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An Analysis on Factors Affecting Local Control and Survival in Nasopharvngeal Carcinoma (비인두암의 국소 종양 치유와 생존율에 관한 예후 인자 분석)

  • Chung Woong-Ki;Cho Jae-Shik;Park Seung Jin;Lee Jae-Hong;Ahn Sung Ja;Nam Taek Keun;Choi Chan;Noh Young Hee;Nah Byung Sik
    • Radiation Oncology Journal
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    • v.17 no.2
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    • pp.91-99
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    • 1999
  • Propose : This study was performed to find out the prognostic factors affecting local control, survival and disease free survival rate in nasopharyngeal carcinomas treated with chemotherapy and radiation therapy. Materials and Methods : We analysed 47 patients of nasopharyngeal carcinomas, histologically confirmed and treated at Chonnam University Hospital between July 1986 and June 1996, retrospectively. Range of patients' age were from 16 to 80 years (median; 52 years). Thirty three (70$\%$) patients was male. Histological types were composed of 3 (6$\%$) keratinizing, 30 (64$\%$) nonkeratinizing squamous cell carcinoma and 13 (28$\%$) undifferentiated carcinoma. Histoiogicai type was not known in 1 patient (2$\%$). We restaged according to the staging system of 1997 American Joint Committee on Cancer Forty seven patients were recorded as follows: 71: 11 (23$\%$), T2a; 6 (13$\%$), T2b; 9 (19$\%$), 73; 7 (15$\%$), 74: 14 (30$\%$), and NO; 7 (15$\%$), Nl: 14 (30$\%$), N2; 21 (45%), N3: 5 (10%). Clinical staging was grouped as follows: Stage 1; 2 (4$\%$), IIA: 2 (4$\%$), IIB; 10 (21$\%$), III; 14 (30$\%$), IVA; 14 (30$\%$) and IVB; 5 (11$\%$). Radiation therapy was done using 6 MV and 10 MV X- ray of linear accelerator. Electron beam was used for the Iymph nodes of posterior neck after 4500 cGy. The range of total radiation dose delivered to the primary tumor was from 6120 to 7920 cGy (median; 7020 cGy). Neoadjuvant chemotherapy was performed with cisplatin +5-fluorouracil (25 patients) or cisplatin+pepleomycin (17 patients) with one to three cycles. Five patients did not received chemotherapy. Local control rate, survival and disease free suwival rate were calculated by Kaplan-Meier method. Generalized Wilcoxon test was used to evaluate the difference of survival rates between groups. multivariate analysis using Cox proportional hazard model was done for finding prognostic factors. Results: Local control rate was 81$\%$ in 5 year. Five year survival rate was 60$\%$ (median survival; 100 months). We included age, sex, cranial nerve deflicit, histologic type, stage group, chemotherapy, elapsed days between chemotherapy and radiotherapy, total radiation dose, period of radiotherapy as potential prognostic factors in multivariate analysis. As a result, cranial none deficit (P=0.004) had statistical significance in local control rate. Stage group and total radiation dose were significant prognostic factors in survival (P=0.000, P=0.012), and in disease free survival rates (P=0.003, P=0.008), respectively. Common complications were xerostomia, tooth and ear problems. Hypothyroidism was developed in 2 patients. Conclusion : In our study, cranial none deficit was a significant prognostic factor in local control rate, and stage group and total radiation dose were significant factors in both survival and disease free survival of nasopharyngeal carcinoma. We have concluded that chemotherapy and radiotherapy used in our patients were effective without any serious complication.

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Division of the N2 Stage According to the Multiplicity of the Involved Nodal Stations May be Necessary in the N2-NSCLC Patients Who are Treated with Postoperative Radiotherapy (비소세포성 폐암으로 수술 후 방사선치료가 시행된 N2병기 환자들에서 다발 부위 종격동 림프절 전이 여부에 따른 N2병기 구분의 임상적 의미)

  • Yoon, Hong-In;Kim, Yong-Bae;Lee, Chang-Geol;Lee, Ik-Jae;Kim, Song-Yih;Kim, Jun-Won;Kim, Joo-Hang;Cho, Byung-Chul;Lee, Jin-Gu;Chung, Kyung-Young
    • Radiation Oncology Journal
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    • v.27 no.3
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    • pp.126-132
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    • 2009
  • Purpose: We wanted to evaluate the prognostic factors for the pathologic N2 non-small cell lung cancer (NSCLC) patients who were treated by postoperative radiotherapy. Materials and Methods: We retrospectively reviewed 112 pN2 NSCLC patients who underwent surgery and postoperative radiotherapy (PORT) From January 1999 to February 2008. Seventy-five (67%) patients received segmentectomy or lobectomy and 37 (33%) patients received pneumonectomy. The resection margin was negative in 94 patients, and it was positive or close in 18 patients. Chemotherapy was administered to 103 (92%) patients. Nine (8%) patients received PORT alone. The median radiation dose was 54 Gy (range, 45 to 66), and the fraction size was 1.8~2 Gy. Results: The 2-year overall survival (OS) rate was 60.2% and the disease free survival (DFS) rate was 44.7% for all the patients. Univariate analysis showed that the patients with multiple-station N2 disease had significantly reduced OS and DFS (p=0.047, p=0.007) and the patients with an advanced T stage ($\geq$T3) had significantly reduced OS and DFS (p<0.001, p=0.025). A large tumor size ($\geq$5 cm) and positive lymphovascular invasion reduced the OS (p=0.035, 0.034). Using multivariate analysis, we found that multiple-station N2 disease and an advanced T stage ($\geq$T3) significantly reduced the OS and DFS. Seventy one patients (63.4%) had recurrence of disease. The patterns of failure were loco-regional in 23 (20.5%) patients, distant failure in 62 (55.4%) and combined loco-regional and distant failure in 14 (12.5%) patients. Conclusion: Multiple involvement of mediastinal nodal stations for the pN2 NSCLC patients with PORT was a poor prognostic factor in this study. A prospective study is necessary to evaluate the N2 subclassification and to optimize the adjuvant treatment.

Effect of Eddy on the Cycle of 210Po and 234 in the central Region of Korean East Sea (동해 중부해역에서 210Po과 234Th의 순환에 대한 소용돌이의 영향)

  • YANG, HAN SOEB;KIM, SOUNG SOO;LEE, JAE CHUL
    • 한국해양학회지
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    • v.30 no.4
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    • pp.279-287
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    • 1995
  • The vertical profiles of natural 210Pb, 210Po and 234Th activities were measured for the upper 100 m of water column at three stations in the middle region of the Korean East Sea during May 1992. And the distribution of these radionuclides was discussed associated with the formation of warm eddy or water mass. The main thermocline was maintained between the depth of 50 and 100 m at the southern station (Sta. A1), and between the depth of 10 to 50 m at the coastal station of Sockcho (Sta. B10). Contrastingly, a main thermocline at Sta. A10, which locates near the center of warm eddy, was observed below 230 m depth. Between 50 and 220 m depth of Sta. A10 is there a relatively homogeneous water mass of 10.1${\pm}$0.5$^{\circ}C$, which is significantly higher in temperature and lower in nutrient than the other two stations. It seems to be due to sinking of the warm surface water in which nutrients were completely consumed. Both 210Pb and 210Po show the highest concentration at Sta. A1 and the lowest at Sta. B10 among the three stations. Also, the 210Pb activity is generally higher in the upper layer than in the lower layer, while 210Po activity represents the reversed pattern at all three stations. At Sta. A1 and Sta. B10, the activities of 210Po relative to its parent 210Pb were deficient in the water column above the main thermocline, but were excess below the thermocline. However, the station near the center of warm eddy(Sta. A10), shows no excess of 210Po in the depths below 50 m, although its defficiency is found in the upper layer like the other stations. At Sta. A1 and b10. 234Th activities are slightly lower in the surface mixed layer than in the deeper region However, at Sta. A10, 234Th activity in the upper 30 m is higher than below 50 m or in the same depth of the other stations, probably because of the high concentration of particulate matter. The residence time of 210Po in the surface mixed layer at Sta. A10 is 0.4 year, much shorter than at the other two stations(about one year). Above 100 m depth, the residence times of 234Th range from 18 to 30 other two stations(about on year). Above 100 m depth, the residence times of 234Th range from 18 to 30 days at all stations, without significant regional variation. The percentages of recycled 210Po within the thermocline are 39% and 92% at Sta. A1 and Sta. B10, respectively. Much higher value at Sta. B10 may be due to a thin thickness of the mixed layer as well as the slower recycling rate of 210Po in the main thermocline.

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Referral Patterns and Needs for Specialist Care among Patient Referred from Health Center (보건소의 진료의뢰 양상과 의뢰환자들의 전문과목 요구도)

  • Hwang, Tae-Yoon;Kim, Chang-Yoon;Kang, Pock-Soo
    • Journal of Preventive Medicine and Public Health
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    • v.29 no.1 s.52
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    • pp.133-143
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    • 1996
  • This study was conducted to assess the referral patterns to specialist from general practitioners in health center and perceived needs of referred patients for specialist care in health center. The study subjects were 249 patients who visited to health centers and were referred to other medical facilities. The data were obtained from questionnaire survey which was conducted in Kyongju-City Health Center, Seongju-Gun Health Center and Koryong-Gun Health Center in Kyongsangbuk-Do, from June 10 to October 17, 1995. The total referral rate was 2.7%. The proportion of patients who wished to be referred to medical specialists was 85.9%, and the proportion of patients referred by general practitioners in health centers was 14.1%. Among the patients who wished to be referred to medical specialists, 45.9% visited directly to health centers, 34.6% visited health centers via local clinics and 19.5% visited health centers to get referral permission only. The reasons for getting referral permission in health centers were easy geographical accessibility(34.6%), easy to get referral permission in health centers(27.1%), and very difficult to get referral permission in local clinics(16.4%). Among the diseases of referred patients, diseases of the musculoskeletal system and connective tissue were most prevalent on a whole, but diseases of nervous system and sensory organs were comparatively high among the patients who wished to be referred to medical specialists and infectious and parasitic diseases were comparatively high among the patients referred by general practitioners in health centers. The most favorable medical facility was general hospital including university hospital in both groups of patients who wished to be referred to medical specialist and the patient referred by general practitioners in health centers. Regarding the needs for specialist care in health center, 75.2% of patients who wished to be referred to medical specialists and 74.3% of patients referred by general practitioners in health center wanted the specialist care. The most frequently requested specialty is internal medicine(47.1%), and then orthopedics and general surgery. Based on above results, this study revealed that the majority of patients referred from health center wished to be referred to medical specialists at their own will, so, referral system at health center level should be changed. And if specialist care in health center be provided, the medical care by internist could be provided first, and then that of orthopedics and general surgery could be provided. These kinds of medical cares could be covered by local clinicians as a part-time job on a voluntary basis.

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Image Quality Evaluation of CsI:Tl and Gd2O2S Detectors in the Indirect-Conversion DR System (간접변환방식 DR장비에서 CsI:Tl과 Gd2O2S의 검출기 화질 평가)

  • Kong, Changgi;Choi, Namgil;Jung, Myoyoung;Song, Jongnam;Kim, Wook;Han, Jaebok
    • Journal of the Korean Society of Radiology
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    • v.11 no.1
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    • pp.27-35
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    • 2017
  • The purpose of this study was to investigate the features of CsI:Tl and $Gd_2O_2S$ detectors with an indirect conversion method using phantom in the DR (digital radiography) system by obtaining images of thick chest phantom, medium thickness thigh phantom, and thin hand phantom and by analyzing the SNR and CNR. As a result of measuring the SNR and CNR according to the thickness change of the subject, the SNR and CNR were higher in CsI:Tl detector than in $Gd_2O_2S$ detector when the medium thickness thigh phantom and thin hand phantom were scanned. However, when the thick chest phantom was used, for the SNR at 80~125 kVp and the CNR at 80~110 kVp in the $Gd_2O_2S$ detector, the values were higher than those of CsI:Tl detector. The SNR and CNR both increased as the tube voltage increased. The SNR and CNR of CsI:Tl detector in the medium thickness thigh phantom increased at 40~50 kVp and decreased as the tube voltage increased. The SNR and CNR of $Gd_2O_2S$ detector increased at 40~60 kVp and decreased as the tube voltage increased. The SNR and CNR of CsI:Tl detctor in the thin hand phantom decreased at the low tube voltage and increased as the tube voltage increased, but they decreased again at 100~110 kVp, while the SNR and CNR of $Gd_2O_2S$ detector were found to decrease as the tube voltage increased. The MTF of CsI:Tl detector was 6.02~90.90% higher than that of $Gd_2O_2S$ detector at 0.5~3 lp/mm. The DQE of CsI:Tl detector was 66.67~233.33% higher than that of $Gd_2O_2S$ detector. In conclusion, although the values of CsI:Tl detector were higher than those of $Gd_2O_2S$ detector in the comparison of MTF and DQE, the cheaper $Gd_2O_2S$ detector had higher SNR and CNR than the expensive CsI:Tl detector at a certain tube voltage range in the thick check phantom. At chest X-ray, if the $Gd_2O_2S$ detector is used rather than the CsI:Tl detector, chest images with excellent quality can be obtained, which will be useful for examination. Moreover, price/performance should be considered when determining the detector type from the viewpoint of the user.

The Effects of Cattle Slurry Application and Mixed Sowing with legumes on Productivity and Feed Values of Barley and Rye (액상우분뇨와 콩과식물 혼파재배가 보리, 호밀의 생산성과 사료가치에 미치는 영향)

  • Jo, IK-Hwan
    • Korean Journal of Organic Agriculture
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    • v.17 no.3
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    • pp.371-380
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    • 2009
  • This study was conducted to assess effects of supplying different types of nitrogen sources as fertilizers on productivity and feed values of barley and rye as winter forage crops, and ultimately done to get good quality of organic forages with higher fertilization of soil. For barley, N+P+K plots were significantly (P<0.05) higher in annual dry matter (DM) and total digestible nutrients (TDN) yields than other plots. However, cattle manure plots had significantly (P<0.05) higher annual DM and TDN than P+K and non-fertilizer plots. Plots of 50%-cattle manure and mixed sowing with hairy vetch or forage pea were higher than only 50%-cattle manure plot, particularly, these were significantly higher than non-fertilizer, and their crude protein (CP) yields were much higher than other plots. Crude protein contents were significantly higher in N+P+K and 50%-cattle manure slurry plots than non-fertilizer and P+K plots, and plots of mixed sowing with hairy vetch or forage pea in application of 50%-cattle manure had higher CP content than other plots. ADF content was lowest in 50%-cattle manure+forage pea plots, but highest in 100%-cattle manure plots. NDF content was lowest in legumes-mixed sowing, but highest in 100%-cattle manure plots. TDN content was the highest in forage pea plots, and plots of 50%-cattle manure and legumes-mixed sowing had high RFV, but cattle manure plots rich in ADF and NDF content had the lowest TDN and RFV. For rye, plots of 50%-cattle manure+hairy vetch mixed sowing, and N+P+K application had significantly higher annual DM, CP and TDN than other plots except for cattle manure. DM productive efficiency to nitrogen fertilization was markedly higher for cattle manure plots than for chemical fertilizer. This tendency was more conspicuous in plots of 50% cattle manure+legumes-mixed sowing. CP content was higher for N+P+K plot than for all plots, and plots of 50%-cattle manure + legumes-mixed sowing were significantly higher than other plots. On the contrary, forage pea-mixed sowing plot had the lowest ADF and NDF, but TDN and RFV were significantly (P<0.05) higher than other plots. Grass crop cultivation together with legumes by applying livestock manure to soil may lead to higher palatability of livestock, and better quality of forage. Furthermore, cattle manure application increased production yield per ha and CP contents. Thus, when applying forage crops produced by cattle manure application and mixed sowing to organic livestock production, it was conceived that forages produced might become a substitute for foreign organic grain as protein sources.

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Early and Mid-term Results of Operation for Infective Endocarditis on Mitral Valve (감염성 승모판 심내막염의 중단기 수술 성적)

  • Ahn, Byong-Hee;Chun, Joon-Kyung;Yu, Ung;Ryu, Sang-Wan;Choi, Yong-Sun;Kim, Byong-Pyo;Hong, Sung-Bum;Bum, Min-Sun;Na, Kook-Ju;Park, Jong-Chun;Kim, Sang-Hyung
    • Journal of Chest Surgery
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    • v.37 no.1
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    • pp.27-34
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    • 2004
  • Background: Infective endocarditis shows higher operative morbidity and mortality rates than other cardiac diseases. The vast majority of studies on infective endocarditis have been made on aortic endocarditis, with little attention having been paid to infective endocarditis on the mitral valve. This study attempts to investigate the clinical aspects and operative results of infective endocarditis on the mitral valve. Meterial and Method: The subjects of this study consist of 23 patients who underwent operations for infective endocariditis on the mitral valve from June 1995 to May 2003. Among them, 2 patients suffered from prosthetic valvular endocarditis and the other 21 from native valvular endocarditis. The subjects were evenly distributed age-wise with an average age of 44.8$\pm$15.7 (11∼66) years. Emergency operations were performed on seventeen patients (73.9%) due to large vegetation or instable hemodynamic status. In preoperative examinations, twelve patients exhibited congestive heart failure, four patients renal failure, two patients spleen and renal infarction, and two patients temporary neurological defects, while one patient had a brain abscess. Based on the NYHA functional classification, seven patients were determined to be at Grade II, 9 patients at Grade III, and 6 patients at Grade IV. Vegetations were detected in 20 patients while mitral regurgitation was dominant in 19 patients with 4 patients showing up as mitral stenosis dominant on the preoperative echocardiogram. Blood cultures for causative organisms were performed on all patients, and positive results were obtained from ten patients, with five cases of Streptococcus viridance, two cases of methicillin-sensitive Staphylococcus aureus, and one case each of Corynebacteriurn, Haemophillis, and Gernella. Operations were decided according to the AA/AHA guidelines (1988). The mean follow-up period was 27.6 $\pm$23.3 (1 ∼ 97) months. Result: Mitral valve replacements were performed on 43 patients, with mechanical valves being used on 9 patients and tissue valves on the other 4. Several kinds of mitral valve repair or mitral valvuloplasty were carried out on the remaining 10 patients. Associated procedures included six aortic valve replacements, two tricuspid annuloplasty, one modified Maze operation, and one direct closure of a ventricular septal defect. Postoperative complications included two cases of bleeding and one case each of mediastinitis, low cardiac output syndrome, and pneumonia. There were no cases of early deaths, or death within 30 days following the operation. No patient died in the hospital or experienced valve related complications. One patient, however, underwent mitral valvuloplasty 3 months after the operation. Another patient died from intra-cranial hemorrhage in the 31st month after the operation. Therefore, the valve-related death rate was 4.3%, and the valve-related complication rate 8.6% on mid-term follow-up. 1, 3-, and 5-year valve- related event free rates were 90.8%, 79.5%, and 79.5%, respectively, while 1, follow-up. 1, 3-, and 5-year valve- related event free rates were 90.8%, 79.5%, and 79.5%, respectively, while 1, 3-, and 5-year survival rates were 100%, 88.8%, and 88.8%, respectively. Conclusion: The findings suggest that a complete removal of infected tissues is essential in the operative treatment of infectious endocarditis of the mitral valve. It is also suggested that when infected tissues are completely removed, neither type of material nor method of operation has a significant effect on the operation result. The postoperative results also suggest the need for a close follow-up observation of the patients suspected of having brain damage, which is caused by preoperative blood contamination or emboli from vegetation, for a possible cerebral vascular injury such as mycotic aneurysm.

A Study on the Expression of CD44s and CD44v6 in Non-Small Cell Lung Carcinomas (비소세포성 폐암종의 CD44s 및 CD44v6의 발현에 대한 연구 -CD44의 발현에 대한 연구-)

  • Chang, Woon-Ha;Oh, Tae-Yun;Kim, Jung-Tae
    • Journal of Chest Surgery
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    • v.39 no.1 s.258
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    • pp.1-11
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    • 2006
  • Background: CD44 is a glycoprotein on the cell surface which is involved in the cell-to-cell and cell-to-matrix interaction. The standard form, CD44s and multiple isoforms are determined by alternative splicing of 10 exons. Recent studies have suggested that CD44 may help invasion and metastasis of various epithelial tumors as well as activation of Iymphocytes and monocytes. The expression pattern of CD44 can be different according to tumor types. The author studied the expression pattern of CD44s and one of its variants, CD44v6 in non-small cell lung carcinomas (NSCLC) to find their implications on clinicopathologic aspects, including the survival of the patients. Material and Method: A total of 89 primary NSCLSs (48 squamous cell carcinomas, 33 adenocarcinomas, and 8 undifferentiated large cell carcinomas) were retrieved during the years between 1985 to 1994. The immunohisto chemistry was done by using monoclonal antibodies and the CD44 expression for angiogenesis was evaluated by counting the number of tumor microvessels. Result: Seventy-one (79.8$\%$) and 64 (71 .9$\%$) among 89 NSCLSs revealed the expression of CD44s and CD44v6, respectively. The expression of CD44s was well correlated with that of CD44v6 (r=0.710, p < 0.0001). The expression of CD44s and CD44v6 was associated with the histopathologic type of the NSCLCs, and squamous cell carcinoma was the type that showed the highest expression of CD44s and CD44v6 (p < 0.0001). Microvessel count was the highest in adenocarcinomas (113.6$\pm$69.7 on 200-fold magnification and 54.8$\pm$41.1 on 400-fold magnification) and correlated with the tumor size of TNM system (r=0.217, p=0.043) and CD44s expression (r=0.218, p=0.040). In adenocarcinoma, the patients with higher CD44s expression survived shorter than those with lower CD44s expression (p=0.0194) but there was no statistical significance on multivariate analysis(p=0.3298). Conclusion: The expression of both CD44s and CD44v6 may be associated with the squamous differentiation in non-small cell lung carcinomas. The relationship of CD44s expression with micro-vessel density of the tumor suggests an involvement of CD44s in tumor angiogenesis, which in turn would help tumor growth.

Effects of Formaldehyde/Urea Molar Ratio on Bonding Strength of Plywood and Properties of Sliver-PB and Strand-PB (F/U 몰비의 변이가 합판의 접착성과 Sliver-PB, Strand-PB의 물성에 미치는 영향)

  • Park, Heon;You, Young-Sam
    • Journal of the Korean Wood Science and Technology
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    • v.27 no.2
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    • pp.38-45
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    • 1999
  • This study was to figure out proper Formaldehyde/Urea molar ratio of UF resin with satisfactory bonding strength of plywood and properties of particleboard. The six kinds of UF resins were manufactured with F/U molar ratio 1.0, 1.2, 1.4, 1.6, 1.8, and 2.0. The boards were made of three kinds of raw materials : Veneer, Sliver-Particle and Strand-Particle. Manufacturing condition of plywood : amount of mixing resin was 150g/$m^2$. The fourty secs/mm simple-pressing schedule in the pressure 10kgf/$m^2$ was applied for 480mm${\times}$700mm board at the temperature of $110^{\circ}C$ in a hot press. Manufacturing condition of particleboard : Target density was 0.65g/$cm^2$. The stepwise 9 minutes- multi-pressing schedule in the maximum pressure 40kgf/$cm^2$, the minimum pressure 15kgf/$cm^2$ was applied for $480mm{\times}634mm{\times}12mm$ board at the temperature of $150^{\circ}C$ in a hot press. The results are as follows : I. In bonding strength, plywood which was made by F/U molar ratio 1.2 showed the highest value. Other molar ratio resin also gave the satisfied value of KS standard, 7.5kgf/$cm^2$. 2. In internal bond strength of particleboard, Sliver-Particleboard(SLPB) and Strand-Particleboard(STPB) varied respectively from 5.9kgf/$cm^2$ to 4.8kgf/$cm^2$, from 6.7kgf/$cm^2$ to 5.4kgf/$cm^2$. SLPB with F/U=1.2 and STPB with F/U=1.6 had higher IB value. Also, both SLPB and STPB showed lower IB value in F/U molar ratio 2.0 and 1.0. 3. SLPB and STPB with six kinds of UF resin respectively satisfied bending strength of KS standard 150 Type(130kgf/$cm^2$) and 200 Type(180kgf/$cm^2$). Bending strength data for both of SLPB and STPB showed little or no loss from F/U=1.8 to F/U=1.2. Also, STPB was approximately two times higher than that of SLPB. Therefore, the raw material's shape had more effect on bending strength than the FlU molar ratio. 4. F/U=1.6 and 1.4 showed the lower thickness swelling in SLPB and STPB. All of STPBs satisfied thickness swelling of KS standard, under 12%.

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Synthesis and Preliminary Evaluation of $9-(4-[^{18}F]Fluoro-3-hydroxymethylbutyl)$ Guanine $([^{18}F]FHBG)$ in HSV1-tk Gene Transduced Hepatoma Cell (9-(4-$[^{18}F]Fluoro-3-hydroxymethylbutyl)$guanine $([^{18}F]FHBG)$의 합성과 헤르페스 단순 바이러스 티미딘 키나아제 이입 간암 세포주에서의 기초 연구)

  • Moon, Byung-Seok;Lee, Tae-Sup;Lee, Myoung-Keun;Lee, Kyo-Chul;An, Gwang-Il;Chun, Kwon-Soo;Awh, Ok-Doo;Chi, Dae-Yoon;Choi, Chang-Woon;Lim, Sang-Moo;Cheon, Gi-Jeong
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.4
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    • pp.218-227
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    • 2006
  • Purpose: The HSV1-tk reporter gene system is the most widely used system because of its advantage that direct monitoring is possible without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. In this study, we investigate the usefulness of the reporter probe (substrate), $9-(4-[^{18}F]Fluoro-3-hydroxymethylbutyl)$guanine ($[^{18}F]FHBG$) for non-invasive reporter gene imaging using PET in HSV1-tk expressing hepatoma model. Materials and Methods: Radiolabeled FHBG was prepared in 8 steps from a commercially available triester. The labeling reaction was carried out by NCA nucleophilic substitution with $K[^{18}F]/K2.2.2.$ in acetonitrile using N2-monomethoxytrityl-9-14-(tosyl)-3-monomethoxytritylmethylbutyl]guanine as a precursor, followed by deprotection with 1 N HCl. Preliminary biological properties of the probe were evaluated with MCA cells and MCA-tk cells transduced with HSV1-tk reporter gene. In vitro uptake and release-out studies of $[^{18}F]FHBG$ were performed, and was analyzed correlation between $[^{18}F]FHBG$ uptake ratio according to increasing numeric count of MCA-tk cells and degree of gene expression. MicroPET scan image was obtained with MCA and MCA-tk tumor bearing Balb/c-nude mouse model. Results: $[^{18}F]FHBG$ was purified by reverse phase semi-HPLC system and collected at around 16-18 min. Radiothemical yield was about 20-25%) (corrected for decay), radiochemical purity was >95% and specific activity was around >55.5 $GBq/{\mu}\;mol$. Specific accumulation of $[^{18}F]FHBG$ was observed in HSV1-tk gene transduced MCA-tk cells but not in MCA cells, and consecutive 1 hour release-out results showed more than 86% of uptaked $[^{18}F]FHBG$ was retained inside of cells. The uptake of $[^{18}F]FHBG$ was showed a highly significant linear correlation ($R^2=0.995$) with increasing percentage of MCA-tk numeric cell count. In microPET scan images, remarkable difference of accumulation was observed for the two type of tumors. Conclusion: $[^{18}F]FHBG$ appears to be a useful as non-invasive PET imaging substrate in HSV1-tk expressing hepatoma model.