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I Ishida

Publications and source records attributed to I Ishida.

104 records · Page 6Linked to original sources

8-1A, a human monoclonal antibody that reacts with intact human chorionic gonadotropin.

The incidence of choriocarcinoma has decreased over time and therapeutic results have improved about 90% complete remission in patients without extensive metastasis. However, some choriocarcinomas metastasize to other organs and show resistance to chemotherapy, having a poor prognosis despite multidisciplinary treatment. Better methods of early diagnosis for recurrence or micrometastasis, and treatment against cases with intractable gestational trophoblastic neoplasia (GTN) are needed to improve the prognosis. Human chorionic gonadotropin (hCG) is a glycoprotein hormone composed of two dissimilar subunits and a tumor marker to make a diagnosis and monitor therapeutic effect in GTN. Even when hCG levels in the serum become too low to measure with the hCG beta-CTP system which is the most sensitive assay, there are estimated to be approximately 10,000 trophoblastic cells in the body. Residual trophoblast cells may cause symptoms such as bleeding or undergo malignant transformation to choriocarcinoma. Since most monoclonal antibodies developed so far are murine, administration creates human anti-mouse antibodies, resulting in clinical failure. More recent mouse/human chimeric antibodies or humanized antibodies still possess substantial immunogenicity that makes repeated administration difficult. In the present study, KM mice that can produce completely human monoclonal antibodies were used to prepare hCG-specific human monoclonal antibody. This yielded 8-1A, a human monoclonal antibody capable of reacting with intact hCG. In the future, new diagnostic techniques and treatments for chorionic diseases may be developed using this kind of human monoclonal antibody.

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Blockage of alpha beta T-cell development by TCR gamma delta transgenes.

T lymphocytes recognize antigens by means of T-cell receptors (TCR) composed of alpha beta or gamma delta heterodimers. The mechanism governing the development of alpha beta- and gamma delta-bearing T cells from a common precursor T cell is so far unknown. It has been proposed that T-cell precursors rearrange their gamma- and delta-chain genes first, and alpha beta T cells are generated only from those cells that fail to rearrange productively both gamma- and delta-chain genes. Our recent study on gamma delta-transgenic mice contradicted this hypothesis, however, and indicated that repression of gamma-chain gene expression mediated by a transcriptional silencer element has a critical role in the generation of alpha beta T cells. Here we report that the generation of alpha beta T cells is severely blocked in transgenic mice carrying gamma- and delta-chain transgenes without the associated silencer, thereby strengthening the validity of the silencer model of T-cell development.

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