Toyoro Osato

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.

An Epstein-Barr virus-producer line Akata: establishment of the cell line and analysis of viral DNA.

An Epstein-Barr virus (EBV)-producer line, designated Akata, was established from a Japanese patient with Burkitts lymphoma. The Akata line possessed the Burkitts-type chromosome translocation, t(8q-; 14q+), and was derived from the tumor cell. Akata cells produced a large quantity of transforming virus upon treatment of cells with anti-immunoglobulin antibodies (Takada, 1984). Southern blot analysis of viral DNA indicated that the Akata EBV is nondefective and more representative of wild-type viruses. Akata cells should be useful as a source of EBV.

Nasal T-cell lymphoma causally associated with Epstein-Barr virus : Clinicopathologic, phenotypic, and genotypic studies

The authors have previously demonstrated nasal T‐cell lymphoma (NTL) associated with Epstein–Barr virus (EBV). The detailed clinical, phenotypic, and genotypic features and the role of EBV in lymphomagenesis remain to be clarified.

Clonality, expression and methylation patterns of the Epstein-Barr virus genomes in lethal midline granulomas classified as peripheral angiocentric T cell lymphomas

We analysed the terminal repeats of Epstein-Barr virus (EBV) in DNAs isolated from six lethal midline granuloma (LMG) biopsies. A single fused terminal fragment could be detected in each case, indicating that these angiocentric peripheral T cell lymphomas represent clonal proliferations of cells infected with EBV on a single occasion. Using reverse transcriptase-PCR, we detected EBV nuclear antigen (EBNA) 1 and latent membrane protein (LMP) 1, but not EBNA 2 messages in LMG biopsy RNAs. The splicing pattern of the EBNA 1 message was consistent with the usage of a promoter localized in the BamHI F fragment (F promoter). The BamHI W fragment repeats and LMP-coding sequences were highly methylated in all cases. In contrast, the LMP regulatory sequences were found to be hypomethylated or partially methylated, as in LMP-expressing nasopharyngeal carcinomas.

Prevalence of a human retrovirus in native Japanese: Evidence for a possible ancient origin

The origin of a human retrovirus (ATLV or HTLV-I) is, at present, unknown although carriers of the virus have been found in Japan, the Caribbean basin and Africa. By means of a sero-epidemiological study, the Ainu people of Hokkaido, located in the northernmost island of Japan, were shown to have antibody to the virus in high frequency. Since the Ainu are regarded as descendants of the pre-agriculture native population of northern Japan, this finding appears to indicate that the retrovirus was already present in the aboriginal Japanese of prehistoric times.

A possible association between hepatitis-B antigen-negative infantile papular acrodermatitis and Epstein-Barr virus infection

lymph-node cells and hepatocytes in papular acrodermatitis of childhood. J Cutan Pathol 2:97, 1975. 11. Takata M, Fukui Y, Taketani T, and Nakamura Y: Papular aerodermatitis of childhood (Gianottis disease), A report of two cases, J Dermatol 7:357, 1980. 12. Holland PV: Hepatitis B antigen subtypes--history, significance and immunogenicity, Am J Med Sci 270:161, 1975. 13. Mazzur S, Burgert S, and Blumberg BS: Geographical distribution of Australia antigen determinants d, y and w, Nature 247:38, 1974. 14. lshimaru Y, Ishimaru H, Toda G, Baba K, and Mayumi M: An epidemic of infantile papular acrodermatitis (Gianottis disease) in Japan associated with hepatitis-B surface antigen subtype ayw, Lancet 1:707, 1976. 15. Colombo M, Gerber MA, Vernage S J, Gianotti F, and Paronetto F: Immune response to hepatitis B virus in children with papular acro-dermatitis, Gastroenterology 73:1103, 1977. 16. Gianotti F: The Gianotti-Crosti syndrome, JCE Dermatol 18:15, 1979.

Chinese and African Euphorbiaceae plant extracts: markedly enhancing effect on Epstein-Barr virus-induced transformation

Chinese and African Euphorbiaceae plant extracts were shown to have a markedly enhancing effect on Epstein-Barr virus (EBV)-induced transformation of human lymphocytes. When 5 X 10(5) cord blood lymphocytes were seeded into the semisolid agar medium immediately after EBV exposure, 3-10 times more colonies developed in the presence of the plant extracts at their optimal doses. When a smaller number of 5 X 10(4) cells were seeded, transformed colonies were also observed in the presence of the plant extracts but not in their absence. All of the colonies picked up from the agar medium were EBV-determined nuclear antigen (EBNA)-positive and showed the typical blastoid morphology. There were no colonies detected in the EBV-uninfected cultures with the extracts, indicating that the virus was required for the promotion by these plant extracts of this lymphocyte transformation. Euphorbiaceae plants are known to be employed as local herbal drugs in southern China and tropical Africa, and the possible role as a co-factor of the plant extracts in the development of nasopharyngeal carcinoma (NPC) and African Burkitts lymphoma (BL) is discussed.

Chromosome translocation and c-MY Cactivation 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 Burkitts 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.

Breast Milk Is Not a Significant Source for Early Epstein-Barr Virus or Human Herpesvirus 6 Infection in Infants: A Seroepidemiologic Study in 2 Endemic Areas of Human T-Cell Lymphotropic Virus Type I in Japan

In order to evaluate the possibility of Epstein‐Barr virus (EBV) and human herpesvirus 6 (HHV‐6) transmission via breast milk, a total of 331 serum specimens collected from bottle‐fed and breast‐fed children and their mothers, in 2 endemic areas of human T‐cell lymphotropic virus type I (HTLV‐I) in Japan, were assayed for antibodies to EBV and HHV‐6. The seroprevalences of EBV and HHV‐6 were over 95% both in the mothers of bottle‐fed children and in those of breast‐fed children. The seroprevalence of EBV at 12–23 months of age was 54.5% (36/66) and 55.8% (24/43) in breast‐fed children and bottle‐fed children, respectively. The seroprevalence of HHV‐6 at 12–23 months of age was 90.9% (60/66) and 93.0% (40/43) in breast‐fed children and bottle‐fed children, respectively. No difference was observed between the seroprevalences of EBV and HHV‐6 in breast‐fed and bottle‐fed children at 12–23 months of age. Our seroepidemiologic data indicate that breast milk is not a significant source of early EBV or HHV‐6 infection in infancy.

Kawasaki Disease and Epstein-Barr Virus

We report the results of virological (serological and molecular biological) studies of Epstein‐Barr virus (EBV) in patients with Kawasaki disease (KD). Forty‐nine (86%) of 57 Kawasaki disease patients and 15 (68%) of 22 patients with recurrent Kawasaki disease had serological evidence of primary Epstein‐Barr virus infection during the first month after the onset of their disease based on the results of a sensitive method of detecting antibody to viral capsid antigen (VCA). The serological response to EBV was significantly low and transient. EBV sequences were identified directly in peripheral blood mononuclear cell (PBMC) DNA samples from 23 (56%) of 41 KD patients within 2 weeks after onset by means of the polymerase chain reaction (PCR). EBV sequences were also detected in 10 (83%) of 12 repeatedly tested KD patients within 3 months after onset. In contrast, only 7 (18%) of 40 control DNA samples were PCR‐positive. These virological studies indicate that an unusual EBV‐cell interaction may occur in KD.