Katsuhiko Itoh

Aminopeptidase inhibitor ubenimex inhibits the growth of leukaemic cell lines and myeloma cells through its cytotoxicity.

We investigated the effect of ubenimex, which has been demonstrated to have immunomodulating activities, on the proliferation of human leukaemic cell lines (HL 60 and K 562, myelogenic lines, Jurkat, a T-cell line and RPMI 8226, a multiple myeloma cell line) and on human bone marrow mononuclear cells from haematopoietic malignancy patients with acute myeloblastic leukaemia, chronic lymphocytic leukaemia or multiple myeloma. The growth of the myeloid cell lines and of a multiple myeloma cell line, but not the T-cell line, was significantly inhibited by cocultivation with ubenimex in a dose-dependent manner. The results of the experiment with haematopoietic malignancy cells showed inhibitory effects on tumour cells from patients with acute myeloblastic leukaemia and multiple myeloma, but not on those from patients with chronic lymphocytic leukaemia. These findings suggest the usefulness of ubenimex for the treatment of multiple myeloma.

In long-term bedridden elderly patients with dietary copper deficiency, biochemical markers of bone resorption are increased with copper supplementation during 12 weeks

Background: Although the effect of copper on bone has been tested in animals and healthy subjects, no studies concerning the effect of copper supplementation on bone metabolism in patients with copper deficiency have been reported because of the rarity of these patients. This study was conducted to investigate the effect of copper supplementation on bone metabolism in copper-deficient patients. Method: This study included 10 patients (83.7 ± 8.3 years) with dietary copper deficiency under long-term bed rest for more than 12 months. They had their diets supplemented with copper sulfate (3 mg/day) over 12 weeks in addition to their diet of only one kind of enteral food with a low concentration of copper. Serum copper and ceruloplasmin, urinary deoxypyridinoline (DPD) and collagen-type 1 N-telopeptide (NTX) (biomarkers of bone resorption), serum osteocalcin (OC) and bone-specific alkaline phosphatase (Bone ALP) (biomarkers of bone formation) were analyzed at baseline, 4 and 12 weeks after copper supplementation. Results: DPD and NTX excretion were significantly increased 4 weeks after copper supplementation (p = 0.009 and p = 0.013, respectively). Serum bone ALP and OC were not significantly changed 12 weeks after copper supplementation (p = 0.051 and p = 0.594). Conclusions: In patients with nutritional copper deficiency, bone resorption markers are increased with copper supplementation.

Cyclic haemopoiesis at 7‐ or 8‐day intervals

Summary. We report a patient with severe anaemia and cyclic oscillations of reticulocyte and leucocyte counts, as well as serum iron (Fe), unsaturated iron‐binding capacity (UIBC), ferritin, C‐reactive protein (CRP) levels and temperature, at regular intervals of 7 or 8 d. After treatment with prednisolone, anaemia was corrected and the cyclic oscillations of these parameters ceased; whereas treatment with indomethacin, recombinant granulocyte‐colony stimulating factor (G‐CSF) and erythropoietin (Epo) were unsuccessful.

Non-Hodgkin's Lymphoma following Acute Myeloid Leukemia in Complete Remission

A 57-year-old female was admitted with low grade fever, leukocytosis, anemia and thrombocytopenia. Her white blood cell count was 59.7 ! 109/l, with 83% leukemic cells, some of which had Auer rods. The blasts were myeloperoxidase-positive with a myeloid immunophenotype (CD33: 99.1%, CD13: 8.5%, CD19: !1.0%, CD20: !1.0%, HLA-DR: 18.4%). She was diagnosed as having AML (M2) and underwent combination chemotherapy (the Japan Adult Leukemia Study GroupAML89 regimen which includes enocitabine, cytarabine, mercaptopurine, methotrexate, daunorubicin, aclarubicin, mitoxantrone, vindesine, etoposide, prednisolone), resulting in complete remission. She was well thereafter and was followed as an outpatient without treatment. Thirty-seven months following the diagnosis of AML, however, she complained of nausea and abdominal pain. Her serum lactate dehydrogenase level rose from 313 to 844 and 1,371 IU/l within 2 months (normal: less than 310). When she was readmitted for investigation, the peripheral blood counts were normal and examination of her bone marrow showed complete remission. Serum CA 19-9 and CA 125 levels were elevated to 145.6 ng/ml (normal: less than 60) and 315 U/ml (normal: less than 35), respectively. The chest X-ray revealed a small amount of bilateral pleural effusion, and the computed tomography scan of the abdomen showed multiple intrahepatic tumors and a moderate amount of ascites (fig. 1). There was no evidence of another tumor or lymphadenopathy. We suspected that she had carcinoma of the digestive or gynecologic system because of the high levels of the two characteristic tumor markers. However, no abnormality was detected by the gastrointestinal and gynecologic study. Examination of the pleural effusion and ascites showed no malignant or clonal cells, but 1 month later, reexamination of the patient’s ascites showed atypical cells (fig. 2). She died within 1 week of disseminated intravascular coagulation. The autopsy revealed diffuse, medium-sized, B cell non-Hodgkin’s lymphoma [LCA (CD 45); L26 (CD20)and UCHL1 (CD45RO)-positive but neutrophilic esterase-negative] in the liver tumors (maximum diameter 6 cm). There was also microscopic infiltration by the lymphoma cells into the diaphragm, omentum, peritoneum, stomach, parapancreatic region and para-aortic lymph nodes.