Erythropoietin Decreases Renal Fibrosis in Mice with Ureteral Obstruction: Role of Inhibiting TGF-β-Induced Epithelial-to-Mesenchymal Transition

Park, Sun-Hee,Choi, Min-Jeong,Song, In-Kyung,Choi, Soon-Youn,Nam, Ju-Ock,Kim, Chan-Duck,Lee, Byung-Heon,Park, Rang-Woon,Park, Kwon Moo,Kim, Yong-Jin,Kim, In-San,Kwon, Tae-Hwan,Kim, Yong-Lim American Society of Nephrology 2007 Journal of the American Society of Nephrology Vol.18 No.5

<P>The inhibitory effects of recombinant human erythropoietin (rhEPO) were examined against (1) the progression of renal fibrosis in mice with complete unilateral ureteral obstruction and (2) the TGF-beta1-induced epithelial-to-mesenchymal transition (EMT) in MDCK cells. Unilateral ureteral obstruction was induced in BALB/c mice and rhEPO (100 or 1000 U/kg, intraperitoneally, every other day) or vehicle was administered from day 3 to day 14. Immunoblotting and immunohistochemistry revealed increased expressions of TGF-beta1, alpha-smooth muscle actin (alpha-SMA), and fibronectin and decreased expression of E-cadherin in the obstructed kidneys. In contrast, rhEPO treatment significantly attenuated the upregulation of TGF-beta1 and alpha-SMA and the downregulation of E-cadherin. MDCK cells were treated with TGF-beta1 (5 ng/ml) for 48 h to induce EMT, and the cells were then co-treated with TGF-beta1 and rhEPO for another 48 h. Increased expressions of alpha-SMA and vimentin and decreased expressions of zona occludens-1 and E-cadherin were observed after TGF-beta1 treatment, and these changes were markedly attenuated by rhEPO co-treatment. TGF-beta1 increased phosphorylated Smad-2 expression in MDCK cells, which was decreased by rhEPO co-treatment. In conclusion, rhEPO treatment inhibits the progression of renal fibrosis in obstructed kidney and attenuates the TGF-beta1-induced EMT. It is suggested that the renoprotective effects of rhEPO could be mediated, at least partly, by inhibition of TGF-beta1-induced EMT.</P>

Association analysis of N-acetyl transferase-2 polymorphisms with aspirin intolerance among asthmatics.

Kim, Jin-Moo,Park, Byung-Lae,Park, Se-Min,Lee, Shin-Hwa,Kim, Myung-Ok,Jung, Seok,Lee, Eun Hee,Uh, Soo-Taek,Park, Jong Sook,Choi, Jae-Sung,Kim, Yong-Hoon,Kim, Mi-Kyeong,Choi, Inseon S,Cho, Sang Heon,Ch Ashley Publications 2010 Pharmacogenomics Vol.11 No.7

<P>AIMS: Cysteinyl leukotrienes are inactivated by acetyl coenzyme A-dependent N-acetyltransferase (NAT). Thus, functional alterations of the NAT gene may contribute to the risk of aspirin-intolerant asthma. MATERIALS & METHODS: Asthmatics (n = 438) were categorized into aspirin-intolerant asthma (15% or greater decrease in the forced expiratory volume in 1 s or cutaneous reactions, n = 170) or aspirin-tolerant asthma (n = 268) groups. In total, 14 polymorphisms of the NAT2 gene were genotyped by a single-base extension method. RESULTS: The distributions of all loci of the 14 SNPs were in Hardy-Weinberg equilibrium (p > 0.05). Among the 14 SNPs, six common SNPs (minor allele frequency >5%) in a Korean population were used for haplotype construction and further statistical analysis. The logistic regression analysis demonstrated that NAT2 -9246G>C and haplotype 2 (TCACGG) were significantly associated with the risk of aspirin-intolerant asthma. The rare allele frequencies of the SNP and Ht2 were significantly higher in the aspirin-intolerant asthma group than in the aspirin-tolerant asthma group (p(corr) = 0.03 and p(corr) = 0.02 in codominant model). CONCLUSION: In a large genetic epidemiology study of aspirin-intolerant asthma in a Korean population, genetic polymorphisms of NAT2 were found to be related to a risk of aspirin hypersensitivity among asthmatics.</P>

폐종괴로 나타난 폐의 림프관평활근종증 1례

박선철 ( Seon Cheol Park ),박병훈 ( Byung Hoon Park ),신상윤 ( Sang Yun Shin ),전한호 ( Han Ho Jeon ),정경수 ( Kyung Soo Chung ),박준철 ( Jun Chul Park ),정재헌 ( Jae Heon Jeong ),권지은 ( Ji Eun Kwon ),박무석 ( Moo Suk Park ) 대한결핵 및 호흡기학회 2007 Tuberculosis and Respiratory Diseases Vol.63 No.3

Lymphangioleiomyomatosis (LAM) is a rare disease that affects females of reproductive age. It is characterized by the abnormal proliferation of smooth muscle cells in the lung and along the axial lymphatics. We report a case of lymphangioleiomyomatosis presenting as a lung mass. The patient visited the emergency room because of dyspnea upon exertion. The chest X-ray showed a lung mass in the right lower lung field and a pneumothorax in the left lung. Chest computed tomography revealed a 5 x 3 cm sized mass in the right lower lobe and multiple thin-walled small cysts scattered in both lungs. Transbronchial biopsy of the lung mass was performed. The biopsy specimen showed atypical smooth muscle cell proliferation and cystic dilatation of the terminal bronchioles, which confirmed the diagnosis of lymphangioleiomyomatosis. To the best of our knowledge, this is the first case of lymphangioleiomyomatosis presenting as a lung mass. (Tuberc Respir Dis 2007; 63: 289-293)

위와 대장의 선암 및 선종에서 E-cadherin/β-catenin 복합체의 발현

박수헌,김재광,정규원,최명규,한준열,선희식,문성배,강창석,이교영 대한소화기학회 2000 대한소화기학회지 Vol.36 No.4

Background/Aims: Poor expressions of E-cadherin and β-catenin complex in the immunohistochemical staining were frequently observed in the tumors. We investigated the correlation between the expressions of E-cadherin and β-catenin and the clinicopathologic factors of adenocarcinomas and adenomas in the stomach and colon. Methods: Immunohistochemical staining of E-cadherin and β-catenin was performed for the adenocarcinomas of stomach (65) and colon (98) and adenomas of stomach (39) and colon (47). Results: The abnormal stainings of E-cadherin and β-catenin were observed in the most adenocarcinomas of the stomach and colon, and in the certain numbers of adenomas of the stomach and colon. This abnormality was frequently observed in the undifferentiated and infiltrative adenocarcinoma. The abnormal staining of E-cadherin and β-catenin in gastric cancer was closely correlated with poor survival, but not in the colon cancer. Conclusions: These findings show that the decreased expression of E-cadherin and β-caare involved in progress of stomach and colon cancer. The cytoplasmic expression of E-cadherin and β-catenin in some adenocarcinoma seems to be also involved in the carcinogenesis but needs further study.

Association of the GSTP1 and NQO1 Polymorphisms and Head and Neck Squamous Cell Carcinoma Risk

Moo Song Lee,Eun Kyung Choi,Sang Yoon Kim,Seok Ki Lee,Chang Gun Cho,Soon Yhul Nam,Sang Wook Lee,Heon Joo Park 대한의학회 2006 Journal of Korean medical science Vol.21 No.6

위암에서 APC 유전자의 이형접합성 상실과 - Catenin 발현과의 관계

박수헌,김재광,정규원,최명규,한준열,선희식,문성배,추교영 대한소화기학회 2000 대한소화기학회지 Vol.35 No.6

Background/Aims: Wide-type Adenomatous polyposis coli (APC) gene binds to β-catenin and APC mutants lead to cytosolic accumulation of β-catenin which serves as a component of carcinogenesis. We investigated the relationship between loss of heperozygosity (LOH) of APC gene and β-catenin expression in gastric cancer. Methods: We examined the LOH of exon 11 of APC gene in frozen specimens of 28 gastric adenocarcinomas and 28 normal gastric tissues obtained from the same patient using polymerase chain reaction and restriction fragment length polymorphism. The cytoplasmic and nuclear β-catenin were investigated by Western blotting. Results: The heterozygosity of APC gene was observed in 21% (6/28), and LOH of APC gene was observed in 33% (2/6). In 14% (4/28) of gastric cancers, β-catenin was strongly expressed both in the cytoplasm and the nucleus. The LOH of APC gene was not correlated with accumulation of β-catenin. Conclusions: The LOH of exon 11 of APC gene is not correlated with an increase of β-catenistric cancer. The cytoplasmic accumulation of β-catenin may be associated with mutations in APC-β-catenin-Tcf-4 pathway.

Inorganic Arsenite Potentiates Vasoconstriction through Calcium Sensitization in Vascular Smooth Muscle

Lee, Moo-Yeol,Lee, Young-Ho,Lim, Kyung-Min,Chung, Seung-Min,Bae, Ok-Nam,Kim, Heon,Lee, Choong-Ryeol,Park, Jung-Duck,Chung, Jin-Ho National Institute of Environmental Health Science 2005 Environmental health perspectives Vol.113 No.10

<P>Chronic exposure to arsenic is well known as the cause of cardiovascular diseases such as hypertension. To investigate the effect of arsenic on blood vessels, we examined whether arsenic affected the contraction of aortic rings in an isolated organ bath system. Treatment with arsenite, a trivalent inorganic species, increased vasoconstriction induced by phenylephrine or serotonin in a concentration-dependent manner. Among the arsenic species tested—arsenite, pentavalent inorganic species (arsenate), monomethylarsonic acid (MMA<SUP>V</SUP>), and dimethylarsinic acid (DMA<SUP>V</SUP>)—arsenite was the most potent. Similar effects were also observed in aortic rings without endothelium, suggesting that vascular smooth muscle plays a key role in enhancing vasoconstriction induced by arsenite. This hypercontraction by arsenite was well correlated with the extent of myosin light chain (MLC) phosphorylation stimulated by phenylephrine. Direct Ca<SUP>2+</SUP> measurement using fura-2 dye in aortic strips revealed that arsenite enhanced vasoconstriction induced by high K<SUP>+</SUP> without concomitant increase in intracellular Ca<SUP>2+</SUP> elevation, suggesting that, rather than direct Ca<SUP>2+</SUP> elevation, Ca<SUP>2+</SUP> sensitization may be a major contributor to the enhanced vasoconstriction by arsenite. Consistent with these <I>in vitro</I> results, 2-hr pretreatment of 1.0 mg/kg intravenous arsenite augmented phenylephrine-induced blood pressure increase in conscious rats. All these results suggest that arsenite increases agonist-induced vasoconstriction mediated by MLC phosphorylation in smooth muscles and that calcium sensitization is one of the key mechanisms for the hypercontraction induced by arsenite in blood vessels.</P>

초자체절제술 후 전방깊이의 변화에 관한 실험적 연구

안병헌,민병무,박종문 충남대학교 의과대학 지역사회의학연구소 1984 충남의대잡지 Vol.11 No.2

The depth of the anterior chamber decreases with aging. Though the increase in the volume "of the lens with aging is a main influential factor to affect the anterior chamber depth, other unknown factors also work. In human the vitreous occupies about 2/3 of the intraocular volume and is confinded within the rigid scleral shell posteriorly. If there were some changes in the volume of the vitreous, these would result in the displacement of the lens and the iris to change the depth of the anterior chamber directly. We performed vitrectomy in 9 rabbits through the peripheral rerina and observed change in the anterior chamber depth. Slit lamp photography was used to measure the anterior chamber depth. To photograph the identical portion of the anterior chamber consecutively, argon laser photocoaglation was applied on the midperipheral iris at 12 and 6 o'clock positions as the Rlandmarks. We measured and compared the depth of anterior chamber image of the positive film with an aid of micrometer attached to light microscope. The measurement was not real depth of the anterior chamber but that of photographic image. Before vitrectomy the mean depth of the anterior chamber was 2.831±0.111mm. At the postvitrectomy 3rd day and the 1st week, the depth was 2.903±0.123 mm and 2.906±0.092 mm respectively. The depth of the anterior chamber became deeper significantly b t-test (5% significance level). But at the 2nd week, the 4th week and 8th week, the mean of the measurements was 2.885±0.083mm, 2.839±0.096mm, and 2.866±0.113mm respectively. These indicated deeper anterior chamber than those of previtrectomy rabbits, but the results were not significant by t-test. The mean number of scales of Goldmann applanation tonometry before the operation was II. The scale readings were 7 at the postoperative 3rd day, 8 at the 1st week and 9 at the 4th week all, 9 at the 8 th week.

메타분석을 이용한 국내 정상성인의 정중신경 체성감각 유발전위의 정상치 : a Meta-Analysis

이경무,김헌,박은희 충북대학교 의과대학 충북대학교 의학연구소 2003 忠北醫大學術誌 Vol.13 No.1

연구목적:체성감각 유발전위(somatosensory evoked potentials:SEPs) 검사는 말초 감각 수용기로부터 대뇌피질에 이르는 체성감각의 구심성 경로를 평가하는 유용한 방법이다. 체성 감각 유발전위의 잠시와 진폭의 정상치는 대상군의 지역적 분포에 따라 차이가 날 수 있어 각 검사실마다 각각의 정상치를 구하여 사용하고 있다. 그러나 이는 지역적인 특성만을 대변하므로, 범국가적인 대표값으로 보기는 힘들다. 또한 1984년 AES(American Encephalo-graphic Society)의 guideline이 있지만 아직 검사방법의 통일이 이루어지지 않아 해석의 어려움이 있어 검사방법의 표준화가 필요한 실정이다. 본 연구에서는 논문분석을 통하여 각 연구에서 어떠한 검사방법들이 사용되었는지 분석하며 검사방법의 표준화를 위한 기초자료를 얻고자 하였으며, 베타분석을 통하여 정중 신경 체성감각 유발전위의 범국가적인 정상 참고치를 구하여 학술연구와 정도관리에 일조하고자 하였다. 대상 및 방법:1978년부터 2001년까지 정중 신경 somatosensory evoked potential의 정상 치에 관한 국내외 연구논문 15편을 대상으로 검사방법의 종류와 빈도를 분석하며 가장 보편적인 검사방법을 알아보았으며, 7편의 국내 연구논문을 대상으로 메타분석을 통하여 정중 신경 체성감각 유발전위의 범국가적인 정상 참고치를 구하고자 하였다. 결과: 1) 전극의 종류로는 침 전극을 가장 많이 사용하였으며, 전극의 위치는 활동기록전극으로는 C3', C4'를 참고기록전극으로는 Fz가 적당하리라 생각된다. 위상의 잠시를 명명하여 표기한 경우로 N1은 N20으로 표기한 경우가 많았으며, Pl은 P22로, N2는 N25로 표기한 경우가 많았고, P2는 다양하였다. 2) 자극의 빈도는 3 pps가, 자극기간은 0.2 msec가 많이 사용되었다. 자극강도는 대부분 thumb twitch가 있는 정도로 하였으며, 총 자극 횟수는 127회가 3편으로 가장 많았다. Low filter의 범위는 2∼20 Hz사이에 있었고, High filter는 500 Hz∼10 kHz사이의 범위까지로 동일한 주파수 설정은 없었다. 3) 국내 논문을 대상으로 메타분석을 시행하여 구한 한국 정상성인의 잠시의 정상 참고치 는 N1이 20.6 msec, P1이 28.2 msec, N2가 37.2 msec, P2가 48.5 msec였다. 진폭은 변이계수가 크고 개인간의 차이가 심하여 진폭만을 기준으로 이상유무를 알기는 어려울 것으로 생각되었다. 결론; 이상의 연구를 통하여 정중신경 유발전위 검사방법을 빈도순으로 분석하였으며 메타 분석을 통하여 잠시와 진폭의 정상참고치를 제시하였다. 이상의 연구결과는 정중신경 유발전위 검사방법의 표준화를 위한 기초자료로 활용될 수 있으며, 도출된 정상 참고치는 정중신경 체성감각 유발전위 검사의 관련 연구와 정도 관리에 유용하리라 생각된다. Purpose:Somatosensory evoked potentials(SEPs) are valuable in evaluating the somatosensory pathway from peripheral sensory receptor to cerebral cortex. Despite there are numbers of normative studies of median nerve Somatosensory evoked potentials (SEPs), each laboratory has one's own normative database. Obvious difficulties are arised in attempting to compare data from one laboratory to another, there is a need to establish a standardized test method with normal references. We initiated this study to overcome these difficulties. Meterials and Methods:We searched through 15 articles, which had been previously published from 1978 to 2001, concerning scalp recorded median nerve Somatosensory Evoked Potentials. The thorough research of 15 articles came out with a common test, and we obtained a world-wide normal reference value of latencies and amplitudes through a meta-analysis technique by researching 7 articles which reported their own normal reference values among korean adults Results 1) The most common electrode was needle electrode. The site for active electrode was C3', C4' and the site for reference electrode was Fz. The most common used names of N1, P1 and N2 were N20, P22, N25 respectively. 2) The stimulation frequency was 3 pps, the stimulation duration was 0.2 cosec, the stimulation intensity was about thumb twitch level and the total stimulation number was found to be more than 128. The low fiter range was 2~20 Hz, the high filter range was 500Hz~10 kHz. 3) The normal reference values of N1, P1, N2 and P2 were 20.63 msec, 28.23 msec, 37.23 msec, 48.54 msec among Korean adults. Conclusion:Since there are many labs that have not established a normal reference value ans a standardized method, the normal latencies suggested through a meta-analysis and a common test method may be used as a valuable reference for many laboratories.

증식당뇨망막증에서 아르곤레이저 광응고술의 치료 효과

안병헌,민병무,최시환,서병로,박우찬 충남대학교 의과대학 지역사회의학연구소 1992 충남의대잡지 Vol.19 No.2

Vitreous hemorrhage, which is the major cause of blindness in proliferative diabetic retinopathy, has been prevented clinically with laser photocoagulation. We reviewed 57 cases(98 eyes) of proliferative diabetic retinopathy which were treated by argon laser and followed up for more than 6 months. Of these 98 eyes, 81 eyes(83%) showed a satisfactory response after standard panretinal photocoagulation. 14 eyes(14%) revealed the vitreous hemorrhage after panretinal photocoagulation and higher incidence of vitreous hemorrhage in the cases of new vessel on the optic disc. In the cases(26 eyes) of new vessel on the optic disc, 2000 laser burns revealed lower incidence of vitreous hemorrhage(1/5, 20%) in comparison with 1500 laser burns(8/21, 38%). These results indicate that initial augmented laser therapy prevented the vitreous hemorrhage effectively.