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Find video protocols related to scientific articles indexed in Pubmed.
Hepatitis B reactivation in patients with previous hepatitis B virus exposure undergoing rituximab-containing chemotherapy for lymphoma: a prospective study.
J. Clin. Oncol.
PUBLISHED: 10-06-2014
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Patterns of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) -negative, antihepatitis B core antigen antibody (anti-HBc) -positive patients with lymphoma receiving rituximab-containing chemotherapy have not been well described.
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Enhancing T Cell Immune Responses by B Cell-based Therapeutic Vaccine Against Chronic Virus Infection.
Immune Netw
PUBLISHED: 08-22-2014
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Chronic virus infection leads to the functional impairment of dendritic cells (DCs) as well as T cells, limiting the clinical usefulness of DC-based therapeutic vaccine against chronic virus infection. Meanwhile, B cells have been known to maintain the ability to differentiate plasma cells producing antibodies even during chronic virus infection. Previously, ?-galactosylceramide (?GC) and cognate peptide-loaded B cells were comparable to DCs in priming peptide-specific CD8(+) T cells as antigen presenting cells (APCs). Here, we investigated whether B cells activated by ?GC can improve virus-specific T cell immune responses instead of DCs during chronic virus infection. We found that comparable to B cells isolated from naïve mice, chronic B cells isolated from chronically infected mice with lymphocytic choriomeningitis virus (LCMV) clone 13 (CL13) after ?GC-loading could activate CD1d-restricted invariant natural killer T (iNKT) cells to produce effector cytokines and upregulate co-stimulatory molecules in both naïve and chronically infected mice. Similar to naïve B cells, chronic B cells efficiently primed LCMV glycoprotein (GP) 33-41-specific P14 CD8(+) T cells in vivo, thereby allowing the proliferation of functional CD8(+) T cells. Importantly, when ?GC and cognate epitope-loaded chronic B cells were transferred into chronically infected mice, the mice showed a significant increase in the population of epitope-specific CD8(+) T cells and the accelerated control of viremia. Therefore, our studies demonstrate that reciprocal activation between ?GC-loaded chronic B cells and iNKT cells can strengthen virus-specific T cell immune responses, providing an effective regimen of autologous B cell-based therapeutic vaccine to treat chronic virus infection.
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Oleanolic acid regulates NF-?B signaling by suppressing MafK expression in RAW 264.7 cells.
BMB Rep
PUBLISHED: 07-17-2014
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Oxidative stress and inflammation are common to many pathological conditions. Defense mechanisms protect cells from oxidative stress, but can become over-activated following injury and inflammation. NF-?B and Nrf2 transcription factors regulate proinflammatory and antioxidant gene expression, respectively. Studies have shown that many natural dietary compounds regulate NF-?B and Nrf2, preventing inflammation and oxidative stress. Here, we report major compounds of Prunella vulgaris var. lilacina such as rosmarinic acid, oleanolic acid, ursolic acid and caffeic acid as a potential therapeutic for oxidative stress and inflammation. The major compounds exhibited high anti-inflammatory activity, inhibiting NO, PGE2 production, NF-?B expression and activating Nrf2 expression. In addition, we examined the effect of major compounds on MafK expression. Among the compounds, oleanolic acid significantly decreased MafK expression and MafK-mediated p65 acetylation. These findings suggest that oleanolic acid as NF-?B inhibitors can potentially be used in therapeutic applications for the treatment of oxidative stressnduced diseases.
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Differential Diagnosis of Patients with Inconclusive Parkinsonian Features Using [(18)F]FP-CIT PET/CT.
Nucl Med Mol Imaging
PUBLISHED: 06-06-2014
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It is often difficult to differentiate parkinsonism, especially when patients show uncertain parkinsonian features. We investigated the usefulness of dopamine transporter (DAT) imaging for the differential diagnosis of inconclusive parkinsonism using [(18)F]FP-CIT PET.
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Pinus densiflora Sieb. et Zucc. alleviates lipogenesis and oxidative stress during oleic acid-induced steatosis in HepG2 cells.
Nutrients
PUBLISHED: 06-05-2014
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Excess accumulation of lipids and oxidative stress in the liver contribute to nonalcoholic fatty liver disease (NAFLD). We hypothesized that Pinus densiflora Sieb. et Zucc. (PSZ) can protect against NAFLD by regulating lipid accumulation and oxidative stress in the liver. To investigate the effect of PSZ upon NAFLD, we used an established cellular model: HepG2 cells treated with oleic acid. Then, the extent of hepatic steatosis and oxidative stress was assessed and levels of inflammatory markers measured. Oleic acid-treated HepG2 cells, compared with controls, had greater lipid accumulation. PSZ decreased lipid accumulation by 63% in oleic acid-treated HepG2 cells. Additionally, PSZ decreased the target gene expression of lipogenesis such as sterol regulatory element binding protein-1c, fatty acid synthase, stearoyl-CoA desaturase-1, diacylglycerol O-acyltransferase-1, and acetyl-CoA carboxylase-1 by 1.75, 6.0, 2.32, 1.93 and 1.81 fold, respectively. In addition, Oleic acid-treated HepG2 cells elicited extensive accumulation of tumor necrosis factor-? (TNF?) by 4.53 fold, whereas PSZ-treated cells decreased the expression of TNF? mRNA by 1.76 fold. PSZ significantly inhibited oxidative stress induced by reactive oxygen species. These results suggest that PSZ has effects on steatosis in vitro and further studies are needed in vivo to verify the current observations.
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Enhanced apoptosis by pemetrexed and simvastatin in malignant mesothelioma and lung cancer cells by reactive oxygen species-dependent mitochondrial dysfunction and Bim induction.
Int. J. Oncol.
PUBLISHED: 05-28-2014
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Pemetrexed is a multitarget antifolate currently used for the treatment of malignant mesothelioma and non-small cell lung cancer (NSCLC). Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors used primarily for hyperlidpidemia, have been studied for their antiproliferative and pro-apoptotic effects. However, the effects of simvastatin on pemetrexed-induced apoptosis have not been investigated. In this study, we investigated whether combination treatment with pemetrexed and simvastatin potentiates the apoptotic activity above that is seen with either drug alone in malignant mesothelioma and NSCLC cells. We found that the combination of pemetrexed and simvastatin induced more extensive caspase-dependent apoptosis than either drug alone in malignant mesothelioma cells (MSTO-211) or NSCLC cells (A549). In addition, reactive oxygen species (ROS) generation in cells treated with both pemetrexed and simvastatin was markedly increased compared to cells treated with either pemetrexed or simvastatin alone. Combination treatment also increased the loss of mitochondrial membrane potential, increased cytosolic release of cytochrome c, and altered expression of inhibitor of apoptosis proteins (IAP) and B-cell lymphoma-2 (Bcl-2) families of apoptosis related proteins. On the other hand, pretreatment with N-acetylcysteine (NAC) prevented apoptosis and mitochondrial dysfunction by pemetrexed and simvastatin. In addition, Bim siRNA conferred protection against apoptosis induced by pemetrexed and simvastatin. These results suggest that combination of pemetrexed and simvastatin potentiates their apoptotic activity beyond that of either drug alone in malignant mesothelioma and lung cancer cells. This activity is mediated through ROS-dependent mitochondrial dysfunction and Bim induction.
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Microfluidic techniques for development of 3D vascularized tissue.
Biomaterials
PUBLISHED: 04-04-2014
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Development of a vascularized tissue is one of the key challenges for the successful clinical application of tissue engineered constructs. Despite the significant efforts over the last few decades, establishing a gold standard to develop three dimensional (3D) vascularized tissues has still remained far from reality. Recent advances in the application of microfluidic platforms to the field of tissue engineering have greatly accelerated the progress toward the development of viable vascularized tissue constructs. Numerous techniques have emerged to induce the formation of vascular structure within tissues which can be broadly classified into two distinct categories, namely (1) prevascularization-based techniques and (2) vasculogenesis and angiogenesis-based techniques. This review presents an overview of the recent advancements in the vascularization techniques using both approaches for generating 3D vascular structure on microfluidic platforms.
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Polymeric stent materials dysregulate macrophage and endothelial cell functions: implications for coronary artery stent.
Int. J. Cardiol.
PUBLISHED: 03-12-2014
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Biodegradable polymers have been applied as bulk or coating materials for coronary artery stents. The degradation of polymers, however, could induce endothelial dysfunction and aggravate neointimal formation. Here we use polymeric microparticles to simulate and demonstrate the effects of degraded stent materials on phagocytic activity, cell death and dysfunction of macrophages and endothelial cells.
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Cancer Stem Cells under Hypoxia as a Chemoresistance Factor in Breast and Brain.
Curr Pathobiol Rep
PUBLISHED: 03-04-2014
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Over the last fifteen years, basic science and clinical studies have aimed to identify cancer stem cells (CSCs) in multiple types of cancer in order to unravel their mechanistic roles in cancer recurrence for therapeutic exploitation. Exposure of cells and tissues to hypoxia, or sub-atmospheric concentrations of oxygen (< 21% O2), stimulates various stress response pathways that bias the cells towards a self-preserving, anti-apoptotic phenotype. Despite major advances in our understanding of hypoxia, CSCs, and their interrelated nature, some of the most promising cancer therapies have shown limited efficacy in clinic for the past few years, in part due to the inherently hypoxic nature of growing tumors. In the present article, we discuss recent findings regarding the behavior of breast and brain CSCs under hypoxia, as well as the mechanisms that have been shown to drive their chemo-/radioresistance and metastatic potential.
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Immune response to hepatitis B vaccination in drug using populations: a systematic review and meta-regression analysis.
Vaccine
PUBLISHED: 02-25-2014
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Injecting and non-injecting drug users are at increased risk of contracting HBV infection, and show lower antibody response to hepatitis B vaccination compared to the general population. This systematic review and meta-regression analysis aimed to estimate seroprotection rates and identify host or vaccine factors associated with varying immune response following hepatitis B vaccination in drug using populations. Original research articles were searched using online databases (Medline, PubMed, and Embase) and from reference lists of eligible articles. HBV vaccine intervention studies reporting seroprotection rates in drug users, published in English during or after 1989 were eligible. Of 978 citations reviewed, 11 studies were eligible and included for final analysis. The reported seroprotection rates ranged from 54.5% to 97.1%. The studies were significantly heterogeneous (Q=180.850, p=0.000). Measurement of anti-HBs antibody at 2 months after the third vaccine dose (RR=2.62, 95%CI=1.16-5.94, p=0.026) was significantly associated with higher seroprotection rates compared to measurement at 1 month and 6 month following third vaccine dose. Age, gender, current drug use, vaccine dose and schedule, anti-HBc, anti-HCV and anti-HIV antibody seropositivity, and proportion of IDU study population did not show a significant association with seroprotection rates. Recommendations for future research include the definition of a standardized time point for the measurement of anti-HBs antibody levels, to enhance comparability of the immune response between different studies. Studies should strive to accurately report all potentially relevant factors affecting immune response to vaccine. Long-term follow up studies are needed to assess the seroprotection status in drug using populations receiving hepatitis B vaccine by standard or accelerated schedules.
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Organelle-selective fluorescent Cu2+ ion probes: revealing the endoplasmic reticulum as a reservoir for Cu-overloading.
Chem. Commun. (Camb.)
PUBLISHED: 02-12-2014
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Two novel Cu(2+) sensors, 1 and 2, bearing naphthalimide and a DPA moiety were synthesized to study copper accumulation in organelles by selective Cu(2+) sensing. The ER-selective Cu(2+) sensor 1 that we developed serves as a valuable tool for understanding the subcellular compartmentalization and roles of copper ions in physiology and pathophysiology.
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Enhanced neural cell adhesion and neurite outgrowth on graphene-based biomimetic substrates.
Biomed Res Int
PUBLISHED: 01-30-2014
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Neural cell adhesion and neurite outgrowth were examined on graphene-based biomimetic substrates. The biocompatibility of carbon nanomaterials such as graphene and carbon nanotubes (CNTs), that is, single-walled and multiwalled CNTs, against pheochromocytoma-derived PC-12 neural cells was also evaluated by quantifying metabolic activity (with WST-8 assay), intracellular oxidative stress (with ROS assay), and membrane integrity (with LDH assay). Graphene films were grown by using chemical vapor deposition and were then coated onto glass coverslips by using the scooping method. Graphene sheets were patterned on SiO2/Si substrates by using photolithography and were then covered with serum for a neural cell culture. Both types of CNTs induced significant dose-dependent decreases in the viability of PC-12 cells, whereas graphene exerted adverse effects on the neural cells just at over 62.5?ppm. This result implies that graphene and CNTs, even though they were the same carbon-based nanomaterials, show differential influences on neural cells. Furthermore, graphene-coated or graphene-patterned substrates were shown to substantially enhance the adhesion and neurite outgrowth of PC-12 cells. These results suggest that graphene-based substrates as biomimetic cues have good biocompatibility as well as a unique surface property that can enhance the neural cells, which would open up enormous opportunities in neural regeneration and nanomedicine.
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GABA from reactive astrocytes impairs memory in mouse models of Alzheimer's disease.
Nat. Med.
PUBLISHED: 01-10-2014
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In Alzheimer's disease (AD), memory impairment is the most prominent feature that afflicts patients and their families. Although reactive astrocytes have been observed around amyloid plaques since the disease was first described, their role in memory impairment has been poorly understood. Here, we show that reactive astrocytes aberrantly and abundantly produce the inhibitory gliotransmitter GABA by monoamine oxidase-B (Maob) and abnormally release GABA through the bestrophin 1 channel. In the dentate gyrus of mouse models of AD, the released GABA reduces spike probability of granule cells by acting on presynaptic GABA receptors. Suppressing GABA production or release from reactive astrocytes fully restores the impaired spike probability, synaptic plasticity, and learning and memory in the mice. In the postmortem brain of individuals with AD, astrocytic GABA and MAOB are significantly upregulated. We propose that selective inhibition of astrocytic GABA synthesis or release may serve as an effective therapeutic strategy for treating memory impairment in AD.
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Valganciclovir suppressed Epstein Barr virus reactivation during immunosuppression with alemtuzumab.
J. Clin. Virol.
PUBLISHED: 01-04-2014
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Reactivation of latent herpes viruses occurs with immunosuppression. Alemtuzumab is an antibody targeting CD52, which is expressed on all B- and T-cells. Treatment with alemtuzumab leads to profound T-cell suppression, and reactivation of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) occurs. Valganciclovir is used as an anti-CMV prophylaxis during alemtuzumab therapy.
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ESET methylates UBF at K232/254 and regulates nucleolar heterochromatin plasticity and rDNA transcription.
Nucleic Acids Res.
PUBLISHED: 11-14-2013
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The remodeling of chromatin in the nucleolus is important for the control of ribosomal DNA (rDNA) transcription and ribosome biogenesis. Herein, we found that upstream binding factor (UBF) interacts with ESET, a histone H3K9 methyltransferase and is trimethylated at Lys (K) 232/254 by ESET. UBF trimethylation leads to nucleolar chromatin condensation and decreased rDNA transcriptional activity. UBF mutations at K232/254A and K232/254R restored rDNA transcriptional activity in response to ESET. Both ESET-?SET mutant and knockdown of ESET by short hairpin RNA reduced trimethylation of UBF and resulted in the restoration of rDNA transcription. Atomic force microscopy confirmed that UBF trimethylated by ESET modulates the plasticity of nucleolar chromatin. We further demonstrated that UBF trimethylation at K232/254 by ESET deregulates rDNA transcription in a cell model of Huntingtons disease. Together, our findings show that a novel epigenetic modification of UBF is linked to impaired rDNA transcription and nucleolar chromatin remodeling, which may play key roles in the pathogenesis of neurodegeneration.
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Deactivation of nanoscale zero-valent iron by humic acid and by retention in water.
Environ Technol
PUBLISHED: 11-07-2013
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The effects of the deactivation of nanoscale zero-valent iron (NZVI), induced by humic acid (HA) and by the retention of NZVI in water, on nitrate reduction were investigated using a kinetic study. Both the nitrate removal and generation of ammonia were significantly inhibited as the HA adsorption amount and retention time were increased. However, HA removal was greatly enhanced when the NZVI was used after 1 d or 25 d of retention in water. The results are caused by the formation of iron oxides/hydroxides, which increased the specific surface area and the degree of NZVI aggregation which was observed by transmission electron microscopy (TEM). However, the nitrate reduction was greater at the beginning of reaction in the presence of HA when fresh NZVI was used, because of the enhanced electron transfer by the HA in bulk phase and on NZVI surface as train sequences. The pseudo second order adsorption kinetic equation incorporating deactivation and a Langmuir-Hinshelwood (LH) type kinetic equation provided accurate descriptions of the nitrate removal and ammonia generation, respectively. The deactivation constant and the reaction rate constant of the LH type kinetic equation were strongly correlated with the HA amount accumulated on NZVI. These results suggest that the HA accumulation on the NZVI surface reactive sites plays the dominant role in the inhibition and the inhibition can be described successfully using the deactivation model. The HA accumulation on NZVI was verified using TEM.
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Molecular Mechanism of GTPase Activation at the Signal Recognition Particle (SRP) RNA Distal End.
J. Biol. Chem.
PUBLISHED: 10-22-2013
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The signal recognition particle (SRP) RNA is a universally conserved and essential component of the SRP that mediates the co-translational targeting of proteins to the correct cellular membrane. During the targeting reaction, two functional ends in the SRP RNA mediate distinct functions. Whereas the RNA tetraloop facilitates initial assembly of two GTPases between the SRP and SRP receptor, this GTPase complex subsequently relocalizes ?100 ? to the 5,3-distal end of the RNA, a conformation crucial for GTPase activation and cargo handover. Here we combined biochemical, single molecule, and NMR studies to investigate the molecular mechanism of this large scale conformational change. We show that two independent sites contribute to the interaction of the GTPase complex with the SRP RNA distal end. Loop E plays a crucial role in the precise positioning of the GTPase complex on these two sites by inducing a defined bend in the RNA helix and thus generating a preorganized recognition surface. GTPase docking can be uncoupled from its subsequent activation, which is mediated by conserved bases in the next internal loop. These results, combined with recent structural work, elucidate how the SRP RNA induces GTPase relocalization and activation at the end of the protein targeting reaction.
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Cytotoxicity and Structure-activity Relationships of Naphthyridine Derivatives in Human Cervical Cancer, Leukemia, and Prostate Cancer.
Korean J. Physiol. Pharmacol.
PUBLISHED: 10-14-2013
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Naphthyridine compounds are important, because they exhibit various biological activities including anticancer, antimicrobial, and anti-inflammatory activity. Some naphthyridines have antimitotic effects or demonstrate anticancer activity by inhibiting topoisomerase II. These compounds have been investigated as potential anticancer agents, and several compounds are now part of clinical trials. A series of naphthyridine derivatives were evaluated for their in vitro cytotoxic activities against human cervical cancer (HeLa), leukemia (HL-60), and prostate cancer (PC-3) cell lines using an MTT assay. Some compounds (14, 15, and 16) were more potent than colchicine against all three human cancer cell lines and compound (16) demonstrated potency with IC50 values of 0.7, 0.1, and 5.1 µM, respectively. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used for quantitative structure-activity relationship (QSAR) molecular modeling of these compounds. We obtained accurate and predictive three-dimensional QSAR (3D-QSAR) models as indicated by the high PLS parameters of the HeLa (q(2), 0.857; r(2), 0.984; r(2) pred, 0.966), HL-60 (q(2), 0.777; r(2), 0.937; r(2) pred, 0.913), and PC-3 (q(2), 0.702; r(2), 0.983; r(2) pred, 0.974) cell lines. The 3D-QSAR contour maps suggested that the C-1 NH and C-4 carbonyl group of the naphthyridine ring and the C-2 naphthyl ring were important for cytotoxicity in all three human cancer cell lines.
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The prognosis of patients with lung cancer admitted to the medical intensive care unit.
Asia Pac J Clin Oncol
PUBLISHED: 10-08-2013
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Lung cancer remains the leading cause of cancer mortality worldwide. Despite their poor prognosis, patients with lung cancer are increasingly being admitted to the medical intensive care unit (MICU) for treatment of critical illnesses. The aim of this study was to assess the outcome of patients with lung cancer who are admitted to an MICU and to identify the measurable predictors of their MICU outcome.
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Clostridium difficile Infection in lung cancer patients.
Jpn. J. Infect. Dis.
PUBLISHED: 09-20-2013
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Clostridium difficile infection (CDI) is a common nosocomial infection. Lung cancer patients have a high risk of developing CDI because of continuous antibiotic treatment or chemotherapy, prolonged hospitalization, and general weakness. This study aimed to analyze predisposing or associated risk factors for CDI in lung cancer patients receiving chemotherapy. This study was a retrospective review of 188 lung cancer patients who were admitted to the Wonkwang University Hospital between 2008 and 2009. Of the 188 patients, 44 were diagnosed with CDI. The albumin levels were significantly lower and the performance status (PS) score was significantly higher in lung cancer patients with CDI than in those without CDI (P < 0.05). In conclusion, clinicians should consider the possibility of CDI occurrence in lung cancer patients receiving chemotherapy, particularly in those with low albumin levels and high PS scores, because most lung cancer patients have a high risk of developing CDI.
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Nucleolar dysfunction in Huntingtons disease.
Biochim. Biophys. Acta
PUBLISHED: 09-10-2013
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Huntingtons disease (HD) is a fatal genetic disorder characterized by triad clinical symptoms of chorea, emotional distress, and cognitive decline. Genetic mutation in HD is identified by an expansion of CAG repeats coding for glutamine (Q) in exon 1 of the huntingtin (htt) gene. The exact mechanism on how mutant htt leads to the selective loss of medium spiny neurons (MSNs) in the striatum is still unknown. Recent studies suggest that nucleolar stress and dysfunction are linked to the pathogenesis of HD. Alterations of the nucleolar activity and integrity contribute to deregulation of ribosomal DNA (rDNA) transcription in HD pathogenesis. Furthermore, epigenetic modifications in the nucleolus are associated with neuronal damage in HD. In this review, we discuss about how post-translational modifications of upstream binding factor (UBF) are affected by histone acetyltransferase and histone methyltransferase and involved in the transcriptional regulation of rDNA in HD. The understanding of epigenetic modulation of UBF-dependent rDNA transcription in the nucleolus may lead to the identification of novel pathological markers and new therapeutic targets to treat HD. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.
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Epigenetic mechanisms of neurodegeneration in Huntingtons disease.
Neurotherapeutics
PUBLISHED: 09-06-2013
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Huntingtons disease (HD) is an incurable and fatal hereditary neurodegenerative disorder of mid-life onset characterized by chorea, emotional distress, and progressive cognitive decline. HD is caused by an expansion of CAG repeats coding for glutamine (Q) in exon 1 of the huntingtin gene. Recent studies suggest that epigenetic modifications may play a key role in HD pathogenesis. Alterations of the epigenetic "histone code" lead to chromatin remodeling and deregulation of neuronal gene transcription that are prominently linked to HD pathogenesis. Furthermore, specific noncoding RNAs and microRNAs are associated with neuronal damage in HD. In this review, we discuss how DNA methylation, post-translational modifications of histone, and noncoding RNA function are affected and involved in HD pathogenesis. In addition, we summarize the therapeutic effects of histone deacetylase inhibitors and DNA binding drugs on epigenetic modifications and neuropathological sequelae in HD. Our understanding of the role of these epigenetic mechanisms may lead to the identification of novel biological markers and new therapeutic targets to treat HD.
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NF-?B-targeted anti-inflammatory activity of Prunella vulgaris var. lilacina in macrophages RAW 264.7.
Int J Mol Sci
PUBLISHED: 08-24-2013
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Prunella vulgaris var. lilacina, a herbal medicine, has long been used in Korea for the treatment of sore throat, and to alleviate fever and accelerate wound healing. Although the therapeutic effect of P. vulgaris var. lilacina is likely associated with anti-inflammatory activity, the precise underlying mechanisms are largely unknown. Here, we sought to elucidate the possible mechanisms of the anti-inflammatory activity. We have investigated the anti-inflammatory activity of the various solvent fractions (hexane, butanol, chloroform and water) from the ethanol extract of P. vulgaris var. lilacina in activated macrophages. The hexane fraction exhibited higher anti-inflammatory activities, inducing inhibition of nitric oxide and prostaglandin E2 production as well as inducible nitric oxide synthase, cyclooxygenase-2, and tumor necrosis factor-? mRNA expression in response to lipopolysaccharide stimulation. Moreover, the hexane fraction from P. vulgaris var. lilacina significantly inhibited the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) and the nuclear translocation of the NF-?B p50 and p65 subunits. These results indicate that P. vulgaris var. lilacina has an anti-inflammatory capacity in vitro, suggesting that it could be a potential source of natural anti-inflammatory agents.
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Breakthrough invasive fungal diseases during echinocandin treatment in high-risk hospitalized hematologic patients.
Ann. Hematol.
PUBLISHED: 08-06-2013
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The frequency of breakthrough invasive fungal diseases (IFDs) during echinocandin therapy is unclear. We retrospectively analyzed 534 hematologic patients treated with echinocandin (caspofungin, N?=?55; micafungin, N?=?306; anidulafungin, N?=?173). Four proven IFDs were found, caused by Candida parapsilosis (N?=?2), C. parapsilosis and Candida glabrata (N?=?1), and Fusarium species (N?=?1). Four cases of possible IFDs were observed, all showing pulmonary infection. One case showed features suggestive of hepatosplenic candidiasis. Six of these eight cases had previously received the purine analog clofarabine. Breakthrough IFD during echinocandin treatment occurred infrequently (1.5 %), caused predominantly by Candida species. Clofarabine usage was an important risk factor.
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Can high serum anti-Müllerian hormone levels predict the phenotypes of polycystic ovary syndrome (PCOS) and metabolic disturbances in PCOS patients?
Clin Exp Reprod Med
PUBLISHED: 07-19-2013
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To evaluate correlations between serum anti-Müllerian hormone (AMH) levels, phenotypes of polycystic ovary syndrome (PCOS), obesity, and metabolic parameters in patients with PCOS.
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Comparison of the Xpert MTB/RIF and Cobas TaqMan MTB assays for detection of Mycobacterium tuberculosis in respiratory specimens.
J. Clin. Microbiol.
PUBLISHED: 07-17-2013
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The Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA) is a fully automated, cartridge-based real-time PCR assay designed to detect Mycobacterium tuberculosis and rifampin resistance within 2 h. The performance of the Xpert assay has been evaluated in various clinical settings. However, there are few data comparing the Xpert assay to the Cobas TaqMan MTB test (Roche Diagnostics, Basel, Switzerland), one of the most widely utilized molecular assays for M. tuberculosis detection. In this prospective study, 320 consecutive respiratory specimens were processed simultaneously using acid-fast bacillus (AFB) staining, mycobacterial cultures with both solid and liquid media, and the Cobas and Xpert assays. The Xpert assay was performed with direct respiratory specimens, while the Cobas assay was done with decontaminated concentrated specimens. Based on the culture as a reference method, the overall sensitivities of the Cobas and Xpert assays were 71.4% and 67.9%, respectively. When AFB smear results were taken into consideration, the sensitivities of the Cobas assay for smear-positive and -negative specimens were 87% and 54%, while those of the Xpert assay were 67% and 69%, respectively. The Cobas assay showed 100% specificity and 100% positive predictive value (PPV) regardless of smear results, while the Xpert assay showed 100% specificity and 100% PPV for smear-positive specimens but 98% specificity and 60% PPV for smear-negative specimens. In conclusion, the Xpert assay showed performance that was slightly inferior to that of the Cobas assay but seems useful for the rapid detection of M. tuberculosis, considering that it was performed without laborious and time-consuming decontamination and concentration procedures.
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In vitro antioxidant and anticancer effects of solvent fractions from prunella vulgaris var. lilacina.
BMC Complement Altern Med
PUBLISHED: 07-12-2013
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Recently, considerable attention has been focused on exploring the potential antioxidant properties of plant extracts or isolated products of plant origin. Prunella vulgaris var. lilacina is widely distributed in Korea, Japan, China, and Europe, and it continues to be used to treat inflammation, eye pain, headache, and dizziness. However, reports on the antioxidant activities of P. vulgaris var. lilacina are limited, particularly concerning the relationship between its phenolic content and antioxidant capacity. In this study, we investigated the antioxidant and anticancer activities of an ethanol extract from P. vulgaris var. lilacina and its fractions.
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Intracellular distribution of differentially phosphorylated dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A).
J. Neurosci. Res.
PUBLISHED: 06-20-2013
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The gene encoding dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is located within the Down syndrome (DS) critical region of chromosome 21. DYRK1A interacts with a plethora of substrates in the cytosol, cytoskeleton, and nucleus. Its overexpression is a contributing factor to the developmental alterations and age-associated pathology observed in DS. We hypothesized that the intracellular distribution of DYRK1A and cell-compartment-specific functions are associated with DYRK1A posttranslational modifications. Fractionation showed that, in both human and mouse brain, almost 80% of DYRK1A was associated with the cytoskeleton, and the remaining DYRK1A was present in the cytosolic and nuclear fractions. Coimmunoprecipitation revealed that DYRK1A in the brain cytoskeleton fraction forms complexes with filamentous actin, neurofilaments, and tubulin. Two-dimensional gel analysis of the fractions revealed DYRK1A with distinct isoelectric points: 5.5-6.5 in the nucleus, 7.2-8.2 in the cytoskeleton, and 8.7 in the cytosol. Phosphate-affinity gel electrophoresis demonstrated several bands of DYRK1A with different mobility shifts for nuclear, cytoskeletal, and cytosolic DYRK1A, indicating modification by phosphorylation. Mass spectrometry analysis disclosed one phosphorylated site in the cytosolic DYRK1A and multiple phosphorylated residues in the cytoskeletal DYRK1A, including two not previously described. This study supports the hypothesis that intracellular distribution and compartment-specific functions of DYRK1A may depend on its phosphorylation pattern. © 2013 Wiley Periodicals, Inc.
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Molecular mechanisms of luteolin-7-O-glucoside-induced growth inhibition on human liver cancer cells: G2/M cell cycle arrest and caspase-independent apoptotic signaling pathways.
BMB Rep
PUBLISHED: 06-12-2013
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Luteolin-7-O-glucoside (LUT7G), a flavone subclass of flavonoids, has been found to increase anti-oxidant and anti-inflammatory activity, as well as cytotoxic effects. However, the mechanism of how LUT7G induces apoptosis and regulates cell cycles remains poorly understood. In this study, we examined the effects of LUT7G on the growth inhibition of tumors, cell cycle arrest, induction of ROS generation, and the involved signaling pathway in human hepatocarcinoma HepG2 cells. The proliferation of HepG2 cells was decreased by LUT7G in a dose-dependent manner. The growth inhibition was due primarily to the G2/M phase arrest and ROS generation. Moreover, the phosphorylation of JNK was increased by LUT7G. These results suggest that the anti-proliferative effect of LUT7G on HepG2 is associated with G2/M phase cell cycle arrest by JNK activation. [BMB Reports 2013; 46(12): 611-616].
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Primary malignant fibrous histiocytoma of the pleura.
Tuberc Respir Dis (Seoul)
PUBLISHED: 05-31-2013
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Malignant fibrous histiocytoma, a type of sarcoma, is a malignant neoplasm with uncertain origin that arises in both the soft tissues and the bone. The occurrence of primary malignant fibrous histiocytoma of the pleura is extremely rare. We report a case of a 65-year-old Korean man who is being diagnosed with primary malignant fibrous histiocytoma of the pleura.
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Cardiomyocyte sensor responsive to changes in physical and chemical environments.
J Biomech
PUBLISHED: 05-30-2013
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Conventional cardiac physiology experiments investigate in vitro beat frequency using cells isolated from adult or neonatal rat hearts. In this study, we show that various cantilever shapes and drug treatments alter cardiomyocyte contraction force in vitro. Four types of cantilevers were used to compare the contractile forces: flat, peg patterned, grooved, and peg and grooved. Contraction force was represented as bending deflection of the cantilever end. The deflections of the flat, peg patterned, grooved, and peg and grooved cantilevers were 24.2nN, 41.6nN, 121nN, and 134.2nN, respectively. We quantified the effect of drug treatments on cardiomyocyte contractile forces on the grooved cantilever using Digoxin, Isoproterenol, and BayK8644, all of which increase contractile force, and Verapamil, which decreases contractile force. The cardiomyocyte contractile force without drugs decreased 8 days after culture initiation. Thus, we applied Digoxin, Isoproterenol, and BayK8644 at day 8, and Verapamil at day 5. Digoxin, Isoproterenol, and BayK8644 increased the cardiomyocyte contractile forces by 19.31%, 9.75%, and 23.81%, respectively. Verapamil decreased the contraction force by 48.06%. In summary, contraction force changes in response to adhesion surface topology and various types of drug treatments. We observed these changes by monitoring cell alignment, adhesion, morphology, and bending displacement with cantilever sensors.
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The association of internet use and depression Among The spinal cord injury population.
Arch Phys Med Rehabil
PUBLISHED: 05-07-2013
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To examine the relationship between the frequency of Internet use and depression among people with spinal cord injury (SCI).
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MafK positively regulates NF-?B activity by enhancing CBP-mediated p65 acetylation.
Sci Rep
PUBLISHED: 04-23-2013
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Reactive oxygen species, produced by oxidative stress, initiate and promote many metabolic diseases through activation/suppression of redox-sensitive transcription factors. NF-?B and Nrf2 are important regulators of oxidation resistance and contribute to the pathogenesis of many diseases. We identified MafK, a novel transcriptional regulator that modulates NF-?B activity. MafK knockdown reduced NF-?B activation, whereas MafK overexpression enhanced NF-?B function. MafK mediated p65 acetylation by CBP upon LPS stimulation, thereby facilitating recruitment of p65 to NF-?B promoters such as IL-8 and TNF?. Consistent with these results, MafK-depleted mice showed prolonged survival with a reduced hepatic inflammatory response after LPS and D-GalN injection. Thus, our findings reveal a novel mechanism by which MafK controls NF-?B activity via CBP-mediated p65 acetylation.
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Elevated prx1 provides resistance to docetaxel, but is not associated with predictive significance in lung cancer.
Tuberc Respir Dis (Seoul)
PUBLISHED: 04-17-2013
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This study was conducted in order to elucidate the effects of docetaxel on the growth of peroxiredoxin 1 (Prx1) knockdown A549 xenograft tumors and further tested the role of Prx1 as a predictor for how a patient would respond to docetaxel treatment.
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The role of trust in delayed HIV diagnosis in a diverse, urban population.
AIDS Behav
PUBLISHED: 04-04-2013
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Delayed diagnosis of HIV infection is a common problem. We hypothesized that persons with less trust in physicians and in the healthcare system would be diagnosed with lower CD4 cell counts than persons with more trust because they would delay seeking healthcare. From January 2006 to October 2007, 171 newly diagnosed HIV-infected persons, not yet in HIV primary care, were recruited from HIV testing sites in Houston, Texas, that primarily serve the under- and un-insured. The participants completed instruments measuring trust in physicians and trust in the healthcare system. Initial CD4 cell counts were obtained from medical record review. Mean trust scores for participants with CD4 cell counts ?200 cells/mm(3) were compared with scores from participants with CD4 cell counts <200 cells/mm(3). We found that 51% of the cohort was diagnosed with a CD4 cell count <200 cells/mm(3). Neither trust in physicians nor trust in the healthcare system was an independent predictor of delayed diagnosis of HIV infection. In multivariate analysis, men who have sex with men and injection drug users were more likely to have early HIV diagnosis. Race/ethnicity was the only variable statistically significantly predictive of trust in physicians and in the healthcare system. Hispanics had the highest trust scores, followed by Blacks and Whites. Low trust is likely not a barrier to timely diagnosis of HIV infection.
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Destabilization of KLF10, a tumor suppressor, relies on thr93 phosphorylation and isomerase association.
Biochim. Biophys. Acta
PUBLISHED: 04-01-2013
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KLF10 is now classified as a member of the Krüppel-like transcription factor family and acts as a tumor suppressor. Although KLF10 is originally named as TGF-?-inducible early gene-1 and mimicking the anti-proliferative effect of TGF-? in various carcinoma cells, the transcriptional upregulatory function of KLF10 has been described for a variety of cytokines and in many diseases. Through in vivo and in vitro phosphorylation assays, we identified that KLF10 is a phosphorylated protein in cells. Using yeast-two hybrid screening and site direct mutagenesis, we also identified PIN1 as a novel KLF10 associated protein. PIN1 is a peptidyl-prolyl isomerase enzyme belonging to the parvulin family, which specifically recognizes phosphorylated Ser/Thr-Pro containing substrates. Through protein-protein interaction assays, we showed that the Pro-directed Ser/Thr-Pro motif at Thr-93 in the KLF10 N-terminal region is essential for the interaction between KLF10 and PIN1. More importantly, PIN1 interacts with KLF10 in a phosphorylation-dependent manner and this interaction promotes KLF10 protein degradation in cells. Therefore, KLF10 shows shorter protein stability compared with mutant KLF10 that lacks PIN1 binding ability after cycloheximide treatments. The reversely correlated expression profile between KLF10 and PIN1 as observed in cell lines was also shown in clinic pancreatic cancer specimen. Using in vitro kinase assays and depletion assays, we were able to show that RAF-1 phosphorylates the Thr-93 of KLF10 and affects the KLF10 expression level in cells. Thus these findings as a whole indicate that RAF-1 phosphorylation and PIN1 isomerization together regulate KLF10 stability and further affect the role of KLF10 in tumor progression.
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The structural analysis of three-dimensional fibrous collagen hydrogels by raman microspectroscopy.
Biopolymers
PUBLISHED: 03-27-2013
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To investigate molecular effects of 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), EDC/N-hydroxysuccinimide (NHS), glyceraldehyde cross-linking as well as polymerization temperature and concentration on the three-dimensional (3D) collagen hydrogels, we analyzed the structures in situ by Raman microspectroscopy. The increased intensity of the 814 and 936 cm(-1) Raman bands corresponding to the C-C stretch of a protein backbone and a shift in the amide III bands from 1241 cm(-1) /1268 cm(-1) in controls to 1247 cm(-1) /1283 cm(-1) in glyceraldehyde-treated gels indicated changes to the alignment of the collagen molecules, fibrils/fibers and/or changes to the secondary structure on glyceraldehyde treatment. The increased intensity of 1450 cm(-1) band and the appearance of a strong peak at 1468 cm(-1) reflected a change in the motion of lysine/arginine CH2 groups. For the EDC-treated collagen hydrogels, the increased intensity of 823 cm(-1) peak corresponding to the C-C stretch of the protein backbone indicated that EDC also changed the packing of collagen molecules. The 23% decrease in the ratio of 1238 cm(-1) to 1271 cm(-1) amide III band intensities in the EDC-modified samples compared with the controls indicated changes to the alignment of the collagen molecules/fibrils and/or the secondary structure. A change in the motion of lysine/arginine CH2 groups was detected as well. The addition of NHS did not induce additional Raman shifts compared to the effect of EDC alone with the exception of a 1416 cm(-1) band corresponding to a COO(-) stretch. Overall, the Raman spectra suggest that glyceraldehyde affects the collagen states within 3D hydrogels to a greater extent compared to EDC and the effects of temperature and concentration are minimal and/or not detectable. © 2012 Wiley Periodicals, Inc. Biopolymers 99: 349-356, 2013.
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Femtosecond laser-patterned nanopore arrays for surface-mediated peptide treatment.
Nanomedicine
PUBLISHED: 03-08-2013
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The major goal of this study was to create easy-to-use, reusable substrates capable of storing any peptides or bioactive molecules for a desired period of time until cells uptake them without the need for bioactive molecule or peptide-specific techniques. Nanopore arrays of uniform size and distribution were machined into fused silica substrates using femtosecond laser ablation and loaded with peptides by simple adsorption. The nanopore substrates were validated by examining the effect of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) loaded nanopores on macrophage phagocytosis and intracellular production of reactive oxygen species (ROS) with and without the pro-inflammatory lipopolysaccharide (LPS). Our results demonstrated that nanopores were generated in a uniform array fashion. Ac-SDKP peptides were stably stored in nanopores and internalized by macrophages. Significant reductions in ROS production and phagocytosis in macrophages were observed over control substrates, even in combination with LPS stimulation, indicating that loading Ac-SDKP peptides in pores significantly improved the anti-inflammatory effects.
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Primary treatment of leukemia relapses after allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning second transplantation from the original donor.
Am. J. Hematol.
PUBLISHED: 02-26-2013
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Acute leukemia relapsing after allogeneic hematopoietic stem cell transplantation (HSCT) has dismal outcome. Consecutive consenting patients (acute myeloid leukemia: N = 71; acute lymphoblastic leukemia: N = 37), at a median age of 37 (16-57) years, who had relapsed 7.9 (1.3-132) months post-HSCT, were treated with three cytarabine-based intensive regimens as reduced-intensity conditioning (RIC), followed by infusion of mobilized HSC from the original donors. There were four treatment-related mortalities (TRMs). Of 104 evaluable cases, 72 patients (67%) achieved complete remission (CR)/CR with incomplete hematologic recovery (CRi). The median overall survival (OS) of the entire cohort was 11.6 months. The OS of patients achieving CR/CRi after the first RIC/HSCT was 18.8 months, as compared with 3.9 months for those not (P < 0.01). For 32 patients with nonremission, 11 received a repeat RIC-HSCT, leading to CR/CRi in three cases. Therefore, 75/108 (69%) of patients achieved CR/CRi after one or two courses of RIC-HSCT. Among CR/CRi patients, 48 cases relapsed again after 6.1 (1.0-64.4) months. Thirty cases received a repeat RIC-HSCT, leading to CR/CRi in 22 patients. Multivariate analyses showed a significant impact of remission duration after initial HSCT (P = 0.026) and the presence of acute graft-versus-host disease after RIC-HSCT (P = 0.011) on CR/CRi. RIC-HSCT as primary treatment for acute leukemic relapses post-HSCT induced a high CR rate with low TRM. Optimal postremission treatment remains to be defined.
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Cytotoxic activity and quantitative structure activity relationships of arylpropyl sulfonamides.
Korean J. Physiol. Pharmacol.
PUBLISHED: 02-22-2013
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B13 is a ceramide analogue and apoptosis inducer with potent cytotoxic activity. A series of arylpropyl sulfonamide analogues of B13 were evaluated for their cytotoxicity using MTT assays in prostate cancer PC-3 and leukemia HL-60 cell lines. Some compounds (4, 9, 13, 14, 15, and 20) showed stronger activities than B13 in both tumor cell lines, and compound (15) gave the most potent activity with IC50 values of 29.2 and 20.7 µM, for PC-3and HL-60 cells, respectively. Three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was performed to build highly reliable and predictive CoMSIA models with cross-validated q(2) values of 0.816 and 0.702, respectively. Our results suggest that long alkyl chains and a 1R, 2R configuration of the propyl group are important for the cytotoxic activities of arylpropyl sulfonamides. Moreover, the introduction of small hydrophobic groups in the phenyl ring and sulfonamide group could increase biological activity.
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Low strength ultrasonication positively affects the methanogenic granules toward higher AD performance. Part I: physico-chemical characteristics.
Bioresour. Technol.
PUBLISHED: 02-22-2013
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To elucidate the correlation between enhanced biogas production and changed physico-chemical properties of methanogenic granules after low strength ultrasonication, in this study, the effects of low strength ultrasonication on the settling velocity, permeability, porosity, and fluid collection efficiency of the methanogenic granules were investigated. In addition, their morphological changes were visualized using a scanning electron microscopic technique. The experimental results indicate that low strength ultrasonication increased both the permeability (37%) and specific surface area (230%) of the granules through the generation of greater craters and cracks on the granular surface compared to the control granules. The penetration of nutrients and substrate into the granules was thereby enhanced, and more favorable conditions for achieving higher anaerobic performance were provided to the ultrasonicated granules. The microbial community shift caused by the changed physico-chemical properties of the methanogenic granules will be further analyzed in part II of this study.
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Epigenetic regulation of cholinergic receptor M1 (CHRM1) by histone H3K9me3 impairs Ca(2+) signaling in Huntingtons disease.
Acta Neuropathol.
PUBLISHED: 02-22-2013
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Huntingtons disease (HD) is an autosomal dominant neurodegenerative disease caused by an expanded trinucleotide CAG repeat in the gene coding for huntingtin. Deregulation of chromatin remodeling is linked to the pathogenesis of HD but the mechanism remains elusive. To identify what genes are deregulated by trimethylated histone H3K9 (H3K9me3)-dependent heterochromatin, we performed H3K9me3-ChIP genome-wide sequencing combined with RNA sequencing followed by platform integration analysis in stable striatal HD cell lines (STHdhQ7/7 and STHdhQ111/111) cells. We found that genes involving neuronal synaptic transmission including cholinergic receptor M1 (CHRM1), cell motility, and neuronal differentiation pathways are downregulated while their promoter regions are highly occupied with H3K9me3 in HD. Moreover, we found that repression of CHRM1 gene expression by H3K9me3 impairs Ca(2+)-dependent neuronal signal transduction in stable cell lines expressing mutant HD protein. Thus, our data indicate that the epigenetic modifications, such as aberrant H3K9me3-dependent heterochromatin plasticity, directly contribute to the pathogenesis of HD.
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Diagnostic value and prognostic significance of pleural C-reactive protein in lung cancer patients with malignant pleural effusions.
Yonsei Med. J.
PUBLISHED: 02-01-2013
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C-reactive protein (CRP) has been implicated in various inflammatory and advanced malignant states. Increased serum CRP (s-CRP) levels have been shown to be associated with independent prognostic factors for survival in patients with advanced lung cancer. However, only few studies have focused on the role of CRP in pleural effusions. This study aimed to evaluate the diagnostic and prognostic value of pleural CRP (p-CRP) in lung cancer patients with malignant pleural effusion (MPE).
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Association of variants in PPAR?², IGF2BP2, and KCNQ1 with a susceptibility to gestational diabetes mellitus in a Korean population.
Yonsei Med. J.
PUBLISHED: 02-01-2013
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Patients with gestational diabetes mellitus (GDM) have been reported to exhibit the same genetic susceptibility as that observed in those with type 2 diabetes mellitus (T2DM). Recent polymorphism studies have shown that several genes are related to T2DM and GDM. The aim of this study was to examine whether certain candidate genes, previously shown to be associated with T2DM, also offer a specific genetic predisposition to GDM.
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Atopic diathesis in patients with Kawasaki disease.
J. Pediatr.
PUBLISHED: 01-28-2013
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To determine the association between Kawasaki disease (KD) and atopic diathesis (atopic dermatitis [AD], allergic rhinitis, and asthma) in children younger than 5 years of age.
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Early response to high-dose methotrexate, vincristine, and procarbazine chemotherapy-adapted strategy for primary CNS lymphoma: no consolidation therapy for patients achieving early complete response.
Ann. Hematol.
PUBLISHED: 01-18-2013
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Optimal treatment strategies for primary central nervous system lymphoma (PCNSL) have not been established. In this study, we investigated the treatment outcomes and prognostic factors of high-dose methotrexate, vincristine, and procarbazine (MVP) chemotherapy followed by an interim response-adapted intensification strategy in immunocompetent patients with PCNSL. We evaluated the evidence of infection with Epstein-Barr virus (EBV) in both brain tumor tissue and whole blood. Forty patients were retrospectively reviewed. Ten (25 %) patients who achieved complete response (CR) in the interim analysis did not receive any additional consolidation treatment after completion of planned high-dose MVP chemotherapy. Additional radiotherapy (n?=?9) or autologous stem cell transplantation (ASCT) (n?=?7) was performed in patients who did not achieve CR in the interim analysis. The median age was 55 years. The overall CR rate was 62.5 % (n?=?25), and the objective response rate was 75.0 %. Two-year overall survival (OS) was 59.8 %, and 2-year progression-free survival was 47.1 %. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 47.5 and 32.5 % of patients, respectively. Treatment-related mortality was 15.0 % (n?=?6), and four patients developed delayed neurotoxicity. There was no evidence of EBV-encoded RNA expression in brain tumor tissue. Ten (29.4 %) of 34 patients showed detectable EBV-DNA in whole blood. Poor performance status and EBV-DNA positivity in whole blood were significantly associated with inferior OS (p?=?0.032, p?=?0.023, respectively). We suggest that high-dose MVP chemotherapy followed by an early response-adapted intensification strategy may be effective and minimize the number of patients who receive radiotherapy or ASCT in the early course of treatment.
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GMP-compliant, large-scale expanded allogeneic natural killer cells have potent cytolytic activity against cancer cells in vitro and in vivo.
PLoS ONE
PUBLISHED: 01-11-2013
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Ex vivo-expanded, allogeneic natural killer (NK) cells can be used for the treatment of various types of cancer. In allogeneic NK cell therapy, NK cells from healthy donors must be expanded in order to obtain a sufficient number of highly purified, activated NK cells. In the present study, we established a simplified and efficient method for the large-scale expansion and activation of NK cells from healthy donors under good manufacturing practice (GMP) conditions. After a single step of magnetic depletion of CD3(+) T cells, the depleted peripheral blood mononuclear cells (PBMCs) were stimulated and expanded with irradiated autologous PBMCs in the presence of OKT3 and IL-2 for 14 days, resulting in a highly pure population of CD3(-)CD16(+)CD56(+) NK cells which is desired for allogeneic purpose. Compared with freshly isolated NK cells, these expanded NK cells showed robust cytokine production and potent cytolytic activity against various cancer cell lines. Of note, expanded NK cells selectively killed cancer cells without demonstrating cytotoxicity against allogeneic non-tumor cells in coculture assays. The anti-tumor activity of expanded human NK cells was examined in SCID mice injected with human lymphoma cells. In this model, expanded NK cells efficiently controlled lymphoma progression. In conclusion, allogeneic NK cells were efficiently expanded in a GMP-compliant facility and demonstrated potent anti-tumor activity both in vitro and in vivo.
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Effects of water chemistry on aggregation and soil adsorption of silver nanoparticles.
Environ Health Toxicol
PUBLISHED: 01-01-2013
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In this study, we investigated the influence of ionic strength and natural organic matter (NOM) on aggregation and soil adsorption of citrate-coated silver nanoparticles (AgNPs).
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Effects of zero-length and non-zero-length cross-linking reagents on the optical spectral properties and structures of collagen hydrogels.
ACS Appl Mater Interfaces
PUBLISHED: 12-21-2011
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We compared the effects of zero-length cross-linkers 1-ethyl-3 (3dimethylaminopropyl) carbodiimide (EDC) and non-zero-length cross-linkers glycolaldehyde and glyceraldehyde on the optical and structural properties of three-dimensional (3D) collagen hydrogels. We evaluated these effects by multiphoton microscopy (MPM) that combined two-photon fluorescence (TPF) and second harmonic generation (SHG) contrasts and transmission electron microscopy (TEM). The collagen hydrogels were incubated separately with the above-mentioned reagents present at the concentration of 0.1 M. The incubation with glycolaldehyde and glyceraldehyde induced strong autofluorescence within the gels. We followed the formation of fluorescence with TPF signals in situ and in real time as well as characterized the micro- and nanostructures within cross-linked hydrogels by examining SHG and TEM images respectively. As detected in the SHG images, glycolaldehyde- and glyceraldehyde-modified 5-10 ?m "fiberlike" collagen structures to longer, 20 ?m and more, aggregated strands while EDC had minimal effect on the microstructure. TEM revealed that glycolaldehyde and glyceraldehyde either completely eliminated collagens characteristic native fibrillar striations or generated uncharacteristic fibrils with extensions. EDC preserved the native striation patterns, decreased the fibril diameters and effectively homogenized the fibrils within hydrogels assembled at 1.8-4.68 g/L collagen concentrations and 37 °C. Our findings provide a clear understanding on how different cross-linking reagents have very different effects on the collagen hydrogels. This understanding is critical for advancing tissue engineering and wound healing applications.
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Poly(L-lactic acid) nanocylinders as nanofibrous structures for macroporous gelatin scaffolds.
J Nanosci Nanotechnol
PUBLISHED: 11-30-2011
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Electrospun Nanofiber sheets have been shown to mimic the structure of extracellular matrix (ECM). Although these nanofibers have shown great potential for use as tissue engineering scaffolds, it is difficult for the electrospun nanofiber based sheets to be shaped into the desired three-dimensional structure. In this study, poly(L-lactic acid) (PLLA), a biodegradable and biocompatible polyester, was electrospun to produce nanofibers that were treated with an amino group containing base in order to fabricate polymeric nanocylinders. The aspect ratio of the PLLA nanocylinders was tunable by varying the aminolysis time and density of the amino group containing base. The effects of changes in nanofibrous morphology of the PLLA nanocylinders/macro-porous gelatin scaffolds on cell adhesion and proliferation were evaluated. The results revealed different cell morphology, adhesion, and proliferation in the nanocylinders composite gelatin scaffold versus gelatin scaffold alone. Confocal laser scanning microscopy observation showed more spreading and a more flattened cell morphology after NIH3T3 cells were cultured on PLLA nanocylinders/gelatin scaffolds for 10 hours and 4 days. These results indicate that the gelatin/PLLA nanocylinder composite is a promising way to fabricate 3D nanofibrous scaffolds that accelerates cell adhesion and proliferation for tissue engineering.
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Development of nanofiber coated indomethacin-eluting stent for tracheal regeneration.
J Nanosci Nanotechnol
PUBLISHED: 11-30-2011
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In the case of tracheal rupture or stenosis, most effective way is to insert a commercially available metal stent. However, the implantation often causes a fever or a pain on the contact surface between trachea and the stent. And also the metal stent should be removed after a certain time implantation. Thus, we developed a functional tracheal drug eluting stent consisting of indomethacin, a nonsteroidal anti-inflammatory drug (NSAID), loaded nanofibers on a bare metal stent. To control the drug release kinetics and enhancement of mucosal regeneration, gelatin and PLCL were coated layer by layer on a metal stent by an electrospinning method. Indomethacin was loaded in the gelatin layer by soaking and drying method (0.1, 0.5, and 1 wt% in ethanol for 10 min). The morphology of functional drug eluting tracheal stent was characterized by scanning electron microscope (SEM). And mechanical properties of the constructs such as air leak pressure, ultimate tensile stress, and modulus were calculated and evaluated. Drug release was performed by a high performance liquid chromatography (HPLC). Stably coated gelatin and poly(L-lactide- co-epsilon-caprolactone) (PLCL) nanofibers were observed by SEM. Bi-layered nanofibers-coated stent showed enough mechanical properties as a tracheal stent, which confirmed by a custom-designed air leak mechanical test. For indomethacin loading on a stent, stent was immersed in a series of drug solutions (different concentrations) for 10 min. At the result of HPLC, total amounts of indomethacin on a stent were approximately 77, 323, and 670 ug/stent, respectively. Time dependent drug release kinetics of the tracheal stent showed a sustained release profile regardless of indomethacin content. Thus, functionally designed nanofiber coated tracheal stent with anti-inflammatory drug may be useful for tracheal regeneration.
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Oral administration of insulin-like growth factor-I from colostral whey reduces blood glucose in streptozotocin-induced diabetic mice.
Br. J. Nutr.
PUBLISHED: 10-10-2011
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The aim of the present study was to investigate the effects of oral administration of the insulin-like growth factor-I-rich fraction (IGF-I-RF) from bovine colostral whey on the regulation of blood glucose levels in streptozotocin (STZ)-induced diabetic mice. We obtained a peptide fraction containing IGF-I (10 ng/mg protein) from Holstein colostrum within 24 h after parturition by using ultrafiltration. The blood glucose levels of STZ-induced diabetic mice fed with IGF-I-RF (50 ?g/kg per d) were significantly reduced by 11 and 33 % at weeks 2 and 4, respectively (P < 0·05). The body weights of STZ-induced diabetic mice increased following the oral administration of the IGF-I-RF. The kidney weights of STZ-induced diabetic mice decreased significantly (P < 0·05) following the administration of the IGF-I-RF, and the liver weights of STZ-induced diabetic mice decreased significantly (P < 0·05) following the administration of 50 ?g/kg per d of the IGF-I-RF. The present results indicate that the IGF-I-RF obtained from Holstein colostrum could be a useful component for an alternative therapeutic modality for the treatment of diabetes in insulin-resistant patients.
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Risk factors for progression from cytomegalovirus viremia to cytomegalovirus disease after allogeneic hematopoietic stem cell transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 08-23-2011
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Cytomegalovirus (CMV) disease is a major cause of infectious complications in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although patients undergoing allo-HSCT receive prophylactic and preemptive treatment for CMV, a subset of patients experience clinically significant CMV disease. This study investigated the risk factors for progression from CMV viremia to CMV disease during or after preemptive therapy in patients undergoing allo-HSCT. Between January 2006 and August 2010, 43 patients received preemptive therapy for CMV viremia after allo-HSCT. These patients experienced 74 episodes of CMV viremia. Nine of the patients (21%) and 12 of the episodes (16%) progressed to CMV disease. Univariate analysis identified several risk factors for progression to CMV disease, including high initial viral load (P = .020), leukopenia (P = .012), and neutropenia (P = .033) at the time of detection of CMV viremia. On multivariate analysis, leukopenia remained an independent predictor (hazard ratio, 4.347; P = .045). The rate of failure to clear CMV viremia after 1 cycle of preemptive therapy was higher in the leukopenia group than in the non-leukopenia group (60.0% versus 16.9%; P = .002). This indicates that leukopenia initially documented with CMV viremia is related to lower viral response to preemptive therapy and is a notable risk factor for progression from CMV viremia to CMV disease.
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Simvastatin inhibits osteoclast differentiation by scavenging reactive oxygen species.
Exp. Mol. Med.
PUBLISHED: 08-12-2011
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Osteoclasts, together with osteoblasts, control the amount of bone tissue and regulate bone remodeling. Osteoclast differentiation is an important factor related to the pathogenesis of bone-loss related diseases. Reactive oxygen species (ROS) acts as a signal mediator in osteoclast differentiation. Simvastatin, which inhibits 3-hydroxy-3-methylglutaryl coenzyme A, is a hypolipidemic drug which is known to affect bone metabolism and suppresses osteoclastogenesis induced by receptor activator of nuclear factor-?B ligand (RANKL). In this study, we analyzed whether simvastatin can inhibit RANKL-induced osteoclastogenesis through suppression of the subsequently formed ROS and investigated whether simvastatin can inhibit H2O2-induced signaling pathways in osteoclast differentiation. We found that simvastatin decreased expression of tartrate-resistant acid phosphatase (TRAP), a genetic marker of osteoclast differentiation, and inhibited intracellular ROS generation in RAW 264.7 cell lines. ROS generation activated NF-?B, protein kinases B (AKT), mitogen-activated protein kinases signaling pathways such as c-JUN N-terminal kinases, p38 MAP kinases as well as extracellular signal- regulated kinase. Simvastatin was found to suppress these H2O2-induced signaling pathways in osteoclastogenesis. Together, these results indicate that simvastatin acts as an osteoclastogenesis inhibitor through suppression of ROS-mediated signaling pathways. This indicates that simvastatin has potential usefulness for osteoporosis and pathological bone resorption.
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Nucleolin antisense oligodeoxynucleotides induce apoptosis and may be used as a potential drug for nasopharyngeal carcinoma therapy.
Oncol. Rep.
PUBLISHED: 07-07-2011
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Nucleolin (C23, NCL) mRNA was up-regulated in nasopharyngeal carcinoma (NPC) cells compared to that of normal nasomucosal (NNM) cells using a cDNA microarray approach. The level of nucleolin protein was also up-regulated in 13 NPC cell lines, 30 biopsy specimens and nine other cancer cell lines compared to five NNM cells or normal stromal cells, which were analyzed using immunoblotting or immunohistochemistry. We transfected nucleolin antisense oligodeoxynucleotides (phosphorothioate-modified oligodeoxynucleotides; S-ODNs) into NPC-TW01 cells to knockdown nucleolin expression to evaluate the function of nucleolin in cancer cells. Nucleolin knockdown induced NPC cells but not NNM cells to undergo apoptosis. Furthermore, treatment of NPC-TW01 xenograft tumors with nucleolin antisense oligodeoxynucleotides suppressed the growth of xenograft tumors without obvious side effects. Therefore, we suggest that nucleolin may be a potential cancer therapeutic target and that nucleolin antisense oligodeoxynucleotides may be used as a potential drug for therapy in NPC.
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Effect of genipin crosslinking on the optical spectral properties and structures of collagen hydrogels.
ACS Appl Mater Interfaces
PUBLISHED: 07-07-2011
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Genipin, a natural cross-linking reagent extracted from the fruits of Gardenia jasminoides, can be effectively employed in tissue engineering applications due to its low cytotoxicity and high biocompatibility. The cross-linking of collagen hydrogels with genipin was followed with one-photon fluorescence spectroscopy, second harmonic generation, fluorescence and transmission electron microscopy. The incubation with genipin induced strong auto-fluorescence within the collagen hydrogels. The fluorescence emission maximum of the fluorescent adducts formed by genipin exhibit a strong dependence on the excitation wavelength. The emission maximum is at 630 nm when we excite the cross-linked samples with 590 nm light and shifts to 462 nm when we use 400 nm light instead. The fluorescence imaging studies show that genipin induces formation of long aggregated fluorescent strands throughout the depth of samples. The second harmonic generation (SHG) imaging studies suggest that genipin partially disaggregates 10 ?m "fiberlike" collagen structures because of the formation of these fluorescent cross-links. Transmission electron microscopy (TEM) studies reveal that genipin largely eliminates collagens characteristic native fibrillar striations. Our study is the first one to nondestructively follow and identify the structure within collagen hydrogels in situ and to sample structures formed on both micro- and nanoscales. Our findings suggest that genipin cross-linking of collagen follows a complex mechanism and this compound modifies the structure within the collagen hydrogels in both micro- and nanoscale.
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Clinical significance of B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
Korean J Hematol
PUBLISHED: 07-03-2011
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BAFF (B cell-activating factor) and APRIL (a proliferation-inducing ligand) are members of the tumor necrosis factor family and promote B cell survival and proliferation. We evaluated the correlation between serum concentration of BAFF or APRIL and severity of acute graft-versus-host disease (GVHD).
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Effect of age and frequency of injections on immune response to hepatitis B vaccination in drug users.
Vaccine
PUBLISHED: 06-13-2011
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Despite the high immunogenicity of the hepatitis B vaccine, evidence suggests that immunological response in drug users is impaired compared to the general population. A sample of not-in-treatment adult drug users from two communities in Houston, TX, USA, susceptible to hepatitis B virus (HBV), was sampled via outreach workers and referral methodology. Participants were randomized to either the standard multi-dose hepatitis B vaccine schedule (0, 1, and 6 months) or to an accelerated (0, 1, and 2 months) schedule. The participants were followed for 1 year. Antibody levels were measured at 2, 6 and 12 months after enrollment in order to determine the immune responses. At 12 months, cumulative adequate protective response was achieved in 65% of the HBV susceptible subgroup using both the standard and accelerated schedules. The standard group had a higher mean antibody titer (184.6 mIU/mL vs 57.6 mIU/mL). But at 6 months, seroconversion at the adequate protective response was reached by a higher proportion of participants and the mean antibody titer was also higher in the accelerated schedule group (104.8 mIU/mL vs. 64.3 mIU/mL). Multivariate analyses indicated a 63% increased risk of non-response for participants 40 years or older (p=0.046). Injecting drugs more than once a day was also highly associated with the risk of non-response (p=0.016). Conclusions from this research will guide the development of future vaccination programs that anticipate other prevalent chronic conditions, susceptibilities, and risk-taking behaviors of hard-to-reach populations.
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IL-10 promoter genetic polymorphisms and risk of Kawasaki disease in Taiwan.
Dis. Markers
PUBLISHED: 04-22-2011
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Kawasaki disease (KD) is the most common cause of pediatric acquired heart disease. KD patients have spontaneously high plasma/serum levels of IL-10 during the acute phase. Therefore, two independent studies were carried out to investigate the association between genetic variants in IL-10 promoter (-1082, -819, and -592) and risk of KD. A total of 134 trios were included for the family-based association study. A significantly preferential transmission of the C allele at loci -819 T > C and -592 A > C for KD cases was observed (P permutation = 0.029 and P permutation = 0.034, respectively). There was a significant increase in the transmission of haplotype CC (p = 0.016) at the above two loci (OR, 1.632; 95% CI, 1.090-2.443; P permutation = 0.019). We also carried out a follow-up case-control study that included 146 KD cases and 315 unrelated healthy children. The haplotype CC (-819, -592) showed an increased risk of KD (but statistically non-significant; OR, 1.332; 95% CI, 0.987-1.797; p = 0.061). In diplotype analysis, a trend was found between number of CC haplotype and risk of KD (but non-significant, p =0.061). In conclusion, CC genotype and CC/CC diplotype at IL-10-819T > C and -592A > C were significantly associated with risk of KD in case-parent trio study, which were replicated partially in our follow-up case-control study.
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Atypical Burkitts lymphoma transforming from follicular lymphoma.
Diagn Pathol
PUBLISHED: 03-28-2011
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Amongst follicular lymphoma that transforms into a high-grade lymphoma, majority are diffuse large B cell lymphoma. Here we reported a rare atypical Burkitts lymphoma transformation from an asymptomatic follicular lymphoma. Lymph node biopsy showed a composite lymphoma with infiltration of the inter-follicular areas by high grade small non-cleaved lymphoma cells amongst neoplastic follicles. Moreover, FISH and molecular genetic study confirmed concomitant MYC translocations and t(14;18) in the high-grade component, thereby suggesting the transformation of atypical Burkitts lymphoma from an undiagnosed antecedent follicular lymphoma. The disease followed an aggressive clinical course, terminating in refractory disease 13 months after diagnosis. This is followed by a comprehensive review of the literature on lymphoma transformations from underlying follicular lymphoma after acquisition of MYC translocation, using Burkitts lymphoma, follicular lymphoma, transformation and MYC translocations as keywords.
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Link between DYRK1A overexpression and several-fold enhancement of neurofibrillary degeneration with 3-repeat tau protein in Down syndrome.
J. Neuropathol. Exp. Neurol.
PUBLISHED: 03-08-2011
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Triplication of chromosome 21 in Down syndrome (DS) results in overexpression of the minibrain kinase/dual-specificity tyrosine phosphorylated and regulated kinase 1A gene (DYRK1A). DYRK1A phosphorylates cytoplasmic tau protein and appears in intraneuronal neurofibrillary tangles (NFTs). We have previously shown significantly more DYRK1A-positive NFTs in DS brains than in sporadic Alzheimer disease (AD) brains. This study demonstrates a gene dosage-proportional increase in the level of DYRK1A in DS in the cytoplasm and the cell nucleus, and enhanced cytoplasmic and nuclear immunoreactivity of DYRK1A in DS. The results suggest that overexpressed DYRK1A may alter both phosphorylation of tau and alternative splicing factor (ASF). Two-dimensional electrophoresis revealed modification of ASF phosphorylation in DS/AD and AD in comparison to controls. Altered phosphorylation of ASF by overexpressed nuclear DYRK1A may contribute to the alternative splicing of the tau gene and an increase by 2.68 × of the 3R/4R ratio in DS/AD, and a several-fold increase in the number of 3R tau-positive NFTs in DS/AD subjects compared with that in sporadic AD subjects. These data support the hypothesis that phosphorylation of ASF by overexpressed DYRK1A may contribute to alternative splicing of exon 10, increased expression of 3R tau, and early onset of neurofibrillary degeneration in DS.
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HIV/AIDS testing at ports of entry in China.
J Public Health Policy
PUBLISHED: 03-03-2011
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In 2007 the Chinese government issued regulations requiring HIV/AIDS testing for Chinese citizens returning at ports of entry if they had resided outside China for 1 year or longer. Three years after publication and partial implementation of the regulations, the Chinese government decided to eliminate compulsory HIV/AIDS testing of returning Chinese. We examine the history of Chinas HIV/AIDS testing regulations on entry-exit populations, showing how China has gradually altered its policy. As of December 2010, the policy of compulsory HIV/AIDS testing of returning Chinese has been abandoned; however, the regulations still compel HIV/AIDS testing for other groups inside China. Our review sheds new light on the dynamics of regulatory changes in the last 3 years. The Chinese experience that we observed may provide useful insights for policymakers in other parts of the world.
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Mycobacterial infection after intravesical bacillus Calmette-Guërin treatment for bladder cancer: a case report.
Korean J Lab Med
PUBLISHED: 02-21-2011
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Bacillus Calmette-Guërin (BCG) has been traditionally used as a vaccine against tuberculosis. Further, intravesical administration of BCG has been shown to be effective in treating bladder cancer. Although BCG contains a live attenuated strain of Mycobacterium bovis, complications such as M. bovis BCG infection caused by BCG administration are extremely rare. Here, we report a case of BCG infection occurring after intravesical BCG therapy. A 67-yr-old man presented with azotemia and weight loss. He had been diagnosed with bladder cancer 4 yr back, and had undergone transurethral resection of the bladder tumor and intravesical BCG (Tice strain) therapy at that time. An acid-fast bacterial strain was isolated from his urine sample. We did not detect Mycobacterium tuberculosis protein 64 (MPT-64) antigen in the isolates obtained from his sample, and multiplex PCR and PCR-reverse blot hybridization assay indicated that the isolate was a member of the M. tuberculosis complex, but was not M. tuberculosis. Finally, sequence analysis of 16S ribosomal RNA and DNA gyrase, subunit B (gyrB) suggested that the organism was M. bovis or M. bovis BCG. Although we could not confirm that M. bovis BCG was the causative agent, the results of the 3 molecular methods and the MPT-64 antigen assay suggest this finding. This is an important finding, especially because M. bovis BCG cannot be identified using common commercial molecular genetics tools.
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Multiphoton imaging of actin filament formation and mitochondrial energetics of human ACBT gliomas.
Photochem. Photobiol.
PUBLISHED: 01-25-2011
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We studied the three-dimensional (3D) distribution of actin filaments and mitochondria in relation to ACBT glioblastoma cells migration. We embedded the cells in the spheroid form within collagen hydrogels and imaged them by in situ multiphoton microscopy (MPM). The static 3D overlay of the distribution of actin filaments and mitochondria provided a greater understanding of cell-to-cell and cell-to-substrate interactions and morphology. While imaging mitochondria to obtain ratiometric redox index based on cellular fluorescence from reduced nicotinamide adenine dinucleotide and oxidized flavin adenine dinucleotide we observed differential sensitivity of the migrating ACBT glioblastoma cells to femtosecond laser irradiation employed in MPM. We imaged actin-green fluorescent protein fluorescence in live ACBT glioma cells and for the first time observed dynamic modulation of the pools of actin during migration in 3D. The MPM imaging, which probes cells directly within the 3D cancer models, could potentially aid in working out a link between the functional performance of mitochondria, actin distribution and cancer invasiveness.
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Improvement of biological and pharmacokinetic features of human interleukin-11 by site-directed mutagenesis.
Biochem. Biophys. Res. Commun.
PUBLISHED: 01-11-2011
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Recombinant human interleukin-11 (rhIL-11) has been shown to increase platelet counts in animals and humans and is the only drug approved for its use in chemotherapy-induced thrombocytopenia (CIT). However, due to its serious side effects, its clinical use has been limited. The current work presents significantly improved efficacy of rhIL-11 via knowledge based re-designing process. The interleukin-11 mutein (mIL-11) was found to endure chemical and proteolytic stresses, while retaining the biological activity of rhIL-11. The improved efficacy of mIL-11 was evident after subcutaneous administration of mIL-11 and rhIL-11 in the rodent and primate models. More than three-fold increase in maximum plasma concentration (Cmax) and area-under-the curve (AUC) was observed. Furthermore, three-fold higher increase in the platelet counts was obtained after seven consecutive daily subcutaneous mIL-11 injections than that with rhIL-11. The mIL-11 demonstrated not only improved stability but also enhanced efficacy over the currently used rhIL-11 regimen, thereby suggesting less toxicity.
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Transforming growth factor-beta 1 in adipose derived stem cells conditioned medium is a dominant paracrine mediator determines hyaluronic acid and collagen expression profile.
Cytotechnology
PUBLISHED: 01-04-2011
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Conditioned medium from adipose derived stem cells (ADSC-CM) stimulates both collagen synthesis and migration of fibroblasts, and accelerates wound healing in vivo. Recently, the production and secretion of growth factors has been identified as an essential function of adipose-derived stem cells (ADSCs). However, the main soluble factor of ADSC-CM which mediates paracrine effects and its underlying mechanism has not been elucidated yet. In this study, we considered transforming growth factor-beta1 (TGF-?1) as a strong candidate for paracrine effect of ADSC-CM and investigated collagen synthesis and hyaluronic acid synthase (HAS) expression. After ADSC-CM addition, collagen type I, type III, HAS and hyaluronic acid (HA) expressions on human dermal fibroblasts (HDFs) were evaluated. Furthermore, to clarify effects of TGF-?1 as a paracrine mediator, TGF-?1 antibody and external supplementary TGF-?1 were treated to HDFs. Collagens type I, type III, HAS-1 and HAS-2 mRNA expressions of HDFs were greatly increased by ADSC-CM treatment, however there was no change in TGF-?1 antibody treated HDFs compared with non-treated control. These results strongly demonstrate that TGF-?1 plays an important role as a paracrine mediator of ECM synthesis. The fact that TGF-?1 contained in ADSC-CM not only accelerates collagen deposition but also increase hyaluronic acid synthesis of HDFs through HAS-1 and HAS-2 expression was also elucidated in this study. Therefore, ADSC-CM shows promise for the treatment of cutaneous wounds and accelerates granulation formation during healing process.
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The role of DYRK1A in neurodegenerative diseases.
FEBS J.
PUBLISHED: 12-13-2010
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Recent studies indicate that the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) gene, which is located on chromosome 21q22.2 and is overexpressed in Down syndrome (DS), may play a significant role in developmental brain defects and in early onset neurodegeneration, neuronal loss and dementia in DS. The identification of hundreds of genes deregulated by DYRK1A overexpression and numerous cytosolic, cytoskeletal and nuclear proteins, including transcription factors, phosphorylated by DYRK1A, indicates that DYRK1A overexpression is central for the deregulation of multiple pathways in the developing and aging DS brain, with structural and functional alterations including mental retardation and dementia. DYRK1A overexpression in DS brains may contribute to early onset neurofibrillary degeneration directly through hyperphosphorylation of tau and indirectly through phosphorylation of alternative splicing factor, leading to an imbalance between 3R-tau and 4R-tau. The several-fold increases in the number of DYRK1A-positive and 3R-tau-positive neurofibrillary tangles in DS support this hypothesis. Moreover, the enhanced phosphorylation of amyloid precursor protein by overexpressed DYRK1A facilitates amyloidogenic amyloid precursor protein cleavage elevating A?40 and 42 levels, and leading to brain ?-amyloidosis. Therefore, inhibiting DYRK1A activity in DS may serve to counteract the phenotypic effects of its overexpression and is a potential method of treatment of developmental defects and the prevention of age-associated neurodegeneration, including Alzheimer-type pathology.
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Multiphoton optical image guided spectroscopy method for characterization of collagen-based materials modified by glycation.
Anal. Chem.
PUBLISHED: 12-08-2010
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The cross-linking with reducing sugars, known as glycation, is used to increase stiffness and strength of tissues and artificial collagen-based scaffolds. Nondestructive characterization methods that report on the structures within these materials could clarify the effects of glycation. For doing this nondestructive evaluation, we employed an in situ one-photon fluorescence as well as multiphoton microscopy method that combined two-photon fluorescence and second harmonic generation signals. We incubated collagen hydrogels with glyceraldehyde, ribose, and glucose and observed an increase in the in situ fluorescence and structural alterations within the materials during the course of glycation. The two-photon fluorescence emission maximum was observed at about 460 nm. The fluorescence emission in the one-photon excitation experiment (?(ex) = 360 nm) was broad with peaks centered at 445 and 460 nm. The 460 nm emission component subsequently became dominant during the course of glycation with glyceraldehyde. For the ribose, in addition to the 460 nm peak, the 445 nm component persisted. The glucose glycated hydrogels exhibited broad fluorescence that did not increase significantly even after 6 weeks. As determined from measuring the fluorescence intensity at the 460 nm maximum, glycation with glyceraldehyde was faster compared to ribose and generated stronger fluorescence signals. Upon excitation of glycated samples with 330 nm light, different emission peaks were observed.
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Influence of trust on HIV diagnosis and care practices: a literature review.
J Int Assoc Physicians AIDS Care (Chic)
PUBLISHED: 11-12-2010
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Delays in accessing HIV health care and failure to adhere to providers advice are common. Patient trust is critical to an individuals willingness to seek care and follow the physicians advice. Conversely, patient distrust can diminish the patients health status. The trust literature is reviewed in an attempt to determine its effect on HIV care. In the HIV literature reviewed, greater trust in health care providers was associated with improved accessing of and remaining in care. Interventions to enhance patient trust have been tested, with no changes in the levels of trust being found. Few studies were rigorous enough to assess causality or temporal relation. It is not clear whether there is a causal association between patient trust and HIV health care outcomes. As these relationships are better understood, interventions can be designed to increase health-promoting behaviors.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.