic Bronchitis (한국인의 만성 기관지염의 급성 악화 환자를 대상으로 한 Moxifloxacin 400mg 1 일 1회 요법과 Clarithromycin 500mg 1일 2회 요법의 치료효과 및 안전성 비교)

  • Kim, Seung-Joon;Kim, Seok-Chan;Lee, Sook-Young;Yoon, Hyeong-Kyu;Kim, Tae-Yon;Kim, Young-Kyoon;Song, Jeong-Sup;Park, Sung-Hak;Kim, Ho-Joong;Chung, Man-Pyo;Suh, Gee-Young;Kwon, O-Jung;Lee, Shin -Hyung;Kang, Kyung-Ho;Lee, Eh-Hyung;Hwang, Sung-Chul;Han, Myung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.6
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    • pp.740-751
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    • 2000
  • Background : Moxifloxacin is a newly developed drug which is more potent and safe compared to previous fluoroquinolones. This drug effectively eradicates organisms such as beta-lactamase-producing or other resistant bacteria. Moxifloxacin is known to be effective in treating respiratory infections such as Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniaeme, Legionella spp. and Mycoplasma pneumoniae. Methods : In a multicenter, randomized, open, comparative study, the efficacy and safety of oral moxifloxacin taken 400 mg once a day and clarithromycin taken 500 mg twice daily for 7 days were compared for the treatment of Korean patients with acute exacerbations of chronic bronchitis. Results : A total of 170 patients were enrolled, and they were divided into two groups: 87 in the moxifloxacin group and 83 in the clarithromycin group. Of those enrolled, 76 (35 for bacteriologic efficacy) in the moxifloxacin group and 77 (31 for bacteriologic efficacy) in the clarithromycin group were included in the efficacy analysis. All were included in the safety analysis. Clinical success was noted in 70 (92.1%) of 76 moxifloxacin-treated patients and 71 (92.2%) of 77 clarithromycin-treated patients. Bacteriologic success rate seemed to be higher in moxifloxacin group (73.5%) than in clarithromycin group (54.8%), but statistically insignificant (p=0.098). Drug susceptibility among organisms initially isolated was higher in moxifloxacin group on Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae (p<0.001). Adverse events were reported by 12.8% of 86 patients receiving moxifloxacin and 21.7% of 83 patients receiving clarithromycin. Headache (4.7% vs 4.8%, moxifloxacin group vs clarithromycin group, respectively) and indigestion (2.3% vs 6.0%, moxifloxacin group vs clarithromycin group, respectively) were the most frequent side effects in the two groups. Conclusion : This study demonstrated that for the treatment of acute exacerbations of chronic bronchitis a 7-day course of moxifloxacin 400 mg od was clinically equivalent and microbiologically superior to clarithromycin 500 mg bid.

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Triptolide-induced Transrepression of IL-8 NF-${\kappa}B$ in Lung Epithelial Cells (폐상피세포에서 Triptolide에 의한 NF-${\kappa}B$ 의존성 IL-8 유전자 전사활성 억제기전)

  • Jee, Young-Koo;Kim, Yoon-Seup;Yun, Se-Young;Kim, Yong-Ho;Choi, Eun-Kyoung;Park, Jae-Seuk;Kim, Keu-Youl;Chea, Gi-Nam;Kwak, Sahng-June;Lee, Kye-Young
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.1
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    • pp.52-66
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    • 2001
  • Background : NF-${\kappa}B$ is the most important transcriptional factor in IL-8 gene expression. Triptolide is a new compound that recently has been shown to inhibit NF-${\kappa}B$ activation. The purpose of this study is to investigate how triptolide inhibits NF-${\kappa}B$-dependent IL-8 gene transcription in lung epithelial cells and to pilot the potential for the clinical application of triptolide in inflammatory lung diseases. Methods : A549 cells were used and triptolide was provided from Pharmagenesis Company (Palo Alto, CA). In order to examine NF-${\kappa}B$-dependent IL-8 transcriptional activity, we established stable A549 IL-8-NF-${\kappa}B$-luc. cells and performed luciferase assays. IL-8 gene expression was measured by RT-PCR and ELISA. A Western blot was done for the study of $I{\kappa}B{\alpha}$ degradation and an electromobility shift assay was done to analyze NF-${\kappa}B$ DNA binding. p65 specific transactivation was analyzed by a cotransfection study using a Gal4-p65 fusion protein expression system. To investigate the involvement of transcriptional coactivators, we perfomed a transfection study with CBP and SRC-1 expression vectors. Results : We observed that triptolide significantly suppresses NF-${\kappa}B$-dependent IL-8 transcriptional activity induced by IL-$1{\beta}$ and PMA. RT-PCR showed that triptolide represses both IL-$1{\beta}$ and PMA-induced IL-8 mRNA expression and ELISA confirmed this triptolide-mediated IL-8 suppression at the protein level. However, triptolide did not affect $I{\kappa}B{\alpha}$ degradation and NF-$_{\kappa}B$ DNA binding. In a p65-specific transactivation study, triptolide significantly suppressed Gal4-p65T Al and Gal4-p65T A2 activity suggesting that triptolide inhibits NF-${\kappa}B$ activation by inhibiting p65 transactivation. However, this triptolide-mediated inhibition of p65 transactivation was not rescued by the overexpression of CBP or SRC-1, thereby excluding the role of transcriptional coactivators. Conclusions : Triptolide is a new compound that inhibits NF-${\kappa}B$-dependent IL-8 transcriptional activation by inhibiting p65 transactivation, but not by an $I{\kappa}B{\alpha}$-dependent mechanism. This suggests that triptolide may have a therapeutic potential for inflammatory lung diseases.

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The Effects of Autologous Blood Pleurodesis in the Pneumothorax with Persistent Air Leak (지속성 기흉에서 자가혈액을 이용한 흉막유착술의 효과)

  • Yoon, Su-Mi;Shin, Sung-Joon;Kim, Young-Chan;Shon, Jang-Won;Yang, Seok-Chul;Yoon, Ho-Joo;Shin, Dong-Ho;Chung, Won-Sang;Park, Sung-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.6
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    • pp.724-732
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    • 2000
  • Background : In patients with severe chronic lung diseases even a small pneumothorax can result in life-threatening respiratory distress. It is important to treat the attack by chest tube drainage until the lung expands. Pneumothorax with a persistent air leak that does not resolve under prolonged tube thoracostomy suction is usually treated by open operation to excise or oversew a bulla or cluster of blebs to stop the air leak. Pleurodesis by the instillation of chemical agents is used for the patient who has persistent air leak and is not good candidate for surgical treatment. When the primary trial of pleurodesis with common agent fails, it is uncertain which agent should be used f or stopping the air leak by pleurodesis. It is well known that inappropriate drainage of hemothorax results in severe pleural adhesion and thickening. Based on this idea, some reports described a successful treatment with autologous blood instillation for pneumothorax patients with or without residual pleural space. We tried pleurodesis with autologous bood for pneumothorax with persistent air leak and then we evaluated the efficacy and safety. Methods : Fifteen patients who had persistent air leak in the pneumothorax complicated from the severe chronic lung disease were enrolled. They were not good candidates for surgical treatment and doxycycline pleurodesis failed to stop up their air leaks. We used a mixture of autologous blood and 50% dextrose for pleurodesis. Effect and complications were assessed by clinical out∞me, chest radiography and pulmonary function tests. Results : The mean duration of air leak was 18.4${\pm}$6.16 days before ABP (autologous blood and dextrose pleurodesis) and $5.2{\pm}1.68$ days after ABP. The mean severity of pain was $2.3{\pm}0.70$ for DP(doxycycline pleurodesis) and $1.7{\pm}0.59$ for ABDP (p<0.05). There was no other complication except mild fever. Pleural adhesion grade was a mean of $0.6{\pm}0.63$. The mean dyspnea scale was $1.7{\pm}0.46$ before pneumothrax and $2.0{\pm}0.59$ after ABDP (p>0.05). The mean $FEV_1$ was $1.47{\pm}1.01$ before pneumothorax and $1.44{\pm}1.00$ after ABDP (p>0.05). Except in 1 patient, 14 patients had no recurrent pneumothorax. Conclusion : Autologous blood pleurodesis (ABP) was successful for treatment of persistent air leak in the pneumothorax. It was easy and inexpensive and involved less pain than doxycycline pleurodesis. It did not cause complications and severe pleural adhesion. We report that ABP can be considered as a useful treatment for persistent air leak in the pneumothorax complicated from the severe chronic lung disease.

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A comparative study on the correlation between Korean foods and the fractures of PFG and all ceramic crowns for posterior applications (구치용 도재소부금관과 전부도재관에 파절을 일으키는 한국음식에 관한 연구)

  • Kim, Jeong-Ho;Lee, Jai-Bong
    • The Journal of Korean Academy of Prosthodontics
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    • v.47 no.2
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    • pp.156-163
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    • 2009
  • Statement of problem: Recently, there have been increased esthetic needs for posterior dental restorations. The failure of posterior dental ceramic restoration are possible not only by the characters of the component materials but also by the type of food. Purpose: The research aim was to compare the in vitro fracture resistance of simulated first molar crowns fabricated using 4 dental ceramic systems, full-porcelain-occlusal-surfaced PFG, half-porcelain-occlusal-surfaced PFG, Empress 2, Ice Zirkon and selected Korean foods. Material and methods: Eighty axisymmetric crowns of each system were fabricated to fit a preparation with 1.5- to 2.0-mm occlusal reduction. The center of the occlusal surface on each of 15 specimens per ceramic system was axially loaded to fracture in a Instron 4465, and the maximum load(N) was recorded. Afterwards, selected Korean foods specimens(boiled crab, boiled chicken with bone, boiled beef rib, dried squid, dried anchovy, round candy, walnut shell) were prepared. 15 specimens per each food were placed under the Instron and the maximum fracture loads for them were recorded. The 95% confidence intervals of the characteristic failure load were compared between dental ceramic systems and Korean foods. Afterwards, on the basis of previous results, 14Hz cyclic load was applied on the 4 systems of dental ceramic restorations in MTS. The reults were analyzed by analysis of variance and Post Hoc tests. Results: 95% confidence intervals for mean of fracture load 1. full porcelain occlusal surfaced PFG Crown: 2599.3 to 2809.1 N 2. half porcelain occlusal surfaced PFG Crown: 3689.4 to 3819.8 N 3. Ice Zirkon Crown: 1501.2 to 1867.9 N 4. Empress 2 Crown: 803.2 to 1188.5 N 5. boiled crab: 294.1 to 367.9 N 6. boiled chicken with bone: 357.1 to 408.6 N 7. boiled beef rib: 4077.7 to 4356.0 N 8. dried squid: 147.5 to 190.5 N 9. dried anchovy: 35.6 to 46.5 N 10. round candy: 1900.5 to 2615.8 N 11. walnut shell: 85.7 to 373.1 N under cyclic load(14Hz) in MTS, fracture load and masticatory cycles are: 1. full porcelain occlusal surfaced PFG Crown fractured at 95% confidence intervals of 4796.8-9321.2 cycles under 2224.8 N(round candy)load, no fracture under smaller loads. 2. half porcelain occlusal surfaced PFG Crown fractured at 95% confidence intervals of 881705.1-1143565.7 cycles under 2224.8 N(round candy). no fracture under smaller loads. 3. Ice Zirkon Crown fractured at 95% confidence intervlas of 979993.0-1145773.4 cycles under 382.9 N(boiled chicken with bone). no fracture under smaller loads. 4. Empress 2 Crown fractured at 95% confidence intervals of 564.1-954.7 cycles under 382.9 N(boiled chicken with bone). no fracture under smaller loads. Conclusion: There was a significant difference in fracture resistance between experimental groups. Under single load, Korean foods than can cause fracture to the dental ceramic restorations are boiled beef rib and round candy. Even if there is no fracture under single load, cyclic dynamic load can fracture dental posterior ceramic crowns. Experimental data with 14 Hz dynamic cyclic load are obtained as follows. 1. PFG crown(full porcelain occlusion) was failed after mean 0.03 years under fracture load for round candy(2224.8 N). 2. PFG crown(half porcelain occlusion) was failed after mean 4.1 years under fracture load for round candy(2224.8 N). 3. Ice Zirkon crown was failed after mean 4.3 years under fracture load for boiled chicken with bone(382.9 N). 4. Empress 2 crown was failed after mean 0.003 years under fracture load for boiled chicken with bone(382.9 N).

Changes of the surface roughness depending on immersion time and powder/liquid ratio of various tissue conditioners (수종의 조직 양화재의 침수시간과 분액비에 따른 표면 거칠기의 변화)

  • Kim, Kyung-Soo;Moon, Hong-Suk;Shim, June-Sung;Jung, Moon-Kyu
    • The Journal of Korean Academy of Prosthodontics
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    • v.47 no.2
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    • pp.108-118
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    • 2009
  • Statement of problem: Volume stability, microstructure reproducibility and fluidity along with compatibility with dental stone must be in consideration in order to use tissue conditioner as a material for functional impression. There are few studies concerning the influence of time factor in oral condition on surface roughness of the stone and optimal retention period in the oral cavity considering such changes in surface roughness. Purpose: The purpose of this study was to find out the influence of various kinds of tissue conditioner, its powder/liquid ratio and immersion time on surface roughness of the stone. Material and methods: Materials used in this study were the three kinds of tissue conditioners(Coe-Comfort, Visco-Gel, Soft-Liner) and were grouped into three: group R-mixed with standard powder/liquid ratio that was recommended by the manufacturers, group M-mixed with 20% more powder, group L-mixed with 20% less powder. Specimens were made with the size of 20 mm diameter and 2 mm width. Each tissue conditioner specimens were subdivided into 5 groups according to the immersion time(0 hour, 1 day, 3 days, 5 days, 7 days), completely immersed into artificial saliva and were stored under $37^{\circ}C$. Specimens of which the given immersion time elapsed were taken out and were poured with improved stone, making the stone specimens. Surface roughness of the stone specimens was measured by a profilometer. Results: Within the limitation of this study, the following results were drawn. 1. Major influencing factor on surface roughness of the stone model made from tissue conditioner was the retention period(contribution ratio($\rho$)=62.86%, P<.05) of the tissue conditioner in oral cavity to make functional impression. 2. In case of Coe-Comfort, higher mean surface roughness value of the stone model with statistical significance was observed compared to that of Soft-Liner and Visco-Gel as immersion time changes(P<.05). 3. In case of group L(less), higher mean surface roughness value of the stone model with statistical significance was observed compared to that of R(recommended) and M(more) group as immersion time changes(P<.05). Conclusion: We may conclude that as the retention period of time in oral cavity influences surface roughness of the stone model the most and as the kind of tissue conditioner and its P/L ratio may influence also, clinician should well understand the optimal retention period in oral cavity and choose the right tissue conditioner for the functional impression, thus making the functional impression with tissue conditioner usefully.

A three-dimensional finite-element analysis of influence of splinting in mandibular posterior implants (스프린팅이 하악 구치부 임플랜트 보철물의 응력분산에 미치는 영향에 관한 삼차원 유한요소분석 연구)

  • Baik, Sang-Hyun;Jang, Ik-Tae;Kim, Sung-Kyun;Koak, Jai-Young;Heo, Seong-Joo
    • The Journal of Korean Academy of Prosthodontics
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    • v.46 no.2
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    • pp.157-168
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    • 2008
  • Statement of problem: Over the past two decades, implant supported fixed prosthesis have been widely used. However, there are few studies conducted systematically and intensively on the splinting effect of implant systems in mandible. Purpose: The purpose of this study was to investigate the changes in stress distributions in the mandibular implants with splinting or non-splinting crowns by performing finite element analysis. Materials and methods: Cortical and cancellous bone were modeled as homogeneous, transversely isotropic, linearly elastic. Perfect bonding was assumed at all interfaces. Implant models were classified as follows. Group 1: $Br{{\aa}}nemark$ length 8.5mm 13mm splinting type Group 2: $Br{{\aa}}nemark$ length 8.5mm 13mm Non-splinting type Group 3: ITI length 8.5mm 13mm splinting type Group 4: ITI length 8.5mm 13mm Non-splinting type An load of 100N was applied vertically and horizontally. Stress levels were calculated using von Mises stresses values. Results: 1. The stress distribution and maximum von Mises stress of two-length implants (8.5mm, 13mm) was similar. 2. The stress of vertical load concentrated on mesial side of implant while the stress of horizontal load was distributed on both side of implant. 3. Stress of internal connection type was spreading through abutment screw but the stress of external connection type was concentrated on cortical bone level. 4. Degree of stress reduction was higher in the external connection type than in the internal connection type.

A STUDY ON THE RELATIONS OF VARIOUS PARTS OF THE PALATE FOR PRIMARY AND PERMANENT DENTITION (유치열과 영구치열의 구개 각부의 관계에 관한 연구)

  • Lee, Yong-Hoon;Yang, Yeon-Mi;Lee, Yong-Hee;Kim, Sang-Hoon;Kim, Jae-Gon;Baik, Byeong-Ju
    • Journal of the korean academy of Pediatric Dentistry
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    • v.31 no.4
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    • pp.569-578
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    • 2004
  • The purpose of this study was to clarify the palatal arch length, width and height in the primary and permanent dentition. Samples were consisted of normal occlusions both in the primary dentition(50 males and 50 females) and in the permanent dentition(50 males and 50 females). With their upper plaster casts were used and through 3-dimensional laser scanning(3D Scanner, DS4060, LDI, U.S.A.), cloud data, polygonization, section curve and loft surface, fit and horizontal plane were based to measure the palatal arch length, width and height(Surfacer 10.0, Imageware, U.S.A.). T-tests were applied for the statistical analyze of the data. The results were as follows : 1. In the measurement values, the values of the male were higher than those of the female except primary anterior palatal height. There were not only statistically significant differences in anterior palatal width(p<0.05) and posterior palatal width(p<0.01) in primary dentition but palatal width(p<0.05), anterior palatal length(p<0.01), middle and posterior palatal length(p<0.05) in permanent dentition between male and female. 2. In the indices of palate, there were statistically significant differences in height-length index(p<0.05) and width-length index(p<0.01) between male and female in primary dentition. In permanent dentition, there was statistically difference between male and female. 3. In the measurement values, posterior palatal width was increased most greatly. Posterior palatal height, anterior palatal width and anterior palatal length were followed by descending order. On the other hand, anterior palatal height and posterior palatal length were decreased. 4. In the indices of palate, the height-length index, the width-length index and posterior height-width index were increased, but the others were decreased.

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Role of PI3K/Akt Pathway in the Activation of IκB/NF-κB Pathway in Lung Epithelial Cells (폐 상피세포에서 PI3K/Akt 경로가 IκB/NF-κB 경로의 활성화에 미치는 영향)

  • Lee, Sang-Min;Kim, Yoon Kyung;Hwang, Yoon-Ha;Lee, Chang-Hoon;Lee, Hee-Seok;Lee, Choon-Taek;Kim, Young Whan;Han, Sung Koo;Shim, Young-Soo;Yoo, Chul-Gyu
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.5
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    • pp.551-562
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    • 2003
  • Background : NF-${\kappa}B$ is a characteristic transcriptional factor which has been shown to regulate production of acute inflammatory mediators and to be involved in the pathogenesis of many inflammatory lung diseases. There has been some evidence that PI3K/Akt pathway could activate NF-${\kappa}B$ in human cell lines. However, the effect of PI3K/Akt pathway on the activation of NF-${\kappa}B$ varied depending on the cell lines used in the experiments. In this study we evaluated the effect of PI3K/Akt pathway on the activation of NF-${\kappa}B$ in human respiratory epithelial cell lines. Methods : BEAS-2B, A549 and NCI-H157 cell lines were used in this experiment. To evaluate the activation of Akt activation and I${\kappa}B$ degradation, cells were analysed by western blot assay using phospho-specific Akt Ab and $I{\kappa}B$ Ab. To block PI3K/Akt pathway, cells were pretreated with wortmannin or LY294002 and transfected with dominant negative Akt (DN-Akt). For IKK activity, immune complex kinase assay was performed. To evaluate the DNA binding affinity and transcriptional activity of NF-${\kappa}B$, electrophoretic mobility shift assay (EMSA) and luciferase assay were performed, respectively. Results : In BEAS-2B, A549 and NCI-H157 cell lines, Akt was activated by TNF-$\alpha$ and insulin. Activation of Akt by insulin did not induce $I{\kappa}B{\alpha}$ degradation. Blocking of PI3K/Akt pathway via wortmannin/LY294002 or DN-Akt did not inhibit TNF-$\alpha$-induced $I{\kappa}B{\alpha}$ degradation or IKK activation. Inhibition of PI3K/Akt did not affect TNF-$\alpha$-induced NF-${\kappa}B$ activation. Overexpression of DN-Akt did not block TNF-$\alpha$-induced transcriptional activation of NF-${\kappa}B$, but wortmannin enhanced TNF-$\alpha$-induced in NF-${\kappa}B$ transcriptional activity. Conclusion : PI3K/Akt was not involved in TNF-$\alpha$-induced $I{\kappa}B{\alpha}$ degradation or transcriptional activity of NF-${\kappa}B$ in human respiratory epithelial cell lines.