Fuminori Abe

Deoxyspergualin in lethal murine graft-versus-host disease

The beneficial effect of deoxyspergualin (DSG, NKT-01) on lethal graft-versus-host disease in mice has been studied in a major histoincompatible donor-recipient combination. Suppression of the effector mechanisms responsible for the lethal outcome in this GVHD model is also noted. This study reveals: (1) DSG has a marked potential for treatment of lethal GVHD; (2) DSG and methotrexate in combination yield longer survival times than DSG or MTX alone; (3) long-term survivors, following DSG treatment, become stable chimeras as evidenced by cell-surface analysis of spleen cells; and (4) high activity of H-2-reactive cytotoxic T lymphocytes is detected in spleens of the mice with lethal GVHD, whereas natural killer activity is only slightly increased. DSG inhibits CTL activity not only in the induction stage but also in the advanced stage of the disease. These findings indicate that DSG might be beneficial in clinical bone marrow transplantation either alone or in combination with MTX.

Autoradiographic study of tissue distribution of [3H]Ubenimex in IMC carcinoma-bearing mice

[3H]Ubenimex was administered to IMC carcinoma-bearing mice, and the tissue distribution of the radioactivity was examined at various times after drug injection by autoradiography of glutaraldehyde-fixed tissues. Silver grains were concentrated on some of the macrophages present around the solid tumor and in thymic medulla, splenic red pulp, and mesenteric lymph node medulla. The grains were also seen at a similar concentration on some nurse cell-like cells in the thymic cortex and on some reticular cells in splenic red pulp. In the liver, grains were concentrated on the hepatocytes and bile duct epithelium. The grains were most densely concentrated on kidney proximal straight tubules, in which strong leucine aminopeptidase activity was also observed.