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Journal of Geriatric Cardiology 2006年第3期3卷 135-151页

作者： Peter K Law Danlin M Law Eugene KW Sim Khawja H Haider Margarita N Vakhromeeva Ilia I Berishvili Leo A Bockeria choong-chin liew Cell Transplants Asia Ltd. Canada National University Medical Institutes National University of Singapore Singapore Department of Pathology and Laboratory Medicine University of Cincinnati Ohio USA Bakoulev Scientific Center for Cardiovascular Surgery Russian Academy of Medical Sciences Russia Bingham and Women's Hospital The Cardiovascular Genome Unit Harvard Medical School USA

Human Myoblast Genome Therapy (HMGT) is a platform technology of cell transplantation, nuclear transfer, and tissue engineering. Unlike stem cells, myoblasts are differentiated, immature cells destined to become muscles. Myoblasts cultured from satellite cells of adult muscle biopsies survive, develop, and function to revitalize degenerative muscles upon transplantation. Injection injury activates regeneration of host myofibers that fuse with the engrafted myoblasts, sharing their nuclei in a common gene pool of the syncytium. Thus, through nuclear transfer and complementation, the normal human genome can be transferred into muscles of patients with genetic disorders to achieve phenotype repair or disease prevention. Myoblasts are safe and efficient gene transfer vehicles endogenous to muscles that constitute 50% of body weight. Results of over 280 HMGT procedures on Duchenne Muscular Dystrophy (DMD) subjects in the past 15 years demonstrated absolute safety. Myoblast-injected DMD muscles showed improved histology. Strength increase at 18 months post-operatively averaged 123%. In another application of HMGT on ischemic cardiomyopathy, the first human myoblast transfer into porcine myocardium revealed that it was safe and effective. Clinical trials on approximately 220 severe cardiomyopathy patients in 15 countries showed a <10% mortality. Most subjects received autologous cells implanted on the epicardial surface during coronory artery bypass graft, or injected on the endomyocardial surface percutaneously through guiding catheters. Significant increases in left ventricular ejection fraction, wall thickness, and wall motion have been reported, with reduction in perfusion defective areas, angina, and shortness of breath. As a new modality of treatment for disease in the skeletal muscle or myocardium, HMGT emerged as safe and effective. Large randomized multi-center trials are under way to confirm these preliminary results. The future of HMGT is bright and exciting.

关键词： heart regeneration human genome therapy myoblasts

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哺乳类心脏肌浆球蛋白重链基因中的富嘧啶基内含子的唯一保守性(英文)

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山西医科大学学报 2001年第Z1期32卷 22-27页

作者：王若翔 choong chin liew 加拿大多伦多大学心血管研究中心分子心脏病学研究室

研究了人类和大鼠的心脏α和 β 肌球蛋白重链基因中的嘧啶基比例。编码MyHC尾的外显子均是缺少嘧啶基的。这一特殊发现 ,即某些内含子是富嘧啶基的 ,而此种富嘧啶基状态在人类和大鼠均有保留 ,使所有四种等位基因共有两个富含嘧啶基的... 详细信息

研究了人类和大鼠的心脏α和 β 肌球蛋白重链基因中的嘧啶基比例。编码MyHC尾的外显子均是缺少嘧啶基的。这一特殊发现 ,即某些内含子是富嘧啶基的 ,而此种富嘧啶基状态在人类和大鼠均有保留 ,使所有四种等位基因共有两个富含嘧啶基的内因子 ,并且每对标准基因均含有两种不同的富含嘧啶基内因子。此种强烈保守性与这些内含子的序列无关。基于基因组序列的对比研究所得到的上述发现提示基因组序列除了编码心脏肌球蛋白重链多肽的作用以外 ,还具有其他附加的功能。

关键词：嘧啶类核苷酸类外显子内含子基因组心脏肌球蛋白重链金仓鼠人类

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Use of blood based biomarkers in the evaluation of Crohn's disease and ulcerative colitis

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World Journal of Gastrointestinal Endoscopy 2015年第17期7卷 1233-1237页

作者： Edward L Barnes choong-chin liew Samuel Chao Robert Burakoff Division of Gastroenterology Hepatologyand EndoscopyBrigham and Women’s Hospital Golden Health Diagnostics Inc. GeneNews

Despite significant improvements in our understanding of Crohn's disease(CD) and ulcerative colitis(UC) in recent years, questions remain regarding the best approaches to assessment and management of these chronic diseases during periods of both relapse and remission. Various serologic biomarkers have been used in the evaluation of patients with both suspected and documented inflammatory bowel disease(IBD), and while each has potential utility in the assessment of patients with IBD, potential limitation remain with each method of assessment. Given these potential shortcomings, there has been increased interest in other means of evaluation of patients with IBD, including an expanding interest in the role of gene expression profiling. Among patients with IBD, gene expression profiles obtained from whole blood have been used to differentiate active from inactive CD, as well as to differentiate between CD, UC, and non-inflammatory diarrheal conditions. There are many opportunities for a non-invasive, blood based test to aid in the assessment of patients with IBD, particularly when considering more invasive means of evaluation including endoscopy with biopsy. Furthermore, as the emphasis on personalized medicine continues to increase, the potential ability of gene expression analysis to predict patient response to individual therapies offers great promise. While whole blood gene expression analysis may not completely replace more traditional means of evaluating patients with suspected or known IBD, it does offer significant potential to expand our knowledge of the underlying genes involved in the development of these diseases.

关键词： Inflammatory bowel disease Ulcerative colitis Gene

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64-row multi-dector computed tomography coronary image from a center with early experience: first illustration of learning curve

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Journal of Geriatric Cardiology 2006年第1期3卷 29-34页

作者： Sze Piaw chin Tiong Kiam ONG Chee Khoon liew M.Tobias Seyfarth Fong Yean Yip ALAN Houng Bang liew Kui Hian SIM Dept of Cardiology Sarawak General Hospital Siemens Cardiac Solutions Erlangen Germany

Background and objectives The recent joint ACCF/AHA clinical competence statement on cardiac imaging with multi-detector computed tomography recommended a minimum of 6 months training and 300 contrast examinations, of which the candidate must be directly involved in at least 100 studies. Whether this is adequate to become proficient in interpretation of coronary computed tomogsignificant coronary stenosis in a center with 1 year's experience using a 64-row scanner. Methods A total of 778 patients underwent contrast-enhanced CTA between January and December 2005. Out of these patients, 301 patients also underwent contrast-enhanced conventional coronary angiography (CCA). These patients were divided into 4 groups according to the time the examination was underwent. Group Q1: first quarter of the year (n=20), Group Q2: second quarter (n=128), Group Q3: third quarter (n=134), and Group Results The sensitivity, specificity, positive, and negative predictive values were Q1 - 64%, 89%, 49% and 94%, respectively; Q2 -79%, 96%, 74% and 97%, respectively; Q3 - 78%, 96%, 74%, 97%, respectively, and Q4 - 100% for all. Conclusions In a center with formal training and high caseload, our accuracy in CTA analysis reached a plateau after 6 months experience. Test-bolus protocols produce better image quality and can improve accuracy. New centers embarking on CTA will need to overcome an initial 6-month learning curve depending upon the caseload during which time they should consider correlation with CCA.

关键词： computed tomography training angiography coronary artery disease

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Assessment of left ventricular ejection fraction: comparison of two dimensional echocardiography, cardiac magnetic resonance imaging and 64-row multi-detector computed tomography

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Journal of Geriatric Cardiology 2006年第1期3卷 2-8页

作者： Chee Khoon liew Rapaee ANNUAR Tiong Kiam ONG Sze Piaw chin Tobias Seyfarth Yean Yip FONG Choon Kiat ANG Houng Bang liew Kui Hian SIM Department of Cardiology Sarawak General Hospital Sarawak Malaysia University Malaysia Sarawak Siemens Cardiac Solutions Erlangen Germany Department of Cardiology Sarawak General Hospital SarawakMalaysia

Objectives To compare left ventricular ejection fraction (LVEF) determined from 64-row multi-detector computed tomography (64-row MDCT) with those determined from two dimensional echocardiography (2D echo) and cardiac magnetic resonance imaging (CMR). Methods Thirty-two patients with coronary artery disease underwent trans-thoracic 2D echo, CMR and contrast-enhanced 64-row MDCT for assessment of LVEF within 48 hours of each other. 64-row MDCT LVEF was derived using the Syngo Circulation software; CMR LVEF was by Area Length Ejection Fraction (ALEF) and Simpson method and 2D echo LVEF by Simpson *** The LVEF was 49.13 ± 15.91% by 2D echo, 50.72 ± 16.55% (ALEF method) and 47.65 ± 16.58%(Simpson method) by CMR and 50.00 ± 15.93% by 64-row MDCT. LVEF measurements by 64-row MDCT correlated well with LVEF measured with CMR using either the ALEF method (Pearson correlation r = 0.94, P ＜0.01) or Simpson method (r = 0.92, P＜0.01). It also correlated well with LVEF measured using 2D echo (r = 0.80, P ＜ 0.01). Conclusion LVEF measurements by 64-row MDCT correlated well with LVEF measured by CMR and 2D echo. The correlation between 64-row MDCT and CMR was better than the correlation between 2D echo with CMR. Standard data set from a 64-row MDCT coronary study can be reliably used to calculate the LVEF.

关键词： ejection fraction echocardiography magnetic resonance imaging computed tomography

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Feasibility and accuracy of coronary imaging in elderly patients using the 64-row multi-detector computed tomography: a correlation study with conventional coronary angiography

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Journal of Geriatric Cardiology 2006年第1期3卷 9-14页

作者： Chee Khoon liew Sze Piaw chin Tiong Kiam ONG Seyfarth Tobias Yean Yip FONG Choon Kiat ANG Houng Bang liew Rapaee ANNUAR Kui Hian SIM Deptartment of Cardiology Sarawak General Hospital SarawakMalaysia Siemens Cardiac Solutions Erlangen Germany Universitv Malaysia Sarawak Malaysia

Background Elderly patients generally have higher occurrence of coronary calcification, increased heart rate and difficulty with prolonged breath-holding. The aim of our study was to investigate the feasibility and accuracy of using 64-row multi-detector computed tomography (MDCT) in the assessment of coronary artery stenoses in elderly patients. Methods One hundred and fifty two patients with suspected or known coronary artery disease were divided into 4 groups according to their age (Group A: 40-49 years,n=34; Group B: 50-59 years, n=57; Group C: 60-69 years, n=48; Group D: 70 years and above; n=13). Coronary CT angiography (CTA) using a 64-row MDCT was performed and the findings were compared with that of conventional coronary angiography (CCA).Using axial images, multi-planar reconstructions (MPR) and maximum intensity projections (MIP), coronary segments of lumen diameter = 1.5mm were analyzed for the presence of significant stenosis (= 50% ). Results Percentages of poor image quality from coronary CTA preventing reliable correlations with CCA were 21%, 14%, 19% and 62% in Groups A to D respectively. Patients in Group D had significantly higher calcium scores compared with the other groups (P＜0.001). In patients where CTA images were of acceptable quality, percentages of accurate correlations with CCA were 89.8%, 93.4%, 86.6% and 78.0% for Groups A to D *** were no significant difference in serum creatinine, heart rate and contrast volume between the 4 groups. Conclusions The 64-row MDCT coronary angiography was less accurate and feasible for patients aged 70 years or above due to heavy coronary calcification and inability to perform a satisfactory breath-hold. However, a high diagnostic accuracy with the MDCT is possible in patients aged less than 70 years.

关键词： computed tomography angiography coronary artery disease elderly

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High-resolution computed tomography in patients with atypical 'cardiac' chest pain: a study investigating patients at 10-year cardiovascular risks defined by the Framingham and PROCAM scores

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Journal of Geriatric Cardiology 2006年第1期3卷 17-21页

作者： Choon Kiat ANG Alan Yean Yip FONG Sze Piaw chin Tiong Kiam ONG Seyfarth M Tobias Chee Khoon liew Rapaee ANNUAR Houng Bang liew Kui Hian SIM Deptartment of Cardiology Sarawak General Hospital Sarawak Malaysia Siemens Medical Solutions Germany Deptartment of Cardiology Sarawak General Hospital SarawakMalaysia University Malaysia Sarawak Malaysia

Background and objective Atypical 'cardiac' chest pain (ACCP) is not usually caused by myocardial ischaemia. Current noninvasive investigations for these symptoms are not yet as accurate as invasive coronary angiography. The latest 64-row multi-detector computed tomography (MDCT) technology is non-invasive, has high specificity and negative predictive values for the detection of significant coronary disease. Our aim was to investigate if this modality can provide more information in the assessment of outpatients with ACCP in addition to established cardiovascular risk scores. Methods Seventy consecutive patients presenting to the outpatient clinic with ACCP underwent 64-row MDCT scan of the coronary arteries. They were categorized into low, medium or high risk groups based upon the Framingham and PROCAM scores. We defined a clinically abnormal MDCT scan as coronary stenosis =50% or calcium score ＞400 Agatston. Results Fifty-three (75.7%) patients did not have clinically abnormal scans. Framingham score classified 43 patients as low-risk while PROCAM classified 59 patients as low-risk. MDCT scans were abnormal for 18.6% and 22.0% of the respective low-risk group of patients. For patients with medium-to-high risk, 33.3% and 36.4% of Framingham and PROCAM patient groups respectively had abnormal MDCT scans. Conclusion MDCT adds valuable information in the assessment of patients with ACCP by identifying a significant proportion of patients categorized as low-risk to have underlying significant coronary stenosis and coronary calcification by established cardiovascular risk scores.

关键词： multi-detector computed tomography atypical 'cardiac' chest pain coronary artery disease risk stratification

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Case Report of Combined Sixth and Twelfth Cranial Nerve Palsy: A Rare Case of Clival Syndrome Arising from Thymoma

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Case Reports in Clinical Medicine 2023年第10期12卷 389-396页

作者： Yew Chung Chan chin Aun liew Darcy Jamih Yin chin Chan Mei Dree Lim Angeline Madatang Sandhya A/P Rajaintharan Department of Internal Medicine Hospital Duchess of Kent Sandakan Sabah Malaysia Department of Internal Medicine Hospital Kuala Lumpur Kuala Lumpur Malaysia Department of Pathology Queen Elizabeth Hospital I Kota Kinabalu Sabah Malaysia

Godtfredsen syndrome or clival syndrome is a rare syndrome of abducens and hypoglossal nerve palsies (cranial nerve 6th and 12th respectively) that localizes to a clival mass. There are few reported cases of this clinical presentation. The aim of this case report is to describe this rare manifestation observed in a woman with clival metastases arising from a thymoma. A previously well 34-year-old native lady presented to a district hospital in Sabah, Malaysia, with history of blurring of vision and headache for 1 month. Cranial nerve examination reveals right abducens nerve palsy (right 6th CN) and right hypoglossal nerve palsy (right 12th CN). Initial imaging with CT brain reveals a subtle extra-axial hyperdense mass adjacent to the clivus and a routine chest x-ray reveals a mediastinal mass. Further imaging of thorax showed right anterior mediastinal mass, which then proceeded with Video-Assisted Thoracoscopic Surgery (VATS) guided biopsy. The biopsy result was consistent with the finding of thymoma, type B2. She was then diagnosed with aggressive form of thymoma, which unfortunately has metastasized to the bone, lung, liver and brain. Despite prognosis at the time of diagnosis is guarded, she still opted to undergo chemotherapy. Despite the completion of 6 cycles of chemotherapy, her disease progressed, and she eventually succumbed to the illness. In short, the presence of combined 6th and 12th palsy should alert clinician to the possibility of clival mass or metastases and hence could earlier workup with appropriate imaging can lead to earlier diagnosis and better treatment outcome.

关键词： Clival Syndrome Godtfredsen Syndrome Abducens and Hypoglossal Nerve Palsies

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CYTOKINE-INDUCED MOBILIZATION OF ENDOTHELIAL PROGENITOR CELLS ENHANCES REPAIR OF INJURED ARTERIES

CYTOKINE-INDUCED MOBILIZATION OF ENDOTHELIAL PROGENITOR CELL...

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第2届世界华人生物医学工程研讨会

作者： Luis G. Melo, PhD choong C liew, PhD Richard E. Pratt, PhD Victor J. Dzau, MD Department of Medicine Brigham and Women’s Hospital Harvard Medical School Boston MA 02115 USA Department of Physiology Queen’s University 20 Stuart Street Kingston Ontario K7L 3N6 Canada Department of Medicine Brigham and Women’s Hospital Harvard Medical School Boston MA 02115 USA Department of Medicine Brigham and Women’s Hospital Harvard Medical School Boston MA 02115 USA Department of Medicine Brigham and Women’s Hospital Harvard Medical School Boston MA 02115 USA

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Regulation of integrated and covalently closed circular form of Hepatitis B virus (HBV) replication by cytokines

Regulation of integrated and covalently closed circular form...

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第五届海峡两岸细胞生物学学术研讨会

作者： Mong-Liang Chen chin-liew Chong Yue-Lin Tsai Tzu-Ling Liu King-Song Jeng National Health Research Institutes Zhunan MiaoliTaiwan

Chronic hepatitis B (CHB) is one of the most serious viral infections worldwide, which is also a high risk factor for cirrhosis and hepatocellular carcinoma (HCC). Several studies have reported that yirus persistence in CHB patients relies on maintaining a pool of viral covalently closed circular DNA (cccDNA) in the nuclei of infected hepatocytes, which presumably served as the template for HBV gene expression and viral replication. Apparently, cccDNA may play a pivotal role in the life cycle of HBV replication and may be responsible

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