• Molecular & Cellular Toxicology
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• 제4권4호
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• pp.323-330
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• 2008

Surrogate tissue analysis incorporating -omics technologies has emerged as a potential alternative method for evaluating toxic effect of the tissues which are not accessible for sampling. Among the recent applications, blood including whole blood, peripheral blood lymphocytes and peripheral blood mononuclear cells (PBMCs) was suggested as a suitable surrogate tissue in determining toxicant exposure and effect at the pre- or early clinical stage. In this application, we investigated transcriptomic profiles in astemizole treated Cynomolgus monkey's PBMCs. PBMCs were isolated from 4-6 years old male monkeys at 24 hr after administration45 Helvetica Light (10 mg/kg, 30 mg/kg). Gene expression profiles of astemizole treated monkey's PBMCs were determined using Affymetrix $GeneChip^{(R)}$ Human Genome U133 plus 2.0 arrays. The expression levels of 724 probe sets were significantly altered in PBMCs at 10 or 30 mg/kg after astemizole administration following determination of paired t-test using statistical criteria of ${\geq}$$1.5-fold changes at P<0.05. Gene expression patterns in PBMCs showed a considerable difference between astemizole 10 and 30 mg/kg administration groups in spite of an administration of the same chemical. However, close examination using Ingenuity Pathway Analysis (IPA) software revealed that several gene sets related to cardiotoxicity were deregulated at astemizole 10 and 30 mg/kg administration groups. The deregulation of cardiac hypertrophy related genes such as TXN, GNAQ, and MAP3K5 was observed at 10 mg/kg group. In astemizole 30 mg/kg group, genes involved in cardiotoxicity including cardiac necrosis/cell death, dilation, fibrosis, and hypertrophy were also identified. These results suggest that toxicogenomic approach using PBMCs as surrogate tissues will contribute to assess toxicant exposures and identify biomarkers at the pre-clinical stage.

• Clinical and Experimental Pediatrics
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• 제65권5호
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• pp.230-238
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• 2022

Myocarditis was previously attributed to an epidemic viral infection. Additional harmful reagents, in addition to viruses, play a role in its etiology. Coronavirus disease 2019 (COVID-19) vaccine-induced myocarditis has recently been described, drawing attention to vaccine-induced myocarditis in children and adolescents. Its pathology is based on a series of complex immune responses, including initial innate immune responses in response to viral entry, adaptive immune responses leading to the development of antigen-specific antibodies, and autoimmune responses to cellular injury caused by cardiomyocyte rupture that releases antigens. Chronic inflammation and fibrosis in the myocardium eventually result in cardiac failure. Recent advancements in molecular biology have remarkably increased our understanding of myocarditis. In particular, microRNAs (miRNAs) are a hot topic in terms of the role of new biomarkers and the pathophysiology of myocarditis. Myocarditis has been linked with microRNA-221/222 (miR-221/222), miR-155, miR-10a^*, and miR-590. Despite the lack of clinical trials of miRNA intervention in myocarditis yet, multiple clinical trials of miRNAs in other cardiac diseases have been aggressively conducted to help pave the way for future research, which is bolstered by the success of recently U.S. Food and Drug Administration-approved small-RNA medications. This review presents basic information and recent research that focuses on myocarditis and related miRNAs as a potential novel biomarker and the therapeutics.

• Archives of Plastic Surgery
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• 제46권6호
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• pp.594-598
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• 2019

Overall complication rates of 9.1% have been reported following implantable cardioverter defibrillator (ICD) placement. Brachial plexus injury is infrequently reported in the literature. We describe a 26-year-old female experiencing left arm nerve pain, a positive Tinel's sign, numbness in the median nerve distribution of the hand and biceps muscle weakness following revision ICD via subclavian vein approach. Nerve conduction studies identified severe partial left brachial plexopathy, which remained incompletely resolved with conservative management. Surgical exploration revealed lateral cord impingement by the ICD generator and a loop of the ICD lead, along with fibrosis, necessitating surgical neurolysis and ICD generator repositioning. As increasing numbers of patients undergo cardiac device implantation, it is incumbent on practitioners to be aware of potential increases in the prevalence of this complication.

• Journal of Chest Surgery
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• 제7권2호
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• pp.201-208
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• 1974

The purpose of this paper is to present author's experience with 6 cases of ruptured aneurysm of sinus of Valsalva which were treated surgically during last 10 years. Among the 6 cases, 5 were male and one was female. All of them originated from the right coronary sinus and 5 cases were ruptured into the RV while remained one into RA. The diagnosis was obtained in 4 cases by cineangiocardiogram. Clinically, we had difficulties in differential diagnosis with combined cases of VSD with A.I. and had special experience in its differentiation during cardiac catheterization. By simultaneous trans-venous and trans-arterial catheterization, identified two catheter tips in the RV, and pull back tracing obtained aortic pressure directly from RV, and RA from RV pressure which were benefit in confirm ruptured aneurysm of the aortic sinus. Surgical correction was performed by means of direct suture closure or combined Teflon pledget Of patch enforcement graft after aneurysm resection by trans-RA or trans-RV approach. All patients had no history of bacterial endocarditis, syphilis, or tuberculosis and operative findings revealed intact coronary sinus except involved one moreover 3 cases combined with high VSD which uggested congenital in origin although pathologic reports revealed only fibrosis. Post-operative course were uneventful in all cases but one who had bleeding and 2 months to 9 years follow up results were good and spend their usual life in all cases.

• Clinical and Experimental Pediatrics
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• 제57권1호
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• pp.19-25
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• 2014

Recently, surgical outcomes of repair of tetralogy of Fallot (TOF) have improved. For patients with TOF older than 3 months, primary repair has been advocated regardless of symptoms. However, a surgical approach to symptomatic TOF in neonates or very young infants remains elusive. Traditionally, there have been two surgical options for these patients: primary repair versus an initial aortopulmonary shunt followed by repair. Early primary repair provides several advantages, including avoidance of shunt-related complications, early relief of hypoxia, promotion of normal lung development, avoidance of ventricular hypertrophy and fibrosis, and psychological comfort to the family. Because of advances in cardiopulmonary bypass techniques and accumulated experience in neonatal cardiac surgery, primary repair in neonates with TOF has been performed with excellent early outcomes (early mortality<5%), which may be superior to the outcomes of aortopulmonary shunting. A remaining question regarding surgical options is whether shunts can preserve the pulmonary valve annulus for TOF neonates with pulmonary stenosis. Symptomatic neonates and older infants have different anatomies of right ventricular outflow tract (RVOT) obstructions, which in neonates are nearly always caused by a hypoplastic pulmonary valve annulus instead of infundibular obstruction. Therefore, a shunt is less likely to preserve the pulmonary valve annulus than is primary repair. Primary repair of TOF can be performed safely in most symptomatic neonates. Patients who have had primary repair should be closely followed up to evaluate the RVOT pathology and right ventricular function.

• 한국수의병리학회지
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• 제1권2호
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• pp.157-160
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• 1997

Two 2 and 7 months-old holstin and one 3 months-old native Korean calf suffering from respiratory illness were submitted to the National Veterinary Research Institute for euthanasia and pathologic examination. At necropsy diffuse lobar pneumonia was present in apical cardiac and diaphragmatic lobes in all calves. Microscopically acute multifocal bronchiolitis and interstitial syncytial cell formation were frequently observed. in addition occlusion of bronchiolar lumen due to cellular proliferation and fibrosis accompanied by interlobular septal emphysema were also present. Immunohistochemically bovine respiratory syncytial virus antigen were positively identified in lung lesions including bronchial and bronchiolar epithelium alveolar macrophages and lymphocytes.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제5권2호
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• pp.192-198
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• 2002

저자들은 지속적인 황달을 주소로 연세의대 세브란스병원에 입원하였던 10개월 된 남아에서 특징적인 얼굴모양, 심혈관계 이상, 간 생검 조직검사상 담즙 정체, 거대세포 형성 및 소염관 담관의 수가 감소되어 있었고, 퇴원 후 간경변으로 이행되어 간 이식수술을 받았던 Alagille증후군 1례를 경험하였기에 문헌 고찰과 함께 보고하는 바이다.

• Molecules and Cells
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• 제45권3호
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• pp.122-133
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• 2022

The aim of this study was to investigating whether lncRNA H19 promotes myocardial fibrosis by suppressing the miR-29a-3p/miR-29b-3p-VEGFA/TGF-β axis. Patients with atrial fibrillation (AF) and healthy volunteers were included in the study, and their biochemical parameters were collected. In addition, pcDNA3.1-H19, si-H19, and miR-29a/b-3p mimic/inhibitor were transfected into cardiac fibroblasts (CFs), and proliferation of CFs was detected by MTT assay. Expression of H19 and miR-29a/b-3p were detected using real-time quantitative polymerase chain reaction, and expression of α-smooth muscle actin (α-SMA), collagen I, collagen II, matrix metalloproteinase-2 (MMP-2), and elastin were measured by western blot analysis. The dual luciferase reporter gene assay was carried out to detect the sponging relationship between H19 and miR-29a/b-3p in CFs. Compared with healthy volunteers, the level of plasma H19 was significantly elevated in patients with AF, while miR-29a-3p and miR-29b-3p were markedly depressed (P < 0.05). Serum expression of lncRNA H19 was negatively correlated with the expression of miR-29a-3p and miR-29b-3p among patients with AF (r_s = -0.337, r_s = -0.236). Moreover, up-regulation of H19 expression and down-regulation of miR-29a/b-3p expression facilitated proliferation and synthesis of extracellular matrix (ECM)-related proteins. SB431542 and si-VEGFA are able to reverse the promotion of miR-29a/b-3p on proliferation of CFs and ECM-related protein synthesis. The findings of the present study suggest that H19 promoted CF proliferation and collagen synthesis by suppressing the miR-29a-3p/miR-29b-3p-VEGFA/TGF-β axis, and provide support for a potential new direction for the treatment of AF.

• Journal of Chest Surgery
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• 제19권2호
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• pp.225-231
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• 1986

Pericardial adhesions following open heart surgery pose a special problems, increasing the risk of cardiac reoperation because of the danger of damaging the heart, coronary artery and veins, or grafts and also the fibrous tissue may obliterate the pericardial space and eventually constrict the heart. This study was undertaken to evaluate the effect of intrapericardial urokinase and dextran 40 on the formation of pericardial adhesions in an animal model. latrogenic traumas on the pericardium were surgically induced in 30 rabbits, simulating injuries possible during actual surgery. In all rabbits, blood [1 ml] was obtained from an ear vessel and injected into the pericardium. Control group of ten rabbits did not receive any further medication, urokinase group of ten received 15, 000-20, 000 IU of urokinase, and remained ten received 1 ml of 10% dextran 40. All rabbits were sacrificed at 4 weeks. At autopsy, the development of adhesions were graded as none [Grade I], minimal [Grade II], moderate [Grade III], and severe [Grade IV]. Histological studies of the parietal pericardium and epicardium were performed. The results were as follows: 1. Group 1[Control group] showed minimal adhesion in 40%, moderate in 50%, and severe in 10% of the group. Sharp dissections were necessary in 60% of adhesions. 2. Group II [Dextran group] showed no adhesions in 20%, minimal in 60%, and moderate in 20% of the group. 3. Group III [Urokinase group] showed no adhesions in 40%, minimal in 40%, and moderate in 20% of the group. Considering in this group, the adhesion activity was significantly suppressed [60% adhesions] compared to the control group [100% adhesions] [P < 0.05]. 4. Histological findings revealed mild serosal fibrosis in none adherent group, loose fibrous connections between two layers of pericardium in minimal adhesion group, tight fibrous connections in moderate adhesion group, and marked fibrous thickening and close attachment of two surfaces were noted in severe adhesion group. These data have revealed the decreased incidence of pericardial adhesions with urokinase and dextran 40.

• The Korean Journal of Physiology and Pharmacology
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• 제22권4호
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• pp.447-456
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• 2018

Angiotensin-(1-9) [Ang-(1-9)], generated from Ang I by Ang II converting enzyme 2, has been reported to have protective effects on cardiac and vascular remodeling. However, there is no report about the effect of Ang-(1-9) on pulmonary hypertension. The aim of the present study is to investigate whether Ang-(1-9) improves pulmonary vascular remodeling in monocrotaline (MCT)-induced pulmonary hypertensive rats. Sprague-Dawley rats received Ang-(1-9) ($576{\mu}g/kg/day$) or saline via osmotic mini-pumps for 3 weeks. Three days after implantation of osmotic mini-pumps, 50 mg/kg MCT or vehicle were subcutaneously injected. MCT caused increases in right ventricular weight and systolic pressure, which were reduced by co-administration of Ang-(1-9). Ang-(1-9) also attenuated endothelial damage and medial hypertrophy of pulmonary arterioles as well as pulmonary fibrosis induced by MCT. The protective effects of Ang-(1-9) against pulmonary hypertension were inhibited by Ang type 2 receptor ($AT_2R$) blocker, but not by Mas receptor blocker. Additionally, the levels of LDH and inflammatory cytokines, such as $TNF-{\alpha}$, MCP-1, $IL-1{\beta}$, and IL-6, in plasma were lower in Ang-(1-9) co-treated MCT group than in vehicle-treated MCT group. Changes in expressions of apoptosis-related proteins such as Bax, Bcl2, Caspase-3 and -9 in the lung tissue of MCT rats were attenuated by the treatment with Ang-(1-9). These results indicate that Ang-(1-9) improves MCT-induced pulmonary hypertension by decreasing apoptosis and inflammatory reaction via $AT_2R$.