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Human myeloma stem cells were detected by their capacity to form colonies in culture. Cells separated from aspirated marrow were cultured for 10 days in semi-solid methylcellulose with medium conditioned by T lymphocytes stimulated by phytohaemagglutinin (PHA-TCM). The colonies formed consisted mostly of lymphoplasmacytoid cells or plasma cells, and the immunoglobulins in the patients' myeloma cells were demonstrated also in the cytoplasm of the colony cells. The number of colonies were proportional to the number of cells plated and to the concentration of PHA-TCM. When the proportion of proliferating colony-forming units of multiple myeloma (CFU-MM) was studied using the (3H)-dT-suicide technique, the high-specific-activity (3H)-dT killed 21-45% of the CFU-MM in 7 myeloma patients. According to a single dose of Co-y-irradiation, the mean doses for impairment of regeneration (Do) were 1.00 and 1.63 Gy in 2 cases, the extrapolation numbers being 1.6 and 2.0.

We explored the effects of local anaesthetics, which are proposed to affect the plasma membrane, on human natural killer (NK) cells. Human NK cell activity was inhibited by lidocaine and procaine in a dose-dependent manner. Procaine inhibited not only NK cytolysis but also the binding of NK cells to target cells when NK cells were pre-incubated with procaine, whereas procaine inhibited NK cytolysis without interfering with the binding when it was added after the binding was completed. These findings suggest that local anaesthetics may inhibit not only the recognition process but also the post-recognition process of human NK cells.

Streptococcal immunopotentiator OK-432 (NSC-B116209) augmented the natural killer (NK) cell activity of peritoneal exudate cells (PEC) in inbred C57BL/6 mice given ip injections of 0.1 mg OK-432 per mouse. The cytotoxic activity of PEC increased as early as 1 day after inoculation, reached its peak on day 3, and gradually declined thereafter, YAC-1, K562, and MOLT-4 target cells were more sensitive to PEC than were EL 4 and P815 target cells. The elimination of adherent cells by a nylon wool column enriched the proportion of cytotoxic cells among PEC. Nylon wool column-passed PEC were resistant to treatment with anti-Thy 1.2 antibody plus complement and sensitive to anti-asialo GM1 serum plus complement. Because 1:40-diluted rabbit antiserum against glycosphingolipid asialo GM1 is capable of eliminating mouse NK cell activity and is not cytotoxic to killer T-cells, the above results strongly suggest that OK-432 augments the NK cell activity in mice.

A human T-cell clone (TA-NB-2) that could lyse both autologous and allogeneic hepatocytes from chronic hepatitis patients with type non-A, non-B virus (NANB) was established. This clone produced CD3+ CD8+ cytotoxic T lymphocytes and expressed an antigen specific for alpha and beta subunits of T-cell receptor. The cytotoxic activity of the clone was abrogated by incubation with anti-CD3 monoclonal antibody. Anti-HLA monoclonal antibodies did not block the lysis of the target hepatocytes by TA-NB-2 cells. The cytotoxicity of TA-NB-2 clone against hepatocytes from patients with chronic NANB hepatitis was 39.8 +/- 13.2% (mean +/- SD; n = 17) (range, 14.2-60.5%), whereas that against hepatocytes from control patients with chronic type-B hepatitis, acute hepatitis B, acute hepatitis A, or alcoholic liver cirrhosis was 4.0 +/- 7.7% (n = 12) (range, -10.8 to 14.0%). The results suggest that TA-NB-2 cells specifically recognize a hepatitis NANB-related antigen expressed on hepatitis NANB-infected hepatocytes by T-cell receptor and that the recognition is not restricted by the major histocompatibility complex antigens. The results also suggest that most, if not all, cases of chronic hepatitis due to NANB are caused by one agent; TA-NB-2 clone may be useful as a tool to identify this particular hepatitis-related antigen.

The effects of corticosteroids on the natural killer (NK) cell activity of human peripheral blood lymphocytes were evaluated. When six untreated female patients with systemic lupus erythematosus were compared with fifteen age-matched, corticosteroid-treated female patients, NK activity in the latter was significantly suppressed. Although the administration of high doses seemed to suppress cytotoxicity to a greater extent, there was no close correlation between the daily doses of steroids and NK activity. When cytotoxicity levels were followed before and during corticosteroid therapy in the same patient, NK activity decreased markedly during treatment, particularly in patients on high-dose corticosteroids.

A patient with gastric carcinoma exhibited an excessive granulocytosis (58,000/microliter) preoperatively, in the absence of overt infection. After resection of the primary tumor, the peripheral leukocyte count decreased promptly to the normal value. In a search for a colony-stimulating factor (CSF), the tumor was transplanted into nude mice. A marked neutrophilia was observed in the tumor-bearing mice, suggesting the production of CSF by the tumor. Media conditioned by the primary culture of the tumor cells revealed the presence of CSF activity as well. CSF-producing carcinomas have been detected in various organs; nevertheless, no cases of gastric carcinoma have hitherto been described. It is of particular interest that in this patient hypercalcemia was not observed, although it often accompanied CSF-producing tumors reported previously. Therefore, it is suggested that this tumor secreted pure CSF and that the CSF produced by the tumor did not necessarily induce hypercalcemia.

Two cases of myeloproliferative disorders terminating in acute megakaryoblastic leukemia are reported. One case began as primary myelofibrosis and the other as chronic myelogenous leukemia. Blast cells in the acute leukemic phase were identified as megakaryoblasts by the presence of platelet peroxidase. The clinical course is described, and the morphology, immunologic studies, and ultrastructure studies of the blast cells are reported. On cytogenetic analysis both cases had a translocation involving the No. 3 chromosome locus q26.2. The present data suggest that 3q26 may be associated with transformation of the megakaryocytic lineage.