Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV core protein has been shown to modulate various cellular signaling pathways including the nuclear factor κB (NF-κB) pathway which is associated with inflammation, cell proliferation and apoptosis. However, there have been conflicting reports about the effect of HCV core protein on NF-κB pathway, and the mechanism by which the core protein affects NF-κB activity remains nuclear. In this study, the functional interaction of HCV core protein and IκB kinase γ (IKKγ) was investigated using the expression plasmids of core and the components of IKK complex. The data revealed that HCV core protein activates NF-κB. Also, HCV core protein up-regulated the phosphorylation and degradation of IκBα. The activating effect of HCV core protein on NF-κB was synergistically elevated by IKKγ. It was noticed that the N-terminal IKKβ binding site, C-terminal leucine zipper, and zinc finger domains of IKKγ are not necessary for its synergistic effect. HCV core protein and IKKγ appeared to activate NF-κB by up-regulating the IKKβ activity resulting in the degradation of IκBα. As expected, HCV core protein induced the expression of NF-κB-targeted pro-inflammatory genes such as iNOS, IL-1β and IL-6 in the transcription level. These results suggest that HCV core protein induces NF-κB through the interaction with IKKγ and may play a critical role in the development of inflammation and related liver diseases.
Apoptosis ; Binding Sites ; Carcinoma, Hepatocellular ; Cell Proliferation ; Hepacivirus* ; Hepatitis C* ; Hepatitis* ; Hepatitis, Chronic ; Inflammation ; Interleukin-6 ; Leucine Zippers ; Liver Cirrhosis ; Liver Diseases ; Phosphorylation ; Phosphotransferases ; Plasmids ; Zinc Fingers

PURPOSE: Human adenovirus infection mimics Kawasaki disease (KD) but can be detected in KD patients. The aim of this study was to determine the clinical differences between KD with adenovirus infection and only adenoviral infection and to identify biomarkers for prediction of adenovirus-positive KD from isolated adenoviral infection. METHODS: A total of 147 patients with isolated adenovirus were identified by quantitative polymerase chain reaction. In addition, 11 patients having KD with adenovirus, who were treated with intravenous immunoglobulin therapy during the acute phase of KD were also evaluated. RESULTS: Compared with the adenoviral infection group, the KD with adenovirus group was significantly associated with frequent lip and tongue changes, skin rash and changes in the extremities. In the laboratory parameters, higher C-reactive protein (CRP) level and presence of hypoalbuminemia and sterile pyuria were significantly associated with the KD group. In the multivariate analysis, lip and tongue changes (odds ratio [OR], 1.416; 95% confidence interval [CI], 1.151–1.741; P=0.001), high CRP level (OR, 1.039; 95% CI 1.743–1.454; P= 0.021) and sterile pyuria (OR 1.052; 95% CI 0.861–1.286; P=0.041) were the significant predictive factors of KD. In addition, the cutoff CRP level related to KD with adenoviral detection was 56 mg/L, with a sensitivity of 81.8% and a specificity of 75.9%. CONCLUSION: Lip and tongue changes, higher serum CRP level and sterile pyuria were significantly correlated with adenovirus-positive KD.
Adenoviridae ; Adenoviridae Infections ; Adenovirus Infections, Human ; Biomarkers ; C-Reactive Protein ; Discrimination (Psychology) ; Exanthema ; Extremities ; Humans ; Hypoalbuminemia ; Immunization, Passive ; Lip ; Mucocutaneous Lymph Node Syndrome ; Multivariate Analysis ; Polymerase Chain Reaction ; Pyuria ; Sensitivity and Specificity ; Tongue

OBJECTIVE: To evaluate the difference of implantation rate (IR) and clinical pregnancy rate (CPR) between two protocols of endometrial preperation in women undergoing frozen-thawed embryo transfer (FET) cycles. METHODS: This study was performed during the different time periods: A retrospective study from January 2000 to June 2001 (phase I) and a prospective study from July 2001 to March 2002 (phase II). All the patients received estradiol valerate (6 mg p.o. daily) starting from day 1 or 2 of the menstrual cycle without pituitary down regulation. Progesterone was administered around day 14 after sonographic confirmation of endometrial thickness > or = 7 mm and no growing follicle. In Group A (n=88, 99 cycles) of phase I, progesterone was administered i.m. at a dose of 50 mg daily from one day prior to thawing of pronuclear (PN) stage frozen embryo or three days prior to thawing of 6-8 cell stage frozen embryo and then each stage embryos were trasnsferred 2 days or 1 day later after thawing. In Group B (n=246, 299 cycles) of phase I, patients recieved progesterone 100 mg i.m. from one day earlier than group A; two days prior to PN embryo thawing, four days prior to of 6-8 cell embryo thawing. During the phase II, to exclude any differences in embryo transfer procedures, in Group 1 (n=23, 28 cycles) of phase II embryo was transfered by one who have used the progesterone protocol since the phase I. In Group 2 (n=122, 139 cycles) of phase II embryo was transfered by one who use the progesterone protocol from the phase II. RESULTS: When compared across the phase and group, there were no significant differences in the characteristics. During the phase I, there were significant increase in IR (14.4% vs 5.9%, p=0.001) and CPR (28.3% vs 14.5%, p=0.000) in group A. During the phases II, IR (11.8% vs 10.6%) and CPR (27.6% vs 27.3%) show no differences between two groups. CONCLUSIONS: In FET cycles, IR and CPR are increased significantly by the change of dosage and timing of progesterone administraton. And the timing is considered to be more important factor because the dosage of progesterone did not affect implantation window in previous studies. Therefore, we suggest that progesterone administration in FET cycle should begin from one day prior to PN stage embryo thawing and three days prior to 6-8 cell stage embryo thawing.
Cardiopulmonary Resuscitation ; Down-Regulation ; Embryo Transfer* ; Embryonic Structures* ; Estradiol ; Female ; Humans ; Menstrual Cycle ; Pregnancy Rate* ; Pregnancy* ; Progesterone* ; Prospective Studies ; Retrospective Studies ; Ultrasonography

Episodic angioedema with eosinophilia was described by Gleich, et al. as a distinct entity characterized by recurrent angioedema, urticaria, leukocytoeis with remarkable eosinophilia, fever and periadically increased body weight. Since then, several cases of this disorder have been reported in the United States, Europe and Japan. We present a Korean patient whose clinical, histopathologic, and laboratory findings are consistent with the syndrome of episodic angioedema with eosinophilia. This case supports the previous study that revealed some differences between Asian and Caucasian patients.
Angioedema* ; Asian Continental Ancestry Group ; Body Weight ; Eosinophilia* ; Europe ; Fever ; Humans ; Japan ; United States ; Urticaria

The ras-related GTP binding protein, rab6, is located in late Golgi compartment. Modulation of beta-and gamma-secretase activity may lead to production of beta-amyloid fragments that are ultimately deposited in senile plaques at the brain of Alzheimer patients. Because modulation of rab6-mediated intracellular transport has been known to affect amyloid precursor protein (APP) processing, we investigated the rab6 immunoreactivity on the hippocampal neurons in the Alzheimer brains, according to the pathological staging of the disease. A total of 30 brains were used for this study. Campbell's silver stain for beta-amyloid and immunohistochemistry for rab6 protein were employed. The cortices of the hippocampal formation and the neighboring temporal neocortex were observed. The results are obtained as follows: 1. In normal elderly brains, no amyloid plaque is seen. In Alzheimer brains, a number of amyloid plaques are seen at the temporal neocortex and dentate gyrus. 2. In normal elderly brains, the perikaria of the pyramidal cells at the CA1 sector shows weak rab6 immunoreactivity. At the CA2 and CA3 sectors, trace immunoreactivity is observed in the pyramidal cells. 3. In preclinical Alzheimer brains, the perikaria of the pyramidal cells at the CA1 sector shows moderate rab6 immunoreactivity and the cells at the CA2 sector show weak immunoreactivity. A weak to moderate imunoreactivity is seen in the pyramidal cells of the CA3 sector. 4. In clinical Alzheimer brains, the pyramidal cells at the CA1 and CA3 sectors show strong rab6 immunoreactivity, but the cells at the CA2 sector shows moderate immunoreactivity. It is suggested that alteration of intracellular protein transport caused by abnormal rab6 activity may modulate amyloid precursor protein processing, which results in beta-amyloid production.
Aged ; Amyloid ; Amyloid Precursor Protein Secretases ; Brain* ; Dentate Gyrus ; GTP-Binding Proteins ; Hippocampus ; Humans ; Immunohistochemistry ; Neocortex ; Neurons ; Plaque, Amyloid ; Protein Transport ; Pyramidal Cells ; Silver

We previously reported that mice lacking JSAP1 (jsap1-/-) were lethal and the brain of jsap1-/- at E18.5 exhibited multiple types of developmental defects, which included impaired axon projection of the corpus callosum and anterior commissures. In the current study, we examined whether the early telencephalic commissures were formed abnormally from the beginning of initial development or whether they arose normally, but have been progressively lost their maintenance in the absence of JSAP1. The early corpus callosum in the brain of jsap1+/+ at E15.5-E16.5 was found to cross the midline with forming a distinct U-shaped tract, whereas the early axonal tract in jsap1-/- appeared to cross the midline in a diffuse manner, but the lately arriving axons did not cross the midline. In the brain of jsap1-/- at E17.5, the axon terminals of lately arriving collaterals remained within each hemisphere, forming an early Probst's bundle-like shape. The early anterior commissure in the brain of jsap1+/+ at E14.5-E15.5 crossed the midline, whereas the anterior commissure in jsap1-/- developed, but was deviated from their normal path before approaching the midline. The axon tracts of the corpus callosum and anterior commissure in the brain of jsap1-/- at E16.5-E17.5 expressed phosphorylated forms of FAK and JNK, however, their expression levels in the axonal tracts were reduced compared to the respective controls in jsap1+/+. Considering the known scaffolding function of JSAP1 for the FAK and JNK pathways, these results suggest that JSAP1 is required for the pathfinding of the developing telencephalic commissures in the early brains.
Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Animals ; Brain/*embryology/*metabolism ; Female ; Focal Adhesion Kinase 1/genetics/metabolism ; Immunohistochemistry ; In Situ Nick-End Labeling ; JNK Mitogen-Activated Protein Kinases/genetics/metabolism ; Mice ; Mice, Knockout ; Nerve Tissue Proteins/genetics/*metabolism ; Pregnancy ; Telencephalon/*embryology/*metabolism

OBJECTIVE: Increased atrial size is frequently seen in ischemic stroke patients in clinical practice. There is controversy about whether left atrial enlargement (LAE) should be regarded as a risk factor for cerebral infarction. We investigated the association between indexed left atrial volume (LAVI) and conventional stroke risk factors as well as stroke subtypes in acute ischemic stroke patients. METHODS: One hundred eighty two acute cerebral infarction patients were included in this study. Brain magnetic resonance imaging and transthoracic echocardiography were done for all patients within 30 days of diagnosis of acute cerebral infarction. Echocardiographic LAE was identified when LAVI was more than 27 mL/m2. Stroke subtypes were classified by the Trial of Org 10171 in acute stroke treatment classification. RESULTS: There were significant differences between subjects with normal and increased LAVI in prevalence of stroke risk factors including atrial fibrillation (p = 0.001), hypertension (p = 0.000), valvular heart disease (p = 0.011) and previous stroke (p = 0.031). An increased LAVI was associated with cardioembolic subtype with an adjusted odds ratio was 6.749 (p = 0.002) compared with small vessel disease. CONCLUSION: Increased LAVI was more prevalent in those who had cardiovascular risk factors, such as atrial fibrillation, hypertension, valvular heart disease and history of previous stroke. LAE influenced most patients in all subtypes of ischemic stroke but was most prevalent in the cardioembolic stroke subtype. Increased LAVI might be a risk factor of cerebral infarction, especially in patients with cardioembolic stroke subtype.
Atrial Fibrillation ; Brain ; Cerebral Infarction ; Echocardiography ; Glycosaminoglycans ; Heart Valve Diseases ; Humans ; Hypertension ; Magnetic Resonance Imaging ; Odds Ratio ; Prevalence ; Risk Factors ; Stroke

OBJECTIVE: Increased atrial size is frequently seen in ischemic stroke patients in clinical practice. There is controversy about whether left atrial enlargement (LAE) should be regarded as a risk factor for cerebral infarction. We investigated the association between indexed left atrial volume (LAVI) and conventional stroke risk factors as well as stroke subtypes in acute ischemic stroke patients. METHODS: One hundred eighty two acute cerebral infarction patients were included in this study. Brain magnetic resonance imaging and transthoracic echocardiography were done for all patients within 30 days of diagnosis of acute cerebral infarction. Echocardiographic LAE was identified when LAVI was more than 27 mL/m2. Stroke subtypes were classified by the Trial of Org 10171 in acute stroke treatment classification. RESULTS: There were significant differences between subjects with normal and increased LAVI in prevalence of stroke risk factors including atrial fibrillation (p = 0.001), hypertension (p = 0.000), valvular heart disease (p = 0.011) and previous stroke (p = 0.031). An increased LAVI was associated with cardioembolic subtype with an adjusted odds ratio was 6.749 (p = 0.002) compared with small vessel disease. CONCLUSION: Increased LAVI was more prevalent in those who had cardiovascular risk factors, such as atrial fibrillation, hypertension, valvular heart disease and history of previous stroke. LAE influenced most patients in all subtypes of ischemic stroke but was most prevalent in the cardioembolic stroke subtype. Increased LAVI might be a risk factor of cerebral infarction, especially in patients with cardioembolic stroke subtype.
Atrial Fibrillation ; Brain ; Cerebral Infarction ; Echocardiography ; Glycosaminoglycans ; Heart Valve Diseases ; Humans ; Hypertension ; Magnetic Resonance Imaging ; Odds Ratio ; Prevalence ; Risk Factors ; Stroke

Clustered occurrences of ankylosing spondylitis (AS) in family have been noticed. We evaluated patients with AS confirmed by the modified New York criteria for familial history of AS (one or more first to third degree relatives). The clinical characteristics and the recurrence risks (number of AS patients/number of familial members) of the familial AS compared to sporadic AS were investigated. Out of a total of 204 AS patients, 38 patients (18.6%) reported that they had a familial history of AS. The recurrence risks in the familial AS patients for first, second and third degree family members were 14.5%, 5.2%, and 4.4% respectively. Erythrocyte sedimentation rate (ESR) (22.6+/-22.2 vs 35.4+/-34.4, P=0.029) and C-reactive protein (CRP) (1.24+/-1.7 vs 2.43+/-3.3, P=0.003) at diagnosis, body mass index (21.9+/-2.7 vs 23.7+/-3.3, P=0.002) and frequency of oligoarthritis (13.2% vs 33.7%, P=0.021) were significantly lower in the familial form. The presence of HLA-B27 (97.4% vs 83.1%, P=0.044) was significantly higher in familial AS. In conclusion, Korean familial AS patients show a lower frequency of oligoarthritis, lower BMI, lower ESR and CRP at diagnosis and higher presence of HLA-B27.
Adult ; Age Factors ; Arthritis, Juvenile/diagnosis/epidemiology ; Blood Sedimentation ; Body Mass Index ; C-Reactive Protein/analysis ; Demography ; Family ; Female ; HLA-B27 Antigen/metabolism ; Humans ; Interviews as Topic ; Male ; Middle Aged ; Phenotype ; Recurrence ; Republic of Korea ; Risk Factors ; Severity of Illness Index ; Sex Factors ; Spondylitis, Ankylosing/*diagnosis

PURPOSE: Delayed hypersensitivity reaction can occur in a couple of hours to several days after injection of iodine-based contrast media (ICM). ICM-related delayed type hypersensitivity is not common but increasing as rapid growth of ICM use. Nevertheless, objective data on delayed type hypersensitivity are still scarce worldwide including Korea. This study was performed to investigate the clinical features of ICM-induced delayed hypersensitivity in Korean patients. METHODS: We retrospectively reviewed the electronic medical records of patients diagnosed with delayed hypersensitivity to ICM from January 2009 to December 2012 at Seoul National University Hospital and analyzed the data to identify the clinical characteristics of these patients. RESULTS: A total of 44 cases were diagnosed as delayed-type hypersensitivity to ICM. The mean age was 54 years, and 70.5% were female. The mean number of previous ICM exposure was 3.8, and skin reactions were the most common symptoms. In 45% of patients, hypersensitivity reaction developed on the first exposure to ICM. Among the 27 patients exposed to ICM again, hypersensitivity reactions recurred in only 4 patients (14.8%). There was no difference of recurrence rate according to the use of premedication or the change in ICM. CONCLUSION: In this study, we observed a female predominance and a low recurrence rate in delayed hypersensitivity to ICM. Premedication and ICM change was not effective in preventing recurrence of delayed type reactions.
Contrast Media* ; Electronic Health Records ; Female ; Humans ; Hypersensitivity* ; Hypersensitivity, Delayed ; Korea ; Premedication ; Recurrence ; Retrospective Studies ; Seoul ; Skin