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Expressions of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-2 with Changes of Interleukin-6 and Interleukin-18 in Atherosclerotic Lesions of Hypercholesterolemic Rabbits (고콜레스테롤혈증 가토의 죽상경화성 병변에서 Interleukin-6와 Interleukin-18의 변화 및 Matrix Metalloproteinase-9과 Tissue Inhibitor of Metalloproteinase-2의 발현)

  • 권영무;김성숙;장봉현
    • Journal of Chest Surgery
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    • v.35 no.6
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    • pp.407-419
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    • 2002
  • Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by progressive accumulation of lipids, cells, and extracellular matrix. Matrix metalloproteinases(MMPs) and tissue inhibitor of metalloproteinases(TIMPS) contribute to vascular matrix remodeling in atherosclerosis, and some cytokines may play role in the synthesis or activation of MMPs or TIMPs. Material and Method: We produced experimental atherosclerotic plaques in 9 rabbits by atherogenic hypercholesterol diet for 12 weeks, and 10 other rabbits were used as control group with standard laboratory chow, At that time, 19 rabbits were sacrificed and aorta, coronary arteries and blood specimens were prepared. The expressions of MMP-9, TIMP-2 and interleukin(IL)-18, and the bioactivity of IL-6 were investigated with H&E stain, immunohistochemical stain, immunoblotting(Western blot analysis), and bioassay. Result: Serum cholesterol in the experimental group increased up to 1258$\pm$262 mg/dL(control group: 41$\pm$7 mg/dL). All experimental group showed well-developed atherosclerotic plaques in aorta and coronary artery. The expression of MMP-9 in aorta and coronary artery of the experimental group showed significant increase than that of the control group by immunohistochemistry. Among the experimental group, complicated lesions with intimal rupture or complete luminal occlusion, demonstrated stronger expression of MMP-9. Interestingly, there was no difference in expression of TIMP-2 between the experimental and the control group. These findings were confirmed by Western blot analysis. The bioassay revealed significant up-regulation of serum bioactivity of IL-6 in the experimental group(4819.60$\pm$2021.25 IU/$m\ell$) compared to that of IL-6 in the control group(27.20 $\pm$ 12.19 IU/$m\ell$). IL-18 was expressed in all atherosclerotic plaques, whereas little or no expression was detected in the control group. Conclusion: The increased MMP-9 expression along with the unchanged TIMP-2 expression seem to be contributory factors in extracellular matrix degradation in atherosclerosis. Focal overexpression of MMP-9 may promote plaque destabilization and cause complications of atherosclerotic plaques such as thrombosis with/without acute coronary syndrome. Elevation of IL-6 and IL-18 may be more than just markers of atherosclerosis but actual participants in lesion development. Identification of critical regulatory pathway is important to improve the understanding of the cellular and molecular basis of atherosclerosis and may open the way for novel therapeutic strategies.

Role of Intra-aortic Balloon Pump in High Risk Patients undergoing Off-Pump Coronary artery bypass graft (심폐바이패스 없이 시행하는 관상동맥 우회술시 고위험군 환자에서 대동맥내 풍선 펌프의 유용성)

  • Cho, Suk-Ki;Jang, Woo-Ik;Lim, Cheong;Lee, Cheul;Lee, Jae-Ik;Kim, Yong-Lak;Ham, Byung-Moon;Kim, Ki-Bong
    • Journal of Chest Surgery
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    • v.34 no.12
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    • pp.895-900
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    • 2001
  • Background : This study aimed to evaluate the usefulness of preoperative placement of intraaortic balloon pump(IABP) in reducing operative risk and facilitating posterior vessel OPCAB in high risk patients with left main disease( 75% stenosis), intractable resting angina, postinfarction angina, or left ventricular dysfunction(ejection fraction 35%). Material and Method : One hundred eighty- nine consecutive patients who underwent multi-vessel OPCAB including posterior vessel revascularization were studied. The patients were divided into group I(n=74) that received preoperative or intraoperative IABP and group II(n=115) that did not receive IABP. In group I, there were 39 patients with left main disease, 40 patients with intractable resting angina, 14 patients with left ventricular dysfunction and 7 patients with postinfarction angina. Ten patients received intraoperative IABP support due to hemodynamic instability during OPCAB. Result : There was one operative mortality in group I and two mortalities in group II. The average number of distal anastomoses was not different between group I and group II(3.5$\pm$0.9 vs 3.4$\pm$0.9, p=ns). There were no significant differences in the number of posterior vessel anastomosis per patient between the two groups. There were no differences in ventilator support time, length of hospital stay, and morbidity between the two groups. There was one case of IABP-related complication in group I. Conclusion : IABP facilitates posterior vessel OPCAB in high risk patients, with comparable surgical results to low risk patients

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The Mid Term Clinical Result and the Risk Factor Analysis of Isolated Aortic Valve Replacement (단독 대동맥판막 치환술의 중기 성적과 그 위험인자에 대한 분석)

  • Park Jae-Min;Jun Hee-Jae;Yoon Young-Chul;Lee Yang-Hang;Hwang Yoon-Ho;Cho Kwang Hyun;Han Il-Yong
    • Journal of Chest Surgery
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    • v.38 no.2 s.247
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    • pp.110-115
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    • 2005
  • Background: The aims of this paper were to review the mid term clinical results and to analyze the preoperative risk factors of isolated aortic valve replacement (AVR). Material and Method: Between January 1992 and February 2003, 80 patients underwent isolated AVR. 58 were male and 22 were female patients, raging from 12 to 75 years of age (mean :$46.8{\pm}13.0$ years). 74 patients except one early death and 5 follow-up loss were contacted by OPD or by telephone. The mean duration of follow-up was $44.2{\pm}29.7$ months and the total cumulative period was 272.8 patient-year. Result: The complications in hospital occurred in 35 cases : 12 wound problems (11 superficial, 1 deep), 11 arrhythmias (9 temporary, 2 persistent), 3 low cardiac output, and so forth. The late deaths were 4 cases : the heart-related deaths were 2 cases ($0.7\%$ patient-year). Conclusion: The risk factors that influenced the early mortality and morbidity were older age (> 60 years)(p=0.04), poor preoperative NYHA functional class (> 3) (p=0.048), high preoperative serum creatinin level (> 1.2 mg/100 ml)(p=0.031), long operation time (aortic clamping time>90 min)(p=0.042). The same factors influenced the late mortality and morbidity. Freedom from valve-related complication was $86.4{\pm}5.3\%,$ actuarial survival rate were $96.8{\pm}2.3\%$ at 3 years and $90.8{\pm}4.6\%$ at 10 years.

The Business Model & Feasibility Analysis of the Han-Ok Residential Housing Block (한옥주거단지 사업모델구상 및 타당성 분석)

  • Choi, Sang-Hee;Song, Ki-Wook;Park, Sin-Won
    • Land and Housing Review
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    • v.2 no.4
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    • pp.453-461
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    • 2011
  • This study is to derive a project model based on potential demand for Korean-style houses, focusing on new town detached housing sites that LH supplies and to test validity of the derived model and to present the direction and supply methods of the projects. The existing high-class new town Korean-style housing developments that have been considered were found to have little business value due to problems in choice of location and discordance of demand, so 6 types of projects were established through the methods of changes in planned scale, combined use, and subdivision of plot of land based on the results of survey. The type that has the highest business value among the project models was block-type multifamily houses, and this can be interpreted as the increase in total construction area leading to increase inrevenues of allotment sales due to economies of scale. The feasibility of mass housing model in which small-scale Korean-style houses are combined with amenities was found to be high, and if the same project conditions as those of the block-type multifamily houses are applied, the business value of the Korean-style tenement houses was found to be high. Besides, the high-class housing models within block-type detached housing areas are typical projects that the private sector generally promotes, and the construction cost was found to be most expensive with 910 million won per house. In order to enhance the business value of the Korean-style housing development, collectivization such as choice of location, diversification of demand classes, optimization of house sizes, and combination of uses is needed. And in order to adopt Korean-style houses in the detached housing sites, the adjustments and division of the existing planned plots are needed, and the strategies to cope with new demand through supplying Korean-style housing types of sites can be suggested. Also breaking away from the existing uniform residential development methods, the development method through supplying original land that is natural land not yet developed besides basic infrastructures (main roads and water and sewage) can be considered, and as the construction of more than 1~2 stories building is impossible due to the structure of Korean-style house roof and furniture. So it can be suggested that original land in the form of hilly land is considered to be most suitable to large-scale development projects.

Preliminary Results of Phase I/II Study of Simultaneous Modulated Accelerated (SMART) for Nasopharyngeal Carcinoma (비인강암의 치료에서 동시차등조사가속치료를 적용한 제1상/2상 연구의 예비적 결과)

  • Park Jin-Hong;Back Geum-Mun;Yi Byong-Yong;Choi Eun-Kyung;Ahn Seung-Do;Shin Seong-Soo;Kim Jung-Hun;Kim Sang-Yoon;Lee Bong-Jae;Nam Soon-Yuhl;Choi Seung-Ho;Kim Seung-Bae;Lee Sang-Wook
    • Radiation Oncology Journal
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    • v.24 no.1
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    • pp.1-10
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    • 2006
  • Puroose: To present preliminary results of intensity-modulated radiotherapy (IMRT) using the simultaneous modulated accelerated radiation therapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC). Materials and Methods: Twenty patients who underwent IMRT for non-metastatic NPC at the Asan Medical Center between September 2001 and December 2003 were prospectively evaluated. IMRT was delivered using the 'step and shoot' SMART technique at prescribed doses of 72 Gy (2.4 Gy/day) to the gross tumor volume (GTV), 60 Gy (2 Gy/day) to the clinical target volume (CTV) and metastatic nodal station, and 46 Gy (2 Gy/day) to the clinically negative neck region. Eighteen patients also received concurrent chemotherapy using cisplatin once per week. Results: The median follow-up period was 27 months. Nineteen patients completed the treatment without interruption; the remaining patient interrupted treatment for 2 weeks owing to severe pharyngitis and malnutrition. Five patients (25%) had RTOG grade 3 mucositis, whereas nine (45%) had grade 3 pharyngitis. Seven patients (35%) lost more than 10% of their pretreatment weight, whereas 11 (55%) required intravenous fluids and/or tube feeding. There was no grade 3 or 4 chronic xerostomia. All patients showed complete response. Two patients had distant metastases and loco-regional recurrence, respectively. Conclusion: IMRT using the SMART boost technique allows parotid sparing, as shown clinically and by dosimetry, and may also be more effective biologically. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.

Hypofractionated Radiotherapy for Small-sized Hepatocellular Carcinoma as Salvage Therapy: Sustained Local Control and Safety (작은 크기의 재발성 간세포암에 대한 구제치료로 소분할 방사선치료: 국소 제어율과 안전성)

  • Bae, Sun-Hyun;Park, Hee-Chul;Lim, Do-Hoon;Lee, Jung-Ae;Choi, Moon-Seok;Lee, Joon-Hyoek;Koh, Kwang-Cheol;Paik, Seung-Woon;Yoo, Byung-Chul
    • Radiation Oncology Journal
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    • v.28 no.2
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    • pp.85-90
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    • 2010
  • Purpose: To evaluate the rate of tumor response, local control, and treatment-related complications after hypofractionated radiotherapy for recurrent hepatocelluar carcinoma (HCC) less than 5 cm in size. Materials and Methods: Among the HCC patients who were treated by radiotherapy (RT) between 2006 and 2007 after the failure of previous treatment, a total of 12 patients were treated with hypofractionated RT. The criteria for hypofractionated RT was as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to a critical organ, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that irradiated 50% of the prescribed dose. Hypofractionated RT was performed with 50 Gy delivered in 10 fractions, at a rate of 5 fractions per week. The evaluation of tumor response was determined by CT scans performed at 3 months after the cessation of RT, followed by the evaluation of toxicity by Common Terminology Criteria for Adverse Events version 3.0. The median follow-up period after radiotherapy was 18 months. Results: A complete response (CR) was achieved in 5 of 12 lesions (41.7%) at CT performed at 3 months after the cessation, whereas the overall complete response was observed in 7 of 12 cases (58.3%). In-field local control rate was sustained in 83.3% of patients. All patients developed intra-hepatic metastases except for 2 patients. The overall survival rate was 90.0% at 1 year and 67.5% at 2 years, respectively. Three patients developed Grade 1 nausea during RT and 1 patient showed a progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. Conclusion: Hypofractionated RT for small-sized HCC as a salvage therapy showed a 58.3% CR rate and 83.3% of local control. Fifty Gy administered in 10 fractions of partial liver irradiation is considered as a tolerable dose that does not cause severe complications.

The Effect of Doxapram on Cardiopulmonary Function in Dogs under Total Intravenous Anesthesia with Remifentanil and Propofol (개에서 Remifentanil과 Propofol에 의한 완전 정맥 내 마취 시 Doxapram 투여가 심폐기능에 미치는 효과)

  • Yun, Sungho;Kwon, Youngsam
    • Journal of Veterinary Clinics
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    • v.32 no.6
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    • pp.491-498
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    • 2015
  • We investigated the effect of constant rate infusion (CRI) with doxapram on cardiopulmonary function during total intravenous anesthesia (TIVA) with remifentanil and propofol CRI in dogs. Fifteen male Beagle dogs were randomly divided into 3 groups. All groups were premedicated with medetomidine ($20{\mu}g/kg$, IV) and anesthetized by remifentanil/propofol CRI for one and half hour. At the initiating of the anesthesia, different doses of doxapram for each group were administrated as the followings; D1 group - doxapram 0.25 mg/kg bolus followed by doxapram $8.33{\mu}g/kg/min$, D2 group - doxapram 2 mg/kg bolus followed by doxapram $66.66{\mu}g/kg/min$, control group - normal saline. The anesthetic depth for surgery was well maintained in all groups throughout the anesthetic periods. The respiratory rate was significantly higher in D2 group than that of control group (p < 0.05). The values of $PaO_2$ and $SaO_2$ were significantly increased in both D1 and D2 groups compared with control group (p < 0.05). High dose of doxapram (D2 group) significantly decreased the level of $PaCO_2$ compared with control group (p < 0.05). The values of systolic, mean and diastolic arterial pressure were significantly increased in doxapram 2 group (p < 0.05). There were no significant differences in the values of heart rate and pH of arterial blood. Therefore, doxapram CRI may be useful to alleviate the suppression of cardiopulmonary function including hypoxia and hypotension during TIVA with remifentanil and propofol in dogs.

Effects of γ-Irradiation from Cobalt-60 on Immunogenicity of Eimeria tenella (Cobalt-60 γ-선 조사가 Eimeria tenella 의 면역원성에 미치는 영향)

  • Youn, Hee-jeong;Kang, Yung-bai;Jang, Du-hwan
    • Korean Journal of Veterinary Research
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    • v.33 no.4
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    • pp.657-664
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    • 1993
  • To reveal the immunogenicity of ${\gamma}-irradiated$ E tenella and its progeny, a series of experiments on the effects of Cobalt-to ${\gamma}-irradiation$ was performed. The SPF chickens inoculated with diffenrt doses of inoculum were challenged with $1{\times}10^5$ oocysts of virulent E tenella. The levels of 100 Gy ${\gamma}-irradiation$ from $^{60}Co$ and of inoculum with $1{\times}10^4$ oocysts were recognized as proper as immunogen by comparison of survival rates, body weight gains, blood in feces and lesion scores in the chickens. In these trials of challenge with virulent E tenella after inoculation with $1{\times}10^4$ oocysts of the ${\gamma}-irradiated$ E tenella and its progeny, the survival rates of the chickens challenged with the virulent E tenella after immunization with the 1st and the 3rd progeny groups of ${\gamma}-irradiated$ E tenella oocysts were higher(l00%) than that(87.0%) of the challenged control group. The signs of blood in feces and the lesion scores were seen markedly lower with the ourput of the smaller number of oocysts, i.e. OPG 103,900 and 25,800 in the groups of the 1st and the 3rd progeny, respectively, than those(OPG 1,658,900) of the challenged control group. The body weight gains of the 1st and the 3rd progeny groups, the 1st week and the 2nd week after challenge, were higher (2.6g and 155.4g, 11.6g and 168.9g respectively) than those(-85.8g and 63.6g, respectively) of the challenged control group, and the feed conversion ratios(FCR 3.28 and 2.96) of the 1st and the 3rd progeny groups were lower than that(FCR 5.60) of the groups challenged control group. The anticoccidial indices(70.5 and 93.9) of the groups challenged with the virulent oocysts of E tenella after immunization with the 1st and the 3rd progeny of the ${\gamma}-irradiated$ E tenella were significantly higher than that (ACI -81.9) of the challenged control group. It was thought that the immunogenicity of ${\gamma}-irradiated$ E tenella would be increase according to increase the number of generation passaged in chicken. That might be because of increasing the pathogenicity of ${\gamma}-irradiated$ E tenella according to increase the number of generation passaged in chicken.

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Histopathological and Serological Observations on Experimental Anisakiasis of Rabbits (실험적 토끼 아니사키스증에서의 조직학적 병변과 혈청 항체가의 경시적 변동 양상)

  • 홍성태;이손형
    • Parasites, Hosts and Diseases
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    • v.25 no.2
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    • pp.168-180
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    • 1987
  • This study was performed to observe histopathological changes and serological reactions in chronic anisakiasis of rabbits. Each rabbit was infected per os with 30 larvae of Anisakis type I. Their sera were collected chronologically and the rabbits were killed for histopathological examination, 3, 13, 20, 30, 60, 90 and 150 days after the infection. The results were summarized as below. 1. Most of the larvae were recovered from the stomach, but a few from the omentum, intestine, mesentery and abdominal wall. The recovery rates and distribution of worms by organ were not differed by duration of infection. 2. Histologically the lesion was abscess type on 13 days, i.e., the dead worms were surrounded by fibrinous exudate, histiocytes and thick zone of numerous inflammatory cells. After 30 days, histiocytes were found to invade the worms and the lesion was changing into abscessgranulomatous type. Also a calcified worm was found on the 30th day. After then the worms were observed to be dissolved slowly until 90 days. On 150 day, only one calcified worm was observed. 3. The levels of serum IgG antibody by ELISA reached their maximum 30 days after the infection. After then, it decreased slowly until 150 days after the infection. Above serological and histopathological findings indicated that antigenic stimulation from degenerating Anisakis larvae was the greatest during the first 30 days after infection. This period was corresponding with the beginning of worm resolution or calcification. Serologic test by ELISA would be a valuable tool for confirming chronic anisakiasis.

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A Randomized, Double-Blind, Placebo-Controlled Trial of Early Ursodeoxycholic Acid Administration for Prevention of Total Parenteral Nutrition-Induced Hepatobiliary Complications (총정맥영양법의 간담도 합병증에 대한 Ursodeoxycholic Acid 조기투여의 이중맹검 위약대조군 연구)

  • Choe, Yon-Ho;Beck, Nam-Sun;Kim, Ji-Hee;Lee, Suk-Hyang;Park, Tae-Sung
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.5 no.2
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    • pp.174-180
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    • 2002
  • Purpose: Ursodeoxycholic acid (UDCA) is known to decrease hepatic injury by promoting the biliary secretion of retained toxic endogenous bile acids in hepatobiliary diseases complicated by total parenteral nutrition (TPN). However, most studies have focused on treatment for complications after TPN. We investigated the preventive role of early administration of UDCA in TPN-induced hepatobiliary complications by a randomized, double-blind, placebo-controlled trial. Methods: Between May 2000 and May 2002, thirteen patients, who were given TPN more than 10 days in the hospital, were assigned randomly to two groups. One was the case group (7 patients) who were given UDCA simultaneously with TPN regimen, and the other, the control group (6 patients) who were given placebo. Their age ranged from 1 day to 13 years. They were affected with diseases impossible for enteral nutrition, such as prematurity, cerebral palsy, chronic diarrhea, anorexia nervosa, pancreatitis, and cyclic vomiting. The duration of TPN ranged from 10 to 70 days. Hematologic parameters including liver function test were measured at regular intervals, and the duration, composition, administration rate, total calorie of TPN were recorded. The serum levels of total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase were compared between groups after cessation of the study. Results: The autoregressive coefficient of the control group was 0.4419 (p=0.0651) in bilirubin, -0.0431 (p=0.7923) in AST, 0.2398 (p=0.2416) in ALT, and 0.2459 (p=0.1922) in alkaline phosphatase by mixed procedure model when the parameters were referred to the case group. Conclusion: The serum level of total bilirubin did not increase in comparison with that of the control group, but statistically insignificant, when both TPN and UDCA were administered simultaneously from the beginning.

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