EBV-Associated Diseases in Humans and their Animal in vivo Models: Part I

Epstein-Barr virus (EBV) is one of human herpesviruses and a member of the gamma herpesvirus family (lymphocryptovirus). Infectious mononucleosis, Burkitt's lymphoma and nasopharyngeal carcinoma are well-known EBV-associated diseases. The range of EBV-associated diseases has recently expanded to include Hodgkin's lymphoma, T-cell lymphoma, pyothorax-associated or methotrexate-associated B-cell lymphoma, primary effusion lymphoma and lymphoepithelioma-like carcinoma of the stomach, thymus and salivary gland, lymphoproliferative disorders (LPDs) or leiomyosarcomas from immunocompromized host, oral hairy leukoplakia and EBV-associated hemophagocytic syndrome. Animal models of human EBV-associated diseases are essential to elucidate the pathogenesis of EBV-infection and EBV-associated diseases. However, only several reports on the animal models of EBV infection have been reported. Here I review the summary of EBV-associated diseases in humans and those previous animal models using EBV or EBV-like herpesviruses and describe some details on our two newly developed rabbit models of LPD induced by simian EBV-like viruses and a mouse model with murine gammaherpesvirus. These animal models are useful and inexpensive alternative experimental model systems for studying the biology and pathogenesis of EBV, and prophylactic and therapeutic regimens

Tissue Culture of Trigeminal Nerves from Rats Administered Transplacentally with Ethylnitrosourea

The morphological and biological changes in long term culture cells of normal-appearing trigeminal nerves from 2, 8, and 30-day-old S-D rats administered transplacentaLly with 75 mg ENU/kg were examined. After a marked degeneration of cells, crisscross multiple proliferative foci of transformed spindle cells appeared at the 3rd passage culture from 2 and 8-day-old rats, but not form 30-day-old rats. The transformed cells with S-100 protein and basal lamina had Schwann cell characteristics. Transformed spindle cells continued to form a crisscross pattern more than 700 days and some transformed spindle cells became round in shape 3-6 months after the primary culture. These transformed cells were transplantable to newborn S-D rats and the transplanted tumors were histologically similar to those of malignant Schwannoma of trigeminal nerves induced by ENU. Round-shaped transformed cells were more malignant than spindle-shaped cells and produced rapidly growing transplanted tumors. Spontaneous transformation with multinucleated giant cells occurred in one of the control cultures. These results indicate that the sequential changes of ENU-treated trigeminal nerves in vitro were corresponded to developmental changes of malignant Schwannoma in vivo induced by ENU. This system will be useful for analysis of ENU-carcinogenesis.</p

EBV-Associated Diseases in Humans and their Animal in vivo Models: Part II

Epstein-Barr virus (EBV) is one of human herpesviruses and a member of the gamma herpesvirus family (lymphocryptovirus). Infectious mononucleosis, Burkitt's lymphoma and nasopharyngeal carcinoma are well-known EBV-associated diseases. The range of EBV-associated diseases has recently expanded to include Hodgkin's lymphoma, T-cell lymphoma, pyothorax-associated or methotrexate-associated B-cell lymphoma, primary effusion lymphoma and lymphoepithelioma-like carcinoma of the stomach, thymus and salivary gland, lymphoproliferative disorders (LPDs) or leiomyosarcomas from immunocompromized host, oral hairy leukoplakia and EBV-associated hemophagocytic syndrome. Animal models of human EBV-associated diseases are essential to elucidate the pathogenesis of EBV-infection and EBV-associated diseases. However, only several reports on the animal models of EBV infection have been reported. Here I review the summary of EBV-associated diseases in humans and those previous animal models using EBV or EBV-like herpesviruses and describe some details on our two newly developed rabbit models of LPD induced by simian EBV-like viruses and a mouse model with murine gammaherpesvirus. These animal models are useful and inexpensive alternative experimental model systems for studying the biology and pathogenesis of EBV, and prophylactic and therapeutic regimens

Detection of oncogene rearrangements in human non-Hodgkin's lymphomas.

Southern blot hybridization was used to detect the rearrangement and amplification of five proto-oncogenes (bcl-2, bcl-1, c-myc, c-myb and c-Ha-ras) and one tumor suppressor gene (RB-1) in 55 Japanese patients with non-Hodgkin's lymphoma; 16 with T-cell lymphomas and 39 with B-cell lymphomas (7 follicular and 32 diffuse lymphomas). Genetic abnormalities of the proto-oncogenes were detected in 7 of the 55 (13%). Genetic abnormalities of bcl-2 plus other genes were detected in 5 of 7 cases of follicular lymphoma (71%), rearrangements of bcl-2 and c-myc, rearrangement of bcl-2 and amplification of c-myb. Genetic abnormalities were observed in only three cases of diffuse lymphoma. In each of 3 cases of B-cell lymphoma, one of the genes, blc-2 mbr, bcl-2 mcr and c-myc, was rearranged respectively. The incidence of genetic abnormalities in diffuse lymphomas (6.3%) was lower than that in follicular lymphomas. None of diffuse lymphomas had double oncogene abnormality. No abnormalities were found in RB-1, bcl-1, and Ha-ras. These findings suggest that follicular lymphomas are associated with some abnormalities of oncogenes not restricted to bcl-2 that facilitate growth which may be associated with their clinical features.</p

Experimental Study of Critical Cascading Flashover on Insulator Assembly Using Model Arrangements (Part II) : The Influence of a Floating Electrode, Placed on a Porcelain Board, on the Formaiton of a Flashover Path

This paper describes the phenomena of cascading flashovers in model arrangements for experimental analysis of critical cascading flashovers occuring in an insulator assembly used on high voltage transmission lines. The testing model used consisted of a pair of rod-rod electrodes, a potentially floating copper wire and a porcelain board. The applied lightning impulse voltage of positive or negative polarity was much higher than the breakdown voltage, when the flashover occurred for only a short time lag. The experimental results included flashover paths and pre-breakdown corona distributions, and cascading flashover rates. The flashover phenomena on the testing model clarified that the cascading flashover rate was related to the position of the porcelain board with the floating wire and that the corona from the floating wire was generated just before the corona from the rod electrode reached the floating wire. In the summary, the influence of the floating electrode on the formation of flashover paths discussed in comparison with previous reports. As a result of this series of experiments, it was clarified that a cascading flashover occurred only through coexistence with the porcelain surface and floating metal

Expression and intracellular localization of FKHRL1 in mammary gland neoplasms.

FKHRL1 (FOXO3a), a member of the Forkhead family of genes, has been considered to be involved in the development of breast tumors; however, the in vivo expression and activation status of FKHRL1 in breast tumors still remains unclear. We immunohistochemically demonstrated the expression and intracellular localization of FKHRL1 in human breast tumors by the novel anti-FKHRL1 antibody which is available for formalin-fixed paraffin-embedded specimens. In a total of 51 cases of benign tumors, FKHRL1 was diffusely expressed in all cases, and its intracellular localization was revealed to be cytoplasmic (inactive form) in 94% of cases of intraductal papillomas (16/17) and 91% cases of fibroadenomas (31/34), with a similar pattern to normal glandular epithelium. In invasive ductal carcinomas, 83% of the cases (93/112) diffusely expressed FKHRL1; however, unlike benign tumors, 71% of the cases (66/93) showed the nuclear-targeted, active form of FKHRL1. Moreover, activated FKHRL1 was predominantly observed in scirrhous (29/36, 81% of the cases) and papillotubular (30/38, 79% of the cases) subtypes, compared to the solid-tubular subtype (7/19, 37% of the cases). Furthermore, the cases with nuclear-targeted FKHRL1 showed a tendency to have lymph nodal metastasis with statistical significance (P < 0.0001). Thus, the activation of FKHRL1 seems to be recognized as one of the specific features of invasive ductal carcinoma of the breast.</p

A case of ovarian leiomyoma.

A case of ovarian leiomyoma is reported, together with histologic, immunohistologic and electron microscopic findings. A solid firm tumor, measuring 6.5 X 5 X 5 cm, was found in the right ovary of a 65-year-old woman. The tumor had an obvious whorled pattern on the cut-surface. Well-differentiated, long spindle-shaped neoplastic cells revealed positive immunoreactivity for anti-desmin. Ultrastructural observations included numerous microfilaments with dense patches in the cytoplasm, micropinocytotic vesicles beneath plasma membranes and continuous basal laminae around neoplastic cells. These findings were compatible with leiomyoma. The possible histogenesis of ovarian leiomyoma was discussed.</p