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1.
Medicine (Baltimore) ; 99(28): e21105, 2020 Jul 10.
Article in English | MEDLINE | ID: mdl-32664132

ABSTRACT

RATIONALE: The incidence of a unicornuate uterus is 0.2% to 0.3% of the whole population. A unicornuate uterus is closely associated with obstetrical complications such as early miscarriages, ectopic pregnancy, and malpresentation. PATIENT CONCERNS: A 32-year-old patient developed a rare ectopic pregnancy arising at a distal, fimbriated end of the undescended fallopian tube. DIAGNOSES: A transvaginal ultrasound scan revealed hemoperitoneum and no gestational sac in the uterine endometrium. A laparoscopic finding showed that high up in the right abdomen, just below the liver, an ectopic mass could be seen arising at a distal, fimbriated end of the fallopian tube, which was developed adjacent to the undescended right ectopic ovary. INTERVENTIONS: After laparoscopic removal of the right salpinx, we removed it with a bag. OUTCOMES: One day after the operation, she was discharged without problems. Postoperative hysterosalpingography showed the unicornuate uterus with patent left and some right salpinx. Magnetic resonance imaging revealed a unicornuate uterus, right ovary at the right inferior hepatic area, a bilateral normal kidney, and double inferior vena cava. LESSONS: This is the first reported case of its type. It demonstrated that ectopic pregnancy may occur in the upper abdomen, not in the pelvic cavity, in uterine anomaly, and double inferior vena cava; hence, we must thoroughly check the whole abdominal cavity. Additional imaging tests are needed after treatment to see if there are any abnormalities.


Subject(s)
Fallopian Tubes/abnormalities , Ovary/abnormalities , Pregnancy, Ectopic/etiology , Urogenital Abnormalities/diagnosis , Uterus/abnormalities , Vascular Malformations/diagnosis , Vena Cava, Inferior/abnormalities , Adult , Endosonography/methods , Female , Gynecologic Surgical Procedures/methods , Humans , Hysterosalpingography , Laparoscopy/methods , Magnetic Resonance Imaging , Pregnancy , Pregnancy, Ectopic/diagnosis , Pregnancy, Ectopic/surgery , Urogenital Abnormalities/complications , Urogenital Abnormalities/surgery , Uterus/surgery , Vagina
2.
Transplant Proc ; 48(7): 2403-2406, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27742309

ABSTRACT

BACKGROUND: Organ donation after brain death is a major source for obtaining transplantable organs for patients with end-stage organ disease. However, the time from declaring brain death to organ procurement is often longer than expected. Analyzing factors that delay organ procurement may help to prevent damage to organs from marginal and unstable donors and aid in preparation for recipient operation. The aim of this study was to examine factors associated with the interval between the time of declaring brain death and organ procurement. METHODS: Medical records of patients who underwent organ procurement after brain death from February 2009 to April 2015 were retrospectively reviewed. RESULTS: Of the 77 patients which were scheduled to undergo organ procurement, 68 eventually underwent procurement of ≥1 organ. The average time interval from 1st exam for brain death to organ procurement decreased from 1,248 minutes in 2009 to 910 minutes in 2015. Although not statistically significant, during the 6-year period, the time interval decreased from 1,105 minutes to 1,075 minutes in the latter half of the period (P = .623). Organ procurement was extensively delayed most commonly owing to false negative electroencephalogram (EEG; 62.5%). CONCLUSIONS: With increasing experience in dealing with brain death donors, the time interval from declaring brain death to organ procurement decreased. We suggest that an EEG be performed during the initial stages of examination for brain death to prevent unnecessary preparation of recipient operation owing to a false EEG test.


Subject(s)
Brain Death/diagnosis , Electroencephalography , Tissue and Organ Procurement/statistics & numerical data , False Negative Reactions , Female , Humans , Male , Middle Aged , Republic of Korea , Retrospective Studies , Time Factors , Tissue Donors , Transplants
3.
J Hum Hypertens ; 30(5): 315-21, 2016 May.
Article in English | MEDLINE | ID: mdl-26155994

ABSTRACT

Reports detailing the response of hypertensive patients to renal denervation (RDN) in Asian patients are limited. We evaluated 6- and 12-month outcomes after RDN in an Asian population and compared outcomes to a primarily Caucasian population. The Global SYMPLICITY Registry (GSR) is a prospective, all-comer, worldwide registry that evaluates the safety and effectiveness of RDN and includes the Korean registry substudy (GSR Korea) and a Caucasian subset (GSR Caucasian). Given differences in baseline characteristics among GSR Korea (n=93) as compared with GSR Caucasian (n=169) patients, including lower baseline office systolic blood pressure (SBP), lower body mass index and differences in medications, propensity score adjustment was performed when comparing the change in SBP between subsets. The 6- and 12-month change in SBP in GSR Korea was -19.4±17.2 and -27.2±18.1 mm Hg, respectively (P<0.001 for both vs baseline). GSR Caucasian had a SBP change similar to GSR Korea at 6 months (-20.9±21.4 mm Hg, unadjusted P=0.547, adjusted P=0.998), whereas at 12 months the change was significantly less pronounced (-20.1±23.9 mm Hg, unadjusted P=0.004, adjusted P=0.002). There were no protocol-defined procedure-related adverse events and no chronic adverse events associated with the device in an Asian population. RDN provided a significant reduction in 6- and 12-month office SBP among Asian patients, with a favorable safety profile. The 12-month SBP reduction was larger than that observed in Caucasian patients.


Subject(s)
Catheter Ablation/statistics & numerical data , Denervation/statistics & numerical data , Hypertension/surgery , Registries , Renal Artery/innervation , Adult , Aged , Antihypertensive Agents/therapeutic use , Blood Pressure , Female , Humans , Hypertension/drug therapy , Male , Middle Aged , Prospective Studies , Treatment Outcome
4.
Mucosal Immunol ; 8(4): 906-17, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25492477

ABSTRACT

Lactoferrin (LF), a pleiotropic iron-binding glycoprotein, is known to modulate the humoral immune response. However, its exact role in Ig synthesis has yet to be elucidated. In this study, we investigated the effect of LF on Ig production by mouse B cells and its underlying mechanisms. LF, like transforming growth factor (TGF)-ß1, stimulated B cells to produce IgA and IgG2b, while downregulating other isotypes. Using limiting dilution analysis, LF was shown to increase the frequency of IgA-secreting B-cell clones. This was paralleled by an increase in Ig germ-line α (GLα) transcripts, indicating that LF plays a role as an IgA switch factor. Interestingly, LF directly interacted with betaglycan (TGF-ß receptor III, TßRIII) and in turn induced phosphorylation of TßRI and Smad3 through formation of the TßRIII/TßRII/TßRI complex, leading to IgA isotype switching. Peroral administration of LF increased intestinal/serum IgA production as well as number of IgA plasma cells in lamina propria. Finally, we found that LF has an adjuvant activity when nontoxigenic Salmonella typhimurium was inoculated perorally, conferring protection against intragastrical infection of toxigenic S. typhimurium. These results suggest that LF has an important effect on the mucosal/systemic IgA response and can contribute to protection against intestinal pathogens.


Subject(s)
Immunoglobulin A/immunology , Immunoglobulin Class Switching , Immunoglobulin G/immunology , Lactoferrin/metabolism , Proteoglycans/metabolism , Receptors, Transforming Growth Factor beta/metabolism , Signal Transduction , Transforming Growth Factor beta/metabolism , Adjuvants, Immunologic , Animals , Antibody Formation/drug effects , Antibody Formation/immunology , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Immunity, Mucosal , Immunoglobulin A/biosynthesis , Immunoglobulin Class Switching/drug effects , Immunoglobulin Class Switching/immunology , Immunoglobulin G/biosynthesis , Lactoferrin/pharmacology , Mice , Protein Binding , Signal Transduction/drug effects , Smad3 Protein/metabolism , Transforming Growth Factor beta/pharmacology
5.
J Viral Hepat ; 21(3): 171-7, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24344773

ABSTRACT

Accumulation of eight key mutations located in the X/preC regions of the hepatitis B virus (HBV) genome (G1613A, C1653T, T1753V, A1762T, G1764A, A1846T, G1896A and G1899A) is a risk marker for the development of hepatocellular carcinoma (HCC). In this study, we analysed the 8 key mutations in 442 serum samples collected from 310 non-HCC and 132 HCC patients to identify the combinations linked to HCC. After the patients were stratified according to the age groups and mutation combinations, clinical parameters were compared between the HCC and the non-HCC groups. Analyses were focused on patient ≥40 years of age infected by HBV genotype C with A1762T and G1764A mutations in the basal core promoter region (BCP double mutation). In patients with ≥6 mutations, the combination of [G1613A + C1653T + A1846T + G1896A] mutations was closely linked to HCC, whereas no specific single or double mutation combination was associated with HCC. In patients with ≤5 mutations, HBeAg and HBV DNA serum titres were lower in the HCC group than those in the non-HCC group. Unlike the number of mutations, no specific combination correlated with advanced clinical stage in HCC. Of the BCP double mutation-based HBV mutant types, combinations of ≥6 mutations that include G1613A + C1653T + A1846T + G1896A, and combinations of ≤5 mutations with reduced HBeAg production, may be more specific indicators of HCC risk than only the number of mutations or any specific combination(s).


Subject(s)
Carcinoma, Hepatocellular/virology , Hepatitis B virus/genetics , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/virology , Liver Neoplasms/virology , Mutation , Trans-Activators/genetics , Adult , Age Factors , Aged , Female , Genome, Viral , Genotype , Hepatitis B e Antigens/immunology , Hepatitis B virus/immunology , Hepatitis B, Chronic/immunology , Humans , Male , Middle Aged , Odds Ratio , Promoter Regions, Genetic , Risk Factors , Sex Factors , Viral Regulatory and Accessory Proteins , Virus Replication
7.
Scand J Immunol ; 77(3): 177-86, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23297678

ABSTRACT

MHC class II molecules, in addition to their essential role as antigen-presenting molecules to CD4(+) T cell receptor, have a signal-transducing role related to B cell function. We identified pro-IL-16 as one of the proteins associated with MHC class II-mediated signalling in an analysis of MHC class II-associated molecules using immunoprecipitation and proteomics data obtained from the 38B9 resting B cell line, and investigated the role of pro-IL-16 in resting B cell activation. We found that pro-IL-16, rather than mature form of IL-16, is present both in the cytoplasm and nucleus of resting B cells, and its expression is influenced by MHC class II-mediated signalling. In addition, overexpression of pro-IL-16 impaired resting B cell proliferation and this inhibitory effect was mediated through regulating nuclear factor (NF)-κB activation. Knock-down of pro-IL-16 expression using siRNA decreased the level of cell-cycle inhibitor p27(kip) and increased the level of Skp2. In addition, knock-down of pro-IL-16 modulated mitogen-activated protein kinase activation. Given that IL-16 acts as an immunomodulator by impairing antigen-induced T cell activation and its precursor, pro-IL-16, plays a role in regulating the cell cycle in T lymphocytes and T cell lymphoma, we concluded that pro-IL-16 is involved in resting B cell proliferation, similar to its function in T lymphocytes.


Subject(s)
B-Lymphocytes/immunology , Cyclin-Dependent Kinase Inhibitor p27/immunology , Histocompatibility Antigens Class II/immunology , Interleukin-16/immunology , Mitogen-Activated Protein Kinases/immunology , NF-kappa B/immunology , Protein Precursors/immunology , S-Phase Kinase-Associated Proteins/immunology , Animals , B-Lymphocytes/metabolism , Blotting, Western , Cell Line , Cell Nucleus/metabolism , Cell Proliferation , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Cytoplasm/metabolism , Histocompatibility Antigens Class II/metabolism , Interleukin-16/genetics , Interleukin-16/metabolism , Lymphocyte Activation/immunology , Mice , Mice, Inbred BALB C , Microscopy, Confocal , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/metabolism , Protein Precursors/genetics , Protein Precursors/metabolism , RNA Interference , S-Phase Kinase-Associated Proteins/metabolism , Tandem Mass Spectrometry
8.
Appl Radiat Isot ; 70(9): 2255-9, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22410296

ABSTRACT

We have developed a high-resolution detection technique for measuring the energy and activity of alpha decay events using low-temperature detectors. A small amount of source material containing alpha-emitting radionuclides was enclosed in a 4π metal absorber. The energy of the alpha particles as well as that of the recoiled nuclides, low-energy electrons, and low-energy x-rays and γ-rays was converted into thermal energy of the gold absorber. A metallic magnetic calorimeter serving as a fast and sensitive thermometer was thermally attached to the metal absorber. In the present report, experimental demonstrations of Q spectroscopy were made with a new meander-type magnetic calorimeter. The thermal connection between the temperature sensor and the absorber was established with annealed gold wires. Each alpha decay event in the absorber resulted in a temperature increase of the absorber and the temperature sensor. Using the spectrum measured for a drop of (226)Ra solution in a 4π gold absorber, all of the alpha emitters in the sample were identified with a demonstration of good detector linearity. The resolution of the (226)Ra spectrum showed a 3.3 keV FWHM at its Q value together with an expected gamma escape peak at the energy shifted by its γ-ray energy.


Subject(s)
Calorimetry/instrumentation , Radiometry/instrumentation , Spectrum Analysis/instrumentation , Transducers , Cold Temperature , Equipment Design , Equipment Failure Analysis , Radiation Dosage
9.
Eur J Clin Nutr ; 65(11): 1250-5, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21697819

ABSTRACT

BACKGROUND/OBJECTIVES: This study was aimed to assess the beneficial effects on metabolic syndrome of functional yogurt NY-YP901 (Namyang Dairy Product Co. Ltd and Nutra R&BT Inc., Seoul, Korea) supplemented with mixture of Streptococcus thermophilus, Lactobacillus acidophilus, Bifidobacterium infantis and extra-ingredients containing Bifidobacterium breve (CBG-C2), Enterococcus faecalis FK-23, fibersol-2 and so on. SUBJECTS/METHODS: This study was designed as an 8-week randomized, double-blind, placebo-controlled, parallel study. Treatment and control groups consumed a functional yogurt NY-YP901 (150 ml) and a placebo yogurt twice a day, respectively, for 8 weeks. Body weight and body mass index (BMI), blood pressure, lipid profiles, fasting glucose with HbA1C and waist circumference were measured before and after treatment. Inclusion criteria were healthy individuals between the ages 20-65 years old who submitted an informed consent. RESULTS: During the period August 2009 to December 2009, 101 healthy participants (31 males and 70 females) finished the study. Treatment group were 53 individuals, and the control group were 48 individuals. In the treatment group consuming NY-YP901, statistically significant beneficial changes were observed in body weight (treatment group vs control group=-0.24±1.50 vs +0.64±1.39 kg, P<0.05), BMI (-0.10±0.58 vs +0.24±0.50 kg/m(2), P<0.05 ) and low-density lipoprotein (LDL)-cholesterol (-7.71±14.14 vs -0.43±15.32 mg/dl, P<0.05) after 8 weeks. The change in other parameters was not different between the treatment and the control groups. CONCLUSIONS: The functional yogurt NY-YP901 reduced LDL-cholesterol, body weight and BMI in the subjects at a 300-ml consumption daily for 8 weeks. From these findings, regular intake of functional yogurt NY-YP901 may be consequently related to improve metabolic syndrome.


Subject(s)
Food, Formulated/microbiology , Metabolic Syndrome/diet therapy , Probiotics/therapeutic use , Yogurt/microbiology , Adult , Bifidobacterium , Body Mass Index , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Cholesterol, LDL/blood , Double-Blind Method , Enterococcus faecalis , Female , Food, Formulated/analysis , Humans , Lactobacillus acidophilus , Male , Metabolic Syndrome/blood , Metabolic Syndrome/physiopathology , Middle Aged , Plant Extracts/administration & dosage , Plant Extracts/therapeutic use , Polysaccharides/administration & dosage , Polysaccharides/therapeutic use , Probiotics/administration & dosage , Republic of Korea/epidemiology , Risk , Streptococcus thermophilus , Weight Loss , Yogurt/analysis
10.
Parasite Immunol ; 33(7): 390-400, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21535020

ABSTRACT

Naegleria fowleri, a free-living amoeba, is the causative pathogen of primary amoebic meningoencephalitis in humans and experimental mice. N. fowleri is capable of destroying tissues and host cells through lytic necrosis. However, the mechanism by which N. fowleri induces host cell death is unknown. Electron microscopy indicated that incubation of Jurkat T cells with N. fowleri trophozoites induced necrotic morphology of the Jurkat T cells. N. fowleri also induced cytoskeletal protein cleavage, extensive poly (ADP-ribose) polymerase hydrolysis and lactate dehydrogenase (LDH) release. Although no activation of caspase-3 was observed in Jurkat T cells co-incubated with amoebae, intracellular reactive oxygen species (ROS) were strongly generated by NADPH oxidase (NOX). Pretreating cells with necroptosis inhibitor necrostatin-1 or NOX inhibitor diphenyleneiodonium chloride (DPI) strongly inhibited amoeba-induced ROS generation and Jurkat cell death, whereas pan-caspase inhibitor z-VAD-fmk did not. N. fowleri-derived secretory products (NfSP) strongly induced intracellular ROS generation and cell death. Necroptotic effects of NfSP were effectively inhibited by pretreating NfSP with proteinase K. Moreover, NfSP-induced LDH release and intracellular ROS accumulation were inhibited by pretreating Jurkat T cells with DPI or necrostatin-1. These results suggest that N. fowleri induces ROS-dependent necroptosis in Jurkat T cells.


Subject(s)
Cell Death , Naegleria fowleri/pathogenicity , Reactive Oxygen Species/toxicity , T-Lymphocytes/immunology , T-Lymphocytes/parasitology , Cytoskeletal Proteins/metabolism , Humans , Jurkat Cells , L-Lactate Dehydrogenase/metabolism , NADPH Oxidases , Poly(ADP-ribose) Polymerases/metabolism
11.
Food Chem Toxicol ; 48(10): 2747-53, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20621152

ABSTRACT

Aflatoxin B(1) (AFB(1))-mediated hepatic damage is involved in production of AFB(1)-8,9-epoxide-bound DNA adducts and this is also affected by a pro-oxidant potential of the toxin. In this study we investigated the effects of quercetin on AFB(1)-treated HepG2 cells. We also examined the biochemical mechanisms associated with the effects of quercetin on AFB(1)-mediated liver damage in mice. Our results revealed that quercetin and isorhamnetin inhibit production of reactive oxygen species and cytotoxicity, and block the decrease of reduced glutathione (GSH) levels in AFB(1)-treated HepG2 cells. Isorhamnetin have inhibitory ability on lipid peroxidation stronger than quercetin in the cells. Oral supplementation with quercetin decreased serum lactate dehydrogenase levels, increased hepatic GSH levels and superoxide dismutase activity, and reduced lipid peroxidation in both the liver and kidney in AFB(1)-treated mice. However, quercetin did not show a significant reduction on serum levels of alkaline phosphate, alanine aminotransferase and aspartate aminotransferase that were increased in AFB(1)-treated mice. HPLC analysis revealed that quercetin in plasma is mainly present as glucoronides and/or sulfates of quercetin. Collectively, it is suggested that quercetin does not directly protect against AFB(1)-mediated liver damage in vivo, but exerts a partial role in promoting antioxidative defense systems and inhibiting lipid peroxidation.


Subject(s)
Aflatoxin B1/antagonists & inhibitors , Aflatoxin B1/toxicity , Chemical and Drug Induced Liver Injury/prevention & control , Quercetin/pharmacology , Animals , Body Weight/drug effects , Carcinoma, Hepatocellular , Cell Line, Tumor , Cell Survival/drug effects , Chemical and Drug Induced Liver Injury/pathology , Chromatography, High Pressure Liquid , Flavonols/pharmacology , Glutathione/metabolism , Humans , Liver/pathology , Male , Malondialdehyde/metabolism , Mice , Mice, Inbred ICR , Organ Size/drug effects , Reactive Oxygen Species/metabolism
12.
Clin Nephrol ; 71(4): 448-50, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19356380

ABSTRACT

Persistent left superior vena cava (PLSVC) is the most common thoracic venous circulation anomaly and discovered incidentally during hemodialysis catheter insertion. PLSVC may have some clinical implications for nephrologists. PLSVC can create difficulties during catheter insertion and cause serious complications; it can be mistaken for placement into other sites and cause inappropriate response such as catheter removal. Nephrologists who place hemodialysis catheters in the left jugular or subclavian vein should be aware of the existence of PLSVC.


Subject(s)
Catheterization, Central Venous/methods , Renal Dialysis/instrumentation , Vena Cava, Superior/abnormalities , Aged , Humans , Male , Tomography, X-Ray Computed , Vena Cava, Superior/diagnostic imaging
13.
Methods Find Exp Clin Pharmacol ; 30(6): 443-50, 2008.
Article in English | MEDLINE | ID: mdl-18850045

ABSTRACT

In this study, we investigated the effect of Daio-Orengedoku-to (DOT) on ischemic brain damage in a rat model of focal ischemia-reperfusion and attempted to identify synergistic effects for the combination of edaravone and DOT against ischemic insult. Ischemia was induced by intraluminal occlusion of the right middle cerebral artery for 2 h and reperfusion followed for 22 h. To determine the neuroprotective effect of DOT, it was administered orally just before reperfusion and then 2 h after reperfusion. To examine the effects of combination therapy on survival, rats were divided into groups treated with edaravone, DOT, and edaravone and DOT. Microglial activation, neutrophil infiltration and brain-derived neurotrophic factor (BDNF) expression were examined in surviving animals. Infarct volume was significantly reduced by DOT (100, 200 and 400 mg/kg; P < 0.05), and edaravone plus DOT markedly improved the survival rate after transient ischemia (P = 0.0133). Microglial activation was reduced by edaravone and DOT and their combination (P < 0.05), and neutrophil infiltration was lowered in these groups (P < 0.05). BDNF-positive cells were increased in the combination edaravone and DOT group (P < 0.05). It appears that the neuroprotective mechanisms of combined therapy involve inhibition of microglial activation, reduction of invading neutrophils and enhancement of BDNF expression.


Subject(s)
Antipyrine/analogs & derivatives , Drugs, Chinese Herbal/therapeutic use , Free Radical Scavengers/therapeutic use , Ischemic Attack, Transient/drug therapy , Neuroprotective Agents , Animals , Antipyrine/therapeutic use , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Drug Therapy, Combination , Edaravone , Immunohistochemistry , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/pathology , Male , Microglia/drug effects , Neutrophil Infiltration/drug effects , Rats , Rats, Sprague-Dawley , Reperfusion Injury/drug therapy , Reperfusion Injury/psychology
14.
Opt Express ; 16(6): 3693-700, 2008 Mar 17.
Article in English | MEDLINE | ID: mdl-18542464

ABSTRACT

We propose a self-optimization and auto-stabilization method for a 1-bit DMZI in DPSK transmission. Using the characteristics of eye patterns, the optical frequency transmittance of a 1-bit DMZI is thermally controlled to maximize the power difference between the constructive and destructive output ports. Unlike other techniques, this control method can be realized without additional components, making it simple and cost effective. Experimental results show that error-free performance is maintained when the carrier optical frequency variation is approximately 10% of the data rate.


Subject(s)
Communication , Computer Communication Networks/instrumentation , Optics and Photonics/instrumentation , Signal Processing, Computer-Assisted/instrumentation , Equipment Design , Equipment Failure Analysis
15.
Oncol Rep ; 19(1): 93-8, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18097580

ABSTRACT

Latent infection of the Epstein-Barr virus (EBV) is strongly associated with the pathogenesis of several human tumor types. The restricted expression of the latent EBV antigens is critical for EBV-associated tumors to escape from immune surveillance. EBV lytic replication can be triggered by various treatments and the induced lytic genes cause strong cytotoxic T lymphocyte (CTL) responses. Histone acetylation or deacetylation is associated with chromatin remodeling and regulates gene expression. Histone deacetylase (HDAC) inhibitors affect cell cycle progression as well as gene expression in a wide variety of transformed cells. We examined whether an HDAC inhibitor, TSA, can affect cell cycle progression and induce EBV lytic replication in EBV-transformed lymphoblastoid cell lines (LCLs). TSA caused cell cycle arrest at low concentrations and induced apoptosis at higher (>300 nM) concentrations in the LCLs and EBV negative BJAB cells. To clarify the underlying mechanism of TSA-induced cell cycle arrest, expression of cell cycle regulatory factors was examined by RNase protection assay and Western blot analysis. Following TSA treatment, a reduced expression of cyclin D2 and an induction of p21 may have played an essential role for G1 arrest in LCLs, while p21 induction might have arrested BJAB cells in G1 phase. A Cdk inhibitor, p57, was increased by 300 nM TSA in both LCLs and BJAB cells, indicating its role in apoptosis. Moreover, immunofluorescene assay and Western blotting showed that TSA induced EBV lytic replication in LCL cells. These results suggest that TSA may exert an enhanced anti-tumor effect for EBV-associated tumors not only by inducing a cell cycle arrest and apoptosis, but also by triggering an EBV lytic cycle.


Subject(s)
B-Lymphocytes/drug effects , B-Lymphocytes/virology , Cell Cycle/drug effects , Cell Transformation, Viral/drug effects , Enzyme Inhibitors/pharmacology , Hydroxamic Acids/pharmacology , Apoptosis/drug effects , Blotting, Western , Cell Line, Transformed , Cell Line, Tumor , Fluorescent Antibody Technique , Gene Expression/drug effects , Genes, Viral/drug effects , Herpesvirus 4, Human , Histone Deacetylase Inhibitors , Humans , Reverse Transcriptase Polymerase Chain Reaction
16.
Oncogene ; 27(18): 2635-47, 2008 Apr 17.
Article in English | MEDLINE | ID: mdl-17968309

ABSTRACT

TMPRSS4 is a novel type II transmembrane serine protease found at the cell surface that is highly expressed in pancreatic, colon and gastric cancer tissues. However, the biological functions of TMPRSS4 in cancer are unknown. Here we show, using reverse transcription-PCR, that TMPRSS4 is highly elevated in lung cancer tissues compared with normal tissues and is also broadly expressed in a variety of human cancer cell lines. Knockdown of TMPRSS4 by small interfering RNA treatment in lung and colon cancer cell lines was associated with reduction of cell invasion and cell-matrix adhesion as well as modulation of cell proliferation. Conversely, the invasiveness, motility and adhesiveness of SW480 colon carcinoma cells were significantly enhanced by TMPRSS4 overexpression. Furthermore, overexpression of TMPRSS4 induced loss of E-cadherin-mediated cell-cell adhesion, concomitant with the induction of SIP1/ZEB2, an E-cadherin transcriptional repressor, and led to epithelial-mesenchymal transition events, including morphological changes, actin reorganization and upregulation of mesenchymal markers. TMPRSS4-overexpressing cells also displayed markedly increased metastasis to the liver in nude mice upon intrasplenic injection. Taken together, these studies suggest that TMPRSS4 controls the invasive and metastatic potential of human cancer cells by facilitating an epithelial-mesenchymal transition; TMPRSS4 may be a potential therapeutic target for cancer treatment.


Subject(s)
Biomarkers, Tumor/biosynthesis , Epithelial Cells/enzymology , Gastrointestinal Neoplasms/enzymology , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Lung Neoplasms/enzymology , Membrane Proteins/biosynthesis , Neoplasm Proteins/biosynthesis , Serine Endopeptidases/biosynthesis , Animals , Biomarkers, Tumor/genetics , Cadherins/antagonists & inhibitors , Cadherins/genetics , Cadherins/metabolism , Cell Adhesion , Cell Communication/drug effects , Cell Communication/genetics , Cell Line, Tumor , Cell Movement/drug effects , Cell Movement/genetics , Epithelial Cells/pathology , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/therapy , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Enzymologic/genetics , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/genetics , Humans , Liver Neoplasms/enzymology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/genetics , Mice , Mice, Nude , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/genetics , Neoplasm Transplantation , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , RNA, Small Interfering/genetics , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Serine Endopeptidases/genetics
17.
Phytomedicine ; 14(6): 390-5, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17084605

ABSTRACT

A traditional herbal medicine, Atractylodes macrocephala Koidz. (AMK), has long been used as a digestive and tonic. Recent investigations have suggested its potential ability in stimulating immune responses, although a scientific basis for this activity has not yet been elucidated. Based on previous results showing that the activity might be due to proteins, we purified protein samples from an original sample preparation of AMK and examined the stimulating ability of the protein samples on mouse splenocytes. The sample treatment markedly stimulated lymphocyte proliferation, antibody production, and cytokine secretion in mouse splenocytes. In particular, the samples showed the ability to induce the preferential stimulation of Th1 type, rather than Th2 type T lymphocytes. Stimulating activity of the samples was associated closely with glycoprotein(s) with molecular weights of around 30 kDa, especially with carbohydrate moiety rather than with protein residues of the glycoprotein(s). Our findings suggest that the glycoprotein(s) might play critical roles in modulating immune-response induction, and could potentially be used as medicinal and pharmacological agents.


Subject(s)
Atractylodes/chemistry , Glycoproteins/pharmacology , Spleen/cytology , Spleen/drug effects , Animals , Cell Proliferation/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Glycoproteins/chemistry , Immunoglobulin G/metabolism , Mice , Phytotherapy
18.
Res Vet Sci ; 82(1): 134-40, 2007 Feb.
Article in English | MEDLINE | ID: mdl-16730762

ABSTRACT

A Vero cell attenuated porcine epidemic diarrhea virus (PEDV) strain, DR13, was distinguished from wild-type PEDV using restriction enzyme fragment length polymorphism (RFLP). Cell attenuated DR13 was orally or intramuscularly (IM) administered to late-term pregnant sows, and mortality resulting from the highly virulent PEDV challenge was investigated in passively immunized suckling piglets of the two different groups. The mortality rate of the oral group (13%) was lower than that of the IM group (60%). In particular, the concentration of IgA against PEDV was higher in piglets of sows in the oral group, compared to the IM group. The attenuated DR13 virus remained safe, even after three backpassages in piglets. The findings of this study support the theory that the Vero cell attenuated DR13 virus may be applied as an oral vaccine for inducing specific immunity in late-term pregnant sows with a high margin of protection against PEDV infection.


Subject(s)
Coronavirus Infections/veterinary , Porcine epidemic diarrhea virus/classification , Porcine epidemic diarrhea virus/pathogenicity , Swine Diseases/prevention & control , Swine Diseases/virology , Viral Vaccines , Administration, Oral , Animals , Antibodies, Viral/blood , Chlorocebus aethiops , Coronavirus Infections/blood , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Female , Porcine epidemic diarrhea virus/immunology , Porcine epidemic diarrhea virus/physiology , Pregnancy , Serial Passage , Swine , Swine Diseases/blood , Time Factors , Vero Cells , Viral Vaccines/administration & dosage , Viral Vaccines/adverse effects , Virus Shedding
19.
Food Chem Toxicol ; 43(6): 961-8, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15811576

ABSTRACT

We characterized the biological function of G-120, glycoprotein isolated from the ethanol extract of the herb, Ulmus davidiana Nakai (UDN). G-120 has anti-tumor activity and significantly inhibited proliferation of MCF-7 cells, as measured by the thymidine uptake assay. In addition, MTT and trypan blue exclusion experiments showed that the G-120-mediated inhibition of DNA synthesis may be due to a cytostatic, rather than a cytotoxic effect. Further studies of DNA analysis and propidium iodide staining revealed that G-120 induces apoptosis in MCF-7 cells. Interestingly, G-120 (100 microg/ml) completely suppressed the binding of NF-kappaB to DNA and increased the cytosolic level of IkappaBalpha which prevented nuclear translocation of NF-kappaB. In addition, G-120 increased the expression of c-Jun, Fra-1, and Fra-2, but did not affect the expression of c-Fos. Collectively, it is believed that G-120 exerts an important role in the induction of apoptosis, suppression of NF-kappaB activation, and induction of c-Jun/Fra-1 or c-Jun/Fra-2 dimerization in MCF-7 cells. Consequently, G-120 could be considered as an anti-cancer agent, although further detailed experiments should be performed.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , DNA, Neoplasm/drug effects , Glycoproteins/pharmacology , Plant Extracts/pharmacology , Tumor Cells, Cultured/drug effects , Ulmus , Antineoplastic Agents/isolation & purification , Breast Neoplasms , DNA, Neoplasm/biosynthesis , DNA, Neoplasm/metabolism , Female , Flow Cytometry , Glycoproteins/isolation & purification , Humans , NF-kappa B/drug effects , NF-kappa B/metabolism , Plant Extracts/isolation & purification
20.
Clin Exp Allergy ; 34(10): 1642-8, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15479282

ABSTRACT

BACKGROUND: We previously reported that ovalbumin-diphtheria toxin (OVA-DT) fusion protein eliminates mast cells bearing OVA-specific IgE and protects OVA-sensitized mice from fatal anaphylaxis induced by OVA challenge. OBJECTIVE: To prove the specificity of therapeutic effect of OVA-DT to allergy induced by OVA only and not by other allergens such as human serum albumin (HSA), and to examine the cytotoxic effect of OVA-DT on B cells bearing OVA-specific IgE. METHODS: Mice were sensitized with two different antigens, OVA and HSA, and then treated with OVA-DT. The therapeutic effect of OVA-DT on the allergy response to each of allergen was evaluated by anaphylactic test. The effect of OVA-DT on the production of allergen-specific Ig isotypes of the sensitized mice and the cytotoxic effect of OVA-DT on B cells expressing OVA-specific IgE were examined. RESULTS: OVA-DT suppressed only OVA-induced allergy but not HSA-induced allergy in mice sensitized with a mixture of OVA and HSA. The suppression was prolonged even to the mice boosted with the same allergen 14 days after last treatment of OVA-DT. In addition, when the sensitized mice were boosted with the same allergens 14 days after last treatment of OVA-DT, the mice showed to increase the production of OVA-specific IgG2a/IgG3 and decreased that of OVA-specific IgE. OVA-DT targeted B cells bearing OVA-specific IgE, and killed them by DT-mediated cytotoxicity. CONCLUSION: The therapeutic effect of OVA-DT was specific to OVA-induced allergy and the suppression of OVA-induced allergy was continuously shown in the mice boosted with the same allergens. This is considered to be caused by the increase of OVA-specific IgG2a and IgG3, and because of the decrease of OVA-specific IgE by killing of B cells bearing OVA-specific IgE.


Subject(s)
Albumins/immunology , Allergens/immunology , Diphtheria Toxin/immunology , Hypersensitivity, Immediate/immunology , Immune Tolerance/immunology , Ovalbumin/immunology , Anaphylaxis/immunology , Animals , B-Lymphocytes/immunology , Cytotoxicity, Immunologic/immunology , Female , Humans , Immunoglobulin E/immunology , Immunoglobulin G/immunology , Immunotherapy/methods , Mice , Mice, Inbred BALB C , Serum Albumin/immunology
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