Insulin resistance mediates high-fat diet-induced pulmonary fibrosis and airway hyperresponsiveness through the TGF-β1 pathway

Park, Yoon Hee,Oh, Eun Yi,Han, Heejae,Yang, Misuk,Park, Hye Jung,Park, Kyung Hee,Lee, Jae-Hyun,Park, Jung-Won Nature Publishing Group UK 2019 Experimental and molecular medicine Vol.51 No.5

<▼1><P>Prior studies have reported the presence of lung fibrosis and enhanced airway hyperresponsiveness (AHR) in mice with high-fat-diet (HFD)-induced obesity. This study evaluated the role of TGF-β1 in HFD-induced AHR and lung fibrosis in a murine model. We generated HFD-induced obesity mice and performed glucose and insulin tolerance tests. HFD mice with or without ovalbumin sensitization and challenge were also treated with an anti-TGF-β1 neutralizing antibody. AHR to methacholine, inflammatory cells in the bronchoalveolar lavage fluid (BALF), and histological features were evaluated. Insulin was intranasally administered to normal diet (ND) mice, and in vitro insulin stimulation of BEAS-2b cells was performed. HFD-induced obesity mice had increased insulin resistance, enhanced AHR, peribronchial and perivascular fibrosis, and increased numbers of macrophages in the BALF. However, they did not have meaningful eosinophilic or neutrophilic inflammation in the lungs compared with ND mice. The HFD enhanced TGF-β1 expression in the bronchial epithelium, but we found no differences in the expression of interleukin (IL)−4 or IL-5 in lung homogenates. Administration of the anti-TGF-β1 antibody attenuated HFD-induced AHR and lung fibrosis. It also attenuated goblet cell hyperplasia, but did not affect the AHR and inflammatory cell infiltration induced by OVA challenge. The intranasal administration of insulin enhanced TGF-β1 expression in the bronchial epithelium and lung fibrosis. Stimulating BEAS-2b cells with insulin also increased TGF-β1 production by 24 h. We concluded that HFD-induced obesity-associated insulin resistance enhances TGF-β1 expression in the bronchial epithelium, which may play an important role in the development of lung fibrosis and AHR in obesity.</P></▼1><▼2><P><B>Obesity: A trigger for asthma onset</B></P><P>Insulin resistance may be an important causative factor underlying the increased risk of asthma and other respiratory issues in obese individuals. Obesity doubles the likelihood of developing asthma, with symptoms that are more difficult to control than in non-obese patients. The connection between these conditions is poorly understood, but researchers led by Jung-Won Park, Yonsei University College of Medicine, Seoul, South Korea, have identified a potential mechanism. They demonstrated that a signaling molecule called TGF-β1 contributes to airway sensitivity and tissue scarring in a mouse model of diet-induced obesity. Subsequent experiments showed that treatment with insulin also gives rise to increased TGF-β1 production in the mouse lung. Since insulin resistance is a common feature of obesity, resulting in abnormally high levels of circulating insulin, this could also account for the increased risk of respiratory problems.</P></▼2>

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

Wechsler 記憶檢査(改訂版)의 妥當度 硏究

韓五洙,柳希姃,金晟倫,金昌潤,李楨敎,李哲,朴仁鎬 서울醫大 1997 精神醫學 Vol.22 No.1

젖소 말초혈액 림프구로부터 소백혈병 바이러스 배양 및 전자현미경적 관찰

윤순식,박중원,변재원,강문일,유한상,한홍율 韓國電子顯微鏡學會 2005 Applied microscopy Vol.35 No.1

국내 젖소의 54.2%가 BLV에 감염되어 있지만 현재까지 국내에서는 소백혈병 바이러스 (BLV) 입자를 확인한 연구 보고가 없기 때문에 BLV 항체 양성 소의 말초혈액림프구를 배양, BLV를 발현시켜 전자현미경으로 바이러스 입자를 검출하였고 배양조건에 따른 바이러스 발현율 및 발현 시간을 비교하였다. 검사 결과 전형적인 C-형 바이러스를 확인할 수 있었으며 BLV 단크론 항체를 이용한 면역염색결과 BLV 항원 양성으로 확인되었다. BLV 는 대부분 세포 외부에 분포하고 있었으며 세포질 막에서 생성, 발아되어 나오는 것도 관찰되었다. 전체 바이러스의 크기는 90~100 nm였으며 nucleocapsid는 40~60nm였다. 소태아혈청 (FBS)과 T- 및 B-림프구 분열촉진물질(mitogen)을 각각 첨가하여 배양한 결과 두 군 모두에서 BLV 발현이 확인되었다. Lipopolysaccharide 첨가군은 배양 12시간, Conconavalin A 첨가군은 배양 24시간에 각각 림프구의 10%에서 바이러스가 관찰되었다. 또한 FBS만 첨가한 군과 FBS와 mitogen을 모두 첨가하지 않은 군에서도 관찰되었으나 바이러스의 수는 적었다. 본 연구에서 확립된 BLV 배양 기법을 활용하면 BLV에 감염된 소 중 바이러스를 발현하는 소, 즉 전파능이 있는 개체를 찾아내어 우선적으로 도태할 수 있기 때문에 BLV 감염으로 인한 피해를 막는데 효과적으로 이용될 수 있을 것으로 사료된다. Many studies have been performed on the bovine leukemia virus (BLV) since bovine leukosis had been reported in 1968 in Korea. However, there was no report on the ultrastructural examination of BLV. An attempt to detect C-type viral particles in the cultured peripheral blood lymphocytes of Holstein-Friesian dairy cattle, was made to determine whether in vitro viral expression might be used as a reliable method to identify the cow which is likely to transmit BLV. In transmission electron microscopic (TEM) examination, the virus particles were found predominantly outside of the lymphocytes even though a few particles were also observed within the membrane bound cytoplasmic vacuoles. All of them were C-type particles consisting of a central, electron-dense core separated by a clear area from a limiting envelope with a unit membrane structure. Virus particles were easily detected in the lymphocyte which was cultured with medium supplemented with either T-lymphocyte mitogen (conconavalin A) or B-lymphocyte mitogen (lipopolysaccharide). Identical viral particles, although fewer, were also consistently present in the lymphocytes cultured with medium which was containing foetal bovine serum (FBS) only and which was containing neither FBS or mitogen. By contrast, no virus particle was detected in extensive examination of lymphocytes before culture. In conclusion, the BLV cultivation and detection methods established in this study could be used as a tool to identify and eliminate the cattle which can transmit the BLV.

범가자미, Verasper variegatus의 난황단백질 분리 및 면역학적 특성

백혜자,한창희,김우진,박중연,김진한,김윤 동의대학교 기초과학연구소 1998 基礎科學硏究論文集 Vol.8 No.1

The yolk protein of spotted flounder, Verasper variegatus was purified by precipitation with cold distilled water, followed by Sepharose CL-6B column chromatography. The purified protein was identified as vitellin by Ouchterlony's immunodiffusion test and immunoelectrophoresis. The purified vitellin from ovarian crude extracts has same antigenic determinants with the female specific serum protein, vitellogenin. The molecular weight of purified vitellin was estimated about 550kD by gel filtration. The vitellin was composed of three major subunits with molecular weight of about 108, 85 and 31 kD, and two minor subunits. The vitellin was identified by western blot analysis using anti-vitellin antibody.

Growth Stimulation and Inhibition of Differentiation of the Human Colon Carcinoma Cell Line Caco-2 with an Anti-Sense Insulin-Like Growth Factor Binding Protein-3 Construct

Yoon,Han,Jung,Park The Korea Science and Technology Center 1999 BMB Reports Vol.32 No.3

The insulin-like growth factor (IGF) system consisting of IGF-1, IGF-II, IGF-receptors, and IGF-binding proteins (IGFBP) regulates the proliferation of a variety of cancer cell types. To examine whether a decrease in endogenous IGFBP-3 stimulates proliferation or inhibits differentiation, Caco-2 cells, a human colon adenocarcinoma cell line, were stably transfected with an anti-sense IGFBP-3 expression construct or pcDNA3 vector as control. Accumulation of IGFBP-3 mRNA and secretion of IGFBP-3 into serum-free conditioned medium, 9 days after plating, were significantly lower in Caco-2 cell clones transfected with anti-sense IGFBP-3 cDNA compared to the controls. The anti-sense clones grew at a similar rate to the controls for 8 days after plating, but achieved a higher final density between days 10 and 12. The levels of sucrase-isomaltase mRNA, a marker of enterocyte differentiation of Caco-2 cells, were lower in the anti-sense clones examined on day 9. In conclusion, proliferation of Caco-2 cells can be stimulated by lowering endogenously-produced IGFBP-3.

내시경적 조임근절개술후에 발생한 췌십이지장 가성동맥류 1예

박수영,김윤정,박진한,전현수,박시형,이영진,이은지,김지현 仁濟大學校 白病院 2010 仁濟醫學 Vol.31 No.-

We reported a case of pancreatic pseudoaneurysm, involving pancreaticoduodenal artery, developed after endoscopic retrograde cholangiopancreatography(ERCP) with endoscopic sphinterotomy. A 54 year old woman was transferred to our hospital due to sustained hematochezia and hypovolemia. A week before admission, she underwent ERCP with endoscopic sphinterotomy for acute cholangitis in local clinics. She developed abdominal pain and hematochezia at 12 hours after the procedures. A post procedure contrast enhanced computed tomography of abdomen demonstrated a pseudoaneurysm in inferior portion of pancreatic head. This was not present on the pre procedure contrast enhanced computed tomography of abdomen and was thought to arise from the pancreaticoduodenal artery as a complication of the pre sphincterotomy. She was brought to our emergency room in a state of hypovolemia. A upper endoscopy showed active bleeding from ampula of vater. An celiac angiography demonstrated pancreatic pseudoaneurysm involving inferior pancreaticoduodenal artery and selective coil embolization of was performed.

GaAs MESFET를 이용한 단일평형 저항성 주파수 혼합기

박정민,윤영중,김건욱,박한규 연세대학교 산업기술연구소 1999 논문집 Vol.31 No.1

In this paper, the method to increase linearity and port-to-port isolation of resistive mixer which uses the channel resistance of a GaAs MESFET to perform frequency mixing was proposed. For better linearity and port-to-port isolation, single-balanced structure is applied, and a short circuit using open stub is constructed to eliminate the port-to-port coupling phenomena. The proposed GaAs MESFET single-balanced resistive mixer exhibited 5.9dB of conversion loss at 0dBm of LO power. In addition, 34.3dBm of input second-order intercept point, and 26.1dBm of input third-order intercept point are achieved. Also LO-to-IF and LO-to-RF isolation are over 42dB and 45dB, respectively.

토양환경지도 자료를 이용한 콩밭 토양의 화학성 비교

박지숙,이민진,정재원,김미혜,이서연,지윤미,한준호,김유학,공명석,한광현,노희명 忠北大學校 農業科學硏究所 2015 農業科學硏究 Vol.31 No.2

It is important to interpret the soil chemical properties in order to effectively manage the farmland. This study was conducted to investigate the soil chemical properties of upland soybean field according to the soil series at 32 upland fields located in the parts of Gangwon-do. Soil sampling sites were selected by using the National Statistics DB and KSIS DB that is a soil environment information system provided by the Rural Development Administration. Soil samples were collected from 0~15 cm of top soil before seeding or transplanting, air-dried, passed through a 2 mm sieve, and analyzed for soil pH, EC, organic matter, available phosphorus (P2O5), exchangeable potassium, exchangeable calcium and exchangeable magnesium. The average chemical properties have exceeded the each nutrient optimum range level of RDA, except the organic matter in experimental soil 2015. And despite application of conventional fertilization, each soil series nutrient contents were change respectively. The results of this study suggest that conventional fertilization should be applied based on the analysis about the amount of accumulated nutrient contents in the soil.

급성전골수성백혈병에서 백혈구성분채집술에 이은 치명적인 뇌출혈 2예

오윤정,박소윤,김윤정,한동석,김현수,최진혁,남동기,임호영,김효철,주희재 아주대학교 의과학연구소 1998 아주의학 Vol.3 No.1

The aim of this study is to report 2 cases of acute promyelocytic leukemia who died from intracranial hemorrhage following leukapheresis and to provide proper preventive measures against hemorrhage following leukapheresis. From 1994 to 1997, a total of twenty-six patients with leukemia underwent leukapheresis to control hyperleukocytosis at Ajou University Hospital. Two patients with acute promyelocytic leukemia received all-trans retinoic acid but developed drug-induced hyperleukocytosis. Shortly after leukapheresis, they died from intracranial hemorrhage. The risk factors for fatal hemorrhage are thought to be coexisting disseminated intravascular coagulation(DIC), thrombocytopenia aggravated by leukapheresis, exacerbated coagulopathy related to mechanical trauma through leukapheresis and the excess use of citrate during leukapheresis. To reduce the risk of the bleeding associated with leukapheresis, it is necessary to replace platelet sufficiently before and after leukapheresis and to give calcium to correct coagulopathy induced by excess citrate which is used as anticoagulant as well as the correction of disseminated intravascular coagulation.