• Journal of the korean academy of Pediatric Dentistry
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• v.26 no.4
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• pp.652-663
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• 1999

Craniosynostosis, the premature fusion of cranial sutures, presumably involves disturbance of the interactions between different tissues within the cranial sutures. Interestingly, point mutaions in the genes encoding for the fibroblast growth factor receptors(FGFRs), especially FGFR2, cause various types of human craniosynostosis syndromes. To elucidate the function of these genes in the early morphogenesis of mouse cranial sutures, we first analyzed by in situ hybridization the expression of FGFR2(BEK) and osteopontin, an early marker of osteogenic differentiation, in the sagittal suture of calvaria during embryonic(E15-E18) and postnatal stage(P1-P3). FGFR2(BEK) was intensely expressed in the osteogenic fronts, whose cells undergo differentiation into osteoprogenitor cells that ultimately lay down the bone matrix. Osteopontin was expressed throughout the parietal bones excluding the osteogenic fronts, the periphery of the parietal bones. To further examine the role of FGF-mediated FGFR signaling in cranial suture, we did in vitro experiments in E15.5 mouse calvarial explants. Interestingly, implantation of FGF2 soaked beads onto both the osteogenic fronts and mid-mesenchyme of sagittal suture after 36 hours organ culture resulted in the increase of the tissue thickness and cell number around FGF2 beads, moreover FGF4-soaked beads implanted onto the osteogenic fronts stimulated suture closure due to an accelerated bone growth, compared to FGF4 beads placed onto mid-mesenchyme of sagittal suture and BSA control beads. In addition FGF2 induced the ectopic expression of osteopontin and Msx1 genes. Taken together, these data indicate that FGF-mediated FGFR signaling has a important role in regulating the cranial bone growth and maintenance of cranial suture, and suggest that FGF-mediated FGFR signaling is involved in regulating the balance between the cell proliferation and differentiation through inducing the expression of osteopontin and Msx1 genes.

• Korean Journal of Digital Imaging in Medicine
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• v.14 no.2
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• pp.23-31
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• 2012

There are AEC mode and fix mode to exposure when the whole spine antero-posterior radiography is done by using DR equipment. This study compared the utility of fix mode to AEC mode, by evaluating organ dose and effective dose and by examining the quality of radiographic image. GE DEFINIUM 8000 and ART-200X Rando Phantom manufactured by Flukebiometical were used for this study. The Rando phantom was set in front of wall detector of X-rays equipment. AEC mode was set at 80kVp and Fix mode was set at 80kVp, 25mAs, 32mAs, 40mAs, and 50mAs. Whole spine AP image were aquired by combining C, T-L and L-S spine images obtained through 3 exposures. When obtaining C, T-L and L-S spine images, were checked for Air kerma (mGy) value calculated by UNFORS Xi meter attached at the phantom surface of center of radiation field. The effective and organ doses were compared by PCXMC program (PC-Based Monte Carlo Program). The quality of obtained radiographic image was evaluated visually by 3 radiologists using resolution chart. When the effective doses was calculated based on tissue weighting factor of ICRP-103, 1.278mSv was measured by AEC mode, and Fix mode measured 0.405mSv at 25mAs, 0.518mSv at 32mAs, 0.649mSv at 40mAs, and 0.810mSv at 50mAS. In addition, the organ dose measured with esposure at 25mAs by Fix mode was almost equivalent to the organ dose by AEC mode, at the esophagus, thyroid, oral mucosa, salivaly glands located at the cervical spine part, while the organ dose by Fix mode was in general lower than the organ dose by AEC mode at the other organs. When Fix mode at 32mAs, 40mAs, and 50mAs was compared to AEC mode for organ dose in 26 organs, AEC mode had higher measurement in 21 organs but not for than brain, trachea, thyroid, oral mucosa, and salivaly glands which are located at the cervical spine part. The image quality evaluated by resolution test chart was much higher with AEC mode than the quality with Fix mode at all exposure conditions. However, while the image quality of cervical spine exposured at 50mAs by Fix mode was lower than the quality of AEC mode, thoraco-lumbar spine and lumbo-sacral spine were calculated and the quality was similar to AEC mode. Scoliosis occurs mainly at thoraco-lumbar and lumbo-sacral spine, not at cervical spine. Compared to AEC mode, Using the appropriate protocol (80kVp, 50mAs) of fix mode for whole spine AP radiography was thought to be useful because the image quality of the thoraco-lumar and lumbo-sacral spine was similar on AEC mode, Also organ and effective doses can be decreased with Fix mode. Therefore, It is considered that fix mode can be used properly with AEC mode for whole spine AP radiography when considering patient's body posture.

• The korean journal of orthodontics
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• v.31 no.1 s.84
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• pp.121-136
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• 2001

This study was performed to analyse the expression of VEGF and it's receptor(VEGFR) in the tension side of the periodontal ligament following orthodontic tooth movement. Upper first molars of Sprague-Dawley rats were moved medially using closed coil spring for 1, 2, 24 hours and 3, 7, 14 days. H&E staining, immunohistochemical staining and in situ hybridization methods were used to analyse the change of the expression of VEGF and VEGFR. The results from this study were as follows : 1. Following tensional force, periodontal ligament showed elongation of fibers, compression and congestion of vessels and regional hemorrhage. These tissue changes were recovered within 3 days of force application. New bone formation was seen after 3 days of force application and continued for the remaining experimental periods. 2. Following tensional force, VEGF and VEGF mRNA expression was increased in the periodontal ligament cells, osteoblasts and cementoblasts. This change was followed by increased vasculature in the periodontal ligament. 3. After 3 days of tensional force, VEGF and VEGF mRNA expression was confined mainly to the osteopaths and the periodontal ligament cells adjacent to the alveolar bone. After 2 weeks of force application, VEGF and VEGF mRNA expression was reduced to the level of control sample. 4. VEGFRs(Flt-1, Flk-1) showed similar expression pattern and it's expression was mainly seen in the endothelial cells and osteoblasts. Following tensional force VEGFR expression was increased in the endothelial cells and osteoblasts. In conclusion, in the tension side of the penodontal ligament, ligament cells, osteoblast and cementoblast showed increased expression of VEGF & VEGF mRNA. It preceded the increase of vasculature and new bone formation. The increased expression of VEGF mRNA in cementoblast may induce periodontal vessels, which distribute mainly the bone side half of periodontal ligament, grow in the direction of tensional force. Increased expression of VEGFR & VEGFR mRNA not only in endothelial cell but in osteoblast, osteocyte and periodontal cells showed VEGF acts not only in paracrine manner but in autocrine one.

• Journal of the korean academy of Pediatric Dentistry
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• v.33 no.2
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• pp.181-191
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• 2006

NFI-C null mice demonstrated aberrant odontoblast differentiation and thus abnormal dentin formation while other tissues/organs in the body, including ameloblasts, appear to be unaffected and normal. However little is known about the mechanism of NFI-C function in odontoblast differentiation and dentin formation. Odontoblasts are tall, highly polarized cells that are responsible for formation and maintenance of the predentin and dentin. An indication of their polarity is the acquisition of specialized intercellular junctions. As preodontoblasts differentiate into odontoblasts, they are Joined and attached at the apical end by well developed terminal webs of cytoskeletal actins, and associated tight as well as adherent njunctions. In this study, in order to investigate if disruption of the NFI-C gene interferes with formation of a specific or other structural proteins of the intercellular junctions, we examined morphological characteristic of the aberrant odontoblast in NFI-C null mice using light and electron microscope. In addition, we determined the expression of major structural proteins of intercellular junctions, ZO-1 and occludin, during the differentiation of odontoblasts using immunohitochemistry. The results were as follows : 1. In light microscopy, abnormal odontoblasts of incisors of the NFI-C null mice were round in shape, lost their polarity, and trapped in osteodentin-like mineralized tissue. Mutant molars have relatively normal crowns, but short and abnormal differentiating adontoblasts in root formation area. 2. Electron microscopy of abnormal odontoblasts revealed the dissociation of the round osteoblast-like cells, the loss of their cellular polarity, and the absence of an intercellular junctional complex known as the tight junctions. 3. A mutant incisor showed labeling for ZO-1 at the proximal and distal ends of secreting ameloblasts, while staining for ZO-1 was not observed in the abnormal odontoblasts. 4. A normal incisor showed immunoreactivity for occludin in the differentiating odontoblasts. However, staining for occludin was not observed in the abnormal odontoblasts of mutant incisor. These results suggest that NFI-C gene causes dissociation of odontoblast and thus abberant odontoblast differentiation and abnormal dentin formation by interfering with the formation of intercellular junctions.

• Journal of the korean academy of Pediatric Dentistry
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• v.28 no.2
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• pp.238-246
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• 2001

Bone morphogenetic proteins(BMPs), members of the transforming growth factor $\beta$(TGF-$\beta$) superfamily were first identified as the factors that induce ectopic bone formation in vivo, when implanted into muscular tissue. Especially BMP-2 inhibits terminal differentiation of C2C12 myoblasts and converts them into osteoblast lineage cells. In the molecular mechanism of the signal transduction of TGF-$\beta$ and related factors, intracellular signaling proteins were identified as Smad. In previous study, it has been reported that Smad 1 and Smad 5, which belong to the R-Smad family mediate BMP signaling, were involved in the induction of osteoblast differentiation in C2C12 cells. To understnad the role of Smads involved in osteogenic transdifferentiation in C2C12 cell, in present study, after we stably transfected C2C12 cells with each. Smad(Smad 1,Smad 5) expression vector, cultured for 3 days and stained for alkaline phophatase activity. ALP activity positive cells appeared in the Smad 1, Smad 5 stably transfected cell even in the abscence of BMP. After transiently co-transfected C2C12 cells with each Smad expression vector and ALP promoter, it was examined that Smad 1 and Smad 5 expression vector had increased about 2 fold ALP promoter activity in the abscence of BMP. These result suggested that both Smad 1 and Smad 5 were involved in the intracellular BMP signals which induce osteoblast differentiation in C2C12 cells. The effect of BMP on C2C12 cells with Smad 1, Smad 5 transfected were studied by using northern blot analysis. the treatment of BMP upregulated ALP mRNA level in three groups, especially upregulation of ALP was larger in Smad 1, Smad 5 transfected cell than control group. Pretreatment with cycloheximide($10{\mu}g/ml$), a protein synthesis inhibitor resulted in blocking the ALP gene expression even in BMP(100ng/ml) treated cell. These results suggested that Smad increased the level of ALP mRNA via the synthesis of a certain transcriptional regulatory protein.

• Korean Journal of Hospice Care
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• v.6 no.1
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• pp.1-11
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• 2006

There are various understandings how to define death. In the context of medicine, death is defined as the irreversible change of the tissue according to the cessation of circulation and respiration. According to the psychologists, a person need to accept the finiteness as a human being and remain conscious that the death is not avoidable. And they say if a person doesn't regard death as unavoidable reality of life he or she will not confront the humanistic death and after all will die like animals. In philosophy, death is viewed as an unwelcome reality in the end of the journey of life. Sociologists usually understand that the society is the organization composed with living persons and human beings which construct and transmit the culture from generation to generation between the both ends of life and death. In society, the generation is changed, maintained, and developed through the phenomenon of death. Although death of human being is natural event in society, the death of a specific person brings a sense of loss, crisis, and anxiety to the communities like family, regional society, nation, and the world. In this context, death is not confined to personal dimension and it can be regarded as a social problem. It is valuable to summarize the religious perspectives on the meaning of death for the better hospice care. In shamanism, there are basic idea that although the flesh of human being disappears, soul never die. If human dies, the flesh of human being disappears but soul never disappear and come back to the origin of soul as it is called chaos. So in shamanism, it is said that shaman can solve the mortified feeling, restore the broken harmony, send the soul to comfortable space- the origin, and guarantee the blessing of descendents. Buddhists regard the death as an essential component through the cycles of life. Through this cycle, human being exits as an endlessly transmigrating being and the death is just a restoration to the original status. In Confucianism, the view on the death based on the philosophy of the "Yin and Yang" and "Five elements". In Buddhist tradition, many believers said the philosophy of "Death is the same as life". Unlike usual thoughts that a god governs "life and death" and "fortune and misfortune", Confucianists deny the governance of a god and emphasize the natural orders in which every phenomenon in the world moves according to the principle. Confucianists understand the death as a natural order with this principle. In Confucianists' belief, the essence of human being remains in their own descendent's lives after the death of ancestor, so in Confucianism there is no concept of immortality of the soul. In the history of Christianity, death has been defined generally as the separation of the immortal soul from the mortal body. In the earlier days of Old Testament, the death is regarded as a disappearance of just a flesh and human never disappear and always live in the relationship with God. Later days in Old Testament, we can find the growing concern for the life after the death because of the entrance of the theodicy. In the New Testament, the death is not regarded as the normal process of the human life and regarded as the abnormal status in which death come to human because of sin as a decisive factor and it should be conquered. In fact, the most of us afraid death because not of the fear of death itself but of the sense of the emptiness and regrets. so many people often make the monument hoping to live forever. But Christian usually regard this behavior as a sinful act because human being usually think themselves as a master of their life and attempt to become immortal in this kind of trial mortal. But if we live with God, we cannot confront such a condition because we aware limits as a mortal human being and entrust everything on Him and want to live according to His guidance. Therefore, in the Christian tradition, the death is regarded as accomplishment of life, fruits of life, invitation to the eternal life, and the last stage of human growth. For human being, the death is the great step of maturation as a human in the final stage of life.

• Tuberculosis and Respiratory Diseases
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• v.40 no.6
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• pp.669-676
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• 1993

Background: DNA content analysis of human solid tumor is now widely performed by flow cytometric study. One of the most interesting and potentially important observation in this field is that proliferative activity(S-Phase fraction of cell cycle) may profoundly affect prognosis. Method: S-Phase fraction(SPF) have been measured by flow cytometric method using tumor cells isolated from paraffin embedded tissue. To evaluate the prognostic significance, SPF of squamous lung cancer cell was assessed in 21 patients who died without any specific treatment. Results: 1) Mean survival time of squamous lung cancer patients was 225(${\pm}162$) days. Survival time were shortened, when TNM stage and PS scale were advanced. 2) Mean value of SPF of squamous lung cancer patients was 23.4(${\pm}11.3$)%. SPF had nothing to do with advance of TNM stage and PS scale. 3) Mean survival time of high SPF group(more than 20% of cell proliferation cycle) and low SPF group were 153(${\pm}99$) days and 342(${\pm}180$) days(p<0.01). In each identical TNM stage and PS scale, there were also statistic significant differences in mean survival time between high and low SPF group. Conclusion: On multivariate analysis including TNM stage and performance status, SPF was the significant and independent prognostic factor in the primary squamous lung cancer patients group.

• Journal of the korean academy of Pediatric Dentistry
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• v.31 no.4
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• pp.651-658
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• 2004

Runx2 is a transcription factor in homologous with Drosophila runt gene and it is essential for bone formation during embryogenesis and a critical gene for osteoblast differentiation and osteoblast function. Runx2-haploinsufficency causes cleidocranial dysplasia (CCD). CCD is an autosomal-dominant inherited disorder characterized by hypoplastic clevicle and delayed ossification in fontanelles and wormian bones. Dental defects are possibly shown to CCD patients : multiple supernumerary teeth, irregular and compressed permanent tooth crowns, hypoplastic and hypomineralized defects in enamel and dentin, an excess of epithelial root remnants, the absence of cellular cementum, and abnormally shaped roots. In addition, delayed eruption of the secondary dentition is a constant finding. The aim of this study is to evaluate the role of Runx2 in the tooth development and eruption through analyzing the expression pattern of Runx2 by in situ hybridization during crown (late bell stage) and root formation of tooth, using postnatal day 1, 4, 7, 14 and 21 mice mandibular molar teeth. mRNA of Runx2-full length is expressed in dental follicle and surrounding tissue at postnatal day1 and 4. At postnatal day 7, it is expressed in ameloblasts of occlusal surface of enamel and bone area surrounding the tooth. In comparison with previous stage, at postnatal day 14, it is expressed in ameloblasts of proximal surface of enamel. At postnatal day 21 it's expression is observed only in bone area. mRNA of Runx2-typeII is not expressed. At postnatal day 1 and 7. At postnatal day 14 and 21, it's expression is observed in the bone area. In this study, we suggest that Runx2 have a relation of ameloblasts differentiation and an important role to tooth eruption made by dental follicle during intraosseous eruption stage. Also we can confirm that Runx2 has a role to bone formation.

• Journal of Chest Surgery
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• v.40 no.2 s.271
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• pp.114-121
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• 2007

Background: Apoptosis plays a crucial role in carcinogenesis, as well as in development and tissue homeostasis. Terminal deoxyribonucleotidyl transferase mediated neck end labelling (TUNEL) and in situ nick end labelling (ISEL) have been used to investigate the apoptosis in tissues. Since the introduction of the M30 monoclonal antibody to overcome drawbacks of TUNEL and ISEL, the apoptosis in various tumors, with the exception of pulmonary carcinomas, has been studied. In this study, attempts were made to examine the correlation of apoptosis in non-small cell carcinomas, using both M30 and the expression of p53 protein, with the clinicopathological factors. Material and Method: Forty five patients with surgically resected non-small cell carcinomas were included. Immunohistochemical staining with M30 and p53 monoclonal antibody were peformed, and their expressions compared with the clinicopathological features. The overall survival time and recurrence-free survival time were calculated, and the factors influencing the survival time analyzed using a univariate analysis. The effects of the expression stati of M30 and p53 on the risks of cancer related to both death and recurrence were evaluated using a multivariate analysis. Result: The p53 positive group had many more M30 positive cells than the p53 negative group (p53 positive group; $61.7{\pm}26.8$ cells vs. p53 negative group; $45.6{\pm}29.6$ cells, p=0.005) and significantly more p53 positive patients showing at least 10 positive cells (apoptotic index, $Al{\ge}1$) on M30 staining (p53 positive group; 52.4% (11/21) vs. p53 negative group 16,7% (4/24), p=0.025). In the univariate analysis, the survival times in relation to smoking (pack-year), performance status (PS) and Al showed significant differences. The multivariate analysis demonstrated the relative risk (R.R) of cancer death increased almost 7.5-fold (R.R 7.482; 95% Cl $1.886{\sim}29.678$; p=0.004) and the risk of recurrence almost 3,8-fold (R.R 3.795; 95% Cl: $1.184{\sim}12.158$; p=0.025) in the high Al (${\ge}1$) compared to the low Al (<1) group. There was no prognostic effect of p53 expression on the survival time or risk of cancer death and recurrence. Conclusion: In non-small cell lung carcinomas, M30 immunohistochemistry was an excellent method for analyzing apoptosis; the high apoptotic index could be an adverse prognostic predictive factor.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.517-529
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• 1998

Purpose : Although many studies have investigated the dosimetric aspects of stereotactic radiosurgery in terms of target volume, the absorbed doses at extracranial sites: especially the lens or thyroid - which are sensitive to radiation for deterministic or stochastic effect -have infrequently been reported. The aim of this study is to evaluate what effects the parameters of radiosurgery have on the absorbed doses of the lens and thyroid in patients treated by stereotactic radiosurgery, using a systematic plan in a humanoid phantom. Materials and Methods : Six isocenters were selected and radiosurgery was planned using the stereotactic radiosurgery system which the Department of Therapeutic Radiology at Seoul National University College of Medicine developed. The experimental radiosurgery plan consisted of 6 arc planes per one isocenter, 100 degrees for each arc range and an accessory collimator diameter size of 2 cm. After 250 cGy of irradiation from each arc, the doses absorbed at the lens and thyroid were measured by thermoluminescence dosimetry. Results : The lens dose was 0.23$\pm$0.08$\%$ of the maximum dose for each isocenter when the exit beam did not pass through the lens and was 0.76$\pm$0.12$\%$ of the maximum dose for each isocenter when the exit beam passed through the lens. The thyroid dose was 0.18$\pm$0.05$\%$ of the maximum dose for each isocenter when the exit beam did not pass through the thyroid and was 0.41$\pm$0.04$\%$ of the maximum dose for each isocenter when the exit beam Passed through the thyroid. The passing of the exit beam is the most significant factor of organ dose and the absorbed dose by an arc crossing organ decides 80$\%$ of the total dose. The absorbed doses of the lens and thyroid were larger as the isocenter sites and arc planes were closer to each organ. There were no differences in the doses at the surface and 5 mm depth from the surface in the eyelid and thyroid areas. Conclusion : As the isocenter and arc plane were placed closer to the lens and thyroid, the doses increased. Whether the exit beams passed through the lens or thyroid greatly influenced the lens and thyroid dose. The surface dose of the lens and thyroid consistently represent the tissue dose. Even when the exit beam passes through the lens and thyroid, the doses are less than 1$\%$ of the maximum dose and therefore, are too low to evoke late complications, but nevertheless, we should try to minimize the thyroid dose in children, whenever possible.