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

Acute necrotizing encephalopathy (ANE) is a rare immune-mediated complication of a viral infection commonly involving the bilateral thalamus and has been reported mainly in children. Here, we describe the MRI findings of coronavirus disease 2019 (COVID-19)-associated ANE in two pediatric patients, including a 7-year-old girl with fever and mental change, and a 6-year-old girl with fever and generalized seizures. Brain MRI revealed symmetrical T2 fluid attenuated inversion recovery high-signal intensity lesions in the bilateral thalamus with central hemorrhage. In one patient, the thalamic lesions showed a trilaminar pattern on the apparent diffusion coefficient map. This report emphasizes the importance of creating awareness regarding these findings in patients with COVID-19, particularly in children with severe neurological symptoms. Furthermore, it provides a literature review of several documented cases of COVID-19 presenting with bilateral thalamic hemorrhagic necrosis, suggesting a diagnosis of ANE.

Acute necrotizing encephalopathy (ANE) is a rare immune-mediated complication of a viral infection commonly involving the bilateral thalamus and has been reported mainly in children. Here, we describe the MRI findings of coronavirus disease 2019 (COVID-19)-associated ANE in two pediatric patients, including a 7-year-old girl with fever and mental change, and a 6-year-old girl with fever and generalized seizures. Brain MRI revealed symmetrical T2 fluid attenuated inversion recovery high-signal intensity lesions in the bilateral thalamus with central hemorrhage. In one patient, the thalamic lesions showed a trilaminar pattern on the apparent diffusion coefficient map. This report emphasizes the importance of creating awareness regarding these findings in patients with COVID-19, particularly in children with severe neurological symptoms. Furthermore, it provides a literature review of several documented cases of COVID-19 presenting with bilateral thalamic hemorrhagic necrosis, suggesting a diagnosis of ANE.

Acute necrotizing encephalopathy (ANE) is a rare immune-mediated complication of a viral infection commonly involving the bilateral thalamus and has been reported mainly in children. Here, we describe the MRI findings of coronavirus disease 2019 (COVID-19)-associated ANE in two pediatric patients, including a 7-year-old girl with fever and mental change, and a 6-year-old girl with fever and generalized seizures. Brain MRI revealed symmetrical T2 fluid attenuated inversion recovery high-signal intensity lesions in the bilateral thalamus with central hemorrhage. In one patient, the thalamic lesions showed a trilaminar pattern on the apparent diffusion coefficient map. This report emphasizes the importance of creating awareness regarding these findings in patients with COVID-19, particularly in children with severe neurological symptoms. Furthermore, it provides a literature review of several documented cases of COVID-19 presenting with bilateral thalamic hemorrhagic necrosis, suggesting a diagnosis of ANE.

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

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

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

Purpose: The purpose of this study is to evaluate Ti-base abutment’s three different heights and three different cement types on the pull-off force of zirconia-based restorations. Materials and Methods: A total of 90 fixture lab analogs were embedded in auto polymerizing resin bloack. 90 Ti-base abutments heights of 3 mm, 5 mm, 7 mm were scanned and zirconia restoration were prepared from scanned files. Zirconia restoration were cemented with three different types of cements (temporary, semi-permanent, permanent) following manufacturer’s instructions. All 90 specimens were placed and tested in a universal testingmachine for pull-out testing. Retention was measured by recording the force at load drop. Statistical analysis was performedusing Kruskal-Wallis test for detecting whether there are any statistical significance along cement types or abutment heights.After that, Mann-Whitney test was used for figuring out differences regarding abutment height and the comparison between 3cements. Results: Temp bond showed significantly lower pull-off force compared to Fujicem regardless of any abutment height.However, there were significant differences between Cem-implant and Fujicem in abutment height of 3 mm and 7 mm, but there was no significant difference in 5 mm. Temp bond and Cem-implant had significant differences only in abutment height of 5 mm. Conclusion Although Ti-base abutment height did not influenced zirconia restorations’ retentiveness, cement types showed significant differences.