• Journal of Chest Surgery
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• v.40 no.3 s.272
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• pp.180-192
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• 2007

Background: As determined from the recent investigations of discordant cardiac xenotransplantation, hyperacute rejection occurs mainly at the endothelial cells in donor microvascular systems, but this does not occur at cardiac valve leaflets or at medium-to-large caliber vessels. On the basis of this background, this study was performed to look into the biocompatibility for transplantation of a middle or large diameter xenogenic blood vessel by conducting xenogenic arterial transplantation with the carotid artery in a pig-to-goat model. Material and Method: The experimental group was composed of 10 pairs of pig-to-goat combinations. They were divided into each period of 1 week, and 1, 3, 6 and 12 months. Four carotid artery grafts obtained through collection of the bilateral carotid arteries from two pigs were preserved at $-70^{\circ}C$ without other treatment, and then they were transplanted into the bilateral carotid arteries of two goats. Doppler ultrasonography was done on a periodic basis after transplantation to evaluate the patency of the grafted blood vessel. At the ends of a predetermined period, the grafts were explanted from the goats and they underwent gross examination. Hematoxylin-eosin and Masson's trichrome staining were conducted. In addition, in order to examine the immunological rejection of the grafted xenogenic blood vessel, immunohistochemical staining was conducted with T-lymphocyte indicator and von Willebrand factor. Result: Two goats at the each one-week period and the one-year period died during the experimental period because of a reason unrelated to the experimental procedure, and the remaining 8 goats survived until the end of each experiment period. On Doppler ultrasonography, unilateral carotid artery occlusion was found in a goat, whose period was specified as 3 months, among the 8 survived goats. However, the vascular patency was maintained well and there was no graft that formed aneurysms in the other goats. On gross examination, the region of vascular anastomosis was preserved well, and calcification of the grafted blood vessel was not shown. Histologically, the endothelial cells of the graft disappeared one week after transplantation, and then there was progressive spread of the recipients' endothelial cells from the anastomotic site. The reendothelialization occurred over the whole graft at one month after transplantation. The neointimal thickening and adventitial inflammation became severe by 3 months after transplantation, but this lessened at 6 months and 12 months, respectively. The rate of CD3 positive cells was very low among the infiltrated inflammatory cells. Conclusion: The fresh-frozen xenogenic artery kept its patency without being greatly influenced by xenogenic immune reaction.

• Radiation Oncology Journal
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• v.14 no.4
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• pp.281-290
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• 1996

Purpose : Chest irradiation leads to a significant cardiac injury in a number of patients. To prevent, or to reduce the risk of radiation-induced cardiac injury, pentoxifylline(PTX), a haemorrheologic agent that improves the blood flow through small blood capillaries has been employed. Materials and Methods : One hundred and eighty ICR mice were divided into three study groups: control, radiation alone, and radiation-pentoxifylline. Each group was subdivided into 12 subgroups: 1 3, 6 and 10 days and 2, 3, 4, 6, 8, 12, 16 and 20 weeks by observation Period after irradiation. The total 15Gy of radiation was delivered in a single fraction through anterior mediastinal port. Pentoxifylline was injected subcutaneously daily 50mg/kg to the back of the mice from the first day of irradiation throughout the observation period. The mice of each group after a certain observation period were sacrificed and sectioned for histopathologic examination of the heart. Result : The findings of acute radiation-induced carditis i.e., heterophilic infiltration and vacuolization and ballooning of endothelial cells were observed upto 6 weeks and reduced sharply afterwards. The late radiation effects including pericarditis with mononuclear cell infiltration, pericardial fibrosis, endothelial cell changes, myocardial degeneration and fibrosis present from 4 weeks onwards after irradiation but with various degree of severity. The overall process of pathologic changes of radiation-pentoxifylline group was similar to those of radiation alone group but the duration of acute stage was relatively short and the severity of late cardiac toxicity was much lesser compared with those of radiation alone group. Conclusion : Pentoxifylline can effectively reduce the late radiation-induced cardiac injury and reslve the acute effects relatively rapidly.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.4
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• pp.483-490
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• 2015

The purpose of this study was to investigate the effects of 50% ethanol extracts of ripe black raspberry (Rubus occidentalis, RBR) on hypertension in spontaneously hypertensive rats (SHR). The final systolic blood pressure of the group treated with RBR for 12 weeks was significantly lower than that of the SHR group. The mRNA expression level of endothelial nitric oxide synthase (eNOS) was significantly decreased in SHR. However, treatment with RBR and captopril increased the level of eNOS mRNA in SHR. Moreover, plasma levels of homocysteine and plasminogen activator inhibitor-1 were significantly reduced by RBR. Plasma total cholesterol, high-density lipoprotein, and low-density lipoprotein cholesterol levels were lower in SHR than Wistar Kyoto rats (WKY). However, there was no significant difference in plasma triglyceride level between WKY and SHR. The number of eosinophilic cardiac muscle cells was reduced in heart muscles after treatment with captopril and RBR. Therefore, this study suggests that RBR extracts may be useful for improvement of hypertension.

• 한국생물공학회:학술대회논문집
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• 2003.10a
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• pp.164-166
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• 2003

Despite recent advances in the treatment of acute myocardial infarction, the ability to repair extensive myocardial damage is limited. Revascularization in ischemic myocardium is required to improve cardiac function and prevent further scar tissue formation. Bone marrow contains endothelial precursors that can be used to induce neovascularization in ischemic myocardium. To develop a new therapy for myocardial infarction, we investigated if implantation of bone marrow mononuclear cells (BM-MNCs) using biodegradable matrices could enhance neovascularization in ischemic myocardium. Eight weeks after implantation, the damaged myocardium implanted with BM-MNCs and fibrin gels exhibited significantly greater angiogenic responses than those implanted with either fibrin gels or BM-MNCs alone. Fibrin gels disappeared completely 8 weeks after implantation. Echocardiography revealed improved heart functions. These results suggest that implantation of BM-MNCs using fibrin gel matrix efficiently induces neovascularization and improved heart functions in ischemic myocardium.

• Korean Journal of Veterinary Service
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• v.19 no.1
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• pp.1-29
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• 1996

This study was conducted to elucidate the pathogenesis of Aujeszky's disease virus(ADV) by histopathologic examination. The first Korean ADV Isolate, which was isolated from piglets with clinical signs of Aujeszky's disease in Yangsan(YS) county, Kyungnam province, was inoculated into 32 days old piglets with a dose of $10^{5.9}$$TCID_{50}/ml$ through intranasal or intramuscular route. These piglets were sacrificed at intervals of every 24hrs for 8 days. The virulence of YS strain was determined by the observation of clinical signs, gross findings, and histopathologic changes in tissues. The virus recovery test was performed from brain, spleen, lung and tonsil in cell culture. The pathogenesis of YS strain was determined by the observation of histopathologlc lesions in CNS and neuronal tracts. The major clinical signs were fever, anorexia, dyspnea, constipation, tremor, ataxia, circling movement, hindleg paralysis and salivation. The clinical signs were more severe in piglets of the group inoculated intranasally than those of the intramuscularly inoculated gorup. Lymphocytopenia was detected on day 5 to day 6 postinoculation (PI). The ADV was recovered from the tissue homogenates of tonsil, lung, spleen and cerebrum in cell culture. The highest virus titer was detected from tonsil between day 6 and day 7 PI. Reddish sublobar consolidation foci were scattered in the apical and cardiac lobes of lung. Although yellowish necrotic foci were detected in tonsil and liver, hemorrhagic lesions were mainly observed in heart, kidney and lymph nodes. Histopathologically, degeneration and necrosis of nerve cells, nonsuppurative meningoe-ncephalitis, nodular gliosis and perivascular cuffings were observed in CNS. Multifocal fibronecrotic foci were observed in lung, liver, lymph nodes and spleen. The major pathologic changes were detected in the midbrain, pons and medulla oblongata. Eosinophilic intranuclear inclusion bodies were mainly observed in epithelia and /or macrophages of tonsil, liver, lung, spleen and submandibular lymph nodes, and neurons of brain, respectively. Observation of viral particles at various stages of replication were possible from the endothelial cells of the alveolar capillaries and tonsillar crypt epithelia by transmission electron microscope.

• Journal of Chest Surgery
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• v.31 no.12
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• pp.1119-1126
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• 1998

Background: In this study, we investigated the early time course of expression of the major histocompatibility(MHC) antigens, intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), interleukin-6 and the histopathological changes in the coronary arteries of cardiac allografts exchanged between inbred mice strains that differ in one loci of class I major histocompatibility antigen (B10.BR to B10.A). Material and Method: No immunosuppressive therapy was used. Both allografts and the hearts of the recipients were harvested at 7(group 1, n=6), 15(group 2, n=6), 21(group 3, n=6), and 30(group 4, n=6) days after transplantation. They were examined by immunohistochemistry, microscopy and morphometry. All allografts had contractions at the time of harvest. Result: A strong MHC class I antigen expression was present on the endothelial and medial cells of the coronary arteries in group 1 and remained unchanged in the rest of the groups. However, MHC class II reactivity was none or very little at any time. Mild to moderate ICAM-1 expression was observed on the endothelial cells, but not on the medial cells at any time by 30 days. VCAM-1 expression was strong both on the endothelial and medial cells at any time. Moderate degree expression of interleukin-6 was observed from 7 to 30 day specimens. Histopathologically, percentage of affected vessels(vessels with intimal thickening) was less than 10 % in 7 day group and increased up to 50 % at 30 days. Mean percent narrowing of the lumen of the affected vessels revealed less than 20 % at 7 days and 40 % at 30 days. The area occupied by tropomyosin positive cells in the intimal lesion, graded from 0 to 3, showed gradual increase but remained between grade 0 to 1 by 30 days. Medial integrity was also well preserved at any time. Moderate perivascular mononuclear cell infiltration was observed at 7 days and it was progressively increased upto 30 days. Recipients' heart revealed no positive immunopathologic findings. Conclusion: In this study, the early time course of progression of the transplantation vasculopathy was demonstrated in the murine heterotopic heart transplant model.

• Korean Journal of Veterinary Research
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• v.42 no.3
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• pp.351-362
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• 2002

Newcastle disease (ND) is a highly contagious infection of poultry, Two pathology-based techniques, in situ RT-PCR and in situ hybridization (ISH) were applied to formalin-fixed, paraffin-embedded tissues from chickens naturally infected with velogenic ND virus (VNDV). Two pairs of primers and a probe for ISH and in situ RT-PCR, respectively, were selected from highly conserved region of matrix gene of NDV. The ISH experiment was carried out using MicroProbe$^{TM}$ capillary action system within 2 hours. In situ RT-PCR was performed using MicroProbe$^{TM}$ capillary action system and GeneAmp In Situ PCR system. With ISH and in situ RT-PCR, viral nucleic acid was detected in the central nervous system of chickens from infected with neurotropic velogenic Newcastle disease virus (NVNDV), whereas viral nucleic acid was detected in various organs or tissues of chickens from infected with viscerotropic velogenic Newcastle disease virus (VVNDV). In the NVND group, positive signals were characteristically defined in the cytoplasm of neuron, vascular endothelial cells, and perivascular mononuclear macrophages in the central nervous system. One of NVND group, chicken from one farm exhibited positive signals in the bronchial epithelium. The VVND group chickens showed positive reaction in the macrophages, vascular endothelium, and bronchiolar epithelium. Markedly, viral nucleic acid was detected in the macrophages of morphologically normal tissues which were peripheral or located in distant areas from lesions. The central nervous system of chickens infected with VVND virus had positive signals in the vascular endothelial cell, perivascular mononuclear macrophages and some neuron. The number and intensity of the positive cells by in situ RT-PCR were more and stronger, respectively, in comparison with those by ISH. Particularly, positive reaction was detected in macrophages infiltrating in cardiac muscle by in situ RT-PCR, but not obtained by ISH. Therefore, these results demonstrated that ISH is a rapid diagnostic method for detection of NDV and in situ RT-PCR can be used as an efficient method for detection of low viral load infection or subclinical viral infection of NDV.

• Journal of Yeungnam Medical Science
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• v.25 no.1
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• pp.41-49
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• 2008

Background : The central physiological derangement of hemorrhagic fever with renal syndrome (HFRS) caused by hantaan virus (HTNV) is a vascular dysfunction, manifested by hemorrhage, impaired vascular tone and increased vascular permeability. Platelet activating factor (PAF), whose actions are mediated through a specific receptor, is a potent bioactive lipid. PAF has diverse biological functions in the vascular system, such as increasing vascular permeability, adhesion of leukocytes to the endothelium and reduction of cardiac output, which result in hypotension and shock. The goal of the present study was to investigate whether PAF is involved in the pathogenesis of HFRS. For this purpose, we evaluated the effect of HTNV on the expression of PAF receptor (PAF-R) and on the activity of PAF-acetylhydrolase (PAF-AH) instead of PAF because PAF is rapidly degraded by PAF-AH in vivo. Materials and methods : To evaluate the expression of PAF-R, we performed reverse-transcription PCR, western blot and FACS analyses using HTNV-infected human umbilical vein endothelial cells (HUVECs) and non-infected (control) HUVECs. In addition, we measured the activity of plasma PAF-AH in HFRS patients and normal healthy persons. Results : The mRNA and protein expression of PAF-R was increased in HTNV-infected HUVECs compared with control HUVECs at 2 and 3 days post-infection (d.p.i.). FACS analysis showed that HTNV induced the surface expression of PAF-R in HUVECs from 2 d.p.i. The activity of plasma PAF-AH was 2.5-fold lower in HFRS patients than in normal healthy persons. Conclusion : Increased PAF-R expression by HTNV might increase the responsiveness to PAF in endothelial cells. Reduced PAF-AH activity in the blood of HFRS patients might delay PAF degradation. These results suggest that changes in PAF-R and PAF-AH by HTNV might influence to PAF activity and might be involved in the vascular dysfunction of HFRS.

• Journal of Korean Physical Therapy Science
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• v.8 no.1
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• pp.745-758
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• 2001

The purpose of study to phenomenological examine and the mechanism regarding the gene(DNA, RNA, Protein) and sports to studied, analyzed. and evaluated. This review considers the evidence for genetic effects in several determinants of endurance performance and resistance performance, namely: body measurements and physique, body fat pulmonary functions, cardiac and circulatory functions, muscle characteristics. substrate utilization, maximal aerobic power and other. Moreover, the response to aerobic training of indicators aerobic work metabolism and endurance performance is reviewed, with emphasis on the specificity of the response and the individual differences observed in training ability. This study indicate that improvement of 'Enhancer Action' in RNA genes changed by exercise or sports. Moreover exercise was effect on Central Dogma with DNA makes RNA makes Protein. and think that occurred with exercise influence on skeletal muscle into cell have to Myosin Heavy Chain (MHC) changed was after exercise performance, which accompanied into skeletal muscle that were exercise-induces gene-modulation that is, take gene mutations. This study known that existed hormone(epinephrine)-immune system with interaction. Exercise were altered insulin binding and MAP Kinase signaling increased into immune cells. This review suggested that the high rate of glutamine utilization by cells of the immune system serves to maintain a high intra cellular concentration of the intermediates of biosynthetic pathways such that optimal rates of DNA, RNA and protein synthesis can be maintained. In the absence of glutamine, lymphocytes do not proliferate in vitro: proliferation increase greatly as the glutamine concentration increase. Glutamine is synthesized in skeletal muscle. Skeletal muscle and plasma glutamine levels are lowered by sepsis, injury, bums, surgery and endurance exercise and in the overtrained athlete. The study of result show that production of ET-1 is markedly increased tissue specifically in the heart by exercise without appreciable changes in endothelin-converting enzyme and endothelial receptor expressions, suggest that myocardial ET-1 may participate in modulation of cardiac function during exercise. Conclusionally, this study indicate that improvement of 'Enhancer Action' in RNA genes changed by exercise or sports. Moreover exercise was effect on Central Dogma with DNA makes RNA makes Protein. This study is expected to contribute the area of sports science, medicine, hereafter more effort is required to establish the relation between gene alters and exercise amount.

• Journal of Yeungnam Medical Science
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• v.16 no.2
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• pp.181-192
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• 1999

Background: Nitric oxide, a vasodilator synthesized from L-arginine by vascular endothelial cells, accounts for the biological activity of endothelium derived relaxing factor. Previous studies demonstrated that nitric oxide inhibitor, $N^{\omega}$-Nitro-L-Arginine(NNA) diminished the hyperdynamic splanchnic and systemic circulation in portal hypertensive rats The present study was done to determine the role of nitric oxide in the development of hyperdynamic circulations in the prehepatic portal hypertensive rat model produced by partial portal vein ligation. Methods: The portal hypertensive rats were divided into water ingestion group and NNA ingestion group. After partial portal vein ligation, NNA ingestion group and water ingestion group received NNA 1mg/kg/day and plain water through the mouth for 14 days, respectively. Cardiac output, mean arterial pressure, organ blood flow and porto-systemic shunting were measured by radioisotope labeled microsphere methods. Vascular resistances were calculated by standard equation. Results: There were significant decreases in mean arterial pressure, increases in cardiac output and cardiac index, and decreases in total systemic and splanchnic vascular resistance in portal hypertensive rats compared to normal control group (p<0.01). Compared to the water ingestion group, significantly increased mean arterial pressure with decreased cardiac output and cardiac index were developed in the NNA ingestion group. Total systemic and splanchnic vascular resistance were significantly increased in the NNA ingestion group compared to water ingestion group (p<0.05). But, there was no significant difference in portal pressure between the two groups. Conclusion: The hemodynamic results of this study indicate that hyperdynamic circulation in prehepatic portal hypertensive rat mode1 was attenuated by ingestion of NNA. Nitric oxide may play an important role in the development of hyperdynamic circulation with splanchnic vasodilation in chronic portal hypertension.