• Investigative Magnetic Resonance Imaging
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• v.8 no.1
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• pp.17-23
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• 2004

Purpose : To evaluate changes in total cerebral blood flow (tCBF) with aging, parenchymal volume changes and vascular abnormalities, using 2 dimensional (D) phase-contrast magnetic resonance imaging (PC MRI). Materials and Methods : Routine brain MRI including T2 weighted image, time-of-flight (TOF) MR Angiography (MRA) and 2D PC MRI were performed in 73 individuals, including 12 volunteers. Normal subjects (12 volunteers, and 21 individuals with normal MRI and normal MRA) were classified into groups according to age (18-29, 30-49 and 50-66 years). For the group with abnormalities in brain MRIs, cerebral parenchymal volume changes were scored according to the T2 weighted images, and atherosclerotic changes were scored according to the MRA findings. Abnormal groups were classified into 4 groups: (i) mild reduction in volume, (ii) marked reduction in volume by parenchymal volume and atherosclerotic changes, and (iii) increased volume and (iv) Moya-moya disease. Volumetric flow was measured at the internal carotid artery (ICA) and vertebral artery bilaterally using the velocity-flow diagrams from PC MRI, and combined 4 vessel flows and tCBF were compared among all the groups. Results : The age-specific distribution of tCBFs in normal subjects were as follows: $12.0{\pm}2.1ml/sec$ in 18-29 years group, $11.8{\pm}1.9ml/sec$ in 30-49 years group, $10.9{\pm}2.2ml/sec$ in 50-66 years group. The distribution of tCBFs in the different subsets of the abnormal population were as follows: $9.5{\pm}2.5ml/sec$ in the group with mild reduction in volume, $7.6{\pm}2.0ml/sec$ in the group with marked reduction in volume, and $7.3{\pm}1.2ml/sec$ and $7.0{\pm}1.1ml/sec$ in the increased parenchymal volume and Moya-moya disease groups respectively. Conclusion : Total cerebral blood flow decreases with increasing age with a concomitant reduction in parenchymal volumes and increasing atherosclerotic changes. It is also reduced in the presence of increased parenchymal volume and Moya-moya disease.2D PC MRI can be used as a tool to evaluate tCBF with aging and in the presence of various conditions that can affect parenchymal volume and cerebral vasculature.

• Journal of Periodontal and Implant Science
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• v.50 no.3
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• pp.159-170
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• 2020

Purpose: Immunization with Porphyromonas gingivalis heat shock protein 60 (PgHSP60) may have an immunoregulatory effect on atherogenesis. The aim of this study was to determine whether nasal immunization with a PgHSP60 peptide could reduce atherosclerotic plaque formation in apolipoprotein E knockout (ApoE KO) mice. Methods: Seven-week-old male ApoE KO mice were assigned to receive a normal diet, a Western diet, a Western diet and challenge with PgHSP60-derived peptide 14 (Pep14) or peptide 19 (Pep19), or a Western diet and immunization with Pep14 or Pep19 before challenge with Pep14 or Pep19. Results: Atherosclerotic plaques were significantly smaller in mice that received a Western diet with Pep14 nasal immunization than in mice that received a Western diet and no Pep14 immunization with or without Pep14 challenge. An immunoblot profile failed to detect serum reactivity to Pep14 in any of the study groups. Stimulation by either Pep14 or Pep19 strongly promoted the induction of CD4⁺CD25⁺ forkhead box P3 (FoxP3)⁺ human regulatory T cells (Tregs) in vitro. However, the expression of mouse splenic CD4⁺CD25⁺FoxP3⁺ Tregs was lower in the Pep14-immunized mice than in the Pep14-challenged or Pep19-immunized mice. Levels of serum interferon gamma (IFN-γ) and transforming growth factor beta were higher and levels of interleukin (IL) 10 were lower in the Pep14-immunized mice than in the other groups. Induction of CD25^- IL-17⁺ T helper 17 (Th17) cells was attenuated in the Pep14-immunized mice. Conclusions: Nasal immunization with Pep14 may be a mechanism for attenuating atherogenesis by promoting the secretion of IFN-γ and/or suppressing Th17-mediated immunity.

• Journal of Chest Surgery
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• v.12 no.3
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• pp.297-305
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• 1979

Occlusive coronary artery disease presents a potential threat to a significant population in the United States. According to many case reports, the increasing incidence of coronary artery disease due to atherosclerosis is noted in Korean, recently. Operative vascular procedures have increased steadily in number over the past 20 years in the United States. There have been many isolated case reports about coronary artery surgery, but these had little clinical impact. Nowadays, major three coronary bypass surgery has developed principally at three cardiac centers in the United States since 1967. Among three coronary bypass operation, the aorta-coronary artery saphenous vein bypass graft was first demonstrated by Favolaro and Effler at the Cleveland Clinic in 1967. We experienced one case of coronary artery disease, which was treated successfully by aorta-coronary saphenous vein graft with mild hypothermia under extracorporeal circulation in May, 1977. Saphenous vein was removed from above the knee and was 2.5 mm in diameter. The left ventricle was not vented for the left ventricle was not overdistended. Temporary artificial pace-maker-Medtronic-was implanted for the prevention and treatment of post-operative arrhythmia and heart block in post-operative first day. He is a 57 year old male businessman who had been suffered from hypertension [200 mmHg in systolic pressure] since 4 years ago, who had intermittent conservative treatment at local clinic. He had been afflicted with severe chest pain with choking sensation for 50 days. This symptom was aggravated exposing cold weather, or cold water, but was respond to rest. Pre-operative ECG revealed no any other ischemic sign except sinus bradycardia. Significant S-T segment depression was noted at lead II, AVF after double 5 minutes exercise, indicating positive Master`s test. Serum cholesterol was slight elevated to 253 mg/dl. Final pre-operative diagnosis was made by coronary arteriogram, which showed about 1.0-cm segmental 90 % occlusive atherosclerotic lesion in the proximal part of right coronary artery above the origin of acute marginal artery. Left coronary artery revealed good patency and there was no collateral circulation between right and left coronary artery .Hospital course was not eventful. He was discharged with good result on the post-operative day. He has been free from chest pain for longer than 2 years. And also the arterial flow in the coronary bypass graft is auscultated with the pocket-sized ultrasonic velocity detector, which shows the patency of the coronary bypass graft good.

• Journal of Radiation Industry
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• v.3 no.1
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• pp.25-29
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• 2009

Microarrays can be used to screen thousands of binding events in a parallel and high throughput fashion and are of major importance in disease diagnosis and drug discovery. The use of radioisotope is conventionally regarded as one of the most sensitive detection methods. Atherosclerosis is a common disorder affecting arterial blood vessels. It happens when fat, cholesterol, and other substances made in the arterial blood vessels form a hard substances called plaque. Lipoprotein-associated phospholipase $A_2$ ($Lp-PLA_2$), a phospholipase $A_2$ enzyme, is used as a marker for cardiac disease. The detection of $Lp-PLA_2$ was accomplished by using radioactive [$^3H-acetyl$] PAF as a substrate and a feasibility study on RI biochip application to detection of $Lp-PLA_2$, a risk factors of atherosclerosis was performed. Inhibitive activity of a native plant extract was also determined by using the RI biochip. It was found to be applicable to a high-throughput screening of inhibitors for developing atherosclerosis therapeutic agents.

• BMB Reports
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• v.54 no.3
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• pp.170-175
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• 2021

Atherosclerosis arising from the pro-inflammatory conditions associated with chronic kidney disease (CKD) increases major cardiovascular morbidity and mortality. Rapamycin (RAPA) is known to inhibit atherosclerosis under CKD and non-CKD conditions, but it can cause dyslipidemia; thus, the co-application of lipid-lowering agents is recommended. Atorvastatin (ATV) has been widely used to reduce serum lipids levels, but its synergistic effect with RAPA in CKD remains unclear. Here, we analyzed the effect of their combined treatment on atherosclerosis stimulated by CKD in apolipoprotein E-deficient (ApoE-/-) mice. Oil Red O staining revealed that treatment with RAPA and RAPA＋ ATV, but not ATV alone, significantly decreased the atherosclerotic lesions in the aorta and aortic sinus, compared to those seen in the control (CKD) group. The co-administration of RAPA and ATV improved the serum lipid profile and raised the expression levels of proteins involved in reverse cholesterol transport (LXRα, CYP7A1, ABCG1, PPARγ, ApoA1) in the liver. The CKD group showed increased levels of various genes encoding atherosclerosispromoting cytokines in the spleen (Tnf-α, Il-6 and Il-1β) and aorta (Tnf-α and Il-4), and these increases were attenuated by RAPA treatment. ATV and RAPA＋ATV decreased the levels of Tnf-α and Il-1β in the spleen, but not in the aorta. Together, these results indicate that, in CKD-induced ApoE-/- mice, RAPA significantly reduces the development of atherosclerosis by regulating the expression of inflammatory cytokines and the co-application of ATV improves lipid metabolism.

• Journal of the Korean Society of Radiology
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• v.82 no.3
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• pp.541-550
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• 2021

The below-the-knee arterial tree is the thinnest of all the leg vessels and is an important path for blood flow to the foot. Hence, lesions including stenosis, especially obstruction, may lead to critical limb ischemia which represents the most severe clinical manifestation of peripheral arterial disease. It is characterized by the presence of ischemic rest pain, ischemic lesions, or gangrene attributable to the objectively proven arterial occlusive disease. Typically, the atherosclerotic disease process involving the below-the-knee arterial tree is diffuse in the majority of patients. The cornerstone of therapy is vascular reconstruction and limb salvage. Revascularization should be attempted whenever technically possible, without delay, in patients presenting critical limb ischemia and when the clinical status is not hopelessly non-ambulatory. Therefore, endovascular treatment can become the gold standard for the full range of patients including below-the-knee, limiting the clinical role of the classically trained surgeons.

• Journal of the Korean Society of Radiology
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• v.81 no.2
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• pp.250-271
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• 2020

Assessment of myocardial ischemia in patients with stable angina is important in deciding whether to treat coronary artery disease and in predicting clinical outcome. The fractional flow reserve is a standard reference for the diagnosis of myocardial ischemia, but this procedure has limitations because of its invasiveness. Coronary computed tomography angiography (CCTA) is now an established tool in the anatomic diagnosis of coronary artery disease; however, there are limits to the diagnosis of hemodynamically important stenosis that causes myocardial ischemia. In order to address this problem, studies using quantification of coronary atherosclerotic plaques, myocardial perfusion, and noninvasive calculation of fractional flow reserve based on CCTA have been actively conducted and recognized for their diagnostic value. In this review, several imaging techniques of CCTA used to assess myocardial ischemia are described.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.6
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• pp.293-301
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• 2006

Purpose: The aim of the study was to evaluate the hemodynamic changes after successful bypass surgery in patients with atherosclerotic stenosis in ICA using $^{99m}Tc-ECD$ SPECT. Materials and Methods: Fourteen patients (M:F=8:6, mean age; $60{\pm}9$ years) who underwent STA-MCA anastomosis for unilateral atherosclerotic cerebrovascular disease were enrolled. $^{99m}Tc-ECD$ basal/acetazolamide perfusion SPECT studies were performed before, 10 days and 6 months after bypass surgery. Perfusion reserve was defined as the % changes after acetazolamide over rest image. Regional cerebral blood flow and perfusion reserve were compared preoperative, early-postoperative and late-postoperative scans. Results: The mean resting perfusion and decrease in perfusion reserve in affected ICA territory on preoperative scan was $52.4{\pm}3.5\;and\;-7.9{\pm}4.7%$, respectively. The resting perfusion was significantly improved after surgery on early-postoperative scan (mean $53.7{\pm}2.7$) and late-postoperative scan (mean $53.3{\pm}2.5$) compared with preoperative images (p<0.05, respectively). Resting perfusion did not showed further improvement on late-postoperative scan compared with early-postoperative scan. The perfusion reserve was $-3.7{\pm}2.6%$ on early-postoperative scan, and $-1.6{\pm}2.3%$ on late-postoperative scan, which was significantly improved after surgery. Additionally, further improvement of perfusion reserved as observed on late-postoperative scan (p<0.05). While, in the unaffected ICA territory, no significant changes in the resting perfusion and perfusion reserve was observed. Conclusion: The improvement of resting perfusion and perfusion reserve in early-postoperative scan reflects the immediate restoration of the cerebral blood flow by bypass surgery. In contrasts, further improvement of perfusion reserve showing on late-postoperative scan may indicate a good collateral development after surgery, which may indicate good surgical outcome after surgery.

• International Journal of Oral Biology
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• v.33 no.4
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• pp.163-177
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• 2008

Periodontal disease, a form of chronic inflammatory bacterial infectious disease, is known to be a risk factor for cardiovascular disease (CVD). Porphyromonas gingivalis has been implicated in periodontal disease and widely studied for its role in the pathogenesis of CVD. A previous study demonstrating that periodontopathic P. gingivalis is involved in CVD showed that invasion of endothelial cells by the bacterium is accompanied by an increase in cytokine production, which may result in vascular atherosclerotic changes. The present study was performed in order to further elucidate the role of P. gingivalis in the process of atherosclerosis and CVD. For this purpose, invasion of human aortic smooth muscle cells (HASMC) by P. gingivalis 381 and its isogenic mutants of KDP150 ($fimA^-$), CW120 ($ppk^-$) and KS7 ($relA^-$) was assessed using a metronidazole protection assay. Wild type P. gingivalis invaded HASMCs with an efficiency of 0.12%. In contrast, KDP150 failed to demonstrate any invasive ability. CW120 and KS7 showed relatively higher invasion efficiencies, but results for these variants were still negligible when compared to the wild type invasiveness. These results suggest that fimbriae are required for invasion and that energy metabolism in association with regulatory genes involved in stress and stringent response may also be important for this process. ELISA assays revealed that the invasive P. gingivalis 381 increased production of the proinflammatory cytokine interleukin (IL)-$1{\beta}$ and the chemotactic cytokines (chemokine) IL (interleukin)-8 and monocyte chemotactic (MCP) protein-1 during the 30-90 min incubation periods (P<0.05). Expression of RANTES (regulation upon activation, normal T cell expressed and secreted) and Toll-like receptor (TLR)-4, a pattern recognition receptor (PRR), was increased in HASMCs infected with P. gingivalis 381 by RT-PCR analysis. P. gingivalis infection did not alter interferon-$\gamma$-inducible protein-10 expression in HASMCs. HASMC nonspecific necrosis and apoptotic cell death were measured by lactate dehydrogenase (LDH) and caspase activity assays, respectively. LDH release from HASMCs and HAMC caspase activity were significantly higher after a 90 min incubation with P. gingivalis 381. Taken together, P. gingivalis invasion of HASMCs induces inflammatory cytokine production, apoptotic cell death, and expression of TLR-4, a PRR which may react with the bacterial molecules and induce the expression of the chemokines IL-8, MCP-1 and RANTES. Overall, these results suggest that invasive P. gingivalis may participate in the pathogenesis of atherosclerosis, leading to CVD.

• Proceedings of the Korean Society of Food Science and Nutrition Conference
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• 2004.11a
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• pp.265-270
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• 2004

Coronary heart disease (CHD) has been the number one killer in western society for a long time, and CHD in most instances is due to atherosclerosis. One of the earliest events in atherogenesis is the intracellular accumulation of lipids, particularly cholesterol esters, in the aortic intima. The lipids presumably came from the uptake of plasma lipoproteins, particularly from LDL. These foam cells were identified as being predominantly as macrophages. Currently, it is believed that oxidation of low density lipoprotein (LDL) might contribute to the generation of foam cells. An outcome of the oxidation hypothesis is that the consumption of antioxidants would be beneficial. In this study, Boldine, an alkaloid of Peumus boldus was tested for their antioxidant potency both in, in vitro oxidation system and in mouse models. Boldine decreased the ex-vivo oxidation of Low-density lipoprotein (LDL). In vivo studies were performed to study the effect of these compounds on the atherosclerotic lesion formation in LDL r-/- mice. Three groups of LDL r-/- mice (N=12 each) were fed an atherogenic diet. Group 1 was given vehicle and group 2 and 3 were given 1 and 5 mg of Boldine/day in addition to the atherogenic diet. The results indicated that there was a decrease in lesion formation reaching a 40% reduction due to Boldine compared to controls. The in vivo tolerance of Boldine in humans (has been used as an herbal medicine in other diseases) should make it an attractive alternative to vitamin E.