Embryonic stem cells (ESCs) can be propagated in vitro on feeder layers of mouse STO fibroblast cells. The STO cells secrete several cytokines that are essential for ESCs to maintain their undifferentiated state. In this study, we found significant growth inhibition of mouse ESCs (mESCs) cultured on STO cells infected with adenovirus containing a dominant-negative mutant form of IkappaB (rAd-dnIkappaB). This blockage of the NF-kappaB signal pathway in STO cells led to a significant decrease in [3H]thymidine incorporation and colony formation of mESCs. Expression profile of cytokines secreted from the STO cells revealed an increase in the bone morphogenetic protein4 (BMP4) transcript level in the STO cells infected with adenoviral vector encoding dominant negative IkappaB (rAd-dnIkappaB). These results suggested that the NF-kappaB signaling pathway represses expression of BMP4 in STO feeder cells. Conditioned medium from the rAd-dnIkappaB-infected STO cells also significantly reduced the colony size of mESCs. Addition of BMP4 prevented colony formation of mESCs cultured in the conditioned medium. Our finding suggested that an excess of BMP4 in the conditioned medium also inhibits proliferation of mESCs.
Animals ; *Bone Morphogenetic Protein 4/genetics/metabolism ; Cell Differentiation/genetics ; Cell Proliferation ; Culture Media, Conditioned ; *Embryonic Stem Cells/cytology/metabolism ; *Feeder Cells/cytology/metabolism ; *Fibroblasts/cytology/metabolism ; Gene Expression Regulation/genetics ; *I-kappa B Proteins/genetics/metabolism ; Mice ; Mutation ; NF-kappa B/genetics/metabolism ; Signal Transduction

The effects of midazolam and diazepam which were used as an induction agent of general anesthesia were evaluated. And flumazenil which is a potent competitive inhibitor of the specific binding of benzodiazepines at the receptor level was evaluated too. Sixty patients were divided into three groups as follows: Group I (n=20); Midazolam (average 0.24 mgkg-1) was administered as an induction agent and flumazenil (average 0.24 mgkg-1) was administered in recovery room Group II (n=20); Diazepam (average 0.35 mgkg-1) was administered as an induction agent and flumaxenil (average 0.25 mgkg-1) was administered in recovery room Group III (n=20); Midazolam (average 0.24 mgkg-1) was administered as an induction agent and normal saline was administered in recovery room instead of flumaxenil The result were as follows: 1) Systolic and diastolic blood pressure and heart rate were not changed significantly, except diastolic blood pressure decreased significantly (p<0.05) in group II, after intravenous administration of midazolam and diazepam. But these were all increased significantly (p<0.001) after endotracheal intubation in all groups. 2) Systolic and diastolic blood preasure and heart rate were not changed significantly after intravenous administration of flumazenil in group I, II and there were no significant differences between each groups. 3) Tidal volume was increased significantly (p<0.05) in group 1 from 15 min after administration of flumazenil. There were no significant changes in all groups in respiratory rate. SaO2 was increased significantly (p<0.05, p<0.001) in group I, II from 5 min after administration of flumazenil. But it was increased significantly (p<0.05) in group III from 20 min after administration of normal saline too. EtCO2 was decreased insignificantly in all groups. 4) Recovery from anesthesia according to Modified Steward Coma Scale was much improved immediately after administration of flumazenil and was significant (p<0.001) statistically in group I, II from 5 min after administration of flumazenil and reached complete recovery from 20 min after administration of flumaxenil. It was increased gradually and become significant in group III from 10 min after administration of normal saline. These changes of group I, II were significant (p<0.05) compared with group III and reached complete recovery from 60 min after administration of flumazenil.
Administration, Intravenous ; Anesthesia ; Anesthesia, General ; Benzodiazepines ; Blood Pressure ; Coma ; Diazepam ; Flumazenil* ; Heart Rate ; Humans ; Intubation, Intratracheal ; Midazolam* ; Recovery Room ; Respiratory Rate ; Tidal Volume

Thiopental sodium has been used in anesthesia of Caesarean section since 1936 and is regarded as the standard induction agent. Propofol has properties which suggest that it might be a useful alternative to thiopental. We compared propofol with thiopental for induction of anesthesia in elective Caesarean section in the present study. Particular attentaion was paid to induction characterisitics and the neonatal effects of both agents. The results were as follows. 1) Side effect during induction were rare in both groups. But both agents caused mild discomfort on injection. 2) There were significant increase in systemic arterial pressure, diastoric pressure and heart rate at postintubation I minute in both groups. But there were no significant differences in cardio vascular response between both groups during the induction. 3) The Apgar scores of the neonates did not differ significantly, and the blood gas analyses of neonates were within the normal range in both groups. We conclude that propofol, in a dose of 2.5 mg/kg, is an acceptable alternative to thiopental for the induction of general anesthesia in Caesarean section.
Anesthesia* ; Anesthesia, General ; Arterial Pressure ; Blood Gas Analysis ; Cesarean Section* ; Female ; Heart Rate ; Humans ; Infant, Newborn ; Pregnancy ; Propofol* ; Reference Values ; Thiopental*

Biliary cystadenomas are very rare cystic neoplasms usually arising from the intrahepatic bile ducts. The majority of patients are middle-aged women who present with abdominal discomfort and/or a palpable mass. The diagnosis was performed using several methods such as abdominal ultrasonography, computed tomography, percutaneous cholangiography or endoscopic retrograde cholangiopancreatography, and showed multiloculated cystic tumors with multiple internal septation. But confirmatory diagnosis was done by surgical pathology. Because the prognosis is comparatively better than after complete resection and the cystadenoma is warranted to avoid malignant change, early detection and surgical resection must be needed. We have experienced two cases, 30 and 50 year old females, which presented with nonspecific abdominal pain and dyspepsia. They were diagnosed as having intrahepatic biliary cystadenoma histopathologically which was confirmed after surgical resection. We report two cases of intrahepatic biliary cystadenoma with a review of literature.
Abdominal Pain ; Bile Ducts, Intrahepatic ; Cholangiography ; Cholangiopancreatography, Endoscopic Retrograde ; Cystadenoma* ; Diagnosis ; Dyspepsia ; Female ; Humans ; Liver ; Middle Aged ; Pathology, Surgical ; Prognosis ; Ultrasonography

Diffusely infiltrating primary colorectal carcinoma is a rare disease. This type of carcinoma extensively spreads beneath the mucosal layer. Clinically, it resembles inflammatory colorectal disease and metastatic carcinoma and is difficult to diagnosis. Moreover, the prognosis is extremely poor. A 66-year-old man was admitted to our hospital because of lower abdominal pain. Barium enema showed circumferential long segment narrowing in the proximal sigmoid colon without definite mass or ulceration and abdominal CT demonstrated colonic wall thickening. So it was diagnosed as inflammatory condition by image study. Colonoscopic examination showed hypertrophied mucosa and luminal narrowing on the 40 cm from the anal verge, but the oral side couldn't be examined because of stenosis. Biopsy revealed poorly differentiated adenocarcinoma, and left hemicolectomy was done. The pathology showed diffusely infiltrating adenocarcinoma with metastasis in regional lymph node and mesentry involvement.
Abdominal Pain ; Adenocarcinoma ; Aged ; Barium ; Biopsy ; Colon* ; Colon, Sigmoid ; Colonic Neoplasms* ; Colorectal Neoplasms ; Constriction, Pathologic ; Diagnosis ; Enema ; Humans ; Lymph Nodes ; Mucous Membrane ; Neoplasm Metastasis ; Pathology ; Phenobarbital ; Prognosis ; Rare Diseases ; Tomography, X-Ray Computed ; Ulcer

BACKGROUND: We studied the time course of gene expression of dynorphin, enkephalin, c-fos, and the changes of allodynia, and the effect of chemical sympathectomy on the gene expression and allodynia in neuropathic rat. METHODS: In two groups of rat (Sprague-Dawley), the left L5 and L6 spinal nerves were tight ligated. In gene expression group (N=25), behavioral tests for mechanical allodynia and cold allodynia were perfomed for the next two weeks. After the test of allodynia, the expression of dynorphin, enkephalin, c-fos were assessed by Northern blot hybridization. In chemical sympathectomy group (N=16), after chemical sympathectomy (guanethidine 70 mg/kg intraperitoneally, from postoperative 7 days to 9 days), the changes of allodynia and the gene expression of enkephalin, c-fos were tested. RESULTS: Mechanical allodynia and cold allodynia was developed on the postoperative 3, 5, 7, 14 days. Preprodynorphin mRNA expression was reached peak level at the postoperative 8 hrs, sustained increase by the postoperative 3 days, but preproenkephalin mRNA expression increased slightly after operation. c-Fos mRNA expression was increased immediately at the postoperative 30 min, 1 hr, returned to normal level thereafter, and increased again on the postoperative 3, 5, 7 days that neuropathic pain was developed. Mechanical allodynia and cold allodynia were decreased by chemical sympathectomy. The increased c-fos mRNA expression and pain at postoperative 7 days was reduced by chemical sympathectomy. CONCLUSION: These results suggest that the transient gene expression of dynorphin and c-fos after tight ligation of L5 and L6 spinal nerves induces the development neuropathic pain, and late c-fos expression is related to neuropathic pain.
Animals ; Blotting, Northern ; Dynorphins* ; Enkephalins* ; Gene Expression* ; Hyperalgesia ; Ligation ; Neuralgia ; Rats* ; RNA, Messenger ; Spinal Nerves ; Sympathectomy, Chemical

BACKGROUND/AIMS: Tamoxifen has been tried in patients with hepatocellular carcinoma (HCC), however, its inhibitory mechanism remains unknown. In this study, we evaluated the effects of tamoxifen on HCC cell growth and the expression of transforming growth factor-beta1 (TGF-beta1) which had been known as an important cytokine in growth of HCC. METHODS: Hep 3B cells were cultivated in estrogen free media with 0.1 micro M, 0.5 micro M, 1 micro M, 5 micro M, and 10 micro M of tamoxifen for 6 days. Viable cells were counted daily and the TGF-beta1 concentrations in supernatant were measured by ELISA method. RESULTS: The number of viable HCC cells increased rather significantly after the treatment of tamoxifen of lower concentration (0.1 micro M) compared with that of the control (2.59x10(7) vs. 1.97x10(7); p<0.05). As the concentration of treated tamoxifen was higher, the number of viable HCC cells became gradually less, resulting in the significant decrease of it at the highest concentration (10 micro M) compared with that of the control (1.40x10(7) vs. 1.97x10(7); p<0.05). TGF-beta1 concentration in supernatant of tamoxifen-treated samples was significantly decreased compared with those of controls, regardless of the amount of treated tamoxifen. CONCLUSIONS: These results suggest that tamoxifen may suppress TGF-beta1 expression to an extent, although it has different effects on the proliferation of HCC cells, at the various concentrations of this agent in vitro. Such effects of tamoxifen on TGF-beta1 expression may inhibit the growth and progression of HCCs over-expressing TGF-beta1 in vivo.
Antineoplastic Agents, Hormonal/*pharmacology ; Carcinoma, Hepatocellular/*metabolism/pathology ; Cell Division/drug effects ; Cell Line, Tumor/metabolism ; Humans ; Liver Neoplasms/*metabolism/pathology ; Tamoxifen/*pharmacology ; Transforming Growth Factor beta/*biosynthesis ; Transforming Growth Factor beta1

Background: Tenofovir disoproxil fumarate (TDF, Viread® ) had been used as a standard treatment option of chronic hepatitis B (CHB). This clinical trial was conducted to evaluate the efficacy and safety of DA-2802 (tenofovir disoproxil orotate) compared to TDF. Methods: The present study was a double blind randomized controlled trial. Patients with CHB were recruited from 25 hospitals in Korea and given DA-2802 at a dose of 319 mg once daily or Viread® at a dose of 300 mg once daily for 48 weeks from March 2017 to January 2019. Change in hepatitis B virus (HBV) DNA level at week 48 after dosing compared to baseline was the primary efficacy endpoint. Secondary efficacy endpoints were proportions of subjects with undetectable HBV DNA, those with normal alanine aminotransferase (ALT) levels, and those with loss of hepatitis B envelop antigen (HBeAg), those with loss of hepatitis B surface antigen (HBsAg). Adverse events (AEs) were also investigated. Results: A total of 122 patients (DA-2802 group: n = 61, Viread® group: n = 61) were used as full analysis set for efficacy analysis. Mean age, proportion of males, laboratory results and virologic characteristics were not different between the two groups. The change in HBV DNA level at week 48 from baseline was −5.13 ± 1.40 in the DA-2802 group and −4.97 ± 1.40 log 10 copies/mL in the Viread® group. The analysis of primary endpoint using the nonparametric analysis of covariance showed statistically significant results (P < 0.001), which confirmed non-inferiority of DA-2802 to Viread® by a prespecified noninferiority margin of 1. The proportion of undetectable HBV DNA was 78.7% in the DA-2802 group and 75.4% in the Viread® group (P = 0.698). The proportion of subjects who had normal ALT levels was 75.4% in the DA-2802 group and 73.3% in the Viread® group (P = 0.795). The proportion of those with HBeAg loss was 8.1% in the DA-2802 group and 10.8% in the Viread® group (P = 1.000). No subject showed HBsAg loss. The frequency of AEs during treatment was similar between the two groups. Most AEs were mild to moderate in severity. Conclusion DA-2802 is considered an effective and safe treatment for patients with CHB.

BACKGROUND: Hepatitis B virus (HBV) infection leads to hepatic and extrahepatic manifestations including chronic kidney disease (CKD). However, the association between HBV and CKD is not clear. This study investigated the association between chronic HBV infection and CKD in a nationwide multicenter study. METHODS: A total of 265,086 subjects who underwent health-check examinations in 33 hospitals from January 2015 to December 2015 were enrolled. HBV surface antigen (HBsAg) positive cases (n = 10,048), and age- and gender-matched HBsAg negative controls (n = 40,192) were identified. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m² or proteinuria as at least grade 2+ of urine protein. RESULTS: HBsAg positive cases showed a significantly higher prevalence of GFR < 60 mL/min/1.73 m² (3.3%), and proteinuria (18.9%) than that of the controls (2.6%, P < 0.001, and 14.1%, P < 0.001, respectively). In the multivariate analysis, HBsAg positivity was an independent factor associated with GFR < 60 mL/min/1.73 m² along with age, blood levels of albumin, bilirubin, anemia, and hemoglobin A1c (HbA1c). Likewise, HBsAg positivity was an independent factor for proteinuria along with age, male, blood levels of bilirubin, protein, albumin, and HbA1c. A subgroup analysis showed that HBsAg positive men but not women had a significantly increased risk for GFR < 60 mL/min/1.73 m². CONCLUSION: Chronic HBV infection was significantly associated with a GFR < 60 mL/min/1.73 m² and proteinuria (≥ 2+). Therefore, clinical concern about CKD in chronic HBV infected patients, especially in male, is warranted.
Anemia ; Antigens, Surface ; Bilirubin ; Case-Control Studies* ; Female ; Glomerular Filtration Rate ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Humans ; Male ; Multivariate Analysis ; Prevalence ; Proteinuria ; Renal Insufficiency, Chronic*