1.4-Hydroxybenzaldehyde Restricts the Intracellular Growth of Toxoplasma gondii by Inducing SIRT1-Mediated Autophagy in Macrophages
Jina LEE ; Jae-Won CHOI ; Hye Young HAN ; Woo Sik KIM ; Ha-Yeon SONG ; Eui-Baek BYUN ; Eui-Hong BYUN ; Young-Ha LEE ; Jae-Min YUK
The Korean Journal of Parasitology 2020;58(1):7-14
Toxoplasma gondii is an intracellular protozoan parasite that infects approximately one third of the human popu- lation worldwide. Considering the toxicity and side effects of anti-toxoplasma medications, it is important to develop effec- tive drug alternatives with fewer and less severe off-target effects. In this study, we found that 4-hydroxybenzaldehyde (4- HBA) induced autophagy and the expression of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) in primary murine bone marrow-derived macrophages (BMDMs). Interestingly, treatment of BMDMs with 4-HBA significantly reduced the number of macrophages infected with T. gondii and the proliferation of T. gondii in infected cells. This effect was impaired by pretreating the macrophages with 3-methyladenine or wortmannin (selective autophagy inhibitors) or with sirtinol or EX527 (SIRT1 inhibitors). Moreover, we found that pharmacological inhibition of SIRT1 prevented 4-HBA-mediated expres- sion of LC3-phosphatidylethanolamine conjugate (LC3-II) and the colocalization of T. gondii parasitophorous vacuoles with autophagosomes in BMDMs. These data suggest that 4-HBA promotes antiparasitic host responses by activating SIRT1- mediated autophagy, and 4-HBA might be a promising therapeutic alternative for the treatment of toxoplasmosis.
2.A Case of Discovery of Heterotopic Pregnancy After Elective Abortion.
Sung Hong JOO ; Sang Kug BYUN ; Hwa Young CHOE ; Yong Ho JO ; Eui Sik JUNG ; Sung Jin CHO
Korean Journal of Obstetrics and Gynecology 2002;45(7):1233-1235
Heterotopic pregnancy, simultaneous intrauterine and extrauterine pregnancy, is an extremely rare case. The incidence of heterotopic pregnancy was about 1 to 30,000 pregnancy, but it has been increased. Ectopic pregnancy is associated with significant mortality if not promptly diagnosed. Careful pelvic examination combined serial beta-hCG determinations and transvaginal sonography to evaluation the adnexal region are necessary prerequisites for early diagnosis. We report a case of discovery of heterotopic pregnancy after elective abortion with brief review of literature.
Early Diagnosis
;
Female
;
Gynecological Examination
;
Incidence
;
Mortality
;
Pregnancy
;
Pregnancy, Ectopic
;
Pregnancy, Heterotopic*
3.Extrauterine Adenomyoma of the Liver Mimicking a Hepatic Adenoma: A Case Report
Young Joo WON ; Ji Young WOO ; Jieun BYUN ; Min Eui HONG
Journal of the Korean Radiological Society 2020;81(1):197-202
Extrauterine adenomyoma of the liver is extremely rare. Only a few cases have been reported, and these reports have focused mainly on histopathology. Herein, we report the specific imaging findings of extrauterine adenomyoma of the liver in a 43-year-old woman with epigastric pain, which was initially diagnosed as a hepatic adenoma. CT and MRI revealed a solid and cystic mass with hemorrhagic foci and weak persistent enhancement, located in the subcapsular region of the right hepatic lobe.
4.Apoptosis in dilated cardiomyopathy.
Bum Kee HONG ; Hyuck Moon KWON ; Ki Hyun BYUN ; Dongsoo KIM ; Eui Young CHOI ; Tae Soo KANG ; Seok Min KANG ; Kook Jin CHUN ; Yangsoo JANG ; Hyun Seung KIM
The Korean Journal of Internal Medicine 2000;15(1):56-64
OBJECTIVE: Cardiomyopathy, a popular diagnosis that always obscures more than it reveals, nevertheless has several characteristic histological features. These prominently include widespread focal myocardial fibrosis and associated hypertrophy of surviving cardiac myocyte. In fact, focal noninflammatory degeneration (not necrosis) has been demonstrated as a feature of many forms of cardiac hypertrophy. We hypothesized that this loss of myocardial cells in dilated cardiomyopathy (DCMP) may result from cell death by apoptosis. METHODS: Endomyocardial biopsy specimens from the right ventricles of six patients who suffered from DCMP were studied, and myocardial specimens from two persons who died in motor vehicle accidents were used as negative controls. For identification of apoptosis, immunohistochemistry with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling was performed. In addition, apoptosis was confirmed morphologically by confocal laser scanning microscopy with propidium iodide. RESULTS: Apoptosis, that was represented by an apoptotic index ranging from 19.8 to 25.4+ACU-, could be extensively seen in myocytes and also rarely in non-myocytes of interstitium and vascular endothelium. Morphologically, there were a lot of nuclei with clumps of condensed chromatin, suggestive of apoptosis. CONCLUSION: The present study demonstrated that myocyte loss in DCMP might be mainly due to the apoptosis of myocytes and interstitial cells, rather than inflammation or cell necrosis.
Adult
;
Analysis of Variance
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Apoptosis/physiology+ACo-
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Biopsy, Needle
;
Cardiomyopathy, Congestive/physiopathology
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Cardiomyopathy, Congestive/pathology+ACo-
;
Caspases/analysis
;
Enzyme Precursors/analysis
;
Female
;
Human
;
Immunohistochemistry
;
In Situ Nick-End Labeling
;
Male
;
Microscopy, Confocal
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Middle Age
;
Myocardium/pathology+ACo-
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Reference Values
;
Statistics, Nonparametric
5.Upregulation of extracellular matrix metalloproteinase inducer (EMMPRIN) and gelatinases in human atherosclerosis infected with Chlamydia pneumoniae: The potential role of Chlamydia pneumoniae infection in the progression of atherosclerosis.
Eui Young CHOI ; Dong Soo KIM ; Bum Kee HONG ; Hyuck Moon KWON ; Young Goo SONG ; Ki Hyun BYUN ; Hyun Young PARK ; Ki Chul WHANG ; Hyun Seung KIM
Experimental & Molecular Medicine 2002;34(6):391-400
Chlamydia pneumoniae infection implicated as an important etiologic factor of atherosclerosis, especially in coronary artery disease (CAD), was found in vitro to be associated with the induction of matrix metalloproteinases (MMPs). An extracellular matrix metalloproteinase inducer (EMMPRIN)/membrane-type 1 matrix metalloproteinase (MT1-MMP) system which induces and activates MMPs,is suggested to be functional and were upregulated in the failing myocardium. However, the upstream regulation of MMPs by C. pneumoniae within atheroma itself remains unclear. We evaluated the seroepidemiologic study of C. pneumoniae infection in CAD patients (n = 391) and controls (n = 97) and performed histopathological and in vitro analysis in atherosclerotic vascular tissues obtained from patients with seropositive to C. pneumoniae (n = 20), by using immunochemistry for C. pneumoniae, EMMPRIN/MT1-MMP, MMP-2, and MMP-9. The seropositive rates of both anti-C. pneumoniae IgG and IgA were 56.7% in CAD group and 43.3% in control group (P =0.033). Seropositive rate was increased in subgroups of CAD patients without conventional coronary risk factors compared to those with conventional risk factors. Immunoreactivities of EMMPRIN, MT1-MMP, MMP-2, and MMP-9 were increased in the atheromatous plaque itself, predominantly in immunoreactive macrophages/mononuclear cells to C. pneumoniae. Furthermore, Western blot analysis showed that EMMPRIN and MMP-2 were detected more prominently in atherosclerotic tissues infected with C. pneumoniae compared to control tissues. Zymographic analysis revealed that activities of MMP-2 and MMP-9 were more increased in atherosclerotic tissues infected with C. pneumoniae compared to control tissues. The present study demonstrated upstream regulation of MMPs can be induced by C. pneumoniae within atheromatous plaque itself. These findings help to understand the potential role of C. pneumoniae in the progression of atherosclerosis.
Aged
;
Animals
;
Arteriosclerosis/complications/enzymology/*microbiology/*pathology
;
Blotting, Western
;
Chlamydia Infections/*complications/enzymology/epidemiology/immunology
;
Chlamydophila pneumoniae/immunology/*pathogenicity
;
Disease Progression
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Extracellular Matrix/enzymology
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Female
;
Gelatinases/*metabolism
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Human
;
Immunohistochemistry
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Male
;
Matrix Metalloproteinases/*metabolism
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Membrane Glycoproteins/*metabolism
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Middle Aged
;
Up-Regulation
6.Apolipoprotein E polymorphism in non-diabetic patients with acute coronary syndrome.
In Jai KIM ; Bum Kee HONG ; Byoung Kwon LEE ; Hyuck Moon KWON ; Dongsoo KIM ; Eui Young CHOI ; Ki Hyun BYUN ; Jeong Ho KIM ; Kyung Soon SONG ; Hyun Seung KIM
Yonsei Medical Journal 1999;40(4):377-382
Since a decade ago, apolipoprotein (apo) E polymorphism has been focussed as a risk factor for cardiovascular disease. ApoE plays a central role as a receptor ligand for the uptake of lipoproteins from the circulation. There was an agreement on apoE polymorphism being one of the major risk factors for coronary artery disease (CAD) by its effects on lipid profiles. However, the effects of apoE have not been noted in all populations and conflicting results in the risk of CAD have been noted. Recently, in situ expression of apoE on the atherosclerotic plaque has been studied. We, therefore, investigated the effects of apoE genotype on patients with acute coronary syndrome, including unstable angina and acute myocardial infarction, in non-diabetic patients. While we could not find significant risk effects of apoE on coronary artery disease and lipid profiles on simple comparison with the normal control group, we could find significantly decreased frequencies of apo epsilon 3 allele in patients with acute coronary syndrome compared with stable angina patients (77.8% vs 88.8%). We suggest that the apoE genotype could be associated with acute coronary events in CAD and further study with in situ biochemical methods will be needed on the effects of apoE polymorphism on plaque stability.
Apolipoproteins E/genetics*
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Coronary Disease/genetics*
;
Genotype
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Human
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Polymorphism (Genetics)/genetics*
;
Syndrome
7.Study on Circulating Factor(s) in Patient with Recurrent Focal Segmental Glomerulosclerosis.
Eui Won HWANG ; Seung Il KIM ; Eun Na KIM ; Hyun Jin LIM ; Jung Duk BYUN ; Hyung Kun PARK ; Eun Young LEE ; Dong Ho YANG ; Sae Yong HONG
Korean Journal of Nephrology 2001;20(4):631-638
BACKGROUND: Although a significant number of studies were done on focal segmental glomerulosclerosis(FSGS), its pathogenesis has not been sufficiently established yet. Recent studies suggested certain types of circulating factor(s) played an important role in development and recurrence after renal transplantation of FSGS by modifying the glomerular permeability of albumin. The purpose of this study performed on animals and through molecular-biological experiments is to certify the role of circulating factor (s), which cause proteinuria, by manipulating plasma of a FSGS patient who showed massive of proteinuria and wide effacement of glomerular epithelial foot processes in histologic examination after renal transplantation. also, whose massive proteinuria decreased significantly after plasma exchange. METHODS: The patient's plasma prior to(plasma A) or post to(plasma B) plasma exchange were injected into tail veins of two groups of male Sprague-Dawley rats, six in each. The ratio of 24 hour urine protein and urine creatinine(Uprt/Ucr) was calculated for each case. The 2D gel electrophoresis was performed in plasma A and plasma B. The pattern of 2D gel electrophoresis of plasma A was compared to those of plasma B and healthy human serum. RESULTS: Compared to control group, there was no significant differences in 24-hour Uprt/Ucr afer injecting 1, 2, 3, 5 mL of plasma A(p>0.05). There was no significant difference in 24-hour Uprt/Ucr between the injecting groups of plasma A and plasma B(p>0.05). We were not able to observe any new protein which did not appear in plasma B or healthy human serum in 2D gel electrophoresis. CONCLUSION: These results suggest that the proteinuria developed in a few hours after renal transplantation and is related to wide effacement of glomerular epithelial foot processes, and that it may be induced by a certain factor which is eliminated by the plasma exchange or restrained by the immunosuppressive agents. However, we were not able to find certain circulating factor(s) which rapidly changes albumin permeability in the patient's plasma with FSGS.
Animals
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Electrophoresis, Gel, Two-Dimensional
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Foot
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Glomerulosclerosis, Focal Segmental*
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Humans
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Immunosuppressive Agents
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Kidney Transplantation
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Male
;
Permeability
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Plasma
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Plasma Exchange
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Proteinuria
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Rats, Sprague-Dawley
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Recurrence
;
Veins
8.Analysis of Heart Rate Variability in 24-Hour Holtor onitoring of Patients with Vasovagal Syncope.
Tae Soo KANG ; Dong Joo KIM ; Hyuck Moon KWON ; Ki Hyun BYUN ; In Jai KIM ; Seok Min KANG ; Bum Kee HONG ; Dongsoo KIM ; Eui Young CHOI ; Jun Hee LEE ; Woon Hyoung PARK ; Hyun Seung KIM
Korean Circulation Journal 2000;30(11):1417-1422
BACKGROUND AND OBJECTIVES: Syncope is defined as a sudden temporary loss of consciousness associated with a loss of postural tone with spontaneous recovery. It is a common clinical problem with complex and heterogeneous etiologies, but vasovagal syncope is the main cause of unexplained syncope. Bradycardia and hypotension by transient dysfunction of cardiac autonomic nervous system have been cited as the main pathophysiology of the vasovagal syncope. Therefore, we studied whether analysis of heart rate variability (HRV) by 24-hour ambulatory ECG monitoring would reflect autonomic imbalance between cardiac sympathetic and vagal efferent activity in the patients of vasovagal syncope. MATERIALS AND METHOD: 45 patients (male=2, female=3, mean age=2.214 years) with syncope were enrolled, and divided into 2 subgroups according to the results of head-up tilt test: head-up tilt test positive (group S1) and negative (group S0). A sex-matched control group consisted of 9 healthy volunteers (male=, female=, mean age=16 years, Group C). The 24-hour ambulatory ECG monitoring was performed in all groups, and R-R intervals were analyzed by time- and frequency-domain methods. The time-domain measurements of HRV were mean NN(mean of all coupling intervals between normal beat), ASDNN(mean of the standard deviations of all normal R-R intervals for 5-minute segments of the entire recording), SDNN(standard deviation of all normal R-R intervals over 24 hours), SDANN(standard deviation of average R-R intervals in all 5 minutes segments of the entire recording), rMSSD(square root of the mean squared differences of successive R-R interval) and pNN50(percent of differences between adjacent normal R-R intervals more than 50ms during 24 hours), and frequency-domain measurements were low frequency (LF), high frequency (HF) components and LF/HF ratio. RESULTS: The LF/HF ratio was significantly higher in syncope patients with positive results of head-up tilt test and syncope patients with negative results than in control (p<0.05). The LF, HF, mean NN, ASDNN, SDNN, SDANN, rMSSD, and pNN50 were not significantly different among these three groups. CONCLUSION: These results suggest that the cardiac autonomic nervous system in patients with vasovagal syncope has sympathetic-activated balanced without changes of total power of both sympathetic and parasympathetic components.
Autonomic Nervous System
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Bradycardia
;
Electrocardiography
;
Healthy Volunteers
;
Heart Rate*
;
Heart*
;
Humans
;
Hypotension
;
Syncope
;
Syncope, Vasovagal*
;
Unconsciousness
9.Serum Levels of Advanced Glycation End Products Are Associated with In-Stent Restenosis in Diabetic Patients.
Eui Young CHOI ; Hyuck Moon KWON ; Chul WOO ; Geun TAEK ; Boyoung JOUNG ; Bum Kee HONG ; Young Won YOON ; Dongsoo KIM ; Ki Hyun BYUN ; Tae Soo KANG ; Se Jung YOON ; Sung Woo KWON ; Sung Ju LEE ; Jong Kwan PARK ; Hyun Seung KIM
Yonsei Medical Journal 2005;46(1):78-85
The formation of advanced glycation end products (AGEs), in various tissues has been known to enhance immunoinflammatory reactions and local oxidant stresses in long standing diabetes. Recently, AGEs have been reported to play a role in neointimal formation in animal models of arterial injury. We attempted to determine whether the serum levels of AGEs are associated with coronary restenosis in diabetic patients. Blood samples were collected from diabetic patients with coronary artery disease undergoing stent implantation and the serum levels of AGEs were analyzed by the fluorescent intensity method. The development of in-stent restenosis (ISR) was evaluated by a 6-month follow-up coronary angiography. A total of 263 target lesions were evaluated, in 203 patients. The ISR rate in the high-AGE (> 170 U/ml) group (40.1%) was significantly higher than in the low-AGE group (< or =170 U/ml) (19.6%) (p < 0.001). Furthermore, multivariate analysis revealed that a high level of serum AGEs is an independent risk factor for the development of ISR (odds ratio, 2.659; 95% CI, 1.431-4.940; p=0.002). The serum levels of AGEs constitute an excellent predictive factor for ISR, and should be one of the guidelines for medical therapy and interventional strategy to prevent ISR in diabetic patients.
Aged
;
Coronary Arteriosclerosis/epidemiology/*metabolism/*therapy
;
Coronary Restenosis/epidemiology/*metabolism
;
Diabetes Mellitus, Type 2/epidemiology/*metabolism
;
Female
;
Glycosylation End Products, Advanced/*blood
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Humans
;
Male
;
Middle Aged
;
Research Support, Non-U.S. Gov't
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Risk Factors
;
*Stents
10.Clinical Features and Treatment Pattern of Migrainous Vertigo in Korea: A Nationwide Prospective Multicenter Study
Seong Ki AHN ; Kyusik KANG ; Ja Won KOO ; Kyu Sung KIM ; Beom Gyu KIM ; Byung Kun KIM ; Ji Soo KIM ; Kyoung Ho PARK ; Shi Nae PARK ; Eun Ho PARK ; Hong Ju PARK ; Jae Yong BYUN ; Myung Whan SUH ; Ki Bum SUNG ; Sun Young OH ; Chung Ku RHEE ; Tae Kyeong LEE ; Seong Hae JEONG ; Won Ho CHUNG ; Chang Il CHA ; Sung Won CHAE ; Eui Kyung GOH
Journal of the Korean Balance Society 2009;8(2):122-131
BACKGROUND AND OBJECTIVES It is being increasing recognized that the morbidities of migraine and balance disorders are interrelated. In fact, migrainous vertigo (MV) is one of frequent causes of recurrent vertigo in patients presenting to specialized dizziness clinics. Nevertheless, not many studies have reported clinical manifestations and treatment. Therefore, the aim of study was designed to assess clinical features and treatment patterns by a nationwide multicenter study. MATERIALS AND METHODS Patients between 9 and 74 years of age who visited 17 Korean tertiary referral centers and 1 clinic from February to March 2009 were investigated using two forms of questionnaires. RESULTS Overall, 318 patients with MV were enrolled. MV was responsible for ~8.45% of visits to the specialized dizziness clinics. One hundred seventy-five of these patients had definite MV and were included in assessing the clinical features. Vertigo characteristics of patients with definite MV were various. Vertigo was regularly as sociated with headache in 87% of the patients. The duration of vertigo ranged from seconds to days. For the treatment patterns, an acute and prophylactic therapies were carried in most clinics. There were no differences in either acute or prophylactic therapies between department of neurology and otorhinolaryngology. CONCLUSIONS The results of this study suggest that MV the clinical features of MV also varies in Korea. In addition, most clinics provide similar patterns of practice in treatment for MV. The syndrome of MV deserves further research activity as it is relatively common and clinically relevant.
Dizziness
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Headache
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Humans
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Korea
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Migraine Disorders
;
Neurology
;
Prospective Studies
;
Tertiary Care Centers
;
Vertigo