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)

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>

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.

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>

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.

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).

2 ㎓ 선형 위상 천이 특성을 갖는 소형 아날로그 위상천이기

오현석(Hyun-Seok Oh),최재홍(Jae-Hong Choi),정해창(Hae-Chang Jeong),허윤성(Yun-Seong Heo),염경환(Kyung-Whan Yeom) 한국전자파학회 2011 한국전자파학회논문지 Vol.22 No.1

본 논문에서는 2 ㎓ 선형 위상 천이 특성을 갖는 위상천이기를 설계 및 제작하여 보였다. 소형의 위상 천이기 구현을 위해 집중소자로 구성된 전통과 회로망(all pass network)을 기반으로 위상천이기를 구성하고, 박막 세라믹 공정을 이용하여 제작하였다. 또한, 선형의 위상 천이 특성을 얻기 위해 버랙터(varactor) 다이오드에 직렬 커패시터를 연결하여, 전압에 대한 커패시턴스를 선형화함으로써 비선형성을 개선하였다. 전통과 회로망에 나타나는 인덕터는 스파이럴 인덕터로 구현하고, 이를 다이오드 바이어스 회로에 활용하여 4 ㎜×4 ㎜ 면적을 가지는 소형 위상천이기를 구성할 수 있었다. 또한, 온-웨이퍼(on wafer)로 측정을 위해 입출력은 CPW(Coplanar Waveguide) 형상으로 구현하였으며, 제작된 위상천이기는 버랙터 조정 전압 0~5 V에 대하여, 2 ㎓에서 삽입 손실은 약 4.2~4.7 ㏈, 위상 변화량은 약 79°였으며, 예상한대로 선형 위상 천이 특성을 보였다. In this paper, we present a 2 ㎓ compact analog phase shifter with linear phase-tune characteristic. The compact phase shifter was designed base on a lumped all pass network and implemented using a ceramic substrate fabricated with thin-film technique. For a linear phase-tune characteristic, a capacitance of the varactor diode for a tuning voltage was linearized by connecting series capacitor and subsequently produced an almost linear capacitance change. The inductor and bias circuit in the all pass network was implemented using a spiral inductors for small size, which results in the size reduction to 4 ㎜×4 ㎜. In order to measure the phase shifter using the probe station, two CPW pads are included at the input and output. The fabricated phase shifter showed an insertion loss of about 4.2~4.7 ㏈ at 2 ㎓ band and a total 79° phase change for DC control voltage from 0 to 5 V, and showed linear phase-tune characteristic as expected in the design.

출산에 따른 그레이브스병의 재발 및 관련이자

임창훈,최현아,한승석,김해성,이창욱,정호연,한기옥,장학철,박원근,윤현구,한인권 대한내분비학회 2002 Endocrinology and metabolism Vol.17 No.2

Background: Pregnancy affects the course of Graves' Disease (GD), and patients who initially maintain euthyroid function into their middle trimester with minimum doses of antithyroid drugs become exacerbated after delivery. Even patients who are completely cured, requiring no treatment during pregnancy, can relapse after delivery. In this study, we examined the postpartum changes in the thyroid functions of patients with GD, and attempted to determine the factors contributing to these changes. Methods: The study subjects were recruited from pregnant women visiting our outpatient clinic for routine prenatal evaluations. 45 women previously diagnosed with GD, who had been treated and cured with hyperthyroidism, and were no longer taking any thyroid medications, were evaluated for 1 year post delivery. Results: Among 45 patients, 20 (44.4%) developed thyroid disorders following delivery. Postpartum thyroiditis (PPT) developed in 8 patients (17.8%), and GD developed in 12 (26.0%). The onset of the PPT disease 3.1 ± 1.4 months following delivery, which was significantly earlier than the 6.7 ± 2.7 months required for the post delivery onset of GD (p=0.003). The TBII values, measured during the thyrotoxic state in each womaen, were negative in women with PPT and positive in 71.4% of women with GD (p=0.030). The duration of treatment for hyperthyroidism prior or pregnancy, the number of recurrences, and the time interval without treatment, were not associated with the development of postpartum thyroid disorders. Whereas, the mean number of past pregnancies for women who developed PPT was 3.9 ± 2.1, and was significantly higher than the 2.2 ± 1.7 for women developing no thyroid dysfunctions (p=0.044). In 13 women their initial onset of GD occurred within one year postpartum, 7 (53.8%) having had a recurrence, which was significantly higher than in women whose disease onset occurred unrelated to delivery (5 of 32 women: 15.6%). Conclusion: Women with GD developed postpartum thyroid dysfunctions in 44.4% of cases. Women whose initial disease onset occurred within one year postpartum had higher recurrences of GD, and women who developed PPT had a history of higher gravidity compared to the euthyroid women postpartum. Therefore, if women with GD develop postpartum thyroid dysfunctions, the diagnosis should be made, and a treatment modality planned, following careful considerations of the patients' past obstetric history, changes in clinical manifestations and the TBII values

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.