Liver cirrhosis is one of the major complications of hepatitis C virus (HCV) infection, but the mechanisms underlying HCV-related fibrogenesis are still not clear. Although the roles of HCV core protein remain poorly understood, it is supposed to play an important role in the regulation of cellular growth and hepatocarcinogenesis. The aim of this study was to examine the role of HCV core protein on the hepatic fibrogenesis. We established an in vitro co-culture system with primary hepatic stellate cell (HSC) isolated from rats, and a stable HepG2-HCV core cell line which had been transfected with HCV core gene. The expressions of fibrosis-related molecules transforming growth factor beta1 (TGF-beta1), transforming growth factor b receptor II (TGF beta RII), alpha-smooth muscle actin (alpha-SMA) and connective tissue growth factor (CTGF) were analyzed via histological or molecular methods. In addition, the expression levels of matrix metaloprotinase-2 (MMP-2) and collagen type I (Col I) from the co-cultured media were measured by zymogram and ELISA, respectively. The expressions of alpha-SMA, TGF-beta1, Col I, TGF beta RII and MMP-2 were significantly increased in the co-culture of stable HepG2-HCV core with HSC. Moreover, the significant increases of CTGF and TGF-beta1 in the HCV core-expressing cells were observed by either Northern or Western blot analysis. These results suggest that HCV core protein may contribute to the hepatic fibrogenesis via up-regulation of CTGF and TGF-beta1.
Actins/metabolism ; Animals ; Cell Line, Tumor ; Cells, Cultured ; Coculture Techniques ; Collagen Type I/metabolism ; Gelatinase A/metabolism ; Immediate-Early Proteins/*biosynthesis ; Intercellular Signaling Peptides and Proteins/*biosynthesis ; Liver/metabolism/*pathology ; Liver Cirrhosis/*metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Transforming Growth Factor beta/metabolism ; Research Support, Non-U.S. Gov't ; Transforming Growth Factor beta/*metabolism ; Up-Regulation ; Viral Core Proteins/genetics/*metabolism

PURPOSE: Episodic memory is described as an 'autobiographical' memory responsible for storing a record of the events in our lives. We performed functional brain activation study using H215O PET to reveal the neural basis of the encoding and the retrieval of episodic memory in human normal volunteers. MATERIALS AND METHODS: Four repeated H215O PET scans with two reference and two activation tasks were performed on 6 normal volunteers to activate brain areas engaged in encoding and retrieval with verbal materials. Images from the same subject were spatially registered and normalized using linear and nonlinear transformation. Using the means and variances for every condition which were adjusted with analysis of covariance, t-statistic analysis were performed voxel-wise. RESULTS: Encoding of episodic memory activated the opercular and triangular parts of left inferior frontal gyrus, right prefrontal cortex, medial frontal area, cingulate gyrus, posterior middle and inferior temporal gyri, and cerebellum, and both primary visual and visual association areas. Retrieval of episodic memory activated the triangular part of left inferior frontal gyrus and inferior temporal gyrus, right prefrontal cortex and medial temporal area, and both cerebellum and primary visual and visual association areas. The activations in the opercular part of left inferior frontal gyrus and the right prefrontal cortex meant the essential role of these areas in the encoding and retrieval of episodic memory. CONCLUSION: We could localize the neural basis of the encoding and retrieval of episodic memory using H215O PET, which was partly consistent with the hypothesis of hemispheric encoding/retrieval asymmetry.
Brain ; Cerebellum ; Gyrus Cinguli ; Healthy Volunteers ; Humans* ; Memory ; Memory, Episodic* ; Positron-Emission Tomography ; Prefrontal Cortex

PURPOSE: Verapamil is one of the most extensively characterized modulators of P-glyco- protein (P-gp) mediated multi-drug resistance (MDR), but its plasma concentration required to reverse MDR can cause cardiovascular toxicity. KR-30035 is a newly synthesized verapamil analogue with more potent cytostatic effects, but has lower cardiovascular effects than verapamil. We have assessed the MDR reversing effects of KR-30035 by measuring Tc-99m MIBI uptake in cultured tumor cells and in nude mice bearing human tumor xenografts. MATERIALS AND METHODS: In-vitro uptake of Tc-99m MIBI was measured in murine leukemia cells (L-1210) and those MDR-positive variants after incubation with different concentrations of KR-30035. Results were compared to those with verapamil. Organ and tumoral uptake of Tc-99m MIBI was compared between P-gp (+) human colon cancer (HCT15 cells) and P-gp (-) lung cancer (A549 cells) in nude mice, treated with either KR-30035 or verapamil. RESULTS: There was no significant difference in in-vitro uptake of Tc-99m MIBI between verapamil and KR-30035 group at any concentrations. MIBI uptake in P-gp (+) cells continuously increased either with verapamil or KR-30035 in a dose-dependent manner. Tc-99m MIBI uptake ratios of the tumor [P-gp (+' tumor uptake divided by P-gp (-) uptake] were significantly higher with KR-30035 than with verapamil in tumor bearing nude mice. Washout rate of Tc-99m MIBI from P-gp (+) HCT15 cells was lower in verapamil or KR-30035 groups than in the control group, which was 0.19, 0.19 and 0.27 respectively. CONCLUSION: These studies revealed that KR-30035 can potentially be used as an active modulator of MDR, with its significantly lesser cardiovascular toxicity than verapamil. Our results warrants further evaluation of this novel agent.
Animals ; Colonic Neoplasms ; Drug Resistance, Multiple ; Heterografts ; Humans ; Leukemia ; Lung Neoplasms ; Mice ; Mice, Nude ; P-Glycoprotein ; Plasma ; Robenidine ; Tumor Cells, Cultured ; Verapamil

Objective: Unlike the temporary nature of an emergency resident's job, the position of an emergency physician is one of a lifelong commitment requiring stability and persistence. However, it is hard to pursue a healthy lifestyle because of the 24 hours a day, 7 days a week (24/7) working schedule. The emergency room environment demands high physical and mental stamina, and hence the health problems of emergency physicians have a significant impact on the patient’s outcome. Our study was designed to analyze the emergency physician’s health status and influencing factors based on the data from the 2020 Korean Emergency Physician Survey. Methods: Based on the results of the survey, the factors affecting health were classified into several categories, such as personal character, working conditions, lifestyle, and emotional status. Statistical methods have been used to determine whether these factors can affect self-rated health. Results: The self-rated health worsened for emergency physicians in their 40s rather than in their 30s. However, drinking, smoking, and eating patterns had no effect on self-rated health. Also, the actual number of shifts was observed to bear no relationship with health. Sleeping, wellness, and mood affected self-rated health. Physicians who felt they were unhealthy, expected an early retirement because of the burden of night shifts. Conclusion Emergency physicians in Korea have a low self-rated health status. Mental stress, exercise, and sleep had an impact on the status. Physicians who served long-term night shifts saw a deleterious effect on their sleep and mood, and this damage was cumulative. The career longevity of an emergency physician thus requires a reasonable night shift schedule and age-modified adjustments.