The heat shock protein 90 inhibitor BIIB021 suppresses the growth of T and natural killer cell lymphomas.

Epstein-Barr virus (EBV), which infects not only B cells but also T and natural killer (NK) cells, is associated with a variety of lymphoid malignancies. Because EBV-associated T and NK cell lymphomas are refractory and resistant to conventional chemotherapy, there is a continuing need for new effective therapies. EBV-encoded "latent membrane protein 1" (LMP1) is a major oncogene that activates nuclear factor kappa B (NF-κB), c-Jun N-terminal kinase (JNK), and phosphatidylinositol 3-kinase signaling pathways, thus promoting cell growth and inhibiting apoptosis.

mTOR inhibitors induce cell-cycle arrest and inhibit tumor growth in Epstein-Barr virus-associated T and natural killer cell lymphoma cells.

Purpose: Epstein-Barr virus (EBV) infects B cells, as well as T cells and natural killer (NK) cells, and is associated with T or NK cell lymphoid malignancies. In various tumor cells, mTOR performs an essential function together with Akt with regard to cell growth. We investigated the effects of mTOR inhibitors on EBV-associated T- and NK-cell lymphomas.

Anti-CCR4 monoclonal antibody mogamulizumab for the treatment of EBV-associated T- and NK-cell lymphoproliferative diseases.

Purpose: Epstein-Barr virus (EBV) infects not only B cells but also T cells and natural killer (NK) cells, and T- and NK-cell lymphoproliferative diseases (T/NK-LPD) that are refractory to conventional chemotherapies may develop. To identify a molecular-targeted therapy for EBV-associated T/NK-LPDs, we investigated whether CC chemokine receptor 4 (CCR4) was expressed on EBV-infected T and/or NK cells and whether a humanized anti-CCR4 monoclonal antibody, mogamulizumab, was effective.

Experimental Design: CCR4 expression was examined in various cell lines.

Increased T-cell responses to Epstein-Barr virus with high viral load in patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma.

The immunological status of patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+ DLBCL) without obvious immunodeficiency has not been elucidated. A multicenter prospective study was conducted to assess pretreatment T-cell responses to EBV, EBV-DNA load and anti-EBV antibody in these patients. The proliferative and interferon (IFN)-γ-producing capacity of T-cells in response to autologous B-lymphoblastoid cell lines was determined using carboxyfluorescein diacetate succinimidyl ester (CFSE)-based assay.

Role of latent membrane protein 1 in chronic active Epstein-Barr virus infection-derived T/NK-cell proliferation.

Epstein-Barr virus (EBV) predominantly infects B cells and causes B-cell lymphomas, such as Burkitt lymphoma and Hodgkin lymphoma. However, it also infects other types of cells, including T and natural killer (NK) cells, and causes disorders, such as chronic active EBV infection (CAEBV) and T/NK-cell lymphoma. The CAEBV is a lymphoproliferative disease with poor prognosis, where EBV-positive T or NK cells grow rapidly, although the molecular mechanisms that cause the cell expansion still remain to be elucidated.

Anti-tumor effects of suberoylanilide hydroxamic acid on Epstein-Barr virus-associated T cell and natural killer cell lymphoma.

The ubiquitous Epstein-Barr virus (EBV) infects not only B cells but also T cells and natural killer (NK) cells and is associated with various lymphoid malignancies. Recent studies have reported that histone deacetylase (HDAC) inhibitors exert anticancer effects against various tumor cells. In the present study, we have evaluated both the in vitro and in vivo effects of suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor, on EBV-positive and EBV-negative T and NK lymphoma cells.

Plasma viral microRNA profiles reveal potential biomarkers for chronic active Epstein-Barr virus infection.

Background: Chronic active Epstein-Barr virus (CAEBV) infection has high mortality and morbidity, and biomarkers for disease severity and prognosis are required. MicroRNAs (miRNAs) are small noncoding RNAs, and EBV encodes multiple miRNAs. Because plasma contains sufficiently stable miRNAs, circulating EBV-associated miRNA profiles were investigated as novel biomarkers in CAEBV infection.

Heat shock protein 90 inhibitors repress latent membrane protein 1 (LMP1) expression and proliferation of Epstein-Barr virus-positive natural killer cell lymphoma.

Epstein-Barr virus (EBV) LMP1 is a major oncoprotein expressed in latent infection. It functions as a TNFR family member and constitutively activates cellular signals, such as NFκB, MAPK, JAK/STAT and AKT. We here screened small molecule inhibitors and isolated HSP90 inhibitors, Radicicol and 17-AAG, as candidates that suppress LMP1 expression and cell proliferation not only in EBV-positive SNK6 Natural Killer (NK) cell lymphoma cells, but also in B and T cells.

Demonstration of type II latency in T lymphocytes of Epstein-Barr Virus-associated hemophagocytic lymphohistiocytosis.

Epstein-Barr virus (EBV) is the most common infectious cause of non-genetic hemophagocytic lymphohistiocytosis (HLH). To investigate EBV-infected lymphocytes and immune dysfunction in EBV-associated HLH, blood samples from a 6-year-old boy were longitudinally analyzed using molecular techniques. EBV-positive lymphocytes were detected as CD5(+) , CD8(+) , and/or HLA DR(+) lymphocytes on Day 25 of the disease, mostly disappearing thereafter.

Immunization with a highly attenuated replication-competent herpes simplex virus type 1 mutant, HF10, protects mice from genital disease caused by herpes simplex virus type 2.

Genital herpes is an intractable disease caused mainly by herpes simplex virus (HSV) type 2 (HSV-2), and is a major concern in public health. A previous infection with HSV type 1 (HSV-1) enhances protection against primary HSV-2 infection to some extent. In this study, we evaluated the ability of HF10, a naturally occurring replication-competent HSV-1 mutant, to protect against genital infection in mice caused by HSV-2.

Application of flow cytometric in situ hybridization assay to Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases.

Epstein-Barr virus (EBV) infects various types of lymphocytes and is associated with not only B cell-origin lymphoma, but also T or natural killer cell lymphoproliferative diseases (T/NK LPD). Recently, we established a novel assay to identify EBV-infected cells using FISH. Using this assay, dual staining with antibodies to both surface antigens and an EBV-encoded small RNA (EBER) probe can be performed.

Antitumor activities of valproic acid on Epstein-Barr virus-associated T and natural killer lymphoma cells.

Epstein-Barr virus (EBV), which infects B cells, T cells, and natural killer (NK) cells, is associated with multiple lymphoid malignancies. Recently, histone deacetylase (HDAC) inhibitors have been reported to have anticancer effects against various tumor cells. In the present study, we evaluated the killing effect of valproic acid (VPA), which acts as an HDAC inhibitor, on EBV-positive and -negative T and NK lymphoma cells.

Replication of Epstein-Barr virus primary infection in human tonsil tissue explants.

Epstein-Barr virus (EBV) may cause a variety of virus-associated diseases, but no antiviral agents have yet been developed against this virus. Animal models are thus indispensable for the pathological analysis of EBV-related infections and the elucidation of therapeutic methods. To establish a model system for the study of EBV infection, we tested the ability of B95-8 virus and recombinant EBV expressing enhanced green fluorescent protein (EGFP) to replicate in human lymphoid tissue.

Bortezomib induces apoptosis in T lymphoma cells and natural killer lymphoma cells independent of Epstein-Barr virus infection.

Epstein-Barr virus (EBV), which infects not only B cells, but also T cells and natural killer (NK) cells, is associated with multiple lymphoid malignancies. Recently, the proteasome inhibitor bortezomib was reported to induce apoptosis of EBV-transformed B cells. We evaluated the killing effect of this proteasome inhibitor on EBV-associated T lymphoma cells and NK lymphoma cells.

Immunologic and virologic analyses in pediatric liver transplant recipients with chronic high Epstein-Barr virus loads.

Background: Long-term Epstein-Barr virus (EBV) monitoring for potentially life-threatening posttransplant lymphoproliferative disorder (PTLD) has identified asymptomatic patients who maintain high EBV loads over long periods.

Methods: Thirty-one pediatric liver transplant recipients were designated as 11 chronic high EBV load carriers (EBV DNA level >5000 copies/mL of whole blood for >6 months) and 20 control recipients. Serial quantification of EBV DNA, measurement of interleukin 10 (IL-10) concentrations, EBV-specific tetramer staining, and relative quantification of EBV gene expression in peripheral blood mononuclear cells were performed.

Multiplex real-time PCR assay for simultaneous quantification of BK polyomavirus, JC polyomavirus, and adenovirus DNA.

In recent years, virus-induced nephropathy caused mainly by BK polyomavirus (BKPyV), JC polyomavirus (JCPyV), and adenovirus has emerged as a problem in renal transplant patients. In the present study, we developed a multiplex real-time PCR assay to quantify the viral load of BKPyV, JCPyV, and adenovirus simultaneously. The dynamic range covered at least 6 orders of magnitude.

Quantitative analysis of Epstein-Barr virus (EBV)-related gene expression in patients with chronic active EBV infection.

Chronic active Epstein-Barr virus (CAEBV) infection is a systemic Epstein-Barr virus (EBV)-positive lymphoproliferative disorder characterized by persistent or recurrent infectious mononucleosis-like symptoms in patients with no known immunodeficiency. The detailed pathogenesis of the disease is unknown and no standard treatment regimen has been developed. EBV gene expression was analysed in peripheral blood samples collected from 24 patients with CAEBV infection.

Identification of Epstein-Barr virus (EBV)-infected lymphocyte subtypes by flow cytometric in situ hybridization in EBV-associated lymphoproliferative diseases.

To diagnose Epstein-Barr virus (EBV)-associated diseases and to explore the pathogenesis of EBV infection, not only must the EBV load be measured, but EBV-infected cells must also be identified. We established a novel flow cytometric in situ hybridization assay to detect EBV(+) suspension cells using a peptide nucleic acid probe specific for EBV-encoded small RNA (EBER). By enhancing fluorescence and photostability, we successfully stained EBER and surface antigens on the same cells.

Interpretation scheme for nonexpert pediatricians evaluating magnetic resonance images of children with cerebral palsy.

This study evaluated the usability of our MRI interpretation scheme among pediatricians with different skill levels in evaluating MRI of patients with cerebral palsy. We divided MRI findings into three groups: no abnormalities, pre/perinatally acquired lesions, and other abnormalities. Pre/perinatally acquired lesions were divided into six subgroups.

Rapid detection of Epstein-Barr virus DNA by loop-mediated isothermal amplification method.

Background: The loop-mediated isothermal amplification (LAMP) method is a novel technique for the amplification of specific DNA sequences.

Objectives: To establish the LAMP method for amplifying Epstein-Barr virus (EBV) DNA and to examine its reliability for the detection of EBV DNA in clinical specimens.

Study Design: Sera from 108 patients, who were initially suspected of primary EBV infection, were tested by the EBV LAMP method, and the results were compared with those of the real-time PCR assay.

Efficacy and adverse effects of rectal thiamylal with oral triclofos for children undergoing magnetic resonance imaging.

We studied the efficacy and adverse effects of rectal thiamylal in combination with oral triclofos in sedation for pediatric magnetic resonance imaging. Five hundred forty-six children underwent MRI examination from January of 1997 to December of 2001. Among them, 10mg/kg of rectal thiamylal was administrated after oral triclofos in 378 children.

Partitionings and kinetic behaviors of major-to-ultratrace elements between industrial waste incineration fly and bottom ashes as studied by ICP-AES and ICP-MS.

The partitionings of major-to-ultratrace elements between industrial waste incineration fly ash (IWIFA) and industrial waste incineration bottom ash (IWIBA) in industrial waste incinerators were investigated by measuring their concentration distributions, where the incineration ash samples were collected from three different types of industrial waste incinerators. The concentrations of the elements in the incineration ash samples were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES) and inductively coupled plasma mass spectrometry (ICP-MS). As a result, ca.