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Ju Han Kim

Publications and source records attributed to Ju Han Kim.

49 records · Page 3Linked to original sources

Gene expression profiling of anti-GBM glomerulonephritis model: the role of NF-kappaB in immune complex kidney disease.

BACKGROUND: Immune complexes may cause an irreversible onset of chronic renal disease. Most patients with chronic renal disease undergo a final common pathway, marked by glomerulosclerosis and interstitial fibrosis. We attempted to draw a molecular map of anti-glomerular basement membrane (GBM) glomerulonephritis in mice using oligonucleotide microarray technology. METHODS: Kidneys were harvested at days 1, 3, 7, 11, and 16 after inducing glomerulonephritis by using anti-GBM antibody. In parallel with examining the biochemical and histologic changes, gene expression profiles were acquired against five pooled control kidneys. Gene expression levels were cross-validated by either reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, or immunohistochemistry. RESULTS: Pathologic changes in anti-GBM glomerulonephritis were confirmed in both BALB/c and C57BL/6 strains. Among the 13,680 spotted 65mer oligonucleotides, 1112 genes showing significant temporal patterns by permutation analysis of variance (ANOVA) with multiple testing correction [false discovery ratio (FDR) < 0.05] were chosen for cluster analysis. From the expression profile, acute inflammatory reactions characterized by the elevation of various cytokines, including interleukin (IL)-1 and IL-6, were identified within 3 days of disease onset. After 7 days, tissue remodeling response was prominent with highly induced extracellular-matrix (ECM) genes. Although cytokines related to lymphocyte activation were not detected, monocyte or mesangial cell proliferation-related genes were increased. Tumor necrosis factor-alpha (TNF-alpha) and nuclear factor-kappaB (NF-kappaB) pathway were consistently activated along the entire disease progression, inducing various target genes like complement 3, IL-1b, IL-6, Traf1, and Saa1. CONCLUSION: We made a large-scale gene expression time table for mouse anti-GBM glomerulonephritis model, providing a comprehensive overview on the mechanism governing the initiation and the progression of inflammatory renal disease.

Animals↗

Effect of combined intracoronary adenosine and nicorandil on no-reflow phenomenon during percutaneous coronary intervention.

BACKGROUND: This study aimed to clarify the effect of intracoronary administration of combined adenosine and nicorandil on the no-reflow phenomenon. METHODS AND RESULTS: Fifty patients (67+/-10 years, 30 male) with acute myocardial infarction (AMI) who developed no-reflow phenomenon during primary percutaneous coronary intervention (PCI) between June 2001 and May 2003 comprised the study group, which was divided into 2 groups: group I [25 patients, 67+/-10 years, 13 male; adenosine (24 microg/ml) alone in addition to nitrate] and group II [25 patients, 66+/-9 years, 17 male; combined intracoronary administration of adenosine and nicorandil (2 mg/ml) in addition to nitrate]. In-hospital and 6-month major adverse cardiac events (MACE) after PCI were compared between the 2 groups. Risk factors of coronary disease, left ventricular ejection fraction and wall motion score were not significantly different between the 2 groups (p=NS). Time interval from the onset of chest pain to PCI, number of involved vessels, lesion type according to ACC/AHA classification and TIMI flow grade (TFG) were not significantly different in both groups (p=NS). Incidence of thrombosis or dissection after balloon angioplasty, diameter and length of stent, and use of Reopro during PCI were not significantly different. TFG after PCI (2.0+/-0.9 vs 2.6+/-0.6, p=0.024), DeltaTFG (1.5+/-1.1 vs 2.2+/-1.0, p=0.033) and difference in TIMI frame count (TFC) before and after PCI (DeltaTFC) were greater in group II than group I (45.2+/-24.5 vs 63.6+/-23.2, p=0.014). Myocardial blush score 3 was obtained more frequently in group II than group I (44% vs 76%, p=0.014). In-hospital death did not occur in any of group II, but 4 patients of group I died (p=0.043). Two cases of MACE developed in each group and heart failure occurred in 3 (12%) of group I and 1 (4%) of group II patients during the 6-month follow-up (p=NS). CONCLUSIONS: Intracoronary administration of adenosine combined with nicorandil may improve both the occurrence of no-reflow in patients during PCI for AMI and short-term clinical outcome, compared with adenosine alone.

Adenosine↗

A novel method of brachytherapy using local delivery of 99mTc-HMPAO for coronary stent restenosis.

BACKGROUND: Restenosis after percutaneous coronary intervention (PCI) is a matter that still remains to be resolved. Herein, the inhibitory effect of locally delivered 99mTc-HMPAO (hexamethyl propylene amine oxime) on neointimal hyperplasia after coronary stenting was examined in a pocine model, and its safety and efficacy observed in patients with coronary stent restenosis. METHODS: After a stent overdilation injury, local radioisotope delivery using 99mTc-HMPAO was applied to one coronary artery (Group I) and control therapy to another (Group II) in each of 10 pigs. Follow-up coronary angiogram (CAG) and histopathologic assessment were performed 4 weeks after stenting. Eleven patients (10 males and one female, 62.4 +/- 5.7 years of age) underwent local administration of 30 mCi/ 2 mL 99mTc-HMPAO shortly after PCI, via a Dispatch Catheter, followed by a whole body scan to evaluate the distribution of the 99mTc-HMPAO, as well as a thallium-201 (TI-201) myocardial scan to evaluate myocardial perfusion. The major adverse cardiac events (MACE) were assessed during a one-year clinical follow-up. RESULTS: On histopathological analysis, the neointimal areas were 1.2 +/- 0.6 and 2.7 +/- 0.4 mm2 (p=0.002), and the histopathological areas of stenosis were 27.16.3 and 53.4 +/- 5.2% in Groups I and II (p=0.001), respectively. In the clinical study, there was no in-hospital MACE. On a quantitative coronary angiographic analysis, the minimal luminal diameter was increased from 0.4 +/- 0.3 to 2.9 +/- 0.2 mm, and diameter stenosis decreased from 84.2 +/- 9.5 to 16.3 +/- 11.0% following PCI. Follow-up CAG was performed in 9 cases (81.8%) and restenosis occurred in 2 (22.2%). On a follow-up CAG, the minimal luminal diameter, diameter stenosis rate, lumen loss and loss index were 2.0 +/- 0.8 mm, 27.7 +/- 2.9%, 0.7 +/- 0.7 mm and 0.2 +/- 0.3, respectively. During the one-year clinical follow-up there were no cases of death or acute MI, but two cases of target vessel revascularization (18.2%). CONCLUSION: Local delivery of 99mTc-HMPAO, a novel radiotherapy, can be used safely and effectively for coronary stent restenosis.

Angioplasty, Balloon, Coronary↗

The long-term clinical results of a platelet glycoprotein IIb/IIIa receptor blocker (Abciximab: Reopro) coated stent in patients with coronary artery disease.

BACKGROUND: Previously, the inhibition of coronary restenosis with Abciximab (ReoPro)-coated stent in a porcine model was reported. ReoPro inhibits platelet aggregation, the proliferation of vascular smooth muscle cells and the inflammatory reaction. METHODS: A prospective randomized trial was performed to compare two types of stent for revascularization in the native coronary artery. The primary effective end points were major adverse coronary events (MACE): cardiac death, acute myocardial infarction, target vessel revascularization (TVR) and restenosis at the 6-month clinical and angiographic follow-ups. RESULTS: One hundred and fifty-five patients were enrolled between August 2001 and June 2003. The mean ages (56.0 +/- 10.0 vs. 56.9 +/- 10.8 years), baseline diameter of stenosis and minimal luminal diameter were no different between the two groups. There was one myocardial infarction and revascularization during the hospital stay in control stent group. During the clinical follow-up there were two myocardial infarctions in control group. Follow-up coronary angiograms were performed in 62.3% (48/77) and 65.4% (51/78) of the coated and control groups, respectively. The diameter of stenosis and late loss were significantly less in the ReoPro-coated stent group compared with the controls (16.4 +/- 5.8% vs. 34.3 +/- 6.1%, p = 0.009; and 0.33 +/- 0.28 mm vs. 0.88 +/- 0.41 mm; p = 0.002). The restenosis and TVR rates of the ReoPro-coated stent were relatively lower compared with the control stent [14.6% (7/48) vs. 29.4% (15/51), p = 0.062; and 9.2% (7/76) vs. 14.7% (11/75); p = 0.327]. CONCLUSION: A ReoPro-coated stent is safe, and may be effective in the prevention of coronary restenosis.

Abciximab↗

Estrogen receptor alpha gene polymorphisms and breast cancer risk.

We conducted a hospital-based case-control study to evaluate the association between the XbaI and PvuII restriction fragment length polymorphisms (RFLPs) in intron I of the estrogen receptor alpha (ER alpha) gene and breast cancer risk. The study population consisted of 205 histologically confirmed incident breast cancer cases and 205 age-matched controls with no present and previous history of cancer. The PvuII genotype distribution did not show any difference between cases and controls, but the adjusted odds ratio (OR) for the XbaI X allele containing genotypes was 0.4 (95% CI: 0.3-0.6) compared with the xx genotype. The decrease in the OR appeared to be more attributable to the postmenopausal women; the ORs were 0.3 (95% CI: 0.1-0.5) and 0.5 (95% CI: 0.3-0.9) for postmenopausal and premenopausal women, respectively. Our results therefore suggest that the ER alpha XbaI polymorphism modifies individual susceptibility to breast cancer in Korean women.

Adult↗

Effects of beta-radiation using a holmium-166 coated balloon on neointimal hyperplasia in a porcine coronary stent restenosis model.

Brachytherapy is a promising method of preventing and treating coronary stent restenosis. The present study was designed to observe the therapeutic effects of a radioactive balloon loaded with Holmium-166 ((166)Ho) in a porcine coronary stent restenosis model. A radioisotope of (166)Ho was coated onto the balloon surface using polyurethane (20 Gy at 0.5 mm depth). Stent overdilation injuries were induced in 2 coronary arteries in each pig (n=8). Four weeks after the injury, control balloon dilation was performed in one coronary artery (Group I) and radiation therapy using the (166)Ho coated balloon in the other coronary artery (Group II) in each pig. Follow-up coronary angiography and histopathologic assessment were performed at 4 weeks after the radiation therapy or the control balloon dilations. With regard to complete blood cell counts, liver function tests, lipid profiles and coagulation tests, there were no differences between the baseline and after radiation. On quantitative coronary angiographic analysis, reference and target artery diameter showed no differences between the 2 groups before, or 4 and 8 weeks after stenting. On histopathologic analysis of groups I and II, the injury score was 1.34+/-0.09 and 1.32+/-0.10, the area of internal elastic lamina was 4.99+/-0.17 mm(2) and 4.82+/-0.20 mm(2), and the luminal area was 3.20+/-0.10 mm(2) and 3.45+/-0.14 mm(2), respectively (p=NS). The neointimal area was 1.78+/-0.11 mm(2) in group I and 1.36+/-0.12 mm(2) in group II (p=0.017), and the histopathologic area of stenosis was 35.1+/-1.6% in group I and 27.6+/-1.9% in group II (p=0.005). In conclusion, beta-radiation of the stented porcine coronary artery using a radioactive (166)Ho coated balloon inhibited stent restenosis without any side effects.

Animals↗

The role of C-reactive protein on the long-term clinical outcome after primary or rescue percutaneous coronary intervention.

BACKGROUND: We examined the clinical and angiographic outcomes, success rate of the percutaneous coronary intervention (PCI) and long-term survival rate after primary or rescue PCI in patients with acute myocardial infarction (AMI) according to the level of the C-Reactive Protein (CRP) on admission. METHODS: Two hundred and eight consecutive patients with AMI who underwent primary or rescue PCI between 1997 and 1999 at Chonnam National University Hospital were divided into two groups: Group I (n = 86, 59.9 +/- 9.3 years, male 74.4%) with a normal CRP (< 1.0 mg/dL, mean value = 0.43 +/- 0.14 mg/dL) on admission and Group II (n = 122, 59.1 +/- 10.4 years, male 83.6%) with an elevated CRP (> or = 1.0 mg/dL, mean value = 3.50 +/- 0.93 mg/dL) on admission. RESULTS: There were no significant differences in teh baseline characteristics noted between the two groups. The incidence of cardiogenic shock was higher in Group II than in Group I (Group I; 3/86, 3.5% vs. Group II; 15/122, 12.3%, p = 0.026). The coronary angiographic findings did not differ between the two groups. The ejection fraction and Thrombolysis In Myocardial Infarction flow grade improved after PCI in both groups. The primary success rate of PCI was 94.2% (81/86) in Group I and 95.1% (116/122) in Group II (p = 0.776). The survival rates for Group I were 97.7%, 97.7% and 96.5%, and those for Group II were 91.8%, 91.0% and 86.9% at 1, 6 and 12 months, respectively (p = 0.043 at 1 month, p = 0.040 at 6 months, p = 0.018 at 12 months). CONCLUSION: A high incidence of cardiogenic shock and worse long-term survival after PCI are observed in AMI patients with an elevated CRP.

Age Factors↗

Long-term clinical benefits of a platelet glycoprotein IIb/IIIa receptor blocker, abciximab (ReoPro), in high-risk diabetic patients undergoing percutaneous coronary intervention.

BACKGROUND: High-risk percutaneous coronary interventions (PCIs) are associated with a high complication rate, a low procedural success rate and a high restenosis rate, especially in diabetics. We sought to determine whether abciximab (ReoPro) therapy affects long-term clinical outcomes of Korean patients with diabetes undergoing high-risk PCI. METHODS: One hundred and nineteen patients with 152 lesion sites were administered ReoPro among 2,231 patients who underwent PCI at Chonnam National University Hospital from March 1999 to Feb 2001. These 119 patients were divided into two groups, 30 were allocated to a diabetic group (Group 1, 57.7 +/- 8.2 years, 22 male), and 89 to a non-diabetic group (Group II, 59.6 +/- 10.8 years, 68 male). Early and long-term clinical outcomes after PCI were analyzed. RESULTS: In terms of clinical diagnosis, the number of acute myocardial infarctions in Group I was 25 (83.3%) and 76 in Group II (85.4%). As for risk factors, target artery lesions, and ACC/AHA types, no differences were found between the two groups. The number of patients with total occlusion was 21 (55.3%) and 62 (53.9%), and the number with a thrombus-containing lesion was 28 (93.3%) and 88 (98.9%) in Groups I and II, respectively. The procedure was successful in 27 (90.0%) in Group I, and in 80 (89.9%) in Group II, and no differences were evident between the two groups in terms of bleeding complications. No major adverse cardiac events (MACE), including myocardial infarction, repeat revascularization or cardiac death, were observed in Group I, but 8 cases of MACE occurred in Group II during hospitalization. Clinical follow-up was performed in 116 patients (97.5%) over 18.5 +/- 6.7 (5-28) months. The number of overall MACEs was 10 (3.3%) in Group I and 14 (15.7%) in Group II (p = 0.038). CONCLUSION: ReoPro used in high-risk PCI in diabetics was effective in terms of early clinical outcomes, but its long-term clinical benefits were not proven.

Abciximab↗

The use of low molecular weight heparin to predict clinical outcome in patients with unstable angina that had undergone percutaneous coronary intervention.

BACKGROUND: Antithrombotic therapy with heparin reduces the rate of ischemic events in patients with acute coronary syndrome. Low-molecular-weight heparin, given subcutaneously twice daily, has a more predictable anticoagulant effect than standard unfractionated heparin. Moreover, it is easier to administer and does not require monitoring. METHODS: We prospectively analyzed 180 patients with unstable angina who had undergone percutaneous coronary intervention (PCI) between 1999 and 2001 at Chonnam National University Hospital and had received either 120 U/kg of dalteparin (Fragmin), administered subcutaneously twice daily (Group I; n = 90, 61.8 +/- 8.9 years, male 67.8%), or had received continuous intravenous unfractionated heparin (Group II; n = 90, 62.6 +/- 9.7 years, male 70.0%). During hospitalization and at 6 month after PCI, major adverse cardiac events such as acute myocardial infarction, target vessel revascularization, death, and restenosis were examined. RESULTS: During hospitalization, the incidence of acute myocardial infarction, target vessel revascularization and death were not different between the two groups. At follow-up coronary angiography 6 months after PCI, the incidence of restenosis was lower in group I than in group II (Group I; 26/90, 28.8% vs. Group II; 32/90, 35.6%, p = 0.041) and the incidence of target vessel revascularization was lower in group I than in group II (Group I; 21/90, 23.3% vs. Group II; 27/90, 30.0%, p = 0.039). No difference was found in the rates of major and minor hemorrhages, ischemic strokes or thrombocytopenia between two groups. By multivariate analysis, the factors related to restenosis were lesion length, postprocedural minimal luminal diameter, CRP on admission, diabetes mellitus, the type of heparin, and stent use. CONCLUSION: Dalteparin, a low molecular weight heparin, is superior to standard unfractionated heparin in terms of reducing the restenosis rate and target vessel revascularization without increasing bleeding complications.

Angina, Unstable↗

Social network analysis of gene expression data.

To investigate the structure of genomic interaction network, social affiliation network analysis was performed for the yeast gene expression compendium dataset of hundreds of systematic perturbations. Network density and centrality indices of genes and groups of genes revealed the core-peripheral and the significant intermediary players that may be critical for the control of the biological system.

Computational Biology↗

Visualization and evaluation of clusters for exploratory analysis of gene expression data.

Clustering algorithms have been shown to be useful to explore large-scale gene expression profiles. Visualization and objective evaluation of clusters are two important considerations when users are selecting different clustering algorithms, but they are often overlooked. The developments of a framework and software tools that implement comprehensive data visualization and objective measures of cluster quality are crucial. In this paper, we describe a theoretical framework and formalizations for consistently developing clustering algorithms. A new clustering algorithm was developed within the proposed framework. We demonstrate that a theoretically sound principle can be uniformly applied to the developments of cluster-optimization function, comprehensive data-visualization strategy, and objective cluster-evaluation measures as well as actual implementation of the principle. Cluster consistency and quality measures of the algorithm are rigorously evaluated against those of popular clustering algorithms for gene expression data analysis (K-means and self-organizing maps), in four data sets, yielding promising results.

Algorithms↗

Bioinformatics and genomic medicine.

Bioinformatics is a rapidly emerging field of biomedical research. A flood of large-scale genomic and postgenomic data means that many of the challenges in biomedical research are now challenges in computational science. Clinical informatics has long developed methodologies to improve biomedical research and clinical care by integrating experimental and clinical information systems. The informatics revolution in both bioinformatics and clinical informatics will eventually change the current practice of medicine, including diagnostics, therapeutics, and prognostics. Postgenome informatics, powered by high-throughput technologies and genomic-scale databases, is likely to transform our biomedical understanding forever, in much the same way that biochemistry did a generation ago. This paper describes how these technologies will impact biomedical research and clinical care, emphasizing recent advances in biochip-based functional genomics and proteomics. Basic data preprocessing with normalization and filtering, primary pattern analysis, and machine-learning algorithms are discussed. Use of integrative biochip informatics technologies, including multivariate data projection, gene-metabolic pathway mapping, automated biomolecular annotation, text mining of factual and literature databases, and the integrated management of biomolecular databases, are also discussed.

Computational Biology↗

Successful stenting for congenital coarctation of the distal thoracic aorta (middle aortic syndrome) in an adult.

We report a successful stent implantation for a coarctation lesion of the lower thoracic aorta in a 44-year-old male. This patient had suffered from claudication of both legs for 30 years. An aortogram revealed a coarctation of the distal thoracic aorta at T11 level with 60 mmHg peak systolic pressure gradient of across the lesion. A balloon angioplasty followed by an 18 mm x 40 mm sized stent implantation was performed successfully. The peak systolic gradient across the coarctation decreased from 60 to 15 mmHg. The patient's symptom was relieved immediately after stenting. No significant or adverse events were observed during 7 months clinical follow-up. Follow-up aortogram after 7 months revealed no restenosis with an improved pressure gradient. Adults with congenital coarctation of the descending thoracic aorta can be successfully treated by stent implantation.

Adult↗