• Title/Summary/Keyword: High-Dose

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STIMULATION OF OSTEOBLASTIC PHENOTYPES BY STRONTIUM IN PERIOSTEAL-DERIVED CELLS (골막기원세포에서 strontium에 의한 조골세포 표현형의 활성)

  • Kim, Shin-Won;Kim, Uk-Kyu;Park, Bong-Wook;Hah, Young-Sool;Cho, Hee-Young;Kim, Jung-Hwan;Kim, Deok-Ryong;Kim, Jong-Ryoul;Joo, Hyun-Ho;Byun, June-Ho
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.32 no.3
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    • pp.199-206
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    • 2010
  • This study investigated the effects of strontium on osteoblastic phenotypes of cultured human periostealderived cells. Periosteal tissues were harvested from mandible during surgical extraction of lower impacted third molar. Periosteal-derived cells were introduced into cell culture. After passage 3, the periostealderived cells were further cultured for 28 days in an osteogenic induction DMEM medium supplemented with fetal bovine serum, ascorbic acid 2-phosphate, dexamethasone and at a density of $3{\times}10^4$ cells/well in a 6-well plate. In this culture medium, strontium at different concentrations (1, 5, 10, and 100 ${\mu}g$/mL) was added. The medium was changed every 3 days during the incubation period. We examined the cellular proliferation, histochemical detection and biochemical measurements of alkaline phosphatase (ALP), the RT-PCR analysis for ALP and osteocalcin, and von Kossa staining and calcium contents in the periostealderived cells. Cell proliferation was not associated with the addition of strontium in periosteal-derived cells. The ALP activity in the periosteal-derived cells was higher in 5, 10, and 100 ${\mu}g$/ml strontium-treated cells than in untreated cells at day 14 of culture. Among the strontium-treated cells, the ALP activity was appreciably higher in 100 ${\mu}g$/ml strontium-treated cells than in 5 and 10 ${\mu}g$/ml strontium-treated cells. The levels of ALP and osteocalcin mRNA in the periosteal-derived cells was also higher in strontium-treated cells than in untreated cells at day 14 of culture. Their levels were increased in a dose-dependent manner. Von Kossa-positive mineralization nodules were strongly observed in the 1 ${\mu}g$/ml strontium-treated cells at day 21 and 28 of culture. The calcium content in the periosteal-derived cells was also higher in 1 ${\mu}g$/ml strontium-treated cells at day 28 of culture. These results suggest that low concentration of strontium stimulates the osteoblastic phenotypes of more differentiated periosteal-derived cells, whereas high concentration of strontium stimulates the osteoblastic phenotypes of less differentiated periosteal-derived cells. The effects of strontium on osteoblastic phenotypes of periosteal-derived cells appear to be associated with differentiation-extent.

Accuracy of Spirometry at Predicting Restrictive Pulmonary Impairment (제한성 환기장애의 진단에서 폐활량검사의 정확성)

  • Ahn, Young Mee;Koh, Won-Jung;Kim, Cheol Hong;Lim, Seong Yong;An, Chang Hyeok;Suh, Gee Young;Chung, Man Pyo;Kim, Hojoong;Kwon, O Jung
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.3
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    • pp.330-337
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    • 2003
  • Background : Low spirometric forced vital capacity(FVC) in conjunction with a normal or high ratio of the forced expiratory volume at 1 second to the forced vital capacity($FEV_1$/FVC%) has traditionally been classified as a restrictive abnormality. However, the gold-standard diagnosis of a restrictive pulmonary impairment requires a measurement of the total lung capacity (TLC). This study was performed to determine the predictive value of spirometric measurements of the FVC for diagnosing a restrictive pulmonary abnormality. Methods : Test results from 1,371 adult patients who undertook both spirometry and lung volume measurements on the same visit from January 1999 to December 2000 were enrolled in this study. The test values for the FVC, the TLC that was below 80% of predicted value, and a $FEV_1$/FVC% that was below 70%, were classified as being abnormal. Results : Of the 1,371 patients, 353 patients had a reduced a FVC. Of these patients, 186 patients had a reduced TLC. Therefore, the positive predictive value was 52.7%. Of the 196 patients with a normal $FEV_1$/FVC% and a reduced FVC, 148(75.5%) patients had a lower TLC. Thirty eight (24.2%) patients out of 157 patients with a low $FEV_1$/FVC% and a low FVC showed a restrictive defect. Conclusion : Spirometry is useful to rule out a restrictive pulmonary abnormality, but a restrictive pattern on the spirometry dose not mean there is a true restrictive disease. For the patients with a low FVC, TLC measurements are essential for diagnosing a restrictive pulmonary impairment.

Concurrent Docetaxel/Cisplatin and Thoracic Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer (국소 진행성 비소세포 폐암에서 Docetaxel Cisplatin을 사용한 화학-방사선 동시치료의 효과)

  • Jang, Tae Won;Park, Jung Pil;Kim, Hee Kyoo;Ok, Chul Ho;Jeung, Tae Sig;Jung, Maan Hong
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.3
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    • pp.257-264
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    • 2004
  • Background : There are many combinations of treatment for locally advanced non-small cell lung cancer (NSCLC). Recent studies have showed the efficacy of concurrent chemoradiotherapy (CCRT) in NSCLC. At present, however, there is no consensus about the optimal dosages and timing of radiation and chemotherapeutic agents. The aims of study were to determine the feasibility, toxicity, response rate, and survival rate in locally advanced NSCLC patients treated with doxetaxel and cisplatin based CCRT. Method : Sixteen patients with unresectable stage III NSCLC were evaluated from May 2000 until September 2001. Induction chemoradiotherapy consisted of 3 cycles of docetaxel (75 $mg/m^2/IV$ on day 1) and cisplatin (60 $mg/m^2/IV$ on day 1) chemotherapy every 3 weeks and concomitant hyperfractionated chest irradiation (1.15 Gy/BID, total dose of 69 Gy) in 6 weeks. Patient who had complete or partial response, and stable disease were applied consolidation chemotherapy of docetaxel and cisplatin. Results : All patients showed response to CCRT. Four patients achieved complete response (25%), partial responses in 12 patients (75%). The major common toxicities were grade III or more of neutropenia (87.3%), grade III esophagitis (68.8%), pneumonia (18.8%) and grade III radiation pneumonitis (12.5%). Thirteen patients were ceased during follow-up period. Median survival time was 19.9 months (95% CI; 4.3-39.7 months). The survival rates in one, two, and three years are 68.7%, 43.7%, and 29.1%, respectively. Local recurrence was found in 11 patients (66.8%), bone metastasis in 2, and brain metastasis in 1 patient. Conclusion : The response rate and survival time of CCRT with docetaxel/cisplatin in locally advanced NSCLC were encouraging, but treatment related toxicities were high. Further modification of therapy seems to be warranted.

Feasibility of Automated Detection of Inter-fractional Deviation in Patient Positioning Using Structural Similarity Index: Preliminary Results (Structural Similarity Index 인자를 이용한 방사선 분할 조사간 환자 체위 변화의 자동화 검출능 평가: 초기 보고)

  • Youn, Hanbean;Jeon, Hosang;Lee, Jayeong;Lee, Juhye;Nam, Jiho;Park, Dahl;Kim, Wontaek;Ki, Yongkan;Kim, Donghyun
    • Progress in Medical Physics
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    • v.26 no.4
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    • pp.258-266
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    • 2015
  • The modern radiotherapy technique which delivers a large amount of dose to patients asks to confirm the positions of patients or tumors more accurately by using X-ray projection images of high-definition. However, a rapid increase in patient's exposure and image information for CT image acquisition may be additional burden on the patient. In this study, by introducing structural similarity (SSIM) index that can effectively extract the structural information of the image, we analyze the differences between daily acquired x-ray images of a patient to verify the accuracy of patient positioning. First, for simulating a moving target, the spherical computational phantoms changing the sizes and positions were created to acquire projected images. Differences between the images were automatically detected and analyzed by extracting their SSIM values. In addition, as a clinical test, differences between daily acquired x-ray images of a patient for 12 days were detected in the same way. As a result, we confirmed that the SSIM index was changed in the range of 0.85~1 (0.006~1 when a region of interest (ROI) was applied) as the sizes or positions of the phantom changed. The SSIM was more sensitive to the change of the phantom when the ROI was limited to the phantom itself. In the clinical test, the daily change of patient positions was 0.799~0.853 in SSIM values, those well described differences among images. Therefore, we expect that SSIM index can provide an objective and quantitative technique to verify the patient position using simple x-ray images, instead of time and cost intensive three-dimensional x-ray images.

Development of Manual Multi-Leaf Collimator for Proton Therapy in National Cancer Center (국립암센터의 양성자 치료를 위한 수동형 다엽 콜리메이터 개발)

  • Lee, Nuri;Kim, Tae Yoon;Kang, Dong Yun;Choi, Jae Hyock;Jeong, Jong Hwi;Shin, Dongho;Lim, Young Kyung;Park, Jeonghoon;Kim, Tae Hyun;Lee, Se Byeong
    • Progress in Medical Physics
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    • v.26 no.4
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    • pp.250-257
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    • 2015
  • Multi-leaf collimator (MLC) systems are frequently used to deliver photon-based radiation, and allow conformal shaping of treatment beams. Many proton beam centers currently make use of aperture and snout systems, which involve use of a snout to shape and focus the proton beam, a brass aperture to modify field shape, and an acrylic compensator to modulate depth. However, it needs a lot of time and cost of preparing treatment, therefore, we developed the manual MLC for solving this problem. This study was carried out with the intent of designing an MLC system as an alternative to an aperture block system. Radio-activation and dose due to primary proton beam leakage and the presence of secondary neutrons were taken into account during these iterations. Analytical calculations were used to study the effects of leaf material on activation. We have fabricated tray model for adoption with a wobbling snout ($30{\times}40cm^2$) system which used uniform scanning beam. We designed the manual MLC and tray and can reduce the cost and time for treatment. After leakage test of new tray, we upgrade the tray with brass and made the safety tool. First, we have tested the radio-activation with usually brass and new brass for new manual MLC. It shows similar behavior and decay trend. In addition, we have measured the leakage test of a gantry with new tray and MLC tray, while we exposed the high energy with full modulation process on film dosimetry. The radiation leakage is less than 1%. From these results, we have developed the design of the tray and upgrade for safety. Through the radio-activation behavior, we figure out the proton beam leakage level of safety, where there detects the secondary particle, including neutron. After developing new design of the tray, it will be able to reduce the time and cost of proton treatment. Finally, we have applied in clinic test with original brass aperture and manual MLC and calculated the gamma index, 99.74% between them.

Micro-CT System for Small Animal Imaging (소동물영상을 위한 마이크로 컴퓨터단층촬영장치)

  • Nam, Ki-Yong;Kim, Kyong-Woo;Kim, Jae-Hee;Son, Hyun-Hwa;Ryu, Jeong-Hyun;Kang, Seoung-Hoon;Chon, Kwon-Su;Park, Seong-Hoon;Yoon, Kwon-Ha
    • Progress in Medical Physics
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    • v.19 no.2
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    • pp.102-112
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    • 2008
  • We developed a high-resolution micro-CT system based on rotational gantry and flat-panel detector for live mouse imaging. This system is composed primarily of an x-ray source with micro-focal spot size, a CMOS (complementary metal oxide semiconductor) flat panel detector coupled with Csl (TI) (thallium-doped cesium iodide) scintillator, a linearly moving couch, a rotational gantry coupled with positioning encoder, and a parallel processing system for image data. This system was designed to be of the gantry-rotation type which has several advantages in obtaining CT images of live mice, namely, the relative ease of minimizing the motion artifact of the mice and the capability of administering respiratory anesthesia during scanning. We evaluated the spatial resolution, image contrast, and uniformity of the CT system using CT phantoms. As the results, the spatial resolution of the system was approximately the 11.3 cycles/mm at 10% of the MTF curve, and the radiation dose to the mice was 81.5 mGy. The minimal resolving contrast was found to be less than 46 CT numbers on low-contrast phantom imaging test. We found that the image non-uniformity was approximately 70 CT numbers at a voxel size of ${\sim}55{\times}55{\times}X100\;{\mu}^3$. We present the image test results of the skull and lung, and body of the live mice.

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Changes in platelet counts caused by valproate in children with epilepsy (소아 간질 환자에서 valproate 투여 후 혈소판 수의 변화)

  • We, Ju Hee;Kim, Young Mi;Nam, Sang Ook
    • Clinical and Experimental Pediatrics
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    • v.52 no.1
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    • pp.75-80
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    • 2009
  • Purpose : In adults, valproate (VPA) has been reported to be associated with thrombocytopenia. However, few studies have investigated this association in children, and the factors affecting platelet counts remain controversial. This study was undertaken to investigate changes in platelet counts following VPA therapy and related factors in children with epilepsy. Methods : Our subjects comprised 75 epileptic children who had received VPA monotherapy for at least 1 year between January 2000 and December 2005. We regularly examined platelet counts at intervals of 6 to 12 months after baseline platelet counts before VPA treatment. We analyzed changes in platelet counts according to several factors such as sex, seizure type, underlying causes of epilepsy, age at the start of medication as well as at the last follow up, duration of VPA administration, VPA dose, serum VPA level, and body weight at the last follow up. Results : Overall, the platelet counts decreased significantly after VPA therapy. The average baseline platelet count was $312.5{\pm}109.1{\times}10^6/mL$. At the last follow up, the average platelet count was $261.7{\pm}72.2{\times}10^6/mL$. We observed the relationship between platelet counts and serum levels of VPA; while children with serum VPA <$75{\mu}g/mL$ showed no change in platelet counts (P=0.102), children with serum VPA >$75{\mu}g/mL$ showed a significant decrease in platelet counts. Conclusion : VPA may cause a significantly decreased platelet count in children with epilepsy. High serum VPA levels were associated with development of thrombocytopenia.

Dependence Potential of the Synthetic Cannabinoids JWH-073, JWH-081, and JWH-210: In Vivo and In Vitro Approaches

  • Cha, Hye Jin;Lee, Kwang-Wook;Song, Min-Ji;Hyeon, Yang-Jin;Hwang, Ji-Young;Jang, Choon-Gon;Ahn, Joon-Ik;Jeon, Seol-Hee;Kim, Hyun-Uk;Kim, Young-Hoon;Seong, Won-Keun;Kang, Hoil;Yoo, Han Sang;Jeong, Ho-Sang
    • Biomolecules & Therapeutics
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    • v.22 no.4
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    • pp.363-369
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    • 2014
  • Synthetic cannabinoids (CBs) such as the JWH series have caused social problems concerning their abuse liability. Because the JWH series produces euphoric and hallucinogenic effects, they have been distributed illegally under street names such as "Spice" and "Smoke". Many countries including Korea have started to schedule some of the JWH series compounds as controlled substances, but there are a number of JWH series chemicals that remain uncontrolled by law. In this study, three synthetic CBs with different binding affinities to the $CB_1$ receptor (JWH-073, 081, and 210) and ${\Delta}^9$-tetrahydrocannabinol (${\Delta}^9$-THC) were evaluated for their potential for psychological dependence. The conditioned place preference test (unbiased method) and self-administration test (fixed ratio of 1) using rodents were conducted. $K_i$ values of the three synthetic cannabinoids were calculated as supplementary data using a receptor binding assay and overexpressed $CB_1$ protein membranes to compare dependence potential with $CB_1$ receptor binding affinity. All mice administered JWH-073, 081, or 210 showed significantly increased time spent at unpreferred space in a dose-dependence manner in the conditioned place preference test. In contrast, all tested substances except ${\Delta}^9$-THC showed aversion phenomenon at high doses in the conditioned place preference test. The order of affinity to the $CB_1$ receptor in the receptor binding assay was JWH-210 > JWH-081 >> JWH-073, which was in agreement with the results from the conditioned place preference test. However, no change in self-administration was observed. These findings suggest the possibility to predict dependence potential of synthetic CBs through a receptor binding assay at the screening level.

Characteristics of Kawasaki Disease Patients who are Unresponsive to High-dose Intravenous Immunoglobulin Therapy (가와사끼병에서 정맥용 면역글로불린 불응군의 특성)

  • Kook, Dong-Hyuk;Ko, Yong-Min;Lee, Keun-Young;Kim, Dong-Un;Lee, Kyung-Yil;Lee, Joon-Sung
    • Pediatric Infection and Vaccine
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    • v.15 no.2
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    • pp.180-187
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    • 2008
  • Purpose : We wanted to determine the characteristics of patients with Kawasaki disease (KD) who were unresponsive to intravenous immunoglobulin (IVIG). Methods : The patients with KD were divided into two groups: the IVIG responsive group (25 cases) and the IVIG unresponsive group (14 cases). We analyzed various parameters before and after the administration of IVIG, including the complete blood cell count with the differential count (%), the erythrocyte segmentation rate (ESR), the C-reactive protein (CRP) level and the protein and lipid profiles. Results : The IVIG unresponsive group had a prolonged duration of fever and a higher incidence of CAL compared to the IVIG responsive group (P<0.001, respectively). Before IVIG infusion, the neutrophil differential, the ESR and the CRP values were higher (P<0.001), and the total protein and albumin values were lower in the IVIG unresponsive group (P=0.01) compared to the IVIG responsive group. After IVIG infusion, there were no significant changes in the WBC count and CRP levels in the IVIG unresponsive group. The reduction of the HDL-cholesterol levels by IVIG was more significant in the unresponsive group (P=0.02). Conclusion : A more severe and prolonged inflammatory response occurred in the IVIG unresponsive group at an early stage, and this finding can be detected by such inflammatory parameters as the neutrophil count and the CRP and HDL-cholesterol levels after IVIG infusion.

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Effects of Herbal Complex on Blood Glucose in Streptozotocin-induced Diabetic Rats and in Mice Model of Metabolic Syndrome (생약복합제의 Streptozotocin 유발 당뇨 및 대사성증후군 모델 동물에서의 혈당에 미치는 효과)

  • Park, Han-Seok;Lee, Yeon-Sil;Choi, Se-Jin;Kim, Jin-Kyu;Lee, Yun-Lyul;Kim, Hyun-Gwen;Koo, Sam-Hoi;Ku, Dae-Hoy;Ki, Seung-Il;Lim, Soon-Sung
    • Korean Journal of Pharmacognosy
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    • v.40 no.3
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    • pp.196-204
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    • 2009
  • This study was carried out to investigate the in vivo and in vitro inhibitory effect of a traditional herbal complex (HC) extract prepared from a mixture of four oriental herbs (Dioscorea Rhizoma, Glycine soja Sieb. et Zucc, Bombycis corpus, Fermented Glycine soja) that have been widely used for the treatment and prevention of diabetes mellitus on hyperglycemia. The water extract of HC showed potent inhibitory effect on $\alpha$-glucosidase with $IC_{50}$ value of 1.24 mg/mL. Additionally, the ethanol extract of HC was also found to exhibit significant inhibitory effect against protein tyrosine phosphatase $1{\beta}$ ($PTP1{\beta}$), which is known as a major regulator of both insulin and leptin signaling. In the $PTP1{\beta}$ inhibitory assay, the most active n-hexane fraction obtained from the ethanol extract of HC, was identified as a mixture of fatty acid derivatives by gas chromatography-mass spectrometry (GC-MS). In high-fat diet-low dose streptozotocin (STZ)-induced diabetic rat, the water extract of HC improved the oral glucose intolerance as compared with rosiglitazone. HC also caused a marked decrease of body weight and fasting blood glucose and a significant improvement on glucose tolerance in metabolic syndrome mice model. These findings support that this traditional HC may be useful in the control of blood glucose in diabetes mellitus and metabolic syndrome.