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Low Frequency of ETV6-RUNX1 (t 12; 21) in Saudi Arabian Pediatric Acute Lymphoblastic Leukemia Patients: Association with Clinical Parameters and Early Remission

  • Aljamaan, Khaled;Aljumah, Talal khalid;Aloraibi, Saleh;Absar, Muhammad;Iqbal, Zafar
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7523-7527
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    • 2015
  • Background: Pediatric acute lymphoblastic leukemia (pALL) patients at King Abdulaziz Medical City represent a pure Saudi Arabian population. ETV6-RUNX1 positive pALL patients have good prognosis as compared to ETV6-RUNX1 negative counterparts. Therefore, frequencies of these two patient groups have a huge consideration in treatment strategies of pALL in a given population. Different geographical locations have been reported to have different frequencies of ETV6-RUNX1 ranging from 10% in Southeast Asia to 30% in Australia. Aim: Therefore, the objective of this study was to establish the ETV6-RUNX1 status of Saudi Arabian pALL patients and its association with clinical parameters and early remission. Materials and Methods: Clinical parameters and ETV6-RUNX1 status (using FISH technique) of pALL patients attending the Pediatric Oncology Clinic, King Abdulaziz Medical City, Riyadh from 2006 to 2011 were studied. Comparisons between ETV6-RUNX1 positive and negative groups were accomplished using chi-square test or Fisher's exact test. All statistical analyses were performed using SAS version 9.2 (SAS Institute, Inc., Cary, NC). Results: Out of 54 patients, 33 were male and 21 were females (ratio 1.57:1). B- and T-cell lineages were found in 47 (87%) and 7 (13%) patients respectively. Only 5 (9.3%) patients were ETV6-RUNX1 positive while 49(80.7%) were ETV6-RUNX1 negative. All ETV6-RUNX1 patients (100%) were of B-cell lineage and 80% (4/5) were in the 3-7 year age group. None of the ETV6-RUNX11 patients had ${\geq}5%$ blasts (no remission) at day 14 as compared with 9% in the ETV6-RUNX1 negative group (Figure 1). Conclusions: Frequency of ETV6-RUNX1 positive patients (less than 10%) in our pALL patients is much lower than reported for most European countries, North America, Australia and Japan while it is in accordance with ETV6-RUNX1 frequencies from Egypt (11.6%), Pakistan (10%), Spain (2%) and India (5-7%). This shows ethnic differences in genetics of pALL as well as higher frequencies of ETV6-RUNX1 positive pALL mostly in more industrialized countries, probably due to some industrial pollutants or westernized lifestyle.

Dietary Aloe Reduces Adipogenesis via the Activation of AMPK and Suppresses Obesity-related Inflammation in Obese Mice

  • Shin, Eun-Ju;Shin, Seul-Mee;Kong, Hyun-Seok;Lee, Sung-Won;Do, Seon-Gil;Jo, Tae-Hyung;Park, Young-In;Lee, Chong-Kil;Hwang, In-Kyeong;Kim, Kyung-Jae
    • IMMUNE NETWORK
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    • v.11 no.2
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    • pp.107-113
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    • 2011
  • Background: Metabolic disorders, including type II diabetes and obesity, present major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has become the focus of a great deal of attention as a novel therapeutic target for the treatment of metabolic syndromes. In this study, we evaluated whether dietary aloe could reduce obesity-induced inflammation and adipogenesis. Methods: Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Results: Aloe QDM complex downregulated fat size through suppressed expression of scavenger receptors on adipose tissue macrophages (ATMs) compared with HFD. Both white adipose tissue (WATs) and muscle exhibited increased AMPK activation through aloe supplementation, and in particular, the Aloe QDM complex. Obesity-induced inflammatory cytokines (IL-$1{\beta}$ and -6) and $HIF1{\alpha}$ mRNA and protein were decreased markedly, as was macrophage infiltration by the Aloe QDM complex. Further, the Aloe QDM complex decreased the translocation of NF-${\kappa}B$ p65 from the cytosol in the WAT. Conclusion: Dietary aloe formula reduced obesity-induced inflammatory responses by activation of AMPK in muscle and suppression of proinflammatory cytokines in the WAT. Additionally, the expression of scavenger receptors in the ATM and activation of AMPK in WAT led to reduction in the percent of body fat. Thus, we suggest that the effect of the Aloe QDM complex in the WAT and muscle are related to activation of AMPK and its use as a nutritional intervention against T2D and obesity-related inflammation.

Unique Cartilage Matrix-Associated Protein Alleviates Hyperglycemic Stress in MC3T3-E1 Osteoblasts (Unique cartilage matrix-associated proteins에 의한 MC3T3-E1 조골세포에서의 고혈당 스트레스 완화 효과)

  • Hyeon Yeong Ju;Na Rae Park;Jung-Eun Kim
    • Journal of Life Science
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    • v.33 no.11
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    • pp.851-858
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    • 2023
  • Unique cartilage matrix-associated protein (UCMA) is an extrahepatic vitamin K-dependent protein rich in γ-carboxylated (Gla) residues. UCMA has been recognized for its ability to promote osteoblast differentiation and enhance bone formation; however, its impact on osteoblasts under hyperglycemic stress remains unknown. In this paper, we investigated the effect of UCMA on MC3T3-E1 osteoblastic cells under hyperglycemic conditions. After exposure to high glucose, the MC3T3-E1 cells were treated with recombinant UCMA proteins. CellROX and MitoSOX staining showed that the production of reactive oxygen species (ROS), which initially increased under high-glucose conditions in MC3T3-E1 cells, decreased after UCMA treatment. Additionally, quantitative polymerase chain reaction revealed increased expression of antioxidant genes, nuclear factor erythroid 2-related factor 2 and superoxide dismutase 1, in the MC3T3-E1 cells exposed to both high glucose and UCMA. UCMA treatment downregulated the expression of heme oxygenase-1, which reduced its translocation from the cytosol to the nucleus. Moreover, the expression of dynamin-related protein 1, a mitochondrial fission marker, was upregulated, and AKT signaling was inhibited after UCMA treatment. Overall, UCMA appears to mitigate ROS production, increase antioxidant gene expression, impact mitochondrial dynamics, and modulate AKT signaling in osteoblasts exposed to high-glucose conditions. This study advances our understanding of the cellular mechanism of UCMA and suggests its potential use as a novel therapeutic agent for bone complications related to metabolic disorders.

Lupeol Improves TNF-α Induced Insulin Resistance by Downregulating the Serine Phosphorylation of Insulin Receptor Substrate 1 in 3T3-L1 Adipocytes (3T3-L1 지방세포에서 루페올의 IRS-1의 인산화 조절을 통한 TNF-α 유도 인슐린 저항성 개선 효과)

  • Hyun Ah Lee;Ji Sook Han
    • Journal of Life Science
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    • v.33 no.11
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    • pp.859-867
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    • 2023
  • Lupeol is a type of pentacyclic triterpene that has been reported to have therapeutic effects for treating many diseases; however, its effect on insulin resistance is unclear clear. This study examined the inhibitory effect of lupeol on the serine phosphorylation of insulin receptor substrate-1 in insulin resistance-induced 3T3-L1 adipocytes. 3T3-L1 cells were cultured and treated with tumor necrosis factor-α (TNF-α) for 24 hours to induce insulin resistance. Cells treated with different concentrations of lupeol (15 μM or 30 μM) or 100 nM of rosiglitazone were incubated. Then, lysed cells underwent western blotting. Lupeol exhibited a positive effect on the negative regulator of insulin signaling and inflammation-activated protein kinase caused by TNF-α in adipocytes. Lupeol inhibited the activation of protein tyrosine phosphatase-1B (PTP-1B)-a negative regulator of insulin signaling-and c-Jun N-terminal kinase (JNK); it was also an inhibitor of nuclear factor kappa-B kinase (IKK) and inflammation-activated protein kinases. In addition, Lupeol downregulated serine phosphorylation and upregulated tyrosine phosphorylation in insulin receptor substrate-1. Then, the downregulated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway was activated, the translocation of glucose transporter type 4 was stimulated to the cell membrane, and intracellular glucose uptake increased in the insulin resistance-induced 3T3-L1 adipocytes. Lupeol may improve TNF-α-induced insulin resistance by downregulating the serine phosphorylation of insulin receptor substrate 1 by inhibiting negative regulators of insulin signaling and inflammation-activated protein kinases in 3T3-L1 adipocytes.

The Behaviors of Phosphorus-32 and Ptoassium-42 under the Control of Thermoperiod and Potassium Level (가리(加里)와 온도주기성(溫度週期性)이 고구마 생육(生育) 및 인(燐)-32, 가리(加里)-42 동태(動態)에 미치는 영향(影響))

  • Kim, Y.C.
    • Korean Journal of Soil Science and Fertilizer
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    • v.1 no.1
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    • pp.89-115
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    • 1968
  • 1. The experiment was carried out for investigating the interaction between potassium nutrition and thermoperiod (as an environment regulating factor) in relation to behaviors of several nutrients including phosphorus-32 and Potassium-42 in IPOMOEA BATAS. 2. To obtain same condition to trace the behaviors of phosphorus and potassum-42 they were simultaneously incorporated to roots. The determination of each CPM by counting twice with adequate interval and calculating true CPM of each isotope according to different half-life, was carried out with satisfactory. 3. Some specific symptoms i.e, chlorosis and withering of growing point under the condition of lower potassium level were found and was accelerated by the low night temperature. 4. A manganese shortage in growing point of the lower potassium level was found by activiation analysis and very low distribution ratio of phosphorus-32 and potassium-42 in the growing point of the lower potassium level was manifested, though the contents of nitrogen, phosphorus, potassium, sodium and magnesium were not in great difference. 5. In addition to the low water content with appearence of "hard", shorterning internode and lower ratio of roots to shoot as well as the symptoms of potassium deficiency such as brown spot in leaf blade and necrosis of leaf margin were appeared at later stage of experiment at the lower potassium level. 6. Very stimulating vegetative growth, e.g, large plant length, leaf expansion, increasing node number and fresh weight as well as high ratio of roots to shoot, high water content was resulted in the condition of higher potassium level. 7. A specific interaction between higher potassium level and thermoperiod was found, that is, the largest tuber production and the largest ratio of roots to shoot were resulted in the combined condition of higher potassium level and constant temperature while the largest plant length, fresh weight etc. i.e. the most stimulative vegetative growth was resulted in the combined condition of higher potassium level and low night temperature. 8. Comparatively low water content in the former condition of stimulative tuber production was resulted(especially at the tuber thickening stage), while high water content in the latter condition of stimulative vegetation was resulted though the higher potassium level made generally high water contents. 9. The nitrogen contents of soluble and insoluble did not make distinct difference between the lower and higher potassium level. 10. Though the phosphorus contents were not distinctly different by the potassium level, the lower potassium level made the percentage of phosphorus increased at tuber forming stage accumulating more phosphorus in roots, while the higher potassium level decreased percentage of phosphorus at that stage. 11. The higher potassium level made distinctly high potassium contents than the lower potassium level and increased contents at the tuber forming stage through both conditions. 12. The sodium contents were low in the condition of higher potassium level than the lower potassium level and decreased at tuber forming stage in both conditions, on the contary of potassium. 13. Except the noticeable deficeney of manganese in the growing point of the lower potassium level, mangense and magnesium contents in other organs did not make distinct difference according to the potassium level. 14. Generally more uptake and large absorption rate of phosphorus-32 and potassium-42 were resulted at the higher potassium level, and the most uptake, and the largest absorption rate of phosphorus and potassium-42 (especially potassium-42 at tuber forming stage) were resulted in the condition of higher potassium level and constant temperature which made the highest tuber production. 15. The higher potassium level stimulated the translocation of phoshorus-32 and potassium-42 from roots to shoots while the lower potassium level suppressed or blocked the translocation. 16. Therefore, very large distribution rate of $p^{32}$, $K^{42}$ in shoot, especially, in growing point, compared with roots was resulted in the higher potassium level. 17. The lower potassium level suppressed the translocation of phosporus-32 from roots to shoot more than that of potassium-42. 18. The uptake of potassium-42 and translocation in IPOMOEA BATATAS were more vivid than phosphorus-32. 19. A specific interaction between potassium nutrition and thermoperiod which resulted the largest tuber production etc. was discussed in relation to behaviors of minerals and potasium-42 etc. 20. Also, the specific effect of the lower and higher potassium level on the growth pattern of IPOMOEA BATATAS were discussed in relation to behaviors of minerals and isotopes. 21. An emphasize on the significance of the higher potassium level as well as the interaction with the regulating factor and problem of potassium level (gradient) for crops product ion were discussed from the point of dynamical and variable function of potassium.

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Ecological Characteristics and Management Proposal of Abeliophyllum distichum Subpopulations in the Byeonsanbando National Park (변산반도국립공원 내 미선나무 아개체군의 생태적 특성과 관리제언)

  • Lim, Dong-Ok;Hwang, In-Chon;Choi, Hyon-Woo;Kim, Yong-Shik
    • Korean Journal of Environment and Ecology
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    • v.23 no.2
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    • pp.116-126
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    • 2009
  • This study was carried out focused an ecological characteristics and habitat management of Abeliophyllum distichum subpopulations in the Byeonsanbando National Park, Korea. Among three subpopulations of the target species in the studied area, Gamaso region are known as translocation site due to the dam construction while the wild populations which is located at both the lower terrain of the Buandaem bank and Chongnim-ni, which is designated as Natural Monument No 370, is threat due to an intensive site management likes clearance of scrub amongst the Abeliophyllum plants. Vascular plant taxa in the studied sites were summarized as 182 taxa; 65 families, 143 genera, 164 species, 17 varieties and 1 form, and Gamaso area, the lower terrain of the Buandaem and Cheongnim-ni areas are summarized as 75, 102 and 89 taxa, respectively. The plant species likes persimmon tree, paulownia tree and wild mulberry tree are dominant species in the Gamaso subpopulation, while Quercus variabilis is dominant at the lower terrain of the Buandaem. The intensive site management was applied to the Cheongnim-ni subpopulation, one of the original wild habitats of the species. The population dymanics was varied; the one or two sprouting number of stems was over 87% both at Gamaso area and the lower terrain of the Buandam, while the Cheongnim-ni subpopulation recorded as 74.8%. Also three sprouting number recorded as 16% and as 9.2% for sprouting on numbers of four to eleven. The invaded species likes Chenopodium album, Rumex obtusifolius, Phytolacca americana, Pharbitis nil, Solanum lyratum, Erigeron canadensis and Erigeron annuus, were found at the wild habitat of the species, and those invaded species grow faster than Abeliophyllum plants. Among three habitats of the target species in the studied area, the habitat which in located at the lower terrain of the Buandam and Gamaso region are known as translocated due to the dam construction, and wild subpopulation at Chongnim-ni, which is designated as Natural Monument No 370, is under threatened due to an intensive site management likes clearance of scrub amongst the Abeliophyllumplants. It is one of the evidence that Cuscuta japonica at the population indicated an intensive site management likes clearance of scrub is not proper habitat management protocol. Thus, further researches should be followed to determine the effect of canopy removal and other disturbance factors as management techniques.

The Role of Ref-1 in the Differentiation Process of Monocytic THP-1 Cells (단핵구세포주 THP-1의 분화과정에서 Ref-1의 역할)

  • Da Sol Kim;Kang Mi Kim;Koanhoi Kim;Young Chul Park
    • Journal of Life Science
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    • v.34 no.4
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    • pp.271-278
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    • 2024
  • Redox factor (Ref)-1, a ubiquitously expressed protein, acts as a modulator of redox-sensitive tran- scription factors and as an endonuclease in the repair pathway of damaged DNA. However, the function of Ref-1 in the differentiation of monocytes into macrophages has not been defined. In this study, we investigated the effects of Ref-1 on the monocyte differentiation process using the human monocytic cell line THP-1. The differentiation agent PMA increased cell adhesion over time and showed a sig- nificant increase in phagocytic function but decreased the intracellular amount of Ref-1. Ref-1 inhibitor E3330 and Ref-1 knockdown using the siRNA technique reduced cell adhesion and the expression of differentiation markers, such as CD14, ICAM-1, and CD11b, by PMA stimulation. This means that the role of Ref-1 is absolutely necessary in the initial process of differentiating THP-1 cells stimulated by PMA. Next, the distribution of Ref-1 was examined in the cytoplasm and nucleus of THP-1 cells stimulated with PMA. Surprisingly, PMA stimulation resulted in the rapid translocation of Ref-1 to the nucleus. To prove that movement of Ref-1 to the nucleus is required for monocyte differentiation, a Ref-1 vector with the nuclear localization sequence (NLS) deleted was used. As a result, overexpression of ∆NLS Ref-1, which restricted movement to the nucleus, suppressed the expression of differentiation markers and notably reduced phagocytic function in PMA-stimulated THP-1 cells. In conclusion, these data suggest that the differentiation of monocytic THP-1 cells requires Ref-1 nuclear translocation during the initial process of biochemical events following stimulation from PMA.

Proinflammatory Cytokine and Nitric Oxide Production by Human Macrophages Stimulated with Trichomonas vaginalis

  • Han, Ik-Hwan;Goo, Sung-Young;Park, Soon-Jung;Hwang, Se-Jin;Kim, Yong-Seok;Yang, Michael Sungwoo;Ahn, Myoung-Hee;Ryu, Jae-Sook
    • Parasites, Hosts and Diseases
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    • v.47 no.3
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    • pp.205-212
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    • 2009
  • Trichomonas vaginalis commonly causes vaginitis and perhaps cervicitis in women and urethritis in men and women. Macrophages are important immune cells in response to T. vaginalis infection. In this study, we investigated whether human macrophages could be involved in inflammation induced by T. vaginalis. Human monocyte-derived macrophages (HMDM) were co-cultured with T. vaginalis. Live, opsonized-live trichomonads, and T. vaginalis Iysates increased proinflammatory cytokines, such as TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 by HMDM. The involvement of nuclear factor (NF)-${\kappa}B$ signaling pathway in cytokine production induced by T. vaginalis was confirmed by phosphorylation and nuclear translocation of p65 NF-${\kappa}B$. In addition, stimulation with live T. vaginalis induced marked augmentation of nitric oxide (NO) production and expression of inducible NO synthase (iNOS) levels in HMDM. However, trichomonad-induced NF-${\kappa}B$ activation and TNF-${\alpha}$ production in macrophages were significantly inhibited by inhibition of iNOS levels with L-NMMA (NO synthase inhibitor). Moreover, pretreatment with NF-${\kappa}B$ inhibitors (PDTC or Bay11-7082) caused human macrophages to produce less TNF-${\alpha}$. These results suggest that T. vaginalis stimulates human macrophages to produce proinflammatory cytokines, such as IL-1, IL-6, and TNF-${\alpha}$, and NO. In particular, we showed that T. vaginalis induced TNF-${\alpha}$ production in macrophages through NO-dependent activation of NF-${\kappa}B$, which might be closely involved in inflammation caused by T. vaginalis.

Calcium Deficiency Causes Pithiness in Japanese Pear (Pyrus pyrifolia cv. Niitaka) Fruit (칼슘 결핍에 의한 '신고' 배 (Pyrus pyrifolia cv. Niitaka) 과실에서의 바람들이)

  • Moon, Byung Woo;Jung, Hae Woong;Lee, Hee Jae;Yu, Duk Jun
    • Korean Journal of Environmental Agriculture
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    • v.32 no.2
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    • pp.102-107
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    • 2013
  • BACKGROUND: Pithy pear fruit are not distinguished externally from sound fruit and thus often cause unexpected economic losses. To find out the cause of pithiness, the pithiness incidence and characteristics of Japanese pear (Pyrus pyrifolia cv. Niitaka) fruit picked from a spot frequently produced pithy fruit in an orchard were compared with those of fruit picked from another spot produced sound fruit every year. And the soil chemical properties of the two spots and mineral contents in fruit, shoots, and leaves of Japanese pear trees cultivated in the two spots were also examined. METHODS AND RESULTS: The pithiness incidence was 0, 8.8, and 11.3% at 7 days before and 0 and 7 days after optimal harvest date, respectively, in the spot frequently produced pithy fruit. Flesh firmness was significantly lower in pithy fruit than in sound fruit, while soluble solids content was slightly higher in pithy fruit than in sound fruit. Unlike other mineral contents, Ca content was significantly lower in pithy fruit than in sound fruit. These results indicate that Ca deficiency in fruit is closely associated with decrease in flesh firmness and thus pithiness development. Ca content in soil of the spot frequently produced pithy fruit was also significantly lower than that in soil of the spot produced sound fruit. However, shoots or leaves did not exhibit significant difference in Ca and/or other mineral contents between the two spots, indicating that Ca deficiency in fruit is dependent on the translocation of Ca within a plant rather than soil Ca status. Although total-N, available $P_2O_5$, K, and Ca contents were significantly lower in soil of the spot frequently produced pithy fruit than in soil of the spot produced sound fruit, Mg and Na contents and pH were not different between the soil conditions. CONCLUSION(S): Fruit maturity and Ca level in fruit are closely related to the incidence of pithiness in 'Niitaka' Japanese pear.

Unroofing Procedure in the Treatment of Anomalous Origin of Right Coronary Artery from Left Sinus of Valsalva between Aorta and Pulmonary Trunk (대동맥과 주폐동맥 사이의 좌관상동맥동에서 이상기시하는 우관상동맥의 Unroofing 술식을 이용한 치료)

  • Park Chan Beom;Jo Min Seop;Kim Young Du;Kang Chul Ung;Jin Ung;Cho Deog-Gon;Park Kuhn;Cho Kyu-Do;Kim Chi Kyung
    • Journal of Chest Surgery
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    • v.38 no.11 s.256
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    • pp.776-779
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    • 2005
  • Anomalous origin of right coronary artery from left sinus of valsalva is associated with sudden unexpected death, syncope, arrhythmia and myocardial ischemia. The mechanism that explains the restriction of coronary flow in the anomalous coronary artery is unclear but several surgical methods have been proposed, such as coronary artery bypass graft, coronary reimplantation, translocation of pulmonary artery, and unroofing procedure. We reported the surgical correction of the anomalous origin of right coronary artery from left sinus of valsalva between the aorta and pulmonary trunk using the unroofing procedure.