• KSBB Journal
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• v.20 no.5 s.94
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• pp.363-370
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• 2005

Neural stem cells (NSCs) of the central nervous system (CNS) have raised a great interest not only for their importance in basic neural development but also for their therapeutic potentials in neurologically degenerative diseases such as Parkinson's, Alzheimer and stroke. During the CNS development, two molecular cascades determine specification of midbrain dopamine system. In one pathway, FGF-8, sonic hedgehog and transcription factor Nurr1 specify dopamine neurotransmitter phenotype. In the other, transcription factors $Lm{\times}lb\;and\;Pt{\times}3$ are required for induction of dopaminergic neurons. In Nurr1 knockout mouse, tyrosine hydroxylase (TH) positive cells fail to appear in substantia nigra, indicating that Nurr1 is essential in specification of dopaminergic cell phenotype. In this study, we used the immortalized human NSCs retrovirally transduced with Nurr1 gene to probe the Nurr1 mediated mechanism to induce dopamine phenotype. While Nurr1 over-expression alone did not generate dopamine phenotype in NSCs, applications of retinoid and forskolin induced expression of TH and AADC mRNAs. In addition, co-cultures of Nurr1 expressing NSCs with human astrocytes induced a marked increase of TH expression. In this co-culture system, the addition of retinoid and forskolin dramatically increased expression of TH. These results indicate that the immortalized human NSCs with Nurr1 gene could have a clinical utility for cell replacement for the Parkinson patients.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.5
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• pp.373-384
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• 2001

Cellular proliferation is an intricately regulated process mediated by the coordinated interactions of critical growth control genes. Two of these factors in mammalian cells are the p53 and mdm-2 genes. A protein product of the mem-2 oncogene has been recently shown to associate with the protein encoded by the tumor suppressor gene p53. The p53 tumor suppressor protein is stabilized in response to DNA damage and other stress signals and causes the cell to undergo growth arrest or apoptosis, thus preventing the establishment of mutations in future cellular generations. Mutation or loss of p53 is a very common event in tumor progression. It occurs in about 50% of all tumors analysed including of colon, lung, breast and liver. The cellular mdm-2 gene, which has potential transforming activity that can be activated by overexpression, is amplified in a significant percentage of human sarcoma and in other mammalian tumors. Proteins encoded by the mdm-2 gene are able to bind to the p53 protein and, when overexpressed, can inhibit p53's transcriptional activation function, thus mdm-2 can act as a negative regulator of p53 function. Experimental study was performed to observe the relationship between p53 gene mutation and mdm-2 protein expression and apply the results to the clinical activity. 36 golden syrian hamster each weighing $60{\sim}80g$ were used and painted with 0.5% DMBA by 3 times weekly on the right buccal cheek(experimental side) for 6, 8, 10, 12, 14 and 16 weeks. Left buccal cheek(control side) was treated with mineral oil as the same manner to the right side. The hamsters were sacrificed on the 6, 8, 10, 12, 14 & 16 weeks. Normal and tumor tissues from paraffin block were examined for histology and immunohistochemistry observation, and were completely dissected by microdissection and DNA from both tissue were isolated by proteins K/phenol/chloroform extraction. Segments of the hamster p53 exons 5, 6, 7 and 8 were amplified by PCR using the oligonucleotide primers, and then confirmational change was observed by SSCP respectively. The results were as follows : 1. Dysplasia at 6 weeks, carcinoma in situ at 8 weeks and invasive carcinoma from 10 weeks could be observed in experimental groups. 2. p53 mutations were detected in 10 of the 36(28%) and the exons 6(6 of the 10 : 60%) was the most hot spot area among the highy conserved region(exons 5, 6, 7 & 8). 3. Immunohistochemical study confirmed 22 of the 36(61%) of p53 expression involving 10 of p53 mutations. 4. mdm-2 expression of was showed in 3 of the 36(8%) involving 1 of the 22 of p53 expression and 2 of the 14 of p53 non-expression. From the above results, mutation of p53 gene or expression of p53 protein may have the influence of the DMBA induced carcinoma of hamster buccal pouch but the expression of mdm-2 protein may not have relationship with tumorigenesis.

• Journal of Dental Rehabilitation and Applied Science
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• v.30 no.4
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• pp.278-288
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• 2014

Purpose: The aim of the study was to evaluate preprosthetic initial survival rate and factors associated with survival of osseointegrated implants placed in edentulous area of maxilla and mandible and to suspect the possible causes leading to failure. Materials and Methods: A total of 2158 endosseous implants that had been inserted between 2004 through 2013 were placed in 770 patients. The clinical comparisons were performed to evaluate implant loss in relation to age and gender of patients, position, system, length and diameter of implant, and bone graft technique. Results: According to position, the survival rates were 98.23% in maxillary anterior site, 96.98% in maxillary posterior site, 97.85% in mandibular anterior site and 98.76% in mandibular posterior site (P < 0.05). According to diameter of implant, the survival rates were 100% under 3.0 mm, 97.09% between 3.0 to 3.5 mm, 98.19% between 3.5 to 4.0 mm and 98.29% between 4.0 to 4.5 mm but relatively lower survival rate was 75% in 5.0 mm-over (P < 0.05). The survival rates of implants were 89.51%, 98.28%, 98.34% and 99.27% in the group with isolated sinus graft, with isolated GBR, with sinus graft and GBR simultaneously and without bone graft, especially (P < 0.05). Conclusion: This study establishes a relationship between survival rate of implant and position, diameter of implant system and bone graft technique. In conclusion, there were low survival rates in maxillary posterior site, in dental implants with wide diameter of 5 mm-over, and in the group with isolated sinus graft.

• Tuberculosis and Respiratory Diseases
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• v.71 no.3
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• pp.195-201
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• 2011

Background: Osteopontin (Opn) is recognized as an important adhesive bone matrix protein and a key cytokine involved in immune cell recruitment and tissue repair and remolding. However, serum levels of osteopontin have not been evaluated in patients with chronic obstructive pulmonary disease (COPD). Thus, the aim of this study was to evaluate and compare the serum levels of osteopontin in patients experiencing COPD exacerbations and in patients with stable COPD. Methods: Serum samples were obtained from 22 healthy control subjects, 18 stable COPD patients, and 15 COPD with exacerbation patients. Serum concentrations of osteopontin were measured by the ELISA method. Results: Serum levels of osteopontin were higher in patients with acute exacerbation than with stable COPD and in healthy control subjects ($62.4{\pm}51.9ng/mL$, $36.9{\pm}11.1ng/mL$, $30{\pm}11ng/mL$, test for trend p=0.003). In the patients with COPD exacerbation, the osteopontin levels when the patient was discharged from the hospital tended to decrease compared to those at admission ($45{\pm}52.1ng/mL$, $62.4{\pm}51.9ng/mL$, p=0.160). Osteopontin levels significantly increased according to patient factors, including never-smoker, ex-smoker and current smoker ($23{\pm}5.7ng/mL$, $35.5{\pm}17.6ng/mL$, $58.6{\pm}47.8ng/mL$, test for trend p=0.006). Also, osteopontin levels showed a significantly negative correlation with forced expiratory volume in one second ($FEV_1$%) predicted in healthy controls and stable COPD patients (r=-0.389; p=0.013). C-reactive protein (CRP) was positively correlated with osteopontin levels in patients with COPD exacerbation (r=0.775; p=0.002). Conclusion: The serum levels of osteopontin increased in patients with COPD exacerbation and tended to decrease after clinical improvement. These results suggest the possible role of osteopontin as a biomarker of acute exacerbation of COPD.

• Radiation Oncology Journal
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• v.23 no.1
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• pp.1-8
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• 2005

Purpose : The objective of this study was to determine whether the expressions of the two components of DNA-dependent protein kinase, Ku70 and DNA-PKcs, influence the response to radiotherapy (RT) and outcome of treatment of non-disseminated nasopharyngeal carcinoma (NPC) in patients who received definitive RT. Materials and Methods : Sixty-six patients with NPC who were treated with radiotherapy alone or with concurrent chemotherapy between June 1995 and December 2001 were divided into groups based on the levels of immunoreactivity for Ku70 and DNA-PKcs in pretreatment biopsy specimens. The over-expression of Ku70 or DNA-PKcs groups Included patients whose biopsy specimens showed at least 50% immunopositive tumor cells; patients in which less than 50% of the tumor cells in the biopsy tissues were immunopositive were placed in the low Ku70 and DNA-PKcs groups. The immunoreactivities for Ku70 and DNA-PKcs were retrospectively compared with the sensitivity of the tumor to radiation and the patterns of therapy failure. Univariate analyses were peformed to determine the prognostic factors that influenced locoregional control of NPC. Results : The five-year locoregional control rate was significantly higher in the low Ku70 group (Ku(-)) (85%) than in the high Ku70 group (Ku(+)) (42%) (p=0.0042). However, there were no differences in the metastases-free survival rates between the two groups (Ku70 (+), 82%; Ku70 (-), 78%; p=0.8672). Univariate analysis indicated that the over-expression of Ku70 surpassed other well-known predictive clinocopathologic parameters as an Independent prognostic factor for locoregionai control. Eighteen of 22 patients who had locoregional recurrences of the tumor displayed an over-expression of Ku70. No significant association was found between the level of DNA-PKcs expression and the clinical outcome. Conclusion : Our data suggest that the level of Ku70 expression can be used as a molecular marker to predict the response to RT and the locoregional control after RT and concurrent chemotherapy in patients with non-disseminated NPC.

• Clinical and Experimental Reproductive Medicine
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• v.40 no.3
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• pp.135-140
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• 2013

Objective: To evaluate correlations between serum anti-M${\ddot{u}}$llerian hormone (AMH) levels, phenotypes of polycystic ovary syndrome (PCOS), obesity, and metabolic parameters in patients with PCOS. Methods: A total of 175 patients with PCOS were diagnosed according to the Rotterdam Consensus were included. Exclusion criteria were age over 40, FSH>25 mIU/mL, and 17a-OHP>1.5 ng/mL. The Phenotypes of PCOS were divided into a severe form (oligo-anovulation, ANOV/hyperandrogenism/polycystic ovary morphology [PCOM]; n=59) and a mild form without HA (ANOV/PCOM, n=105). The serum AMH levels were classified into 3 groups (<5 vs. 5-10 vs. >10 ng/mL). Obesity was defined as body mass index (BMI) ${\geq}25kg/m^2$ (n=34). Results: The mean age was $25.9{\pm}5.7$ year and mean AMH level was $10.1{\pm}5.4$ ng/mL. The BMI ($kg/m^2$) was higher in group 1 ($24.2{\pm}6.3$) than in group 2 ($21.9{\pm}4.3$, p=0.046) or group 3 ($21.6{\pm}3.3$, p=0.019). There was no difference among the three groups in age, menstrual interval, antral follicle counts, androgens, or other metabolic parameters. The obesity group showed significantly lower AMH ($7.7{\pm}3.9$ ng/mL vs. $10.7{\pm}5.6$ ng/mL), p=0.004) and low-density lipoprotein levels ($93.1{\pm}21.2$ mg/dL vs. $107.5{\pm}39.3$ mg/dL, p=0.031), and showed higher total T ($0.74{\pm}0.59$ L vs. $0.47{\pm}0.36$ ng/mL, p=0.001), free T ($2.01{\pm}1.9$ vs. $1.04{\pm}0.8$ pg/mL, p=0.0001), and free androgen index ($6.2{\pm}7.9$ vs. $3.5{\pm}3.0$, p=0.003). After controlling for age factors and BMI, the serum AMH levles did not show any significant correlations with other hormonal or metabolic parmeters. Conclusion: For PCOS patients under the age 40, serum AMH is not negatively correlated with age. High serum AMH levels can not predict the phenotype of PCOS and metabolic disturbances in PCOS patients in the non-obese group. Further study might be needed to define the relation more clearly.

• Radiation Oncology Journal
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• v.12 no.3
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• pp.393-399
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• 1994

Spinal cord compression, an oncologic emergency, is a rare complication of hematologic malignancy Our experience was obtained with a series 32 Patients following retrospective analysis for assessing the role of radiation therapy and identifying the prognostic factors affecting on treatment outcome. Diagnosis was usually made by means of radiologic study such as myelography or computerized tomography (CT) or magnetic resonance imaging (MRI) and neurologic examination. Five cases were diagnosed by subjective symptom only with high index of suspicion. In 31 cases, the treatment consisted in radiation therapy alone and the remained one patient had laminectomy before radiation therapy because of diagnostic doubts. Total treatment doses ranged from 800 cGy to 4000 cGy with median of 2000 cGy. Initially large fraction size more than 250 cGy were used in 13 patients with rapidly progressed neurologic deficit. The clinical parameters considered in evaluating the response to treatment were backache, motor-sensory performance and sphincter function. Half of all patients showed good response. Partial response and no response were noted in $37.5\%$ and $12.5\%$, respectively. Our results showed higher response rate than those of other solid tumor series. The degree of neurologic deficit at that time of diagnosis was the most important predictor of treatment outcome. The elapsed time from development of symptoms to start of treatment was significantly affected on the outcome. But histology of primary tumor total dose and use of initial large fraction size were not significantly affect on the outcome. These results confirmed the value of early diagnosis and treatment especially in radiosensitive hematologic malignancy.

• Clinical and Experimental Pediatrics
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• v.45 no.5
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• pp.575-587
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• 2002

Objective : To investigate the understanding of breast-feeding in pregnant woman and the proper way of encouraging breast-feeding. Methods : Each questionnaire included items about demographic characteristics and the understanding of breast-feeding. The questionnaires were filled up by pregnant women visiting obstetric clinics in Seoul and its vicinities, Busan, Choongjoo and Chungjoo from July 2001 to August 2001. One thousand, two hundred ninety questionnaires were analysed by Chi square tests and multiple logistic regressions. Results : The majority of pregnant women(87.4%) planned breast-feeding. Forty three percent of them had plans to breast-feed for 4-6 months. There were no differences in the level of education, the family size and the source of information about breast-feeding in planning to breast-feed (P>0.05). The main reasons for not choosing to breast-feed were returns to work(41.3%), previous failures of breast-feeding(17.4%), concerns about insufficient amount of breast milk(10.9%), breast and nipple problems(10.3%) and maternal illness(9.4%). The average score on the test of the understanding about breast-feeding was 59.7/100. The average scores on the understanding about the methods and advantages of breast-feeding were 45.3/100 and 86.1/100, respectively. The maternal status of employment, previous history of breast-feeding, the time of decision to breastfeed, person advocating breast-feeding and the understanding on the advantages of breast-feeding were significant determinant factors in planning to breast-feed(P<0.05). Conclusion : Pediatricians should take steps to make an effort to increase the breast-feeding rate and to encourage breast-feeding by timely education. Beyond the medical field, political and social supports for breast-feeding are urgently needed.

• Clinical and Experimental Pediatrics
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• v.45 no.5
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• pp.609-614
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• 2002

Purpose : The purpose of our investigation was to explore the natural course, and the factors that influence the natural course, in ostium secundum atrial septal defect(ASD) diagnosed within the first 4 weeks of life. Methods : We studied patients with ASD diagnosed within the first 4 weeks of life during the period from September 1995 to September 1999 in our hospital. The diagnosis and measuring of the size of ASD was carried out by two-dimensional echocardiogram(2DE, Hewlett-Packard Sonos $2500^{(R)}$) from subcostal long and short axis views. Results : There were 61 patients - 29 males and 32 females. According to the size of their defects, we divided them into four groups; group A(less than 4 mm : 24 cases), group B(four mm-six mm : 27 cases), group C(six mm-eight mm : six cases), group D(more than eight mm : four cases). In groups A and B, 22 of 24 patients(91.7%) and 23 of 27 patients(85.2%) had each closed spontaneously. In group C, four of six patients had closed spontaneously. In group D, no patient had closed spontaneously and three of four patients had been closed surgically. There were significant differences in the rate of spontaneous closure between less than six mm group and more than six mm group in the size of the defect(P<0.05). There were no significant differences in the rate of spontaneous closure between ASD combined with simple cardiac defect and isolated secundum ASD. Conclusion : We conclude that defects smaller than six mm in diameter are very likely to close spontaneously.

• Journal of Plant Biotechnology
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• v.33 no.3
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• pp.195-207
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• 2006

Stem cells are the primordial, initial cells which usually divide asymmetrically giving rise to on the one hand self-renewals and on the other hand progenitor cells with potential for differentiation. Zygote (fertilized egg), with totipotency, deserves the top-ranking stem cell - he totipotent stem cell (TSC). Both the ICM (inner cell mass) taken from the 6 days-old human blastocyst and ESC (embryonic stem cell) derived from the in vitro cultured ICM have slightly less potency for differentiation than the zygote, and are termed pluripotent stem cells. Stem cells in the tissues and organs of fetus, infant, and adult have highly reduced potency and committed to produce only progenitor cells for particular tissues. These tissue-specific stem cells are called multipotent stem cells. These tissue-specific/committed multipotent stem cells, when placed in altered environment other than their original niche, can yield cells characteristic of the altered environment. These findings are certainly of potential interest from the clinical, therapeutic perspective. The controversial terminology 'somatic stem cell plasticity' coined by the stem cell community seems to have been proved true. Followings are some of the recent knowledges related to the stem cell. Just as the tissues of our body have their own multipotent stem cells, cancerous tumor has undifferentiated cells known as cancer stem cell (CSC). Each time CSC cleaves, it makes two daughter cells with different fate. One is endowed with immortality, the remarkable ability to divide indefinitely, while the other progeny cell divides occasionally but lives forever. In the cancer tumor, CSC is minority being as few as 3-5% of the tumor mass but it is the culprit behind the tumor-malignancy, metastasis, and recurrence of cancer. CSC is like a master print. As long as the original exists, copies can be made and the disease can persist. If the CSC is destroyed, cancer tumor can't grow. In the decades-long cancer therapy, efforts were focused on the reducing of the bulk of cancerous growth. How cancer therapy is changing to destroy the origin of tumor, the CSC. The next generation of treatments should be to recognize and target the root cause of cancerous growth, the CSC, rather than the reducing of the bulk of tumor, Now the strategy is to find a way to identify and isolate the stem cells. The surfaces of normal as well as the cancer stem cells are studded with proteins. In leukaemia stem cell, for example, protein CD 34 is identified. In the new treatment of cancer disease it is needed to look for protein unique to the CSC. Blocking the stem cell's source of nutrients might be another effective strategy. The mystery of sternness of stem cells has begun to be deciphered. ESC can replicate indefinitely and yet retains the potential to turn into any kind of differentiated cells. Polycomb group protein such as Suz 12 repress most of the regulatory genes which, activated, are turned to be developmental genes. These protein molecules keep the ESC in an undifferentiated state. Many of the regulator genes silenced by polycomb proteins are also occupied by such ESC transcription factors as Oct 4, Sox 2, and Nanog. Both polycomb and transcription factor proteins seem to cooperate to keep the ESC in an undifferentiated state, pluripotent, and self-renewable. A normal prion protein (PrP) is found throughout the body from blood to the brain. Prion diseases such as mad cow disease (bovine spongiform encephalopathy) are caused when a normal prion protein misfolds to give rise to PrP$^{SC}$ and assault brain tissue. Why has human body kept such a deadly and enigmatic protein? Although our body has preserved the prion protein, prion diseases are of rare occurrence. Deadly prion diseases have been intensively studied, but normal prion problems are not. Very few facts on the benefit of prion proteins have been known so far. It was found that PrP was hugely expressed on the stem cell surface of bone marrow and on the cells of neural progenitor, PrP seems to have some function in cell maturation and facilitate the division of stem cells and their self-renewal. PrP also might help guide the decision of neural progenitor cell to become a neuron.