The influence of Epstein-Barr virus reactivation in patients with Graves' disease.

In Graves' disease, the IgG class autoantibody against thyrotropin receptor (TRAb) is produced excessively and induces hyperthyroidism. Epstein-Barr virus (EBV) is one of the human herpesviruses that persists for life, mainly in B lymphocytes, and is occasionally reactivated. Therefore, EBV may affect the antibody production of B lymphocytes that would normally produce TRAb.

Epstein-Barr virus can infect rabbits by the intranasal or peroral route: an animal model for natural primary EBV infection in humans.

Epstein-Barr virus (EBV) is spread universally in humans, and it causes infectious mononucleosis and sometimes induces serious EBV-associated disease. The detailed mechanism of primary infection in humans has remained unclear, because it is difficult to examine the dynamics of EBV in vivo. In this study, a natural EBV-infection rabbit model by intranasal or peroral inoculation is described.

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.

A new animal model for primary and persistent Epstein-Barr virus infection: human EBV-infected rabbit characteristics determined using sequential imaging and pathological analysis.

Most adults have persistent Epstein-Barr virus (EBV)-infection. Adolescents and young adults with primary EBV-infection frequently develop infectious mononucleosis. Latent EBV-infection is associated with various diseases, neoplasms, and hematological disorders.

The vIL-10 gene of the Epstein-Barr virus (EBV) is conserved in a stable manner except for a few point mutations in various EBV isolates.

A gene of the Epstein-Barr virus (EBV), BamHI-C fragment rightward reading frame 1 (BCRF1), codes viral interleukin-10 (vIL-10), which is a close homolog to human IL-10. EBV strain variations are known at EBV latent membrane protein 1 (LMP1), and the distinct forms of LMP1 have been identified. In order to further elucidate the variations of EBV strains, the BCRF1 (vIL-10) gene was analyzed using PCR-direct sequencing in African Burkitt's lymphoma (BL) cell lines Raji, P3HR-1, EB1 and Daudi, Japanese BL cell line Akata, lymphoblastoid cell line OB and 22 wild EBV isolates from eight gastric carcinoma tissues and 14 throat washes.

[Viral infections in chronic fatigue syndrome].

Chronic fatigue syndrome (CFS) is a heterogeneous illness in which patients can have different, overlapping signs and symptoms. No single underlying cause has been established for all CFS patients. Epidemiological studies reveal that a flu-like sickness precedes the onset in the majority of cases.

Carboxyl-terminal sequence variation of latent membrane protein 1 gene in Epstein-Barr virus-associated gastric carcinomas from Eastern China and Japan.

Objectives: To elucidate variations of latent membrane protein 1 (LMP1) in Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) and explore the LMP1 variations of neighboring countries, China and Japan.

Methods: In 12 and 8 EBVaGCs from eastern China and Japan, respectively, the C-termini of LMP1 were analyzed using PCR and sequencing. The sequences were compared with previously published strains and were characterized on a phylogenetic tree.

The role of p38 mitogen-activated protein kinase in regulating interleukin-10 gene expression in Burkitt's lymphoma cell lines.

In malignant B lymphoma cells interleukin-10 (IL-10) expression is frequently upregulated. This effect is thought to support to the malignant transformation of these cells and to be a potential target for pharmacotherapy. To define better the mechanism for upregulation of the IL-10 gene, we tested the association between IL-10 and p38 mitogen-activated protein kinase (MAPK) in several Epstein-Barr virus (EBV) infected and non-infected Burkitt's lymphoma (BL) cell lines.

Accumulation of Epstein-Barr virus (EBV) BMRF1 protein EA-D during latent EBV activation of Burkitt's lymphoma cell line Raji.

As a new model to elucidate molecular mechanisms in Epstein-Barr virus (EBV) activation, we tested the tetracycline-inducible (Tet-On)/BZLF1-oriP plasmid system in Raji cells. Cells transfected with this Tet-On plasmid did not activate EBV by doxycycline and surprisingly EBV latency was disrupted with large amounts of BMRF1 protein (EA-D) being accumulated in the cells. Brilliant EA-D fluorescence was markedly condensed in small sized cells, intra-cellular vesicles, and extra-cellular particles.

Anaphylactic shock caused by exposure to sea anemones.

Background: Since the first report of a dog that developed severe systemic symptoms in response to a second injection of sea anemone toxin by Richet and Portier in 1902, no clear human cases of anaphylaxis related to exposure to sea anemones has been reported in the literature.

Methods: A 24-year-old man with an episode of local urticaria on his first contact with a sea anemone (Stichodactyla haddoni), developed dyspnea, severe urticaria and hypotension on exposure to water containing the dead bodies of the organism. To study whether this reaction was mediated by antigen-specific IgE, we performed a histamine release test with blood, Western blotting with serum and lymphocyte proliferating test with peripheral blood mononuclear cells of the patient, for the homogenate of sea anemones.

Loss of functional transforming growth factor (TGF)-beta type II receptor results in insensitivity to TGF-beta1-mediated apoptosis and Epstein-Barr virus reactivation.

Transforming growth factor (TGF)-beta1 induces not only cell growth inhibition or apoptosis but also Epstein-Barr virus (EBV) reactivation in some Burkitt's lymphoma (BL) cell lines. The purpose of this study was to define the role of TGF-beta signaling molecules in response to TGF-beta1-mediated cell growth inhibition, apoptosis, and EBV reactivation in BL cell lines. First, we confirmed the effect of TGF-beta1 on the cell growth and EBV reactivation in six BL cell lines.

Difference of Epstein-Barr virus isolates from Japanese patients and African Burkitt's lymphoma cell lines based on the sequence of latent membrane protein 1.

Sequence variations in the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) gene have been described in many EBV-isolates. To characterize the genomic relationship between Japanese EBV and the EBV isolates of other countries, we analyzed the LMP1 nucleotide sequences in EBV positive cell lines and clinical specimens, including five African Burkitt's lymphoma (BL) cell lines, a Japanese BL cell line, a B-lymphoblastoid cell line, a nasopharyngeal carcinoma hybrid cell line, six gastric carcinoma tissues, two peripheral blood mononuclear cells, and a B95-8 cell line, which contained the prototype EBV genome. We determined the C-terminal nucleotide sequences of LMP1 by PCR-direct sequencing analysis and characterized the sequence variation of Japanese isolates, made a phylogenetic tree from the sequence patterns of LMP1 by a neighbor-joining method.

Functional role of phosphatidylinositol 3-kinase/Akt pathway on cell growth and lytic cycle of Epstein-Barr virus in the Burkitt's lymphoma cell line, P3HR-1.

The phosphatidylinositol 3-kinase (PI3-K)/Akt pathway is involved in various malignancies, but the role of PI3-K/Akt pathway in Epstein-Barr virus (EBV) infected Burkitt's lymphoma (BL) cells remains unclear. To elucidate therapeutic targets for BL, this study investigates the effect of PI3-K/Akt pathway in: EBV-positive BL cell lines Raji, P3HR-1, Akata and Daudi; and EBV-negative BL cell lines Ramos and BJAB. Results of analyses indicate that Akt was constitutively phosphorylated in BJAB, P3HR-1, Akata, and Daudi but not in Ramos and Raji cells.

Epstein-Barr virus protein kinase BGLF4 is a virion tegument protein that dissociates from virions in a phosphorylation-dependent process and phosphorylates the viral immediate-early protein BZLF1.

Epstein-Barr virus (EBV) BGLF4 is a viral protein kinase that is expressed in the lytic phase of infection and is packaged in virions. We report here that BGLF4 is a tegument protein that dissociates from the virion in a phosphorylation-dependent process. We also present evidence that BGLF4 interacts with and phosphorylates BZLF1, a key viral regulator of lytic infection.

Transactivation of CCL20 gene by Epstein-Barr virus latent membrane protein 1.

CCL20 is expected to play a crucial role in the initiation of immune responses and tumour growth. However, expression of CCL20 in Epstein-Barr virus (EBV)-associated diseases has not been studied. We examined the contribution of EBV infection and EBV-encoded latent membrane protein (LMP)-1 to CCL20 expression.

Inhibition of Epstein-Barr virus (EBV) reactivation by short interfering RNAs targeting p38 mitogen-activated protein kinase or c-myc in EBV-positive epithelial cells.

Latent Epstein-Barr virus (EBV) is reactivated by 12-O-tetradecanoylphorbol-13-acetate (TPA) in EBV-infected cells. In this study, we found that TPA up-regulated phosphorylation of p38, a mitogen-activated protein kinase, and activated c-myc mRNA in EBV-positive epithelial GT38 cells. The EBV immediate-early gene BZLF1 mRNA and its product ZEBRA protein were induced following TPA treatment.

[CD21-independent infection of a human signet ring cell gastric carcinoma cell line by Epstein-Barr virus].

Objective: To understand Epstein-Barr virus (EBV) infection of gastric carcinoma cells.

Methods: The authors tested the infection of a signet ring cell line HSC-39 derived from human gastric carcinoma with Akata and P3HR-1 strains of EBV. Akata and P3HR-1 infected of EBV cell clones were isolated by a limiting dilution method.

Epstein-Barr virus-infected malignant T/NK-cell lymphoma in a patient with hypersensitivity to mosquito bites.

We report an autopsy case of Epstein-Barr virus (EBV)-infected malignant lymphoma in a young male who had hypersensitivity to mosquito bites. The autopsy revealed multiple confluent lymphoma lesions in the lungs, and on the right leg irregular-shaped skin ulcers were seen. The left pleural effusion also contained a large number of lymphoma cells.

Mechanism for induction of hydroxyurea resistance and loss of latent EBV genome in hydroxyurea-treated Burkitt's lymphoma cell line Raji.

Hydroxyurea (HU), as an inhibitor of ribonucleotide reductase (RR) through interaction with the R2 component, has been used in the treatment of malignancies. Recently, therapeutic strategies in Epstein-Barr Virus (EBV)-targeted lymphoma have been reported. In order to study the effect of HU on EBV, infected Burkitt's lymphoma (BL) Raji cells were passaged in medium containing 50 microM HU for more than 2 months.

Characterization of Epstein-Barr virus infection in a human signet ring cell gastric carcinoma cell line, HSC-39.

In order to study the mechanism of Epstein-Barr virus (EBV) infection in gastric carcinoma cells, we characterized the EBV infection in signet ring cell line HSC-39, derived from a human gastric carcinoma. HSC-39 cells were highly susceptible to cell-free EBV infection by Akata and P3HR-1 EBV strains. EBV nuclear antigen (EBNA) and EBV-encoded small RNA (EBER) were detected in the infected cells.

Diagnostic evaluation of 2', 5'-oligoadenylate synthetase activities and antibodies against Epstein-Barr virus and Coxiella burnetii in patients with chronic fatigue syndrome in Japan.

To investigate the association of viral infections with chronic fatigue syndrome (CFS), we assayed 2', 5'-oligoadenylate synthetase (2-5AS) activities in peripheral blood mononuclear cells from CFS patients in Japan. These patients were diagnosed in two hospitals, H1 and H2, located in different areas of the country. The activities were detected in 19 (86%) and 7 (32%) of each of the 22 patients in H1 and H2, respectively, while they were detected in only four (11%) out of the 38 healthy controls.

Characterization of molecular forms of probrain natriuretic peptide in human plasma.

Background: Measurement of brain natriuretic peptide (BNP) in plasma is useful for the diagnosis and prognosis of heart failure. However, the molecular forms of BNP, especially proBNP in the blood, have been poorly characterized.

Methods: To investigate the forms of proBNP in blood, antibodies against four proBNP synthetic peptides (1-13, 22-27, 28-40, and 47-54) were developed and characterized for their reactivity to proBNP by ELISA.

Epstein-Barr virus DNA is detected in peripheral blood mononuclear cells of EBV-seronegative infants with infectious mononucleosis-like symptoms.

We demonstrated Epstein-Barr virus (EBV) DNA in peripheral blood mononuclear cells (PBMCs) from infants with infectious mononucleosis- (IM) like symptoms. Thirteen of the 17 patients did not have EBV antibodies; however, EBV DNA was detected in 8 PBMC from the 13 seronegative patients by PCR. The 4 patients were retested in 6-12 months later.

Contrasting effects of hydroxyurea on cell growth and reduction in Epstein-Barr virus genomes in EBV-infected epithelioid cell lines vs Burkitt's lymphoma cell lines.

Eliminating Epstein-Barr virus (EBV) genomes from infected cells is an intriguing theoretical strategy in therapy for EBV-associated malignant diseases. Respective patterns were characterized for hydroxyurea (HU)-promoted loss of EBV genomes from EBV-infected epithelioid cell lines derived from the noncancerous portion of gastric carcinoma tissues and Burkitt's lymphoma (BL) cell lines. Epithelioid cell lines GT38 and PN were less sensitivity to HU than BL cell lines Akata, Raji, and Daudi in terms of cell growth inhibition and cell cycle arrest.