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recurrent overexpression of c-iap2 in ebv-associated nasopharyngeal carcinomas: critical role in resistance to toll-like receptor 3-mediated apoptosis.the oncogenic process leading to nasopharyngeal carcinoma (npc) requires the combination of genetic and epigenetic alterations, latent infection by the epstein-barr virus and local inflammation. a transcriptome analysis of npc xenografts identified the gene encoding the cellular inhibitor of apoptosis protein 2 (c-iap2) among the top five most intensely expressed. consistently, the very high levels of the c-iap2 protein were detected in 11 of 13 npc biopsies. rmt 5265, a structural analog of sec ...200818953427
[correlation of epstein-barr virus infection and childhood lymphoma].to investigate the correlation of epstein-barr virus (ebv) infection and childhood lymphoma.200818953837
prognostic subgroup distribution in diffuse large b-cell lymphoma of the upper aerodigestive tract.to stratify upper aerodigestive tract (uat) diffuse large b-cell lymphoma (dlbcl) into prognostic subgroups by immunohistochemical staining (ihc) method, and to evaluate the association rate of uat dlbcl with epstein-barr virus (ebv).200918972319
a possible role for epstein-barr virus infection in copd? 200818978143
virus-specific t cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma.cytotoxic t lymphocytes (ctls) directed to nonviral tumor-associated antigens do not survive long term and have limited antitumor activity in vivo, in part because such tumor cells typically lack the appropriate costimulatory molecules. we therefore engineered epstein-barr virus (ebv)-specific ctls to express a chimeric antigen receptor directed to the diasialoganglioside gd2, a nonviral tumor-associated antigen expressed by human neuroblastoma cells. we reasoned that these genetically engineere ...200818978797
rhesus lymphocryptovirus type 1-associated b-cell nasal lymphoma in siv-infected rhesus macaques.epstein-barr virus (ebv) is a worldwide endemic gamma herpesvirus of the genus lymphocryptovirus (lcv) that infects more than 90% of the world's population. ebv has been associated with a variety of malignancies, but it has a demonstrated role in lymphomas, especially in immunosuppressed individuals. lymphomas of the nasal cavity, paranasal sinuses, and nasopharynx are uncommon and constitute less than 5% of all extranodal lymphomas. sinonasal non-hodgkin's lymphomas have been reported in patien ...200818984796
epstein-barr virus renders the infected natural killer cell line, nkl resistant to doxorubicin-induced apoptosis.we established two epstein-barr virus (ebv)-infected nkl sublines, which acquired stress resistant phenotype against dna damage and starvation compared with ebv-negative nkl. ebv-rendered doxorubicin resistance at least partially through nf-kappab activation and the resultant sustenance of antiapoptotic proteins including bcl-x(l) and flip(l/s).200818985034
tumor-derived variants of epstein-barr virus latent membrane protein 1 induce sustained erk activation and c-fos.latent membrane protein 1 (lmp1) of epstein-barr virus (ebv) is a proven oncogene that is essential for transformation of human b cells by the virus. lmp1 induces constitutive activation of several signal transduction pathways involving nuclear factor kappab, phosphatidylinositol 3-kinase/akt, and the mitogen-activated protein kinases (mapk) p38, c-jun n-terminal kinase (jnk), and extracellular signal-regulated kinase (erk). sequencing of lmp1 isolated from a panel of ebv+ b cell lymphomas ident ...200818986987
analysis of epstein-barr virus glycoprotein b functional domains via linker insertion mutagenesis.epstein-barr virus (ebv) glycoprotein b (gb) is essential for viral fusion events with epithelial and b cells. this glycoprotein has been studied extensively in other herpesvirus family members, but functional domains outside of the cytoplasmic tail have not been characterized in ebv gb. in this study, a total of 28 linker insertion mutations were generated throughout the length of gb. in general, the linker insertions did not disrupt intracellular expression and variably altered cell surface ex ...200918987135
association of epstein-barr virus with nasopharyngeal carcinoma and current status of development of cancer-derived cell lines.it is well known that the epstein-barr virus (ebv) contributes directly to tumourigenesis in nasopharyngeal carcinoma (npc), primarily in the undifferentiated form of npc (who type iii; unpc or uc), which is commonly found in south east asia. unfortunately, research in npc has been severely hampered by the lack of authentic ebv-positive (ebv+) human npc cell lines for study. since 1975, there have been more than 20 reported npc cell lines. however, many of these npc-derived cell lines do not exp ...200818989494
generation of mouse-human hybridomas secreting antibodies against peanut allergen ara h1.two clones of mouse-human hybridomas, secreting human monoclonal antibodies to a peanut allergen ara h1, were generated from human peripheral blood lymphocytes transformed with epstein--barr virus, followed by cell fusion with mouse myeloma cells. epitope analysis with overlapping peptides synthesized on a multi-pin apparatus revealed antibody-binding sequences of ara h1 protein.200519003255
cd8+ t cell immunity to epstein-barr virus and kaposi's sarcoma-associated herpes virus.gammaherpesviruses are agents which have evolved to persist within the lymphoid system and many have oncogenic potential; studying gammaherpesvirus infections therefore has the potential to reveal much about the workings of the immune system and the control over viral oncogenesis. the lymphocryptovirus epstein-barr virus (ebv) and the rhadinovirus kaposi's sarcoma-associated herpesvirus (kshv, also known as human herpesvirus 8) are the two human gammaherpesviruses. analysis of the t cell respons ...200819007888
the curious case of the tumour virus: 50 years of burkitt's lymphoma.burkitt's lymphoma (bl) was first described 50 years ago, and the first human tumour virus epstein-barr virus (ebv) was discovered in bl tumours soon after. since then, the role of ebv in the development of bl has become more and more enigmatic. only recently have we finally begun to understand, at the cellular and molecular levels, the complex and interesting interaction of ebv with b cells that creates a predisposition for the development of bl. here, we discuss the intertwined histories of eb ...200819008891
the impact of intercurrent ebv infection on atp levels in cd4+ t cells of pediatric kidney transplant recipients.immuknow measures atp (ng/ml) in pha-activated cd4+ t cells from patient's whole blood. according to published reports, median immuknow is 258 ng/ml in stable pediatric kidney transplant (pkt) recipients > or =12 yr, and 165 ng/ml in those <12 yr. however, data on the effect of infection or ar on immuknow are scarce. we studied the effect of epstein-barr virus (ebv) viremia on immuknow in pkt with gd. twenty-eight pkt with gd were reviewed. group 1 has 19 pkt > or =12 yr, and group 2 has nine pk ...200919017293
irf7 activation by epstein-barr virus latent membrane protein 1 requires localization at activation sites and traf6, but not traf2 or traf3.epstein-barr virus (ebv) latent infection membrane protein 1 (lmp1), a constitutively aggregated and activated pseudoreceptor, activates ifn regulatory factor 7 (irf7) through rip1. we now report that the lmp1 cytoplasmic carboxyl terminal amino acids 379-386 bound irf7 and activated irf7. irf7 activation required traf6 and rip1, but not traf2 or traf3. lmp1 y(384)yd(386), which are required for tradd and rip1 binding and for nf-kappab activation, were not required for irf7 binding, but were req ...200819017798
burkitt lymphoma in brazil is characterized by geographically distinct clinicopathologic features.burkitt lymphoma (bl) is a highly aggressive non-hodgkin lymphoma with a consistent myc translocation. epstein-barr virus (ebv) has been associated with bl at different frequencies, depending on the clinical variant and geographic regions. this is a large-scale study of bl in brazil, including 234 patients from 5 geographic regions that are widely disparate socioeconomically, including pediatric (61.1%) and adult (37.6%) populations. ebv was present in 52.6% of all bl cases, varying from 29% (12 ...200819019773
association of monoclonal expansion of epstein-barr virus-negative cd158a+ nk cells secreting large amounts of gamma interferon with hemophagocytic lymphohistiocytosis.we report the first case of hemophagocytic lymphohistiocytosis (hlh) induced by the monoclonal expansion of epstein-barr virus (ebv)-negative nk cells. consanguinity of the patient's parents made it necessary to discard familial hlh in the patient and her sister with identical hla markers and demonstrate that no cause other than the expansion of nk cells, which secrete high levels of gamma interferon, was inducing hlh in this patient.200919020108
maternal epstein-barr virus and cytomegalovirus infections and risk of testicular cancer in the offspring: a nested case-control study.during recent decades the incidence of testicular cancer (tc) has increased rapidly around the world. associated exogenous etiological factors might therefore be identifiable. we performed a case-control study nested within finnish, swedish and icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of congenital or neonatal infections with epstein-barr virus (ebv) and cytomegalovirus (cmv) as risk factors of tc in the offspring. for each case-index mother pair, ...200819024602
epstein-barr virus in autoimmune diseases.autoimmune diseases such as systemic lupus erythematosus (sle), rheumatoid arthritis (ra), and primary sjögren's syndrome (pss) are complex disorders with a genetic background and the involvement of environmental factors, including viruses. the epstein-barr virus (ebv) is a plausible candidate for playing a role in the pathophysiology of these diseases. both sle and ra are characterized by high titers of anti-ebv antibodies and impaired t-cell responses to ebv antigens. compared with normal subj ...200819028369
optimal treatment for chronic active epstein-barr virus disease. 200919032417
emerging viruses in transplantation: there is more to infection after transplant than cmv and ebv.transplant physicians and surgeons are familiar with the risks, clinical behavior, and management of cytomegalovirus in transplant recipients. donor-transmitted viral infections are uncommon but in recent years have brought to light the clinical manifestations of rabies, west nile virus, and lymphocytic choriomeningitis virus in the early posttransplant period. later posttransplant, infection with viruses circulating in the community can occur with a number of pathogens, including some vaccine-p ...200819033999
quantitative detection of epstein-barr virus in bronchoalveolar lavage from transplant and nontransplant patients.the lower respiratory tract is a latency site of epstein-barr virus (ebv); however, its pathogenic role is poorly known, particularly in transplant patients. the aim of this study was to evaluate the prevalence and role of ebv in bronchoalveolar lavages (bal) from transplant recipients (tr) in comparison with nontransplant (nt) patients.200819034008
[study of clinical and morphological features, immunophenotype and epstein-bar virus infection in situ of infectious mononucleosis].to study the clinical and morphological features, immunophenotype and in situ detection of epstein-barr virus (ebv) infection in infectious mononucleosis (im) to enhance the knowledge and diagnosis of the disease.200819035113
[two young adult cases of epstein-barr virus associated-hemophagocytic lymphohistiocytosis with monoclonal proliferation of virus-infected cells within a short period after primary infection].hemophagocytic lymphohistiocytosis (hlh) is a rare but severe complication of epstein-barr virus (ebv) infection. interactions between ebv-infected t cells and activated macrophages cause several conditions such as pancytopenia, liver dysfunction and coagulopathy. we describe here two young adults with ebv-associated hlh with monoclonal proliferation of ebv-infected t cells within a short period after infectious mononucleosis as a primary infection. one patient was a 16-year-old man who develope ...200819047785
detection of herpesviruses and periodontal pathogens in subgingival plaque of patients with chronic periodontitis, generalized aggressive periodontitis, or gingivitis.herpesviruses may be related to the etiology of aggressive periodontitis (agp) and chronic periodontitis (cp) by triggering periodontal destruction or by increasing the risk for bacterial infection. this case-control study evaluated the presence of herpes simplex virus type i (hsv-1), epstein-barr virus type i (ebv-1), human cytomegalovirus (hcmv), aggregatibacter actinomycetemcomitans (previously actinobacillus actinomycetemcomitans), porphyromonas gingivalis, prevotella intermedia, and tannere ...200819053922
epstein-barr virus, rapamycin, and host immune responses.to summarize recent advances that contribute to our understanding of the pathobiology of epstein-barr virus (ebv)-associated posttransplant lymphoproliferative disease (ptld), the host immune response to virally infected b cells, and the molecular basis for the effects of mammalian target of rapamycin inhibitors on ebv+ b-cell lymphomas.200819060543
lymphoepithelioma-like carcinoma of the skin: new case of an exceedingly rare primary skin tumor.lymphoepithelioma-like carcinoma of the skin (le-lcs) is a very rare, primary skin neoplasm of uncertain origin. the tumor reveals striking morphological similarity to undifferentiated nasopharyngeal carcinoma (lymphoepithelioma). however, the primary skin tumors have never been associated with epstein-barr virus (ebv), in contrast to those at some extracutaneous sites. since the first description by swanson et al. in 1988, only 46 cases have been documented over the last 20 years. this case rep ...200819061572
chronic active epstein-barr virus--is it real and how do you treat it? 200919067922
the biology of hodgkin's lymphoma.hodgkin's lymphoma was first described in 1832. the aetiology of this lymphoma, however, remained enigmatic for a long time. only within the past 10 years has the b-cell nature of the pathognomonic hodgkin and reed-sternberg (hrs) cells been revealed, along with several recurrent genetic lesions. the pathogenetic role for epstein-barr virus infection has also been substantiated. hrs cells in classical hodgkin's lymphoma have several characteristics that are unusual for lymphoid tumour cells, and ...200919078975
hexachlorophene suppresses beta-catenin expression by up-regulation of siah-1 in ebv-infected b lymphoma cells.many studies have shown that the activation of beta-catenin signaling can promote oncogenesis, and it is therefore of interest to find agents that modulate this pathway. recent work has shown using b lymphoma cells that infection by epstein-barr virus (ebv) and expression of its latent membrane protein (lmp)-1, cause increases in the expression of beta-catenin and cellular transformation. conversely, results from cell-based small molecule screening studies have shown that the antibiotic hexachlo ...200919091460
comprehensive profiling of epstein-barr virus micrornas in nasopharyngeal carcinoma.epstein-barr virus (ebv) establishes a long-term latent infection and is associated with a number of human malignancies that are thought to arise from deregulation of different stages of the viral life cycle. recently, a large number of micrornas (mirnas) have been described for ebv, and it has been suggested that their expression may vary between the different latency states found in normal and malignant tissue. to date, however, no technique has been utilized to comprehensively and quantitativ ...200919091858
a case of age-related ebv-associated b-cell lymphoproliferative disorder metachronously showing two distinct morphologic appearances, one of a polymorphic disease resembling classical hodgkin lymphoma, and the other of a large-cell lymphoma.we report a case of age-related ebv-associated b-cell lymphoproliferative disorder (age-related ebv+ b-cell lpd) metachronously showing two distinct morphologic appearances: one of a polymorphic disease resembling classical hodgkin lymphoma (chl), and the other of a large-cell lymphoma. a 71-year-old man was admitted to the st. marianna university hospital because of fever and generalized lymphadenopathy. right axillary lymph node biopsy revealed mixed cellularity classical hodgkin lymphoma (mch ...200919093168
[clonality analysis and mutational status of igvh gene in hodgkin variant of richter syndrome].to detect the clonal relationship, the rearrangement, and the mutational status of igvh gene; the influence of these molecular characteristics on the clinical outcome in hodgkin variant of richter syndrome; and the possible molecular pathogenesis in this transformation.200819094463
the epstein-barr virus replication and transcription activator, rta/brlf1, induces cellular senescence in epithelial cells.epstein-barr virus (ebv) replication and transcription activator (rta/brlf1) is an immediate-early transcription factor that controls the conversion of the latent viral genome into one undergoing lytic replication. by using a doxycycline-inducible expression system, the present study demonstrates that ebv rta efficiently elicits growth arrest in the human epithelial cell line hek293. in cells arrested by ebv rta, the expression of p21 (cdkn1a), p27 (cdkn1b) and cyclin e were increased. in contra ...200919098430
epstein-barr virus in lymphoproliferative processes: an update for the diagnostic pathologist.the epstein-barr virus is an orally transmitted herpesvirus that is widespread in human populations and exhibits marked b-cell tropism. it is associated with more human neoplasms than any other known virus, and its role in the pathogenesis of such neoplasms has been the subject of intense investigation. this review presents an overview and update of the biology of epstein-barr virus and the diagnostic features of lymphoproliferative disorders associated with this intriguing human pathogen.200919098466
acute upper gastrointestinal bleeding associated with epstein-barr virus reactivation in an immunocompetent patient. 200919098888
[clinical features of 414 childhood cases with infectious mononucleosis at different age groups]. 200819099910
multifocal primary extranodal b-cell non-hodgkin's lymphoma involving six extranodal sites.an unusual case of epstein-barr virus-negative primary extranodal b-cell non-hodgkin's lymphoma involving six anatomical sites is described in a report that challenges the role of organotropism in the pathogenesis of extranodal lymphoma.200919103866
prior immunosuppressive therapy with antithymocyte globulin increases the risk of ebv-related lymphoproliferative disorder following allo-sct for acquired aplastic anaemia.we reviewed the incidence and risk factors for ebv-related post-transplant lymphoproliferative disorder (ebv-ptld) in 89 patients with acquired aplastic anaemia (aaa) receiving allogeneic transplants between 1989 and 2006. the overall incidence of ebv-ptld was 6.3% (5/89) with no cases in those receiving an allograft for constitutional bm failure syndromes (n=30) during the same period. there was no impact of age, gender, donor status, cmv seropositivity, gvhd and graft cell dose on the occurren ...200919104495
ebna3c can modulate the activities of the transcription factor necdin in association with metastasis suppressor protein nm23-h1.previous studies have demonstrated the interaction between the epstein-barr virus (ebv) nuclear antigen 3c (ebna3c) and the metastatic suppressor nm23-h1 both in vitro and in vivo (c. subramanian, m. a. cotter ii, and e. s. robertson, nat. med. 7:350-355, 2001). importantly ebna3c can reverse the ability of nm23-h1 to suppress migration of human cells in vitro. ebna3c contributes to ebv-associated human cancers by regulating transcription of a number of cellular and viral promoters as well as ta ...200919116252
the epstein-barr virus g-protein-coupled receptor contributes to immune evasion by targeting mhc class i molecules for degradation.epstein-barr virus (ebv) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. recent evidence indicates that an important component of the persistence strategy involves active interference with the mhc class i antigen processing pathway during the lytic replication cycle. we have now identified a novel role for the lytic cycle gene, bilf1, which encodes a glycoprotein with the properties of a constitutive signaling g-protein-coupled re ...200919119421
aberrant ebv antibody patterns may mimic acute ebv infections. 200919124991
[application of epstein-barr virus-transformed b lymphoblastic cells in identification of ctl epitopes specific for hantaan virus].to establish epstein-barr virus (ebv)-transformed b lymphoblastic cell lines (b-lcl) to present peptides as antigen-presenting cells (apc) and stimulate short-cultured t cells secreting ifn-gamma, by which the t cell epitopes are identified.200919126382
potential triggers of ms.ms is an immune mediated disease of the central nervous system (cns) characterized by demyelination, axonal damage and neurologic disability. the primary cause of this cns disease remains elusive. here we will address our current understanding of the role of viruses as potential environmental triggers for ms. virus infections can act peripherally (outside the cns) or within the cns. the association of viral infections with demyelinating disease, in both animals and humans, will be discussed, as ...201019130026
cancer preventive agents. part 8: chemopreventive effects of stevioside and related compounds.in a search for potential cancer chemopreventive agents from natural resources, stevioside (1), a sweetener, and six related compounds, including two aglycones steviol (6) and isosteviol (7), were screened in an in vitro assay for inhibitory effects on epstein-barr virus early antigen activation. compounds 1, 6 and 7 showed significant activity in this assay and also exhibited strong inhibitory effects in a two-stage carcinogenesis test using mouse skin induced by 7,12-dimethylbenz[a]anthracene ...200919131254
epstein-barr virus in cutaneous t-cell lymphomas: evaluation of the viral presence and significance in skin and peripheral blood.the importance of viral agents in the development of cutaneous t-cell lymphomas (ctcl) is still debated. for this purpose, we retrospectively evaluated the epstein-barr virus (ebv) presence in sézary syndrome (ss), mycosis fungoides (mf), inflammatory dermatoses (id), and healthy donors (hd) using different approaches: ebv-dna was quantified in skin biopsies and peripheral blood using real-time pcr, ebv-encoded small rna (eber) transcripts were detected by in situ hybridization (ish), and latent ...200919131945
recurrent chemical reactivations of ebv promotes genome instability and enhances tumor progression of nasopharyngeal carcinoma cells.nasopharyngeal carcinoma (npc) is an endemic malignancy prevalent in south east asia. epidemiological studies have associated this disease closely with epstein-barr virus (ebv) infection. previous studies also showed that ebv reactivation is implicated in the progression of npc. thus, we proposed that recurrent reactivations of ebv may be important for its pathogenic role. in this study, npc cell lines latently infected with ebv, na and ha, and the corresponding ebv-negative npc cell lines, npc- ...200919132751
natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition.human leukocyte antigen (hla) gene polymorphism plays a critical role in protective immunity, disease susceptibility, autoimmunity, and drug hypersensitivity, yet the basis of how hla polymorphism influences t cell receptor (tcr) recognition is unclear. we examined how a natural micropolymorphism in hla-b44, an important and large hla allelic family, affected antigen recognition. t cell-mediated immunity to an epstein-barr virus determinant (eenlldfvrf) is enhanced when hla-b*4405 was the presen ...200919139173
monitoring of epstein-barr virus load and antibody in pediatric renal transplant patients.epstein-barr virus (ebv) infection can lead to life-threatening post-transplant lymphoproliferative disorder (ptld). the aim of the present study was to establish ebv monitoring methods to prevent ptld.200819143966
interaction of epstein-barr virus bzlf1 c-terminal tail structure and core zipper is required for dna replication but not for promoter transactivation.the epstein-barr virus (ebv) protein bzlf1 contains a bzip dna binding domain in which c-terminal tail residues fold back against a zipper region that forms a coiled coil and mediates dimerization. point mutagenesis in the zipper region reveals the importance of individual residues within the (208)ssendrlr(215) sequence that is conserved in c/ebp for transactivation and ebv dna replication. the restoration of bzlf1 dna replication activity by the complementation of two deleterious mutations (s20 ...200919144704
identification of novel epstein-barr virus microrna genes from nasopharyngeal carcinomas.micrornas (mirnas) represent a conserved class of small noncoding rnas that are found in all higher eukaryotes as well as some dna viruses. mirnas are 20 to 25 nucleotides in length and have important regulatory functions in biological processes such as embryonic development, cell differentiation, hormone secretion, and metabolism. furthermore, mirnas have been implicated in the pathology of various diseases, including cancer. mirna expression profiles not only classify different types of cancer ...200919144710
epstein-barr virus detection in invasive and pre-invasive lesions of the uterine cervix.in the present study, our aim was to investigate whether ebv dna could be found in association with invasive and pre-invasive cervical cancer lesions. we hypothesize that ebv is not merely a commensal agent when present in malignant cervical lesions. dna was extracted from cervical scrapings followed by nested pcr-based amplification. the patients were 66 women with high grade cervical intraepithelial neoplasia and 14 women with invasive cervical cancer. the control group consisted of 89 women w ...200919148514
the evolution of epstein-barr virus inferred from the conservation and mutation of the virus glycoprotein gp350/220 gene.to study variations of epstein-barr virus (ebv), we analyzed the gp350/220 gene for several cell lines and japanese wild isolates using direct sequencing. the n-terminal region was highly conserved in all ebvs except for jijoye/p3hr-1 and a few isolates. the variation of the region coincided with ebv types a and b (also referred to as types 1 and 2) and were, respectively, designated as the types a and b. the type a/a was detected in most japanese cell lines and wild isolates, and was classified ...200919153826
pediatric post-transplant diffuse large b cell lymphoma after cardiac transplantation.post-transplant lymphoproliferative disorders (ptlds) occur in 3.5-9% of patients after pediatric cardiac transplantation. caution is needed when treating patients with ptld because of the risk of allograft rejection frequently caused by withdrawal of immunosuppression. in this report, we describe a 47-month-old boy who developed ptld as an ileocecal mass 29 months after cardiac transplantation. immunosuppressive therapy with cyclosporine a (cya) had been reduced due to an elevation of epstein-b ...200919156500
[construction and function analysis of the epstein-barr virus-encoded latent membrane protein-1 of ctar3 region].the role of carboxyl terminal activating region of latent membrane protein1 (lmp1) in epstein-barr virus infection and oncogenesis is unclear. in this study, we investigated the activating sites and functionary mechanism of lmp1.200819160809
myc sensitizes p53-deficient cancer cells to the dna-damaging effects of the dna methyltransferase inhibitor decitabine.decitabine (also referred to as 5-aza-2'-deoxycytidine) is a drug that has recently been approved by the food and drug administration (fda) for the treatment of myelodysplastic syndrome (mds). the mechanism of action is believed to be the blocking of dna methylation and thereby reactivating silenced genes involved in harnessing mds. when analyzing reactivation of genes involved in burkitt lymphoma (bl), we discovered that decitabine also sensitizes tumor cells by inducing dna damage. this sensit ...200919179467
cardiovascular complications associated with chronic active epstein-barr virus infection.this study aimed to assess the outcome of cardiovascular diseases for patients with chronic active epstein-barr virus infection (caebv). the study enrolled 15 patients (7 boys and 8 girls) who fulfilled the diagnostic criteria for caebv, including 10 patients with t-cell type and 3 patients with natural killer (nk)-cell type. the median age at the caebv onset was 6.3 years (range, 1.2-17.8 years). regular cardiologic studies were performed during the median follow-up period of 8 years (range, 2- ...200919184184
gsk983: a novel compound with broad-spectrum antiviral activity.gsk983, a novel tetrahydrocarbazole, inhibits the replication of a variety of unrelated viruses in vitro with ec(50) values of 5-20 nm. both replication of the adenovirus ad-5 and the polyoma virus sv-40, and episomal maintenance of human papillomaviruses (hpv) and epstein-barr virus (ebv) are susceptible to gsk983. the compound does not inhibit all viruses; herpes simplex virus (hsv-1), human immunodeficiency virus (hiv), and lytic replication of ebv were not susceptible at concentrations below ...200919187793
[infections in immunosuppressed patients].molecular biology techniques represent a major advance in the microbiologic diagnosis of infectious diseases, since these methods are able to detect etiological microorganisms with high sensitivity. moreover, these procedures can also establish prognostic and therapeutic efficacy markers with a sufficiently short turnaround time for the results to have a real impact on the clinical management of immunosuppressed patients. however, these techniques still have substantial limitations that should b ...200819195448
primary central nervous system lymphoma after liver transplantation treated by radiosurgery combined with fractionated radiotherapy.post-transplant primary central nervous system lymphoma is a rare malignant tumor. a 65-year-old man underwent orthotopic liver transplantation for liver carcinoma. nine months later, he presented with left-sided motor weakness and mri of the brain showed a rim-enhancing mass in the right paracentral area. the diagnosis of epstein-barr virus-positive diffuse large b-cell lymphoma was confirmed through stereotactic biopsy. the authors report a case of post-transplant primary central nervous syste ...200919200738
clinical significance of interleukin-10 gene polymorphisms and plasma levels in hodgkin lymphoma.we studied plasma levels of il-10 and five single nucleotide polymorphisms in the interleukin-10 (il-10) gene promoter in patients with hodgkin lymphoma (hl) to address potential genotype-phenotype correlations. patients with elevated il-10 levels were more likely to have advanced stage disease and inferior event-free survival. homozygous carriers of the variant alleles at position -592 (aa) and -1082 (gg) of the il-10 promoter had higher il-10 plasma levels, independent of male gender and advan ...200919201467
cyclical expression of ebv latent membrane protein 1 in ebv-transformed b cells underpins heterogeneity of epitope presentation and cd8+ t cell recognition.cd8(+) t cells specific for ebv latent cycle epitopes can be reactivated in vitro by stimulating with the autologous ebv-transformed b lymphoblastoid cell line (lcl). the resultant cd8(+) clones kill epitope peptide-loaded targets, but frequently do not kill or show only low levels of lysis of the unmanipulated lcl in 5-h cytotoxicity assays. however, they reproducibly show clear lcl recognition in cytokine (ifn-gamma) release assays and inhibit lcl outgrowth in long-term coculture assays. we sh ...200919201845
herpesvirus seropositivity in childhood associates with decreased monocyte-induced nk cell ifn-gamma production.ebv infection is inversely associated with ige sensitization in children, and this association is further enhanced by cmv coinfection. in mice, herpesvirus latency causes systemic innate activation and protection from bacterial coinfection, implying the importance of herpesviruses in skewing immune responses during latent infection. early control of viral infections depends on ifn-gamma release by nk cells, which generally requires the presence of accessory cells. we investigated ifn-gamma produ ...200919201907
monitoring ebv dna in saliva for early diagnosis of ebv reactivation in solid tumour patients after allogeneic haematopoietic sct. 200919204707
a 17-year-old boy with fever, sore throat, and headache. 200919213287
identification and characterization of a new kaposi's sarcoma-associated herpesvirus replication and transcription activator (rta)-responsive element involved in rta-mediated transactivation.kaposi's sarcoma-associated herpesvirus (kshv) replication and transcription activator (rta) is well established as a key transcriptional activator that regulates the kshv life cycle from latency to lytic replication. it is expressed immediately after infection and activates a number of viral genes leading to virus replication. the rta-responsive element (rre) in the rta target gene promoters is critical for rta to mediate this transactivation. a number of non-conserved rres have been identified ...200919223488
detection of herpes viruses in children with acute appendicitis.this study aimed to investigate the incidence of herpes simplex virus (hsv) types-1 and -2, varicella-zoster virus (vzv), cytomegalovirus (cmv), epstein-barr virus (ebv), human herpes virus 6 (hhv-6) and human herpes virus 7 (hhv-7) in childhood acute appendicitis.200919233720
molecular diagnosis of nasopharyngeal carcinoma using detection of epstein-barr virus latent membrane protein-1 gene in cervical metastatic lymph nodes.cervical lymphadenopathy could be a manifestation of occult nasopharyngeal carcinoma (npc). epstein-barr virus (ebv) is frequently detected in npc, and its malignant transformation is associated through the action of the oncoprotein latent membrane protein-1 (lmp-1).200919239950
development of a hybrid baculoviral vector for sustained transgene expression.baculovirus is a promising gene delivery vector but its widespread application is impeded as it only mediates transient transgene expression in mammalian cells. to prolong the expression, we developed a dual baculovirus system whereby one baculovirus expressed flp recombinase while the other harbored an frt-flanking cassette encompassing the transgene and orip/ebna1 derived from epstein-barr virus. after cotransduction of cells, the expressed flp cleaved the frt-flanking cassette off the baculov ...200919240695
antigen-binding properties of monoclonal antibodies reactive with ebna1 and use in immunoaffinity chromatography.epstein-barr virus (ebv) nuclear antigen 1 (ebna1) was overexpressed and purified from escherichia coli. mouse monoclonal antibodies (mabs) were prepared that react with ebna1. eleven high affinity mabs were recovered. nine mabs are isotype igg (all subisotype igg(1)) and two mabs are isotype igm. all mabs react strongly with ebna1 in an elisa assay while only one mab (designated 1eb6) fails to react in a western blot assay. the epitopes for these mabs were mapped to seven different regions, pro ...200919242546
the use of dried blood spot sampling in the national social life, health, and aging project.this paper describes the methods used for and issues associated with collection and analysis of dried blood spot (dbs) samples for the national social life, health, and aging project and provides the basic distributions of the resulting analytes.200919244547
cyclosporine promotes epstein-barr virus-infected human b-cell transformation assayed by three correlated assay methods.we have reported that cyclosporine (csa) has direct effect to promote epstein-barr virus (ebv) transformation of human peripheral blood b lymphocytes. in this article, we have reported that csa promoted ebv-infected, human b-cell transformation as assayed by three methods of colony number counting, cell number counting, and (3)h-thymidine incorporation. at first, we sought to correlate the three methods in ebv-infected human b-cell transformation, observing that they are convenient correlate wit ...200919249558
ebv lmp-1 negatively regulates expression and pro-apoptotic activity of par-4 in nasopharyngeal carcinoma cells.latent membrane protein-1 (lmp-1) of the epstein-barr virus (ebv) is closely associated with nasopharyngeal carcinoma (npc), and in this study we sought to determine whether the pro-apoptotic activity of prostate apoptosis response-4 (par-4) is modulated by lmp-1 in npc cells. we found that lmp-1 diminished the pro-apoptotic activity of par-4 and negatively regulated par-4 protein by de novo synthesis; moreover, although lmp-1 accelerated a par-4 activator, pka, we demonstrated that lmp-1 also a ...200919250735
epstein-barr virus-associated adenocarcinomas and squamous-cell lung carcinomas.the association of epstein-barr virus with pulmonary neoplasms has been restricted to lymphoepithelioma-like carcinomas in asian patients. we have selected 19 pulmonary adenocarcinomas and squamous-cell carcinomas from 1545 pulmonary neoplasms diagnosed from 1996 to 2007 in an occidental population. all of them showed a low-power appearance confusing between an epithelial and a lymphoid neoplasm, with a dense lymphocytic infiltrate intermingled with neoplastic cells giving an image akin to lymph ...200919252476
the epstein-barr virus lytic cycle activator zta interacts with methylated zre in the promoter of host target gene egr1.activation of the host gene egr1 is essential for the lytic replication of epstein-barr virus (ebv). egr1 is activated by zta (bzlf1, zebra). zta interacts directly with dna through a series of closely related zta-response elements (zres). here we dissect the mechanism used by zta to interact with the egr1 promoter and identify a weak interaction with egr1zre that is dependent on the distal part of egr1zre. furthermore, we demonstrate that the ability of zta to interact with egr1zre is enhanced ...200919264650
nf-kappab p50 plays distinct roles in the establishment and control of murine gammaherpesvirus 68 latency.nf-kappab signaling is critical to the survival and transformation of cells infected by the human gammaherpesviruses epstein-barr virus and kaposi's sarcoma-associated herpesvirus. here we have examined how elimination of the nf-kappab transcription factor p50 from mice affects the life cycle of murine gammaherpesvirus 68 (mhv68). notably, mice lacking p50 in every cell type were unable to establish a sufficiently robust immune response to control mhv68 infection, leading to high levels of laten ...200919264770
the epstein-barr virus alkaline exonuclease bglf5 serves pleiotropic functions in virus replication.the epstein-barr virus (ebv) alkaline exonuclease bglf5 has previously been recognized to contribute to immune evasion by downregulating production of hla molecules during virus replication. we have constructed a bglf5-null virus mutant to determine bglf5's functions during ebv viral replication. quantification of virus production in permissive 293 cells carrying a deltabglf5 genome identified a 17- to 21-fold reduction relative to complemented or wild-type controls. detailed monitoring of delta ...200919264771
epstein-barr nuclear antigen 1 modulates replication of orip-plasmids by impeding replication and transcription fork migration through the family of repeats.epstein-barr virus is replicated once per cell-cycle, and partitioned equally in latently infected cells. both these processes require a single viral cis-element, termed orip, and a single viral protein, ebna1. ebna1 binds two clusters of binding sites in orip, termed the dyad symmetry element (ds) and the family of repeats (fr), which function as a replication element and partitioning element respectively. wild-type fr contains 20 binding sites for ebna1.200919265546
inhibition of p38 map kinase pathway induces apoptosis and prevents epstein barr virus reactivation in raji cells exposed to lytic cycle inducing compounds.ebv lytic cycle activators, such as phorbol esters, anti-immunoglobulin, transforming growth factor beta (tgfbeta), sodium butyrate, induce apoptosis in ebv-negative but not in ebv-positive burkitt's lymphoma (bl) cells. to investigate the molecular mechanisms allowing ebv-infected cells to be protected, we examined the expression of viral and cellular antiapoptotic proteins as well as the activation of signal transduction pathways in bl-derived raji cells exposed to lytic cycle inducing agents.200919272151
gastric carcinoma with osteoclast-like giant cells: a case report and review of the literature.gastric carcinoma with osteoclast-like giant cells (ogcs) is an extremely rare tumor. so far, only six cases have been reported in the literature. here we report an additional case of this tumor in a chinese 78-year-old man presented with abdominal pain, vomiting, and hematemesis. physical examination and gastroscopy revealed a tumor in the gastric antrum. the biopsy and pathological findings indicated a gastric adenocarcinoma with ogcs, which were present in both the tumor and the metastatic ly ...200919283880
primary epstein-barr virus-negative nasal-type natural killer/t cell lymphoma of the testis. 200919285723
assessment of human papillomavirus and epstein-barr virus in lung adenocarcinoma.the association of human papillomavirus (hpv) and epstein-barr virus (ebv) infection with non-small cell lung cancer is controversial. hpv and ebv prevalence in a uniform population of lung adenocarcinoma was investigated, hypothesizing that there would be differences seen between smokers and non-smokers and between sexes. patients involved in this study were selected from a single institution database of lung cancer. in total 497 patients with adenocarcinoma were identified and 110 patients had ...200919287995
epstein-barr virus-induced expression of a novel human vault rna.non-protein-coding rnas (ncrnas) have recently emerged on the scene of genomic research as prominent players in the regulation of gene expression. many functionally characterized ncrnas have been shown to be differentially expressed in various organisms during specific environmental or developmental conditions, thus establishing regulatory networks crucial for shaping cellular life. here, we show that the expression of vault rnas (vtrnas) is specifically up-regulated in human lymphocytes upon in ...200919298825
prospective monitoring of epstein-barr virus dna in adult renal transplant recipients during the early posttransplant period: role of mycophenolate mofetil.epstein-barr virus (ebv) is associated with posttransplant lymphoproliferative disease. we monitored the incidence of ebv viraemia in adult renal transplant recipients and investigated the association with clinical parameters.200919300188
primary cerebral lymphomatoid granulomatosis: report of four cases and literature review.lymphomatoid granulomatosis (lyg) is an angiocentric and angiodestructive lymphoreticular proliferation, which usually involves the lungs, but may also involve the central nervous system (cns). unique involvement of the cns has been reported rarely. we report our experience with lyg confined to the brain and review the pertinent literature.200919322520
methylation-dependent binding of the epstein-barr virus bzlf1 protein to viral promoters.the switch between latent and lytic epstein-barr virus (ebv) infection is mediated by the viral immediate-early (ie) protein, bzlf1 (z). z, a homologue of c-jun that binds to ap1-like motifs (zres), induces expression of the brlf1 (r) and brrf1 (na) viral proteins, which cooperatively activate transcription of the z promoter and thereby establish a positive autoregulatory loop. a unique feature of z is its ability to preferentially bind to, and activate, the methylated form of the brlf1 promoter ...200919325883
epstein-barr virus dna as a biomarker for epstein-barr virus-positive lymphomas: are we there yet? 200919330650
whole blood epstein-barr virus dna load as a diagnostic and prognostic surrogate: extranodal natural killer/t-cell lymphoma.we investigated the value of epstein-barr virus (ebv) dna load in unfractionated whole blood for the diagnosis and prognosis of ebv-associated lymphoma. from july 2004 to july 2007, we compared ebv dna loads in 101 patients with lymphoma and 105 control individuals. the median copy number of ebv was higher in patients with ebv-positive lymphoma (p<0.001). in patients with natural killer (nk)/t-cell lymphomas, the median ebv dna load at presentation was significantly related to the stage (p = 0.0 ...200919330658
childhood leukemias and other hematopoietic malignancies: interdependence between an infectious event and chromosomal modifications.a large number of epidemiological observations suggest an infectious origin of hematopoietic malignancies, including various forms of leukemia, nonhodgkin's lymphomas, hodgkin's lymphomas and multiple myelomas. incidence of nonhodgkin's lymphomas and hodgkin's lymphomas, although not of leukemias, is substantially increased under immunosuppression. specific chromosomal modifications (translocations) resulting in fusion genes frequently emerge as early, but not sufficient, events for malignant pr ...200919330827
cd20-negative cd138-positive leukemic large cell lymphoma with plasmablastic differentiation with an igh/myc translocation in an hiv-positive patient.a 49-year-old hiv-positive japanese man was referred to our hospital for multiple skin nodules. many plasmablastic atypical lymphocytes were observed in the peripheral blood. he was diagnosed with diffuse large b cell lymphoma (dlbcl) by a biopsy of the inguinal lymph node. igh/myc translocation was detected by in situ hybridization of the lymph node and chromosomal analysis of bone marrow cells showed 46, xy, t(8 ; 14)(q24 ; q32)add(14)(q32), der(21)t(1 ; 21)(q12 ; p11). he showed a transient r ...200919336959
primary human immunodeficiency virus type 1-specific cd8+ t-cell responses induced by myeloid dendritic cells.induction of an antigenically broad and vigorous primary t-cell immune response by myeloid dendritic cells (dc) in blood and tissues could be important for an effective prophylactic or therapeutic vaccine to human immunodeficiency virus type 1 (hiv-1). here we show that a primary cd8(+) t-cell response can be induced by hiv-1 peptide-loaded dc derived from blood monocytes of hiv-1-negative adults and neonates (modc) and by langerhans cells (lc) and interstitial, dermal-intestinal dc (iddc) deriv ...200919357176
epstein-barr virus and multiple sclerosis.recent studies have revived interest in the long-scrutinized association between epstein-barr virus (ebv) and multiple sclerosis (ms). we review this evidence and discuss it in relation to ms pathological and clinical features and patients' response to immunosuppressive therapies.200919359987
splice-site mutation c.313+1, g>a in intron 3 of the ldl receptor gene results in transcripts with skipping of exon 3 and inclusion of intron 3.familial hypercholesterolemia (fh) patients with the splice site mutation c.313+1, g>a in intron 3 of the low density lipoprotein receptor (ldlr) gene, present with a phenotype similar to that of fh patients in general. however, a mild phenotype would have been expected from the published data showing that the mutation only causes skipping of exon 3.200919361455
cux1/wnt signaling regulates epithelial mesenchymal transition in ebv infected epithelial cells.idiopathic pulmonary fibrosis (ipf) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. ebv, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. a strategy based on microarray-differential gene expression analysis to identify molecular drivers of ebv-associated lung fibrosis was utilized. alveolar epithelial cells wer ...200919361498
epstein-barr virus and multiple sclerosis.epstein-barr virus (ebv) is a human dna herpesvirus infecting more than 90% of the world's population. ebv is the etiological agent of infectious mononucleosis (pfeiffer's disease). furthermore, diverse malignancies such as burkitt and hodgkin lymphoma have been associated with ebv. more recently, a possible role for ebv has been suggested in chronic inflammatory/autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus as well as in multiple sclerosis (ms). ms is currently ...200919361810
brain tumor as an unusual presentation of posttransplant lymphoproliferative disorder.posttransplant lymphoproliferative disorder following solid organ transplant is a lifethreatening form of posttransplant malignancy. its occurrence is typically associated with epstein-barr virus and profound immunosuppressive therapy. we describe a case of posttransplant lymphoproliferative disorder in the brain parenchyma, 4 years after renal transplant.200919364315
cleavage and secretion of epstein-barr virus glycoprotein 42 promote membrane fusion with b lymphocytes.epstein-barr virus (ebv) membrane glycoprotein 42 (gp42) is required for viral entry into b lymphocytes through binding to human leukocyte antigen (hla) class ii on the b-cell surface. ebv gp42 plays multiple roles during infection, including acting as a coreceptor for viral entry into b cells, binding to ebv glycoprotein h (gh) and gl during the process of membrane fusion, and blocking t-cell recognition of hla class ii-peptide complexes through steric hindrance. ebv gp42 occurs in two forms in ...200919369343
[familial predisposition and microbial etiology in dilated cardiomyopathy].cardiomyopathies are an important and diverse group of heart muscle diseases in which the heart muscle itself is structurally or functionally abnormal and in which coronary artery disease, hypertension, valvular and congenital heart disease are absent or do not sufficiently explain the observed myocardial abnormality. this often results in severe heart failure accompanied by arrhythmias and/or sudden death. clinical and morphological diversity of cardiomyopathies can reflect the broad spectrum o ...200919370326
functional analysis of the synonymous r385r mutation in the low-density lipoprotein receptor gene.familial hypercholesterolemia is caused by mutations in the low-density lipoprotein receptor (ldlr) gene. the synonymous mutation r385r has been shown to introduce a cryptic splice site in exon 9. the aims of this study were to establish to what extent the cryptic splice site is selected ahead of the normal splice site and to determine if the aberrant transcript is degraded by nonsense-mediated mrna decay. the relative amount of the aberrant transcript was determined by real-time pcr and found t ...200919371225
expression of epstein-barr virus bzlf1 immediate-early protein induces p53 degradation independent of mdm2, leading to repression of p53-mediated transcription.the epstein-barr virus (ebv) lytic program elicits atm-dependent dna damage response, resulting in phosphorylation of p53 at n-terminus, which prevents interaction with mdm2. nevertheless, p53-downstream signaling is blocked. we found here that during the lytic infection p53 was actively degraded in a proteasome-dependent manner even with a reduced level of mdm2. bzlf1 protein enhanced the ubiquitination of p53 in saos-2 cells. the degradation of p53 was observed even in the presence of nutlin-3 ...200919375142
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