• Title/Summary/Keyword: CAG

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Post-Transcriptional Control of Tropoelastin in Aortic Smooth Muscle Cells Affects Aortic Dissection Onset

  • Qi, You-Fei;Shu, Chang;Xiao, Zhan-Xiang;Luo, Ming-Yao;Fang, Kun;Guo, Yuan-Yuan;Zhang, Wen-Bo;Yue, Jie
    • Molecules and Cells
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    • v.41 no.3
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    • pp.198-206
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    • 2018
  • Aortic dissection (AD) is a catastrophic disease with high mortality and morbidity, characterized with fragmentation of elastin and loss of smooth muscle cells. Although AD has been largely attributable to polymorphisms defect in the elastin-coding gene, tropoelastin (TE), other undermined factors also appear to play roles in AD onset. Here, we investigated the effects of post-transcriptional control of TE by microRNAs (miRNAs) on elastin levels in aortic smooth muscle cells (ASMC). We found that miR-144-3p is a miRNA that targets TE mRNA in both human and mouse. Bioinformatics analyses and dual luciferase reporter assay showed that miR-144-3p inhibited protein translation of TE, through binding to the 3'-UTR of the TE mRNA. Interestingly, higher miR-144-3p levels and lower TE were detected in the ASMC obtained from AD patients, compared to those from non-AD controls. In a mouse model for human AD, infusion of adeno-associated viruses (serotype 6) carrying antisense for miR-144-3p (asmiR-144-3p) under CAG promoter significantly reduced the incidence and severity of AD, seemingly through enhancement of TE levels in ASMC. Thus, our data suggest an essential role of miR-144-3p on the pathogenesis of AD.

Coronary Artery Bypass Graft (CABG) for Intracavitary Coronary Artery Disease - A case report- (심강내관상동맥(Intracavitary Coronary Artery)질환에 대한 관상동맥우회술 -수술치험 1예-)

  • Kim Su-Wan;Sung Kiick;Park Pyo Won;Jun Tae-Gook;Park Kay-Hyun;Lee Young Tak
    • Journal of Chest Surgery
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    • v.38 no.7 s.252
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    • pp.504-506
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    • 2005
  • Intracavitary coronary artery is variant anomalous entrance to right ventricular cavity of left anterior descending artery. Since the disease is extremely rare, there has not been any report of it in Korea and is only found in $0.2\~0.3\%$ of all CABG patients. It is very difficult to be diagnosed by preoperative coronary arteriography (CAG) and secure suture is needed for right ventriculotomy after CABG due to bleeding from right ventricle. Horizontal mattress suture with pledget has been recommended but, it could compress the myocardium surrounding ventriculotomy and result in disturbed flow of left anterior descending artery branch and perforating artery. So we used simple interrupted suture and the patient was recovered as other CABG patients without complications.

Distribution of five common subtypes of spinocerebellar ataxia in the Korean population

  • Choi, In-Hee;Kim, Gu-Hwan;Lee, Beom-Hee;Choi, Jin-Ho;Yoo, Han-Wook
    • Journal of Genetic Medicine
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    • v.11 no.2
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    • pp.69-73
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    • 2014
  • Purpose: Spinocerebellar ataxia (SCA) is a genetically heterogeneous disease for which more than 30 subtypes have been identified. However, 5 subtypes, SCA1, SCA2, SCA3, SCA6, and SCA7, account for more than 60% of cases. In this study, we report the distribution of these 5 subtypes in Korean patients. Materials and Methods: Six hundred and thirty-eight unrelated patients with a presumptive diagnosis of SCA were included in this study. Trinucleotide (CAG) repeat number (TNR) repeat number was determined using fluorescently labeled primers and fragment analysis. Results: A total of 128 unrelated patients (20.1% of all individuals tested) tested positive for SCA subtypes, including SCA1 (5 patients, 3.9% of those testing positive), SCA2 (38 patients, 29.7%), SCA3 (30 patients, 23.4%), SCA6 (39 patients, 30.5%), and SCA7 (16 patients, 12.5%). The mean copy number of pathogenic TNR alleles was $45{\pm}8.5$ for SCA1, $42{\pm}3.1$ for SCA2, $72{\pm}5.4$ for SCA3, $23{\pm}1.5$ for SCA6, and $50{\pm}11.4$ for SCA7. TNR copy number was inversely correlated with onset age in SCA2, SCA6, and SCA7. Conclusion: SCA2, SCA3, and SCA6 are common SCA subtypes in Korean patients and could be screened as a first-line test. Expanded pathogenic allele size was associated with early onset age.

Progress in human ovarian rejuvenation: Current platelet-rich plasma and condensed cytokine research activity by scope and international origin

  • Sills, E. Scott;Wood, Samuel H.
    • Clinical and Experimental Reproductive Medicine
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    • v.48 no.4
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    • pp.311-315
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    • 2021
  • Objective: As clinicians and patients await consensus on intraovarian platelet-rich plasma (PRP) treatment, this project evaluated contemporary research trends in the literature. Methods: A PubMed/NLM search aggregated all ovarian PRP-related publications (n=54) to evaluate their scope, abstract utility, submission-to-publication interval, journal selected, article processing charge (APC), free reader access to full-text manuscripts, number and nationality of authors, and inclusion of international collaborators. The NIH Clinical Trials database was also audited. Results: Published output on intraovarian PRP has increased consistently since 2016, especially among investigators in Greece, Iran, USA, and Turkey. Between 2013 and 2021, 42 articles met the relevancy criteria, of which 40.5% reported clinical studies, small series, or case reports, 33% described experimental animal models, and 23.8% were opinion/review papers. Only two works included a placebo control group. The submission-to-publication interval (mean±standard deviation) was 130±96 days, there were 5.9±3.2 authors per project, and journals invoiced US $1,613±1,466 (range, $0-$3,860) for APCs. Conclusion: There was no correlation between APC and time to publish (Pearson's r=-0.01). Abstract content was inconsistent; sample size and patient age were often missing, yet free full-text "open access" was available for most publications (59.5%). The NIH Clinical Trials portal lists eight registered studies on "ovarian rejuvenation," of which two are actively recruiting patients, while four have been terminated or have an uncertain status. Two studies have concluded, with results from one posted to the NIH website. PRP and its derivatives for ovarian treatment show early promise, but require further investigation. Research is accelerating and should be encouraged, particularly placebo-controlled randomized clinical trials.

Change of coronary artery indices according to coronary dominance pattern in early childhood

  • Lee, Yoon Jin;Park, Kyoung Soo;Kil, Hong Ryang
    • Clinical and Experimental Pediatrics
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    • v.62 no.6
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    • pp.240-243
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    • 2019
  • Purpose: Coronary arterial lesion assessment in children can be difficult, depending on the coronary dominance pattern. Although it is easier to determine coronary dominance with echocardiography in children than in adults, it is still difficult. This study aimed to examine the coronary dominance pattern according to the objective coronary artery (CA) indices. Methods: The CA diameter, aortic valve annulus, and abdominal aorta of 69 children without any cardiovascular disease were measured with cross-sectional echocardiography at Chungnam National University Hospital. To evaluate the coronary dominance pattern, echocardiography was primarily used; additionally, coronary computed tomographic angiography or coronary angiography (CAG). Coronary dominance was determined according to the status of the CA that gives rise to the posterior descending artery. Results: The mean age was $4.02{\pm}2.78years$, and the mean body surface area (BSA) was $0.70{\pm}0.22m^2$. Right dominance was present in 78% and left in 22% of the subjects. In those with left dominance, the CA to aortic valve annulus diameter ratio was $0.125{\pm}0.021$ in the right coronary artery (RCA) and $0.255{\pm}0.032$ in the left coronary artery (LCA). In those with right dominance, the corresponding ratio was $0.168{\pm}0.028$ in the RCA and $0.216{\pm}0.030$ in the LCA (P<0.05). Significant differences were also found in the diametric ratios of the CA to BSA and abdominal aorta (P<0.05). Conclusion: The CA indices showed significant difference according to the coronary dominance pattern in early childhood. It is possible to indirectly determine the coronary dominance pattern with the CA indices in children using echocardiography. The accuracy of coronary artery lesion diagnosis can be improved by taking coronary dominance into account.

Characterization of binding specificity using GST-conjugated mutant huntingtin epitopes in surface plasmon resonance (SPR)

  • Cho, Hang-Hee;Kim, Tae Hoon;Kim, Hong-Duck;Cho, Jae-Hyeon
    • Korean Journal of Veterinary Service
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    • v.44 no.4
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    • pp.185-194
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    • 2021
  • Polyglutamine extension in the coding sequence of mutant huntingtin causes neuronal degeneration associated with the formation of insoluble polyglutamine aggregates in Huntington's disease (HD). Mutant huntingtin can form aggregates within the nucleus and processes of neurons possibly due to misfolding of the proteins. To better understand the mechanism by which an elongated polyglutamine causes aggregates, we have developed an in vitro binding assay system of polyglutamine tract from truncated huntingtin. We made GST-HD exon1 fusion proteins which have expanded polyglutamine epitopes (e.g., 17, 23, 32, 46, 60, 78, 81, and 94 CAG repeats). In the present emergence of new study adjusted nanotechnology on protein chip such as surface plasmon resonance strategy which used to determine the substance which protein binds in drug discovery platform is worth to understand better neurodegenerative diseases (i.e., Alzheimer disease, Parkinson disease and Huntington disease) and its pathogenesis along with development of therapeutic measures. Hence, we used strengths of surface plasmon resonance (SPR) technology which is enabled to examine binding specificity and explore targeted molecular epitope using its electron charged wave pattern in HD pathogenesis utilize conjugated mutant epitope of HD protein and its interaction whether wild type GST-HD interacts with mutant GST-HD with maximum binding affinity at pH 6.85. We found that the maximum binding affinity of GST-HD17 with GST-HD81 was higher than the binding affinities of GST-HD17 with other mutant GST-HD constructs. Furthermore, our finding illustrated that the mutant form of GST-HD60 showed a stronger binding to GST-HD23 or GST-HD17 than GST-HD60 or GST-HD81. These results indicate that the binding affinity of mutant huntingtin does not correlate with the length of polyglutamine. It suggests that the aggregation of an expanded polyglutamine might have easily occurred in the presence of wild type form of huntingtin.

Ginsenoside compound K reduces the progression of Huntington's disease via the inhibition of oxidative stress and overactivation of the ATM/AMPK pathway

  • Hua, Kuo-Feng;Chao, A-Ching;Lin, Ting-Yu;Chen, Wan-Tze;Lee, Yu-Chieh;Hsu, Wan-Han;Lee, Sheau-Long;Wang, Hsin-Min;Yang, Ding-I.;Ju, Tz-Chuen
    • Journal of Ginseng Research
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    • v.46 no.4
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    • pp.572-584
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    • 2022
  • Background: Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of trinucleotide CAG repeat in the Huntingtin (Htt) gene. The major pathogenic pathways underlying HD involve the impairment of cellular energy homeostasis and DNA damage in the brain. The protein kinase ataxia-telangiectasia mutated (ATM) is an important regulator of the DNA damage response. ATM is involved in the phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK plays a critical role in response to DNA damage. Herein, we demonstrated that expression of polyQ-expanded mutant Htt (mHtt) enhanced the phosphorylation of ATM. Ginsenoside is the main and most effective component of Panax ginseng. However, the protective effect of a ginsenoside (compound K, CK) in HD remains unclear and warrants further investigation. Methods: This study used the R6/2 transgenic mouse model of HD and performed behavioral tests, survival rate, histological analyses, and immunoblot assays. Results: The systematic administration of CK into R6/2 mice suppressed the activation of ATM/AMPK and reduced neuronal toxicity and mHTT aggregation. Most importantly, CK increased neuronal density and lifespan and improved motor dysfunction in R6/2 mice. Conversely, CK enhanced the expression of Bcl2 protected striatal cells from the toxicity induced by the overactivation of mHtt and AMPK. Conclusions: Thus, the oral administration of CK reduced the disease progression and markedly enhanced lifespan in the transgenic mouse model (R6/2) of HD.

Evaluation of Radiation Dose to Patients according to the Examination Conditions in Coronary Angiography (심장동맥 조영 검사 시 검사 조건에 따른 환자 선량 평가)

  • Yong-In Cho
    • Journal of radiological science and technology
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    • v.46 no.6
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    • pp.509-517
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    • 2023
  • This study analyzed imaging conditions and exposure index through clinical information collection and dose calculation programs in coronary angiography examinations. Through this, we aim to analyze the effective dose according to examination conditions and provide basic data for dose optimization. In this study, ALARA(As Low As Reasonably Achievable)-F(Fluoroscopy), a program for evaluating the radiation dose of patients and the collected clinical data, was used. First, analysis of imaging conditions and exposure index was performed based on the data of the dose report generated after coronary angiography. Second, after evaluating organ dose according to 9 imaging directions during coronary angiography, with the LAO fixed at 30°, dose evaluation was performed according to tube voltage, tube current, number of frames, focus-skin distance, and field size. Third, the effective dose for each organ was calculated according to the tissue weighting factors presented in ICRP(International Commission on Radiological Protection) recommendations. As a result, the average sum of air kerma during coronary angiography was evaluated as 234.0±112.1 mGy, the dose-area product was 25.9±13.0 Gy·cm2, and the total fluoroscopy time was 2.5±2.0 min. Also, the organ dose tended to increase as the tube voltage, milliampere-second, number of frames, and irradiation range increased, whereas the organ dose decreased as the FSD increased. Therefore, medical radiation exposure to patients can be reduced by selecting the optimal tube voltage and field size during coronary angiography, maximizing the focal-skin distance, using the lowest tube current possible, and reducing the number of frames.

Effect of Attenuation Correction, Scatter Correction and Resolution Recovery on Diagnostic Performance of Quantitative Myocardial SPECT for Coronary Artery Disease (감쇠보정, 산란보정 및 해상도복원이 정량적 심근 SPECT의 관상동맥질환 진단성능에 미치는 효과)

  • Hwang, Kyung-Hoon;Lee, Dong-Soo;Paeng, Jin-Chul;Lee, Myoung-Mook;Chung, June-Key;Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.36 no.5
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    • pp.288-297
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    • 2002
  • Purpose: Soft tissue attenuation and scattering are major methodological limitations of myocardial perfusion SPECT. To overcome these limitations, algorithms for attenuation, scatter correction and resolution recovery (ASCRR) is being developed, while quantitative myocardial SPECT has also become available. In this study, we investigated the efficacy of an ASCRR-corrected quantitative myocardial SPECT method for the diagnosis of coronary artery disease (CAD). Materials and Methods: Seventy-five patients (M:F=51:24, $61.0{\pm}8.9$ years old) suspected of CAD who underwent coronary angiography (CAG) within $7{\pm}12$ days of SPECT(Group-I) and 20 subjects (M:F=10:10, age $40.6{\pm}9.4$) with a low likelihood of coronary artery disease (Group-II) were enrolled. Tl-201 rest/ dipyridamole-stress Tc-99m-MIBI gated myocardial SPECT was performed. ASCRR correction was peformed using a Gd-153 line source and automatic software (Vantage-Pro; ADAC Labs, USA). Using a 20-segment model, segmental perfusion was automatically quantified on both the ASCRR-corrected and uncorrected images using an automatic quantifying software (AutoQUANT; ADAC Labs.). Using these quantified values, CAD was diagnosed in each of the 3 coronary arterial territories. The diagnostic performance of ASCRR-corrected SPECT was compared with that of non-corrected SPECT. Results: Among the 75 patients of Group-I, 9 patients had normal CAG while the remaining 66 patients had 155 arterial lesions; 61 left anterior descending (LAD), 48 left circumflex (LCX) and 46 right coronary (RCA) arterial lesions. For the LAD and LCX lesions, there was no significant difference in diagnostic performance. In Group-II patients, the overall normalcy rate improved but this improvement was not statistically significant (p=0.07). However, for RCA lesions, specificity improved significantly but sensitivity worsened significantly with ASCRR correction (both p<0.05). Overall accuracy was the same. Conclusion: The ASCRR correction did not improve diagnostic performance significantly although the diagnostic specificity for RCA lesions improved on quantitative myocardial SPECT. The clinical application of the ASC-RR correction requires more discretion regarding cost and efficacy.

Clinical Significance of Reverse Redistribution Phenomenon on Delayed Tc-99m Tetrofosmin Myocardial Perfusion Imaging in Patients with Acute Myocardial Infarction (급성 심근경색 환자의 Tc-99m Tetrofosmin 심근 관류 지연영상에서 관찰되는 역재분포 현상의 임상적 의의)

  • Park, Soon-Ah;Kim, Dae-Weung;Kim, Chang-Guhn;Jeong, Jin-Won;Kim, Nam-Ho;Yun, Kyeong-Ho
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.2
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    • pp.112-119
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    • 2009
  • Purpose: This study was performed to investigate the clinical significance of reverse redistribution(RR) phenomenon detected on delayed Tc-99m tetrofosmin myocardial single photon emission computed tomography(SPEG) in patients with acute myocardial infarction after revascularization. Materials and Methods: A Tc-99m tetrofrosmin myocardial SPECT was performed in 67 consecutive patients after revascularization for acute myocardial infarction. Myocardial SPECT imaging was performed for early imaging at 40 min and for delayed imaging at 180 min after reinjection at myocardial stress. Regional myocardial uptakes were scored by 4-point scoring in the left ventricular wall divided into 17 segments. Reverse redistribution was defined as an increase of more than 2 point in the activity score on the delayed image. Follow-up myocardial SPECT and coronary angiography(CAG) were performed 9 months later. Results: On myocardial SPECT performed following revascularization, RR was observed in 100 of all 319 segments(31%) and in 43 patients(64%). The abnormalities of perfusion and regional wall motion were more severe in the patients with RR compared to those without RR(p<0.05). On follow-up myocardial SPECT, the myocardial perfusion, regional wall motion, and myocardial thickness were significantly improved in the patients with RR(p<0.05) however, these changes were not significant in those without RR. There was no significant difference between the patients with RR and those without RR in the occurrence of restenosis on CAG. Conclusions: In patients with acute myocardial infarction, the regions showing the RR phenomenon on delayed Tc-99m tetrofosmin SPECT may reflect viable myocardium and indicate recovery of salvaged myocardium.