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Biomedical subjects

F Mizuno

Publications and source records attributed to F Mizuno.

At least 37 records · Page 2Linked to original sources

Chromosome translocation and c-MYC activation by Epstein-Barr virus and Euphorbia tirucalli in B lymphocytes.

Dual exposure to Epstein-Barr virus and purified 4-deoxyphorbol ester derived from the plant Euphorbia tirucalli induced a high frequency of chromosomal rearrangements in human B lymphocytes in vitro. Rearrangements most commonly affected chromosome 8, the chromosome most often showing structural changes in Burkitt's lymphoma (BL) cells. E tirucalli is indigenous in parts of Africa where BL is endemic and may be an important risk factor for the disease.

B-Lymphocytes↗

Mass spectrometric identification of a phorbol diester 12-O-hexadecanoylphorbol-13-acetate, an Epstein-Barr virus-activating substance, in the soil collected from under Sapium sebiferum.

Soil-extracts collected from the ground from under several Euphorbiaceae plants have been known to possess Epstein-Barr virus (EBV)-activating substances which are thought to be one of the environmental co-factors causing nasopharyngeal carcinoma (NPC) in southern part of China and Burkitt's lymphoma (BL) in tropical Africa. Then, a model experiment aimed at chemical characterization of such active substances was carried out using a soil-extract around Sapium sebiferum, a Japanese representative Euphorbiaceae plant. Chromatographic separation guided by the EBV early antigen (EA) inducing activity gave a highly active fraction. Application of this fraction to desorption chemical ionization mass spectrometry identified a major active substance to be 12-O-hexadecanoylphorbol-13-acetate (HPA), which originally occurs in this plant. The method in this model experiment is suggested to be applicable to other samples from the endemic areas of NPC and BL.

Herpesvirus 4, Human↗

Epstein-Barr virus in nasal T-cell lymphomas in patients with lethal midline granuloma.

Five cases of lethal midline granuloma were identified histologically and phenotypically as peripheral T-cell lymphomas. Epstein-Barr virus (EBV) DNA was detected in the nasal tumour biopsy specimens by Southern blotting and in-vitro hybridisation with simultaneous detection of EBV-determined nuclear antigen (EBNA) and T-cell surface markers by two-colour immunofluorescence. Further immunofluorescence and northern blotting revealed that EBNA2 gene and also latent membrane protein gene were expressed in the nasal tumour cells. The patients had high titres of antibodies to EBV. These findings suggest that lethal midline granuloma is causally associated with EBV.

Adult↗

[A senile case of B-cell lymphoma with high titers of an EB virus-associated antibodies].

An 83-year-old man suffering from general malaise and discomfort in the epigastrium was admitted to hospital. On testing, peripheral blood and bone marrow smears disclosed a number of abnormal lymphocytoid cells, and a CT and a linear echo scan revealed splenomegaly and a multiple intraperitoneal lymphadenopathy, although no superficial lymph nodes were palpable. Further, abnormal lymphocytoid cells were positive for B1, B4, OKIa1, Leu1, Tac, anti-IgM, anti-IgD, and anti-lambda. Thus, a diagnosis of malignant lymphoma of the intermediate B-cell type was made. Surprisingly, serological examination reveared extremely high titers of EB-virus associated antibodies (VCAIgG 20, 480x, VCAIgA 320x, EAIgG 2,560x), but no EBNA or virus particles were detected in the tumor cells, so that no direct relationship was established between the development of the tumor and the EBV infection.

Aged↗

Production of human monoclonal antibodies against Epstein-Barr virus-specific antigens by the virus-immortalized lymphoblastoid cell lines.

The possible production of human monoclonal antibodies against Epstein-Barr virus (EBV) was assessed through the EBV immortalization technique. When individual lymphocyte samples from 50 clinical patients and healthy donors were immortalized by EBV, 4 lymphoblastoid lines yielded antibodies to EBV antigens. These positive lines were cloned and each line yielded cultures that secreted monoclonal antibodies against either viral capsid antigen (VCA) or membrane antigen (MA) component. Above all, a clonal line TAKA-SP-8 produced 5 micrograms MA antibody/10(6) cells/ml for more than 12 months. The culture fluid specifically immunoprecipitated a single polypeptide with a size of 93K from both P3HR-1 and B95-8 cell extracts. FUKA-SP-3, on the other hand, secreted 5 micrograms VCA antibody/10(6) cells/ml for at least 8 months. This antibody recognized two polypeptides with sizes of 123K and 120K, from P3HR-1 and B95-8 cell extracts, respectively. When B95-8 and P3HR-1 EBV were treated with the human MA monoclonal, both nuclear antigen (EBNA) synthesis and early antigen (EA) induction were strongly inhibited. All EBV antibody-producing cultures were exclusively achieved from splenic lymphocytes of patients with autoimmune diseases, but not from other donors.

Antibodies, Monoclonal↗

Epstein-Barr virus infection and oncogenesis in primary immunodeficiency.

Lymphomas occurred in 3 of 16 Japanese patients with ataxia telangiectasia (AT) and Wiskott-Aldrich syndrome (WAS). The patients had a persistently reactivated Epstein-Barr virus (EBV) infection with a remarkable decrease in virus-specific cellular immunity. In these patients, the B lymphocytes were more sensitive to EBV-induced events and to cellular proto-oncogene activation than seen in the healthy counterparts. This immunologic and genetic background was considered to explain the massive lymphoproliferation in these primary immunodeficiency disorders.

Adolescent↗

Epstein-Barr virus-enhancing plant promoters in east Africa.

The extracts of a certain African plant species, Euphorbia tirucalli, were found to have markedly enhancing effects on the activation of latent Epstein-Barr virus (EBV) genomes in the EBV carrying lymphoblastoid cells and also on EBV-induced transformation of human lymphocytes. The Euphorbia tirucalli was especially noticeable in highly endemic areas of Burkitt's lymphoma (BL), an EBV-associated malignancy, in Kenya and Tanzania. The activation of the latent EBV genome and the EBV-induced transformation enhancement were also observed with the soil and drinking water taken around the plants, strongly indicating that the people living in BL endemic areas are frequently exposed to such an EBV-enhancing plant promoter substance.

Africa, Eastern↗