Irinotecan Hydrochloride (CPT-11) in Dialysis Patients with Gastrointestinal Cancer

We investigated changes in drug disposition and toxicities with CPT-11 in 15 dialysis patients with gastrointestinal cancers to clarify whether CPT-11 could be administered safely in such patients. For comparison, the same parameters were also investigated in 10 cancer patients not undergoing dialysis. Items investigated included (1) plasma concentrations of SN-38, SN-38G and CPT-11 at 0, 1, 12, 24, 36, 48 and 72h after administration, together with a comparison of mean AUC values for 3 dose levels of CPT-11 (50, 60 and 70mg/m2) in dialysis patients and controls;and (2) occurrence of adverse events. Several findings emerged from this study:(1) No significant difference was observed in the AUC for SN-38 or CPT-11 between the dialysis and control groups;(2) The AUC for SN-38G at each dose was significantly higher in dialysis patients;and (3) Grade 1-4 leucopenia was observed in 11 of the dialysis patients. One patient developed grade 4 leucopenia and died due to sepsis. Anorexia, diarrhea, nausea, alopecia and interstitial pneumonia occurred in 6 dialysis patients. We found changes in drug dispositions of CPT-11, SN-38 and SN-38G in dialysis patients, suggesting that hepatic excretion, especially that of SN-38G, was increased. No significant difference in occurrence of adverse events was observed between the 2 groups. This indicates that CPT-11 can be administered safely in patients on dialysis.</p

Mechanical issues of FIREX target under cryogenic environment

A typical FIREX target is assembled with a 500 ?m diameter PS shell, a glass fill tube and a gold cone guide. Each part is glued together by an epoxy resin. To date, several assembled targets have been cooled down to cryogenic environment. However, they could not survive a cool down process and appeared to rupture around the glued boundary between the PS shell and cone guide. To reveal a crucial factor of the target destruction, its thermal stress after cool down was calculated using the ANSYS code. A two dimensional axisymmetric calculation model is composed of the PS shell and cone guide glued by an epoxy resin which is covered on by an epoxy fillet. A cool down process from 293 K to 10 K was simulated. The calculation showed that the rupture of the shell would start from the PS shell and gold cone guide boundary and the target validity depended on how the epoxy fillet could reinforce the PS shell

The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction.

Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of its expression appear to correlate with disease progression and metastasis. However, the role of SHH in bone destruction associated with oral squamous cell carcinomas is still unclear. In this study we analyzed SHH expression and the role played by SHH signaling in gingival carcinoma-induced jawbone destruction. From an analysis of surgically resected lower gingival squamous cell carcinoma mandible samples, we found that SHH was highly expressed in tumor cells that had invaded the bone matrix. On the other hand, the hedgehog receptor Patched and the signaling molecule Gli-2 were highly expressed in the osteoclasts and the progenitor cells. SHH stimulated osteoclast formation and pit formation in the presence of the receptor activator for nuclear factor-κB ligand (RANKL) in CD11b+ mouse bone marrow cells. SHH upregulated phosphorylation of ERK1/2 and p38 MAPK, NFATc1, tartrate-resistant acid phosphatase (TRAP), and Cathepsin K expression in RAW264.7 cells. Our results suggest that tumor-derived SHH stimulated the osteoclast formation and bone resorption in the tumor jawbone microenvironment

Asymmetrical normal-zone propagation observed in the aluminum-stabilized superconductor for the LHD helical coils

Transient normal-transitions have been observed in the superconducting helical coils of the Large Helical Device (LHD). Stability tests have been performed for an R&D coil as an upgrading program of LHD, and we observed asymmetrical propagation of an initiated normal-zone. In some conditions, a normal-zone propagates only in one direction along the conductor and it hence forms a traveling normal-zone. The Hall electric field generated in the longitudinal direction in the aluminum stabilizer is a plausible candidate to explain the observed asymmetrical normal-zone propagation

The Type Ic Hypernova SN 2002ap

Photometric and spectroscopic data of the energetic Type Ic supernova (SN) 2002ap are presented, and the properties of the SN are investigated through models of its spectral evolution and its light curve. The SN is spectroscopically similar to the "hypernova" SN 1997ef. However, its kinetic energy [$\sim (4-10) \times 10^{51}$ erg] and the mass ejected (2.5-5 $M_{\odot}$) are smaller, resulting in a faster-evolving light curve. The SN synthesized $\sim 0.07 M_{\odot}$ of $^{56}$Ni, and its peak luminosity was similar to that of normal SNe. Brightness alone should not be used to define a hypernova, whose defining character, namely very broad spectral features, is the result of a high kinetic energy. The likely main-sequence mass of the progenitor star was 20-25 $M_{\odot}$, which is also lower than that of both hypernovae SNe 1997ef and 1998bw. SN 2002ap appears to lie at the low-energy and low-mass end of the hypernova sequence as it is known so far. Observations of the nebular spectrum, which is expected to dominate by summer 2002, are necessary to confirm these values.Comment: 10 pages, 4 figures, accepted for publication in ApJL, 30 April 2002 (minor changes to match the accepted version, with figures being colored

First Cool-Down Performance of the LHD

The first cool-down test of the Large Helical Device (LHD) and the performance of the LHD cryogenic system during the first cycle operation are described. The first cool-down started on Feb. 23, 1998 and finished on Mar. 22. After the cool-down, the excitation tests of the SC coils up to 1.5 T and the first cycle operations for plasma physics experiments were conducted until May 18. The first cycle operation was successfully completed after the warm-up process to room temperature from May 19 to Jun. 15. The cooling characteristics of the LHD, such as temperature distribution during cool-down, heat loads under steady state condition, reliability during long-term operation, are reporte

Testis-Specific Histone Variant H3t Gene Is Essential for Entry into Spermatogenesis

Jun Ueda, Akihito Harada, Takashi Urahama, Shinichi Machida, Kazumitsu Maehara, Masashi Hada, Yoshinori Makino, Jumpei Nogami, Naoki Horikoshi, Akihisa Osakabe, Hiroyuki Taguchi, Hiroki Tanaka, Hiroaki Tachiwana, Tatsuma Yao, Minami Yamada, Takashi Iwamoto, Ayako Isotani, Masahito Ikawa, Taro Tachibana, Yuki Okada, Hiroshi Kimura, Yasuyuki Ohkawa, Hitoshi Kurumizaka, Kazuo Yamagata, Testis-Specific Histone Variant H3t Gene Is Essential for Entry into Spermatogenesis, Cell Reports, Volume 18, Issue 3, 2017, Pages 593-600, ISSN 2211-1247, https://doi.org/10.1016/j.celrep.2016.12.065

Fabrication of high-concentration Cu-doped deuterated targets for fast ignition experiments

In high-energy-density physics, including inertial fusion energy using high-power lasers, doping tracer atoms and deuteration of target materials play an important role in diagnosis. For example, a low-concentration Cu dopant acts as an x-ray source for electron temperature detection while a deuterium dopant acts as a neutron source for fusion reaction detection. However, the simultaneous achievement of Cu doping, a deuterated polymer, mechanical toughness and chemical robustness during the fabrication process is not so simple. In this study, we report the successful fabrication of a Cu-doped deuterated target. The obtained samples were characterized by inductively coupled plasma optical emission spectrometry, differential scanning calorimetry and Fourier transform infrared spectroscopy. Simultaneous measurements of Cu K-shell x-ray emission and beam fusion neutrons were demonstrated using a petawatt laser at Osaka University.Ikeda T., Kaneyasu Y., Hosokawa H., et al. Fabrication of high-concentration Cu-doped deuterated targets for fast ignition experiments. Nuclear Fusion 63, 016010 (2023); https://doi.org/10.1088/1741-4326/aca2ba

A circulating subset of iNKT cells mediates antitumor and antiviral immunity

新規の循環型iNKT細胞を発見 --抗腫瘍・抗ウイルス感染効果の高い免疫細胞療法の開発への貢献に期待--. 京都大学プレスリリース. 2022-10-24.Invariant natural killer T (iNKT) cells are a group of innate-like T lymphocytes that recognize lipid antigens. They are supposed to be tissue resident and important for systemic and local immune regulation. To investigate the heterogeneity of iNKT cells, we recharacterized iNKT cells in the thymus and peripheral tissues. iNKT cells in the thymus were divided into three subpopulations by the expression of the natural killer cell receptor CD244 and the chemokine receptor CXCR6 and designated as C0 (CD244⁻CXCR6⁻), C1 (CD244⁻CXCR6⁺), or C2 (CD244⁺CXCR6⁺) iNKT cells. The development and maturation of C2 iNKT cells from C0 iNKT cells strictly depended on IL-15 produced by thymic epithelial cells. C2 iNKT cells expressed high levels of IFN-γ and granzymes and exhibited more NK cell–like features, whereas C1 iNKT cells showed more T cell–like characteristics. C2 iNKT cells were influenced by the microbiome and aging and suppressed the expression of the autoimmune regulator AIRE in the thymus. In peripheral tissues, C2 iNKT cells were circulating that were distinct from conventional tissue-resident C1 iNKT cells. Functionally, C2 iNKT cells protected mice from the tumor metastasis of melanoma cells by enhancing antitumor immunity and promoted antiviral immune responses against influenza virus infection. Furthermore, we identified human CD244⁺CXCR6⁺ iNKT cells with high cytotoxic properties as a counterpart of mouse C2 iNKT cells. Thus, this study reveals a circulating subset of iNKT cells with NK cell–like properties distinct from conventional tissue-resident iNKT cells

Demonstration of a spherical plasma mirror for the counter-propagating kilojoule-class petawatt LFEX laser system

A counter-propagating laser-beam platform using a spherical plasma mirror was developed for the kilojoule-class petawatt LFEX laser. The temporal and spatial overlaps of the incoming and redirected beams were measured with an optical interferometer and an x-ray pinhole camera. The plasma mirror performance was evaluated by measuring fast electrons, ions, and neutrons generated in the counter-propagating laser interaction with a Cu-doped deuterated film on both sides. The reflectivity and peak intensity were estimated as ∼50% and ∼5 × 1018 W/cm2, respectively. The platform could enable studies of counter-streaming charged particles in high-energy-density plasmas for fundamental and inertial confinement fusion research.Kojima S., Abe Y., Miura E., et al. Demonstration of a spherical plasma mirror for the counter-propagating kilojoule-class petawatt LFEX laser system. Optics Express 30, 43491 (2022); https://doi.org/10.1364/oe.475945