[Inhibitory effect of retinoid on early antigen induction of Epstein-Barr virus].
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Biomedical subjects
Publications and source records attributed to R Umeda.
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The effects of Chinese medicinal herbal drugs (CMH; Daphne genkwa, Wikstroemia indica, Croton oil) were studied for Epstein-Barr virus (EBV) early antigen (EA) induction in established nasopharyngeal hybrid cells. Both ether and water extracts of CMH were found to have inducing activity. However water extracts of the same herbs were not as strong as that of other extracts. The EA positive-cell rate was from 18.2 to 42.2% in ether extracts and 1.0 to 3.8% in water extracts at 10 microgram/ml of the concentration. N-Butyrate alone showed a 40.2% positive rate and in the both treatment of water extracts, a combination effects was seen in induction of the EBV-EA. This in vitro system for the induction of EBV-EA was thought to be useful to determine what is the causal factors for activation of EBV in vivo.
A case of acute suppurative thyroiditis due to a left piriform sinus fistula was reported. A five-year old boy had a acutely painful tumor in the anterior part of the neck. It was a diffuse, firm, warm erythematous tumor, and laboratory, radiologic findings showed the acute inflammation of the left lobe of thyroid. a barium swallow revealed a very thin fistula originating from the apex of the left piriform sinus extending antero-inferiorly. This fistula was considered to be a route of infection in acute suppurative thyroiditis, allowing bacterial infection to begin in the perithyroidal space and spread to the thyroid gland. The complete fistulectomy was required for a permanent cure, but an administration of antibiotics was very effective in this case.
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The authors studied the replication of Epstein-Barr virus (EBV) in the epithelial hybrid cells derived from nasopharyngeal carcinoma (NPCKT) caused by the effects of sub-optimal incubation at 34, 32 and 28 degrees C, respectively, using an immunofluorescence technique. The intensity of EBV induction by sub-optimal temperatures was in the order of 32 degrees C----28 degrees C----34 degrees C. In particular, 18-24% positive cells for early antigen and viral capsid antigen were observed at around 10 to 14 days after shift-down of the incubation temperature from 37 to 32 degrees C.
The present study was made to investigate some characteristics of the epithelial hybrid cells derived from nasopharyngeal carcinoma (NPC-KT cells) both in vivo and in vitro, using immunofluorescence and electron microscopic techniques. Immunofluorescence and electron microscopic studies have shown that the appearance of Epstein-Barr virus (EBV)-related early antigens, EB-viral capsid antigens and virus particles in nude-mouse-grown-tumour cells were rather repressed, in contrast to, in vitro culture of the NPC-KT cells. The tumours after transplantation of the NPC-KT cells to nude mice showed pathological pictures of poorly differentiated carcinoma with EBV-associated nuclear antigen and derived from the NPC-KT cells by means of cytogenetic studies. More importantly, we have detected EBV-related membrane antigens (MA) on the epithelial NPC-KT cells. To our knowledge, the presence of MA on the malignant epithelial cells of the nasopharynx have never been demonstrated. The results reported here show for the first time the presence of MA on nasopharyngeal carcinoma cells.
The effects of human leukocyte interferon (HulFN-alpha) and fibroblast interferon (HulFN-beta) on cell growth and induction of antigens related to Epstein-Barr virus (EBV) in a nasopharyngeal carcinoma hybrid cell line (NPC-KT) were studied. HulFN-alpha showed little antiproliferative and anti-EBV effect on NPC-KT cells. On the other hand, HulFN-beta showed modest antiproliferative effect on NPC-KT cells; the effect was dependent on time and HulFN-beta concentration. HulFN-beta alone was ineffective in inhibiting EBV-related antigens, but NPC-KT cells treated for more than 1 week with HulFN-beta inhibited the action of the chemical inducer of EBV, n-butyric acid, and the appearance of EBV-induced early antigen and EB viral capsid antigen was inhibited more than 50% compared with NPC-KT cells treated with n-butyric acid alone.
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The biologic activities of Epstein-Barr (EB) virus from an epithelioid-nasopharyngeal carcinoma hybrid cell line (NPC-KT) and three subclones from the NPC-KT cells were examined. Much infectious virus was released by treatment with 5-iodo-2'-deoxyuridine. All virus preparations from NPC-KT cells and the subclones were found to possess both transforming and EB virus-induced early antigen (EA)-inducing activities. The lymphoblastoid cell lines, which were established by infection of human cord-blood lymphocytes with the virus, were diploid with normal karyotypes. The cell lines were positive for EB virus-associated nuclear antigen but negative for EA and EB viral capsid antigen.
Primary nasopharyngeal carcinoma (NPC) cells were fused to hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-defective cells derived from adenoid tissues using Sendai virus. Some of the fused cells developed into epithelial-like hybrid cells in a selective HAT medium. The hybrid cells (NPC-KT) were Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA)-positive cells. There have been no reports on the establishment of EBNA-positive epithelial cell lines derived from NPC. Thus, the epithelial-like hybrid cells might serve as an in vitro model for studying the biologic activity of NPC-associated EBV.
We have studied the induction of Epstein-Barr virus (EBV)-specific antigens in nasopharyngeal carcinoma hybrid cells by treatment with the tumor promotor 12-0-tetradecanoylphorbol-13-acetate (TPA), hydrogen peroxide (H2O2) and n-butyric acid. The intensity of EBV induction by these drugs was in the order of n-butyric acid----TPA----H2O2. Furthermore, the combination of H2O2 or TPA and n-butyric acid acted synergistically on EBV-induced antigens.
The pathogenesis of nasopharyngeal carcinoma caused by the Epstein-Barr virus (EBV) has been studied experimentally by infecting monolayer cells derived from human normal nasopharynx with the B-lymphotropic EBV. Direct EBV infection of the cell sheets derived from the human nasopharynx resulted in the appearance of EBV-associated nuclear antigen-positive floating cells, suggesting that the monolayer cells have been transformed. Since these cells seemed to be of the B-type lymphocyte, it may be assumed that there must have been B lymphocytes among the cells of the monolayer which have undergone transformation by the virus. EBV infection of fused human epithelial cells (Ad-AH and D98-AH cells) and B-lymphoblastoid cells (BJAB cells) showed that the EBV receptors had been maintained for no longer than 24 h even when heterokaryons and hybrid cells were formed.
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The spontaneous production of Epstein-Barr virus (EBV) and tumorigenicity in the BALB/c mutant nude mouse were studied with the use of the following 4 cell lines derived from the human nasopharynx: a) Ad-AH, an 8-azahypoxanthine-resistant epithelioid cell line; b) A2L, an EBV-carrying lymphoblastoid cell line; c) A2L/AH, an EBV-carrying epithelioid hybrid cell line established by fusion of Ad-AH cells with A2L cells; and d) NPC-KT, an EBV-carrying epithelioid hybrid cell line established by fusion of Ad-AH cells with nasopharyngeal carcinoma (NPC) primary culture cells. The NPC-KT hybrid cell line was the only cell line to produce EBV antigens of the lytic cycle and virus particles. Cloning efficiency in agarose was clearly related to tumorigenicity in nude mice. Especially high, frequent tumor formation was observed in the heterotransplantation of NPC-KT hybrid cells that presented poorly differentiated carcinoma, and the tumor cells were positive for EBV-associated nuclear antigen. These NPC-KT hybrid cells maintained the characteristics of a histologic type of NPC tumor cells. Thus experimental systems of NPC were established in vitro and in vivo by the application of NPC-KT hybrid cells to NPC model cells.
A rare case of hypertrophied lymphoid tissue in the nasal septum considered to be an ectopic tonsil was reported. The patient was a 53-year-old male, and a polypoid mass attached to the septal wall by a stalk was removed. Histological examination showed that the tumour was an ectopic hyperplastic tonsil presenting in the nasal septum. The pathogenesis of this tumour was not clear, but it was considered as hyperplasia or a new formation of primary or secondary lymphoid follicles. This is the first case report of such a rare condition.
Since antibody titers against Epstein-Barr virus (EBV) antigens are often elevated in sera of patient with active undifferentiated and nonkeratinizing nasopharyngeal carcinoma, anti-EBV serologic tests have been applied for diagnosis of metastatic lymphadenopathy in the neck without an obvious source and/or suspicious tumor of the nasopharynx. In this study it is emphasized that the serologic test procedure was helpful in diagnosing a patient with nasopharyngeal carcinoma that was initially occult but eventually confirmed by biopsy.
To establish EBV-infection in the nasopharyngeal epithelial cells, we carried out cell fusion of the lymphocytes with nasopharyngeal epithelial cells, and proved that it was possible to detect the appearance of EBNA in the epithelial nuclei. It is suggested that the establishment of EBV-infection in nasopharyngeal epithelial cells may include cell fusion and involvement of the EBV receptors.
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