Rat의 복강내에 투여한 5-fluorouracil-polyglycolic acid 제형이 장기에 미치는 영향에 관한 연구

강대영,송규상,최정목,노승무,정경수,오정연,김진향,양준묵,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

For more effective intraperitoneal chemotherapy, the authers made 5-fluorouracil-polyglycolic acid composite disks(FU-PGA disks) with 5-fluorouracil and polyglycolic acid, a biodegradable polymer. We inserted the FU-PGA disk into the peritoneal cavites of Sprague-Dawley male rats, the control and three experimental groups; one FU-PGA disk insert group(300mg/kg), two FU-PGA disk insert group(600mg/kg), and three FU-PGA disk insert group(900mg/kg). The control group received a similar number of PGA disk inserts. A pharmacokinetic study was performed to measure the 5-fluorouracil concentration in the peritoneal fluid, blood, and tissues(liver, kidney and heart) at 24 hours, 72hours and 168 hours after insertion of the FU-PGA disk. Light and electron microscopic studies were done. The results were as follows: 1) The number of white blood cells and platelets decreased after FU-PGA insertion. The degree was proportional to the duration and amounts inserted. The change in the number of red blood cells varied slightly. 2) Light microscopically, slight changes were noted at 168 hours in the 3 disk insert group (900mg/kg). Mild fatty change and hepatocyte degeneration around the central veins of the liver were noted, with vacuolar degeneration in the proximal convoluted tubules of the kidney. 3) Electron microscopically,the liver showed focal increases of lipid droplets in the hepatocytes, and irregular nuclear membrane with focal nucleolar segregation of the fibrillar and granular elements. Also the double membranous structure of the hepatocytes and Kupffer cells was widened with bleb formation. The kidney showed wide separation of the nuclear double membrane in the proximal convoluted tubular cells and mesangial cells, with vacuolation and myelin figure formation in the mitochondria of the proximal convoluted tubular cells, at 72 hours and 168 hours in the 2 to 3 FU-PGA insert groups. The heart showed focal loss of cristae,vacuolation and myelin figure formation in the mitochondria of the 2 to 3 FU-PGA insert groups. In conclusion, despite the large amont of FU-PGA inserted, the histopathological changes in the liver, kidney and heart were slight, and consonant with the very low amount of 5-fluorouracil concentrations detected in the liver, kidney and heart. The above results suggest that the FU-PGA composite can serve as a new device for releasing drugs in a controlled manner and easily targeted to intraperitoneal organs. This device can improve the efficacy of intraperitoneal chemotherapy for gastric cancer.

암세포 증식에 대한 YB-1 안티센스 올리고핵산염의 영향

김명성 ( Myung Sung Kim ),이완식 ( Wan Sik Lee ),박창환 ( Chang Hwan Park ),주영은 ( Young Eun Joo ),김현수 ( Hyun Soo Kim ),최성규 ( Sung Kyu Choi ),유종선 ( Jong Sun Rew ),정영도 ( Young Do Jung ),김세종 ( Sei Jong Kim ),안봉환 대한내과학회 2006 대한내과학회지 Vol.71 No.3

목적: YB-1은 PCNA, DNA 중합효소 및 MDR 유전자 등의 전사인자로 작용한다. YB-1 유전자는 정상 어른의 간에서는 발현되지 않지만 태아의 간이나 재생 중인 간에서는 발현이 현저히 증가되어서 세포의 증식과 밀접한 관련이 있음이 보고되었다. 본 연구에서는 YB-1 유전자의 안티센스 올리고핵산염을 이용하여 YB-1의 발현을 억제함으로써 암세포 증식을 차단 할 수 있는지를 실험하고 암치료를 위한 유전자 요법으로서의 가능성을 알아보았다. 방법: 세포주로는 Chang liver, HepG2, CT-26 세포를 사용하였고, 사람의 정상세포로는 섬유아세포와 내피세포가 혼재된 조직을 사용하였다. YB-1 유전자의 안티센스 올리고핵산염으로는 YB-1 cDNA의 변역 시작 부위에 상보적인 21mer 올리고핵산염을 제작하여 사용하였다. 세포의 성장은 MTT assay를 이용하였고, 유전자 발현은 Northern blot으로 분석하였으며, 세포주기 변화는 propidium iodide로 염색하여 유식세포분석기로 분석하였다. 동물실험에서는 CT-26 세포를 1.0×10(5)개씩 Balb/c 생쥐의 피하에 접종하여 종양을 유도하였다. 종양이 유도된 Balb/c 생쥐에 YB-1 안티센스 올리고핵산염을 꼬리정맥이나 종양조직에 주사한 후 종양의 크기를 측정하여 종양억제 효과를 관찰하였다. 결과: YB-1 안티센스 올리고핵산염은 CT-26 세포에서는 50 nM 이상 농도에서 Chang liver와 HepG2 세포에서는 10 nM 이상 농도에서 세포주의 성장을 강하게 억제하였지만 정상 조직세포의 성장에는 아무런 영향을 미치지 않았다. 안티센스 올리고핵산염을 DOTAP에 담지한 경우 세포성장 억제에 미치는 효과가 안티센스 올리고핵산염 단독 처치 보다 강하였다. 이때 YB-1의 발현은 증식이 억제된 세포주(Chang liver 및 CT-26)에서는 감소하였으나 정상조직세포에서는 변화가 없었다. 증식이 억제된 세포주에서 세포주기를 살펴보면 초기에 S phase가 감소함을 관찰 할 수 있었다. 꼬리정맥이나 종양조직에 YB-1 안티센스 올리고핵산염을 주입 시 종양의 크기가 유의하게 감소하였다. 결론: 이상의 실험 결과 YB-1 안티센스 올리고핵산염은 암세포의 성장을 저해하며 종양 동물모델에서 종양의 성장을 억제할 수 있음을 시사하였다. Background: Human YB-1 is a transcription factor that binds to the inverted CCAAT box in the promoter region of a variety of genes such as PCNA, DNA polymerase and MDR. In this study we evaluated the effect of YB-1 antisense oligonucleotides on tumor cell growth. Methods: Chang liver, HepG2 and CT-26 cells were cultured as immortalized cell lines. The MTT (3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyltetrazolium bromide) assay, Northern blot and flow cytometric analyses were used to determine cell growth, gene expression and cell cycle changes. In an animal model, CT-26 cells were injected into Balb/c mice to induce tumor; YB-1 antisense oligonucleotides were injected into the tail vein or tumor tissue of the mice; change of tumor size was then measured. Results: Phosphorothioated YB-1 antisense oligonucleotides suppressed the proliferation of the immortalized liver cells (Chang liver cells) and a variety of cancer cells (HepG2 and CT-26 cells); however, it did not inhibit normal cell growth. The DOTAP/antisense oligonucleotide mixture showed stronger effects on cell proliferation than did the antisense oligonucleotide alone. The YB-1 antisense oligonucleotide decreased specific expression of the YB-1 mRNA in the immortalized cancer cell lines. Flow cytometric analysis revealed that the inhibition of cell proliferation might have been due to a decrease in the S phase of the cell cycle. We found that in an animal tumor model, the administration of the YB-1 antisense oligonucleotide, in the vein or tumor tissues, decreased the tumor size significantly. Conclusions: These results suggest that the YB-1 antisense oligonucleotide may inhibit growth of a variety of cancer cells.(Korean J Med 71:293-301, 2006)

Effect of Extreme Heatwaves on the Mortality and Cellular Immune Responses of Purplish Bifurcate Mussel Mytilisepta virgata (Wiegmann, 1837) (=Septifer virgatus) in Indoor Mesocosm Experiments

Hyun-Ki Hong,Chang Wan Kim,Jeong-Hwa Kim,Nobuhisa Kajino,Kwang-Sik Choi 제주대학교 해양과학연구소 2021 해양과환경연구소 연구논문집 Vol.45 No.-

In the rocky intertidal environment, the frequency and duration of heatwaves have increased over the last decade, possibly due to global climate change. Heatwaves often result in lethal or sub-lethal disturbances in benthic animals by changing their metabolic activities. In this study, we investigated the impacts of extreme heatwave stress on the hemocyte functions of Mytilisepta virgata and subsequent mortality to gain a better understanding of the potential causes and consequences of mass mortality events in this mussel during summer. We discriminated three types of hemocytes in the hemolymph, granulocytes, hyalinocytes, and blast-like cells, using flow cytometry and revealed that granulocytes were the major hemocyte involved in cellular defensive activities, such as phagocytosis and reactive oxygen species (ROS) production. For the experiment, mussels were exposed to a 40◦C air temperature for 12 h per day over 5 days under laboratory conditions as a simulated semi-diurnal tidal cycle. Mortality began to occur within 3 days after beginning the experiment, and all mussels had died by the end of the experiment. Flow cytometry indicated that the mussels exposed to high air temperatures produced significantly more ROS than did the control mussels within 2 days after the onset of the experiment, which may have caused oxidative stress. Such high levels of ROS in the hemolymph increased DNA damage in hemocytes after 3 days of exposure and decreased the phagocytosis of hemocytes 4 days after the experiment began. The observed mortality and decline in immune capacity suggested that an extreme heat event occurring in the rocky intertidal ecosystem during summer could exert sublethal to lethal impacts on macrobenthic animals.

Cerebral vascular burden on hippocampal subfields in first-onset drug-naïve subjects with late-onset depression

Choi, Woo Hee,Jung, Won Sang,Um, Yoo Hyun,Lee, Chang Uk,Park, Young Ha,Lim, Hyun Kook Elsevier 2017 Journal of affective disorders Vol.208 No.-

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Although there is substantial evidence of associations between frontal-striatal circuits and cerebral vascular burden in late-onset depression (LOD), relationships between vascular burden and hippocampal subfields are not clear. The purpose of this study was to investigate relationships between cerebral vascular burden and hippocampal subfield volume in LOD patients.</P> <P><B>Methods</B></P> <P>Fifty subjects with LOD and 50 group-matched healthy control subjects underwent magnetic resonance imaging scanning. Hippocampal subfields volumes were measured and compared between the groups. In addition, association patterns between white matter hyperintensity (WMH) volumes, clinical measures and hippocampal subfield volumes were investigated in the LOD group.</P> <P><B>Results</B></P> <P>Subjects with LOD exhibited significant hippocampal volume reductions in the total hippocampus, cornu ammonis (CA) 1 and 3 and dentate gyrus (DG) areas compared with healthy subjects. Total WMH volume was negatively correlated with left total hippocampal volume and CA1 in the LOD group. In addition, depression severity was negatively associated with left and right CA3 volumes in the LOD group.</P> <P><B>Limitation</B></P> <P>Our findings of distinctive relationships between WMH and hippocampal subfields demonstrate a simple correlation, but do not prove causation</P> <P><B>Conclusion</B></P> <P>This study is the first to elaborate distinctive association patterns between hippocampal subfield volumes and cerebral vascular burden in LOD. These structural changes in the hippocampal CA1, CA3 and DG areas might be at the core of the underlying neurobiological mechanisms of hippocampal dysfunction in LOD. However, longitudinal studies will be needed to identify the mechanisms of these structural changes.</P> <P><B>Highlights</B></P> <P> <UL> <LI> This study is the first to elaborate distinctive association patterns between hippocampal subfield volumes and cerebral vascular burden in LOD. </LI> <LI> White matter hyperintensity was negatively correlated with left total hippocampal volume and CA1 in the LOD group. </LI> <LI> In addition, depression severity was negatively associated with left and right CA3 volumes in the LOD group. </LI> </UL> </P>

조혈모세포이식 환자에서 발생한 Cytomegalovirus 질환의 특징 : 일개 대학변원에서 최근 10년간의 경험

최수미,이동건,박선희,김시현,김유진,민창기,김희제,이석,최정현,유진홍,김동욱,이종욱,민우성,신완식,김춘추 대한감염학회 2009 감염과 화학요법 Vol.41 No.1

Background : Studies on cytomegalovirus (CMV) diseases in Korean hematopoietic stem cell transplant (HSCT) recipients are lacking and do not reflect the recent trends of advances and changes. Therefore, we tried to analyze the clinical features of CMV diseases in HSCT recipients over the past 10 years at a tertiary university hospital in Korea. Methods : Retrospective review of medical records was done for all adult HSCT patients who received transplant at the Catholic HSCT Center from January 1998 to January 2008. Results : Forty-four cases (2.2%) of CMV diseases were identified. CMV pneumonia was diagnosed in 17 patients, retinitis in 16 patients, enterocolitis in 7 patients, esophagitis 1 patient, gastritis in 1 patient, duodenitis in 1 patient, and hepatitis in 1 patient. The median onset of symptom was 90 days after transplantation. Late CMV diseases accounted for 47.7%. CMV related death varied from 0 to 58.8% according to the involved organ. CMV retinitis was diagnosed relatively later in the course of transplantation mostly in patients who had chronic graft versus host disease (GVHD). On the contrary, CMV enterocolitis mainly occurred in patients who suffered from acute GVHD. The overall concurrent CMV reactivation was documented to be 63.6%: the concurrent CMV reactivation was observed only in 37.5% of patients with retinitis. Conclusions : We observed some differences in the pattern of CMV disease manifestation according to the involved organ and reconfirmed the fact that CMV pneumonia is the most common and fatal disease in HSCT recipients. Additionally, CMV retinitis was not uncommon in HSCT recipients. Since specific marker does not exist in predicting retinitis, regular ocular examination should be done thoroughly, especially in patients with chronic GVHD.

Protective effect of chorioamnionitis on the development of bronchopulmonary dysplasia triggered by postnatal systemic inflammation in neonatal rats

Choi, Chang Won,Lee, Juyoung,Oh, Joo Youn,Lee, Seung Hyun,Lee, Hyun Ju,Kim, Beyong Il Nature Publishing Group 2016 Pediatric research Vol.79 No.2

<P><B>Background:</B></P><P>Prenatal or postnatal systemic inflammation can contribute to the development of bronchopulmonary dysplasia (BPD). We investigated whether prenatal intra-amniotic (i.a.) inflammation or early postnatal systemic inflammation can induce BPD in a rat model.</P><P><B>Methods:</B></P><P>One microgram of lipopolysaccharide (LPS) or vehicle was injected into the amniotic sacs 2 d before delivery (E20). After birth, 0.25 mg/kg of LPS or vehicle was injected into the peritoneum of pups on postnatal day (P)1, P3, and P5. On P7 and P14, peripheral blood (PB), bronchoalveolar lavage fluid (BALF), and lung tissue were obtained and analyzed.</P><P><B>Results:</B></P><P>Postnatal i.p. injections of LPS significantly increased neutrophil counts in PB and BALF on P7 and P14. Similarly, proinflammatory cytokine and angiogenic factor transcript levels were increased in the lung by i.p. LPS on P7. Alveolar and pulmonary vascular development was markedly disrupted by i.p. LPS on P14. However, pretreatment with i.a. LPS significantly negated the detrimental effects of postnatal i.p. LPS on PB and BALF neutrophil counts and on lung proinflammatory cytokine expression and histopathological changes.</P><P><B>Conclusion:</B></P><P>Exposure to early postnatal systemic LPS induces BPD, an arrest in alveolarization, in neonatal rats. Preceding exposure to i.a. LPS protects the lungs against BPD triggered by postnatal systemic inflammation.</P>

운동이 정신지체 성인여성의 골밀도에 미치는 영향

장명재,최지우,최원현,최현희 경희대학교 체육과학연구소 2000 體育學論文集 Vol.28 No.-

The purpose of this study was to investigate the effect of exercise to mentally retarded women's bone mineral density. Subjects were divided into three groups: Group A(age:27.9yr, n=8)-This group was mentally retarded exercise women, who had been doing regularly exercise for over three years. Group B(age:28.8yr, n=8)-This group was mentally retarded non exercise women, who hadn't been doing it as usual. Group C(age:29.0yr, n=8) This group was normal women, who hadn't been doing it as usual. This study analysed and compared the bone mineral density between these three groups. The results were summarized as follow. 1.The BMI of group A(Mentally retarded exercise group) was 22.8±3.28 kg/m2, group B(mentally retarded non exercise group) was 22.6±5.6 kg/m2, and Group C(normal group)was 22.0±2.2 kg/m2. There were no significant differences in BMI between three groups. 2.There were significant difference in grip strength and back strength between three groups(p〈.001). The grip strength of group A was 16.9±6.5 kg, group B was 12.2±4.0 kg, and group C was 31.8±2.1 kg. The back strength of group A was 36.9±16.1 kg, group B was 34.2±8.4 kg, and group C was 96.9±32.7. 3.These were significant difference bone mineral density of lumbar between these groups. Group A was 0.1±0.08 g/cm2, Group B was 0.888±0.10 g/cm2, and group C was 1.05±0.04 g/cm2(p〈.01). 4.These were very significant difference bone mineral density of femur between these groups. Group A was 0.91±0.09g/cm2, group B was 0.74±0.08 g/cm2, and group C was 0.97±0.14 g/cm2(p〈.0001). 5.These were very significant difference bone mineral density of Forearm between these groups. Group A was 0.6±0.02 g/cm2, group B was 0.56±0.03 g/cm2, and group C was 0.63±0.02 g/cm2(p〈.0001). 6.Group A were correlations between bone mineral density of femur(neck) and BMI, weight(p〈.05). 7.Group B were correlations between bone mineral density of forearm(MID, total) and age(p〈.05). 8.Group C were correlations between bone mineral density of lumbar(L1) and age, BMI, back strength(L4).

흉부 X선촬영 기술의 변천에 관한 연구

이창엽,조평곤,김지닐,최소영,김창균,최종학,김정민,김유현 高麗大學校 倂設 保健大學 保健科學硏究所 2002 保健科學論集 Vol.28 No.2

To find elements which enable improving Quality of image of chest radiography, we attempted to make comparison between chest radiography used currently with that of the past, and following conclusion was reached: 1) It could be confirmed that a dependance on chest radiography was declining, because proportion of chest radiography against overall radiography decreased. 2) There was a change of kVp to a high voltage in a chest radiography, and use of high kVp became a generalization 3) Exposure time was reduced and exposure dose was curtailed accordingly. 4) Apparatus was mainly comprised of 3-phase rectifier circuit and inverter type. 5) It could be confirmed that frequency of applying additional filters for high kVp radiography was insufficient. 6) There was almost no difference in the condition of exposure between hospitals using film/screen and hospitals using CR. But when CR is used for radiography, it was increase in exposure dose due to increase in tube current and it will be necessary to have continuous study on exposure dose by an increase use of CR in the future.

Endoscopy and Imaging Modalities/Basic Science of Gastrointestinal Disorders/Miscellaneous : Changing Pattern Of Digestive And Liver Disease In Korea, 1990-2006 Year; A Single Center Study

( Jung Hyun Kwon ),( Sang Woo Kim ),( In Sik Chung ),( Myung Gyu Choi ),( Kwan Woo Nam ),( Jung Pil Suh ),( Jae Hyuck Chang ),( Won Haing Hur ),( Yu Kyung Cho ),( Jae Myung Park ),( In Seok Lee ) 대한소화기학회 2007 SIDDS Vol.9 No.-

Background/Aims: Westernization in many Asian countries have changed lifestyles and diets, so once rare diseases have now become prevalent. The aim of this study is to investigate the changing pattern of digestive and liver disease in Korea, from 1990 to 2006. Methods: We extracted data specific gastrointestina (GI) disease based on the International Classification of Diseases code from the in-patients records at the Kangnam St. Mary`s Hospital in 1990, 1996 and 2006. This hospital is a tertiary-care hospital in Seoul, Korea, which has a capacity of 800 beds. Results: The admission rate for GI disease increased between 1990 and 2006. Overall in-patients were 1,623 persons in 1990, 2,368 persons in 1996 and 4,166 persons in 2006. The mean age of in-patients increased as time went by. A stomach cancer was the most common diagnosis during all periods, but its prevalence has decreased. Colon cancer ranked the 7th in 1990, but markedly increased and now ranks the second. The third was a hepatocellular carcinoma. The bile duct and gallbladder cancer, pancreas and esophageal cancer ranking followed with little interval change. In cases of cancer patients, a regular admission dramatically increased for chemotherapy. The number of patients admitted with pre-malignant neoplasm of stomach and colon increased remarkably with the development of endoscopy. The liver transplant, inflammatory bowel discase, and reflux esophagitis emerged form mid-1990s with greater frequencies, yet much below the levels found in the West. The admission rate for peptic ulcer, especially ulcer bleeding remained relatively stable, despite a decreased rate for ulcer perforation. Liver cirrhosis, hepatitis, cholelithiasis with cholecystitis-cholangitis, appendicitis, hemorrhoid and gastritis all decreased. Conclusions: The stomach cancer is the leading cause of admission, despite a recent decline. Colon cancer showed a marked rise. The liver transplant, inflammatory bowel disease and reflux esophagitis were new diagnosis with an increased tendency.

Age-Associated Changes in the Vascular Renin-Angiotensin System in Mice

Yoon, Hye Eun,Kim, Eun Nim,Kim, Min Young,Lim, Ji Hee,Jang, In-Ae,Ban, Tae Hyun,Shin, Seok Joon,Park, Cheol Whee,Chang, Yoon Sik,Choi, Bum Soon Hindawi Publishing Corporation 2016 Oxidative medicine and cellular longevity Vol.2016 No.-

<P><I>Background</I>. This study evaluated whether the change in the renin-angiotensin system (RAS) is associated with arterial aging in mice.<I> Methods</I>. Histologic changes and expressions of transforming growth factor-<I>β</I> (TGF-<I>β</I>), collagen IV,<I> fibronectin</I>, angiotensin II (Ang II), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), prorenin receptor (PRR), Mas receptor (MasR), endothelial nitric oxide synthase (eNOS), NADPH oxidase 2 and oxidase 4 (Nox2 and Nox4), 8-hydroxy-2′-deoxyguanosine (8-OHdG),<I> 3-nitrotyrosine</I>, and superoxide dismutase 1 and dismutase 2 (SOD1 and SOD2) were measured in the thoracic aortas from 2-month-old, 12-month-old, and 24-month-old C57/BL6 mice.<I> Results</I>. Twenty-four-month-old mice showed significantly increased aortic media thickness and expressions of TGF-<I>β</I>, collagen IV, and fibronectin, compared to 2-month-old and 12-month-old mice. The expressions of PRR, ACE, and Ang II, and AT1R-positive area significantly increased, whereas expressions of ACE2 and MasR and AT2R-positive area decreased with age. The expressions of phosphorylated serine<SUP>1177</SUP>-eNOS, SOD1, and SOD2 decreased, and the 8-OHdG-positive area and the 3-nitrotyrosine-positive area increased with age. The expression of Nox2 significantly increased with age, but that of Nox4 did not change.<I> Conclusions</I>. The enhanced PRR-ACE-Ang II-AT1R axis and reduced ACE2-MasR axis were associated with arterial aging in mice. </P>