Single-turn extraction from a K110 AVF cyclotron by flat-top acceleration.

Single-turn extraction from the Japan Atomic Energy Agency AVF cyclotron with a K number of 110 using a flat-top (FT) acceleration system has been achieved to reduce the energy spread of an ion beam for microbeam formation with energy up to hundreds of MeV and to increase extraction efficiency from the cyclotron. In order to generate a FT waveform voltage using the fifth-harmonic frequency on a dee electrode, a FT resonator was designed using MAFIA code to achieve downsizing and low power consumption. The FT resonator, coupled to the main resonator through a coupling capacitor, covered the full range of the fifth harmonic frequency from 55 to 110 MHz. Various ion beams, accelerated using different acceleration harmonic modes of h=1 and 2, such as 220 MeV (12)C(5+) (h=2), 260 MeV (20)Ne(7+) (h=2), and 45 MeV H(+) (h=1), were developed by FT acceleration. A clear turn separation of the beam bunches was successfully observed at the extraction region of the large-scale AVF cyclotron with number of revolutions greater than 200. As a result, high extraction efficiency (over 95%) from the cyclotron was achieved. Single-turn extraction was confirmed by counting the number of beam bunches out of the cyclotron for an injected beam pulsed by a beam chopping system in the injection line. The energy spread of the 260 MeV (20)Ne(7+) beam was measured using an analyzing magnet, and we verified a reduction in the energy spread from DeltaE/E=0.1% to 0.05% by single-turn extraction after FT acceleration.

Enhanced suppression of pulmonary metastasis of malignant melanoma cells by combined administration of alpha-galactosylceramide and interleukin-18.

alpha-Galactosylceramide (alpha-GalCer) shows antitumor effects by activating natural killer (NK) cells indirectly through stimulation of the secretion of cytokines by NKT cells, whereas interleukin (IL)-18 shows antitumor effects by activating NK cells directly. In the present study, we examined the antitumor effect of the combined administration of alpha-GalCer and IL-18. An injection of NK cell-sensitive mouse B16 melanoma cells into a mouse tail vein produced pulmonary metastasis. The daily administration of alpha-GalCer or IL-18 alone for 4 days starting 1 day after the injection of B16 melanoma cells markedly suppressed the number of pulmonary metastatic foci, and their combined administration enhanced the antitumor effect compared with single administration. The antitumor effect of their combined administration was completely abolished by treatment of mice with anti-asialo GM1 serum, which depletes NK cells but not NKT cells. Combined administration of alpha-GalCer and IL-18 enhanced the cytotoxicity of NK cells and increased the number of NK cells in the lung. Analysis of NKT cell-dependent and NK cell-independent secretion of cytokines, to which NK cells can respond, showed that the administration of alpha-GalCer increased the secretion of IL-2, IL-4, interferon-gamma, IL-12, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and IL-10, and the combined administration of alpha-GalCer and IL-18 enhanced the secretion of IL-2, IL-4, interferon-gamma, and granulocyte-macrophage colony-stimulating factor further but only slightly. These results show that IL-18 in combination with alpha-GalCer exerts an antitumor effect on NK cell-sensitive tumors primarily by the direct stimulation of NK cells by IL-18 and the indirect stimulation of NK cells by alpha-GalCer through its activation of NKT cells.

Effect of interleukin-18 on metastasis of mouse osteosarcoma cells.

The effect of interleukin-18 (IL-18) on metastasis of highly metastatic LM8 mouse osteosarcoma cells was investigated using nude mice treated with anti-asialo GM1 serum to exclude anti-tumor actions of IL-18 through activation of T and natural killer cells. Injection of LM8 cells which do not express IL-18 receptor beta into a tail vain resulted in the formation of pulmonary and hepatic metastatic foci. Daily injection of mice with IL-18 starting the fifth day from the cell injection had no significant effect on the number of metastatic foci, while five daily injections of IL-18 before and after the cell injection resulted in marked decreases. Culture of LM8 cells with IL-18 for 5 days before the injection into mice produced no significant effect on the number of pulmonary and hepatic metastatic foci. In contrast, pretreatment of mice with IL-18 for 5 days before the cell injection markedly decreased metastatic foci. The retention of LM8 cells in the lung 24 h after their injection was also reduced by the pretreatment of mice with IL-18. Serum obtained from mice pretreated with IL-18 for 5 days suppressed mobility of LM8 cells but IL-18 itself did not. These results suggest that IL-18 inhibits metastasis of LM8 cells partly by inducing a factor(s) in the host which suppresses cell mobility.

A case of ochronotic arthropathy treated with total hip arthroplasty.

Abstract We report a case of ochronotic arthropathy treated with total hip arthroplasty. The articular cartilage of the patient's femoral head and synovium displayed black pigmentation. Microscopically, the articular cartilage revealed reddish-brown pigmentation (particularly in deep cartilage), necrotic chondrocytes, and slight black pigmentation in the cytoplasm of chondrocytes. Electron microscopy revealed electron-dense material deposited predominantly along and between collagen fibers.