1.Probing the Utility of Vascular Smooth Muscle Cells as a Target Cell for ex vivo Cardiovascular Gene Therapy.
Jonghoe BYUN ; Jeong Eun HUH ; Eun A JUNG ; Sun Jin PARK ; Jin Ok JEONG ; Hyeon Cheol GWON ; Seung Woo PARK ; Duk Kyung KIM
Korean Circulation Journal 2000;30(6):729-736
BACKGROUND AND OBJECTIVES: Compared to other target cells examined for gene therapy, vascular smooth muscle cells (VSMCs) have the unique advantages including proximity to blood stream and relative abundance in vasculature. With an ultimate goal of developing VSMC-based therapies for cardiovascular disorders, we explored the utility of VSMC as a target cell for ex vivo gene therapy using a set of retroviral vectors. MATERIALS AND METHODS: Cultured VSMCs were transduced with replication-defective recombinant retroviruses harboring LacZ, nlsLacZ, mVEGF, mGM-CSF or bacterial CAT reporter. The VSMCs were examined for G418-selection, transduction efficiency, the level of transgene expression, and longevity of gene expression. ResultsVSMCs were readily transduced with different kinds of retroviral vectors. The bacterial neo r gene-transduced VSMCs were successfully selected with G418. The G418-selected VSMCs could express the transduced genes at a level comparable to NIH3T3. The level of transgene expression did not appear to be affected by the increasing number of passages. CONCLUSION: The results demonstrate an efficient transduction of VSMCs by retroviral vectors in vitro and an sustained expression of retrovirally transduced genes in VSMCs. VSMCs could be one of the ideal target cells for ex vivo cardiovascular gene therapy employing retroviral vector.
Animals
;
Cats
;
Gene Expression
;
Genetic Therapy*
;
Longevity
;
Muscle, Smooth, Vascular*
;
Retroviridae
;
Rivers
;
Transgenes
;
Zidovudine
2.A Case of Pelvic Actinomycosis.
Seung Chul KANG ; In Goo KANG ; Sang Un LEE ; Soon Chul GWON ; Hyun Rak PARK ; Byung Mok YOON ; Suk WON ; Young Chul BAEK ; Jung Geun PARK
Korean Journal of Obstetrics and Gynecology 2000;43(11):2091-2094
Actinomycosis is an oppoturnistic infection of actinomyces, which are relatively avirulent endogenous oral commensals. After trauma or infection, they breach the normally protective mucosal barriers to invade adjacent soft tissue structures. Lesions routinely contain other bacteria, the normal resident flora at the site of primary infection, which act synergistically with actinomyces species to provoke this unique infection, which range from an acute suppurative process to a chronic fibrotic process. According to epidemic studies about pelvic actinomycosis, it should be significantly related to IUD(intrauterine device). It is accounted that IUD cause chronic intrauterine infection, tissue injury and act as nucleus for parasitic infestation. Here we present a case of pelvic actinomycosis related to IUD with brief review of the concerned literature.
Actinomyces
;
Actinomycosis*
;
Bacteria
3.Detection of human papillomavirus(HPV) using the polymerase chain reaction in paraffin-embedded cervical carcnomas anf their metastatic lymph nodes.
Joo Cheol SONG ; Hong Ki KIM ; Seo Ock KANG ; Seung Cheol KIM ; In Geol MOON ; In Gwon HAN ; Sung Ran HONG ; Hee Sook KIM ; Won Hee HAN ; Chong Taek PARK
Korean Journal of Obstetrics and Gynecology 1991;34(3):385-393
No abstract available.
Atrial Natriuretic Factor*
;
Humans*
;
Lymph Nodes*
;
Polymerase Chain Reaction*
4.A case of polycythemia vera with liver cirrhosis.
Yong Min KIM ; Hee Seung MOON ; Jin Seok KIM ; Suk Ho LEE ; Yeong Chan HAN ; Young Tae KIM ; Soyon KIM ; Byong Yik PARK ; Gwon Jun LEE
Korean Journal of Hematology 1991;26(2):405-410
No abstract available.
Liver Cirrhosis*
;
Liver*
;
Polycythemia Vera*
;
Polycythemia*
5.Effect of Local Administration of Lovastatin on Preventing Neointimal Hyperplasia in the Rat Carotid Artery Injury Model.
Sang Chol LEE ; Duk Kyung KIM ; Seung Woo PARK ; Jeong Eun HUH ; Sun Jin PARK ; Hyun Cheol GWON ; June Soo KIM ; Sang Hoon LEE ; Kyung Pyo HONG ; Jeong Euy PARK ; Jung Don SEO ; Won Ro LEE
Korean Circulation Journal 1999;29(8):812-821
BACKGROUND AND OBJECTIVES: ovastatin, a HMG-CoA reductase inhibitor, is known to show antiproliferative effects on VSMC after vessel injury, but a large amount of the drug is needed orally for this purpose. This study investigated the effects of lovastatin given locally to injured carotid arteries of rats on reducing neointimal hyperplasia. MATERIALS AND METHOD: Lovastatin was given perivascularly to balloon-injured carotid arteries of 21 rats in 1 microM to the low-dose group, and 30 microM to the high-dose group. The control group was treated with pluronic gel only. Two weeks later, the lumen area, neointimal areas and the number of actively proliferating cells were obtained and compared. RESULTS: eointimal area was 0.113+/-0.032 mm2, 0.065+/-0.017 mm2, 0.072+/-0.017 mm2 in the control, low-dose and high-dose groups respectively. The area was significantly smaller in the treatment groups (p<0.05), but no significant difference was observed between the treatment groups. The number of actively proliferating cells per mm2 of neointimal area were 714.5+/-227.4, 688.4+/-333.7, and 1526.3+/-744.0 in the groups respectively, and the number was significantly high in the high-dose group (p<0.05). CONCLUSION: Local administration of lovastatin is effective in reducing neointimal hyperplasia after vascular injury, but extremely high doses are not needed locally for this purpose.
Animals
;
Carotid Arteries*
;
Carotid Artery Injuries*
;
Hyperplasia*
;
Lovastatin*
;
Oxidoreductases
;
Rats*
;
Vascular System Injuries
6.Change of Clinical Outcome in Patients with Unstable Angina according to Early Revascularization Therapeutic Strategy.
Wook Hyun CHO ; Jeong Sik PARK ; Shin Bae JOO ; Jin Ok JEONG ; Hyeon Cheol GWON ; Seung Woo PARK ; June Soo KIM ; Duk Kyung KIM ; Sang Hoon LEE ; Kyung Pyo HONG ; Jeong Euy PARK ; Jung Don SEO ; Won Ro LEE
Korean Circulation Journal 1999;29(11):1188-1194
BACKGROUND AND OBJECTIVES: It has been well known that the Braunwald classification is an appropriate clinical parameter in the prediction of the outcome in patients with unstable angina. However, the ability of the classification to predict prognosis of unstable angina according to treatment strategy is not established. We evaluated the relation between severity of angina on admission and outcome of primary unstable angina with early invasive strategy. MATERIALS AND METHOD: 148 patients (M 85, F 63, age 61+/-10) with suspected unstable angina were divided into three subgroups on the basis of the Braunwald classification on admission. The patients were followed up to 6 months prospectively if the final diagnosis was primary unstable angina. Early invasive strategy was used for the treatment of unstable angina. Major cardiac events were assessed during hospitalization and 6 months follow-up period according to the Braunwald classification. RESULTS: Unstable angina was diagnosed in 95 patients (64%). Among these patients, 89 patients with primary unstable angina were followed up to 6 months. Clinical characteristics including number of patients, mean age, sex ratio, risk factors, coronary angiographic findings and revascularization rate during hospitalization were not different in three subgroups of these patients. Among these patients, early coronary revascularizations was performed in 67 patients (75%) and 2 (2%) deaths/myocardial infarctions occurred during hospitalization. During the follow-up period, 1 (1%) myocardial infarction/death and 12 (13%) revascularizations occurred. Cardiac event rate (death, myocardial infarction or revascularization) was not different during hospitalization and 6 months follow-up period among subgroups of severity class. CONCLUSION: Clinical outcome should be reevaluated after early coronary intervention to predict cardiac event in patients with unstable angina.
Angina, Unstable*
;
Classification
;
Diagnosis
;
Follow-Up Studies
;
Hospitalization
;
Humans
;
Infarction
;
Myocardial Infarction
;
Prognosis
;
Prospective Studies
;
Risk Factors
;
Sex Ratio
7.Heart Rate Variability in Stable Angina Patients without History of Myocardial Infarction.
Jin Ku KIM ; June Soo KIM ; Joong Il PARK ; Juhyeon OH ; Hyeon Cheol GWON ; Seung Woo PARK ; Duk Kyung KIM ; Sang Hoon LEE ; Kyung Pyo HONG ; Jeong Euy PARK ; Jung Don SEO ; Won Ro LEE
Korean Circulation Journal 2001;31(5):484-491
BACKGROUND AND OBJECTIVES: Heart rate variability(HRV) reflects the autonomic integration of heart. There were many reports that HRV in patients with myocardial infarction or heart failure is an independent prognostic factor to predict fatal arrhythmia and sudden cardiac death. But, the role of HRV is still controversial in stable angina patients without history of myocardial infarction. In this study, we tried to compare HRV indices between stable angina patients and normal subjects. MATERIALS AND METHODS: Twenty-one stable anginal patients without history of myocardial infarction (mean age : 57 +/- 2 years) and twenty-one relatively healthy persons without history of coronary heart disease (mean age : 53 +/- 2 years) were included in the study and underwent 24-hour ambulatory ECG monitoring. In patients group, all underwent coronary angiography after 24-hour ambulatory ECG monitoring. HRV was analyzed over the whole 24 hours, using time and frequency domain parameters, according to time phases and coronary angiographic severity. RESULTS: There were no significant differences in age, sex and cardiovascular risk factors, except hypertension (p=.001) between two groups. HRV indices such as rMSSD, pNN50, LF, HF, LFnorm and HFnorm were significantly decreased (p<0.05) in patients group. But the angiographic severity of coronary arteries did not show any significant effect on the HRV indices in patients group. CONCLUSIONS: We observed significantly reduced HRV indices in patients with stable angina without history of myocardial infarction.
Angina, Stable*
;
Arrhythmias, Cardiac
;
Coronary Angiography
;
Coronary Disease
;
Coronary Vessels
;
Death, Sudden, Cardiac
;
Electrocardiography
;
Heart Failure
;
Heart Rate*
;
Heart*
;
Humans
;
Hypertension
;
Myocardial Infarction*
;
Risk Factors
8.The Effects of Aldosterone and Cytokines IL-1beta, TNF-alpha on the Expression of Angiotensin Converting Enzyme Gene in Vascular Smooth Muscle Cells.
Duk Kyung KIM ; Jeong Eun HUH ; Yoon Hyuk CHOE ; Sun Jin PARK ; Eun A JUNG ; Jonghoe BYUN ; Hyeon Cheol GWON ; Seung Woo PARK ; June Soo KIM ; Sang Hoon LEE ; Kyung Pyo HONG ; Jeong Euy PARK ; Jung Don SEO ; Won Ro LEE
Korean Circulation Journal 1999;29(1):84-95
BACKGROUND: It has been suggested that all components of the renin-angiotensin-aldosterone system (RAAS) are present in the vascular wall and that the vascular RAAS modulates vascular tone and vascular hypertrophy. One of the catalytic step in the RAAS cascade is the local conversion of angiotensin I to angiotensin II (Ang II) by angiotensin converting enzyme (ACE). One of the major sources of ACE in the vasculature is vascular smooth muscle cells (VSMC). Here, we provide insight into the intrinsic mechanisms by which the components of RAAS regulate gene expression of ACE in cultured smooth muscle cells of the rat and we also investigated the effects of cytokines on ACE mRNA. METHODS: RNA was extracted from the primary cultured VSMCs. We analyzed the expression levels of ACE by competitive reverse transcription-PCR using recombinant RNA as an internal standard. RESULTS: 1) ACE mRNA level was increased markedly by aldosterone in a dose- and time-dependent manner, indicating that there exists positive feedback mechanism within RAAS. 2) The induction of ACE mRNA by aldosterone was inhibited by spironolactone. 3) Aldosterone-stimulated expression of ACE was also inhibited by Ang II, which shows that Ang II acts as a negative regulator of the expression of ACE in RAAS cascade. 4) Interleukin-1beta or TNF-alpha did not induce ACE mRNA expression. 5) However, mixture of interleukin-1betaand TNF-alpha(CytoMix) significantly increased the expression of ACE. It was also shown that CytoMix increased aldosterone-stimulated ACE mRNA expression in an additative manner. CONCLUSION: These results indicate that the expression of ACE in smooth muscle cells is modulated by the components of RAAS and cytokines. The intrinsic positive and negative feedback controls of RAAS would play an important role in the pathogenesis of vascular diseases.
Aldosterone*
;
Angiotensin I
;
Angiotensin II
;
Angiotensins*
;
Animals
;
Cytokines*
;
Gene Expression
;
Hypertrophy
;
Interleukin-1beta
;
Muscle, Smooth, Vascular*
;
Myocytes, Smooth Muscle
;
Peptidyl-Dipeptidase A*
;
Rats
;
Renin-Angiotensin System
;
RNA
;
RNA, Messenger
;
Spironolactone
;
Tumor Necrosis Factor-alpha*
;
Vascular Diseases
9.Heart Rate Variability in Patients with Neurocardiogenic Syncope or Presyncope.
Jin Ku KIM ; June Soo KIM ; Kyoung Ju AHN ; Sang Chol LEE ; Hyeon Cheol GWON ; Seung Woo PARK ; Duk Kyung KIM ; Sang Hoon LEE ; Kyung Pyo HONG ; Jeong Euy PARK ; Jung Don SEO ; Won Ro LEE
Korean Circulation Journal 2000;30(6):716-723
BACKGROUND AND OBJECTIVES: Neurocardiogenic syncope is believed to be caused by a transient imbalance of autonomic nervous system. Actually, there were significant differences in heart rate variability (HRV) indices during head-up tilt test between patients with neurocardiogenic syncope and normal controls. But there was no definite evidence for it during daily activity. So, we tried to evaluate HRV during daily activity with 24-hour ambulatory electrocardiography monitoring. MATERIALS AND METHODS: 27 patients with neurocardiogenic syncope or presyncope (mean age 45+/-3) and 25 normal volunteers (mean age 47+/-2) comparable for age and sex underwent 24-hour ambulatory electrocardiography. Head-up tilt test was used to diagnose neurocardiogenic syncope or presyncope in patients group. HRV was analysed over the whole 24 hours, using time and frequency domain parameters. Student's
Autonomic Nervous System
;
Electrocardiography, Ambulatory
;
Healthy Volunteers
;
Heart Rate*
;
Heart*
;
Humans
;
Syncope*
;
Syncope, Vasovagal*
10.Usefulness of Head-up Tilt Test in Adults with Syncope or Presyncope of Unexplained Origin.
June Soo KIM ; Jae Choon RYU ; Shin Bae JOO ; Hyeon Cheol GWON ; Jin A CHOO ; Young Ran CHOI ; Seung Woo PARK ; Duk Kyung KIM ; Sang Hoon LEE ; Kyung Pyo HONG ; Jeong Euy PARK ; Won Ro LEE
Korean Circulation Journal 1996;26(4):855-864
BACKGROUND: Vasovagal syncope is a common cause of syncope. In some cases, syncopal episode is recurrent, resulting in physical injury. Head-up tilt test with or without isoproterenol provocation has been a tool to diagnose vasovagal syncope. But the protocol of head-up tilt test has not been settled. In this study, we evaluate the usefulness of a head-up tilt test with isoproterenol provocation in patients with syncope or presyncope of unexplained origin. METHODS: Head-up tilt test was performed with patients in the fasting state in the morning. After supine heart rate and blood prewwure were obtained, each patient was tilted to the 70 degree upright position for 30 minutes using a motorized tilt table with a footboard. If the test was negative in the baseline tilt, intravenous isoproterenol was started at 1 microg/min and then increased by 1 microg/min every three minutes to a maximum of 5 microg/min while maintaining 70 degree upright position. The end points of test were positive response, intolerance of isoproterenol, heart rate>150 beats/min, and completion of the protocol. When an end point reached, the patient was rapidly returned to the horizontal position. RESULTS: 1) Of 122 patients with syncope or presyncope, 113 patients(93%) had prodromal symptoms. 2) 23 patients(19%) had physical injury during episode. 3) 93 patients(76%) experienced episodes while they were standing or sitting. 4) A total of 83 patients(68%) had a positve response during head-up tilt test ; 7 patients(8%) of these 83 patients had a positive response during the baseline tilt. But, 76 patients(92%) required isoproternol provocation to elicit this response. 5) The pattern of positive response showed vasodepressive pattern in 55 patients(67%), mixed pattern in 26 patients(31%), and cardioinhibitory pattern in 2 patients(2%). 6) No significant side effect of isoproterenol was noted. 7) There were no significant differences between positive response group and negative response group in terms of clinical characteristics and hemodynamic findings during head-up tilt test. CONCLUSION: A head-up tilt test with isoproterenol provocation could be an useful tool for diagnosing vasovagal syncope or presyncope in adults.
Adult*
;
Fasting
;
Heart
;
Heart Rate
;
Hemodynamics
;
Humans
;
Isoproterenol
;
Prodromal Symptoms
;
Syncope*
;
Syncope, Vasovagal