Analysis of the mechanism of tumor metastasis by the transfection of integrin cDNA

Integrin plays an important role in tumor metastasis through its interaction with extracellular matrix and endothelial cell. We have examined the role of each integrin in tumor metastasis by using transfection of integrin cDNA into various cells. Transfection of integrin alpha 2 subunit into RD cells, human rhabdomyosarcoma cells which do not express integrin alpha 2 beta 1, potentiated the frequency of metastases in various organs; lung, bone, adrenal gland, lymph node. alpha 4-transfectant of Chinese hamster ovary (CHO) cells, which do not have alpha 4 beta 1 on the cell surface, metastasized to bone through its interaction with VCAM-1 in the bone marrow stroma cells. On the other hand, alpha 5-transfectant of CHO cells was much less tumorgenic than parent CHO cells. These data suggest integrin influence tumor metastasis sometimes favorably and sometimes unfavorably according to the activity and the balance of various integrins.     

Development of control technology for HTTR hydrogen production system with mock-up test facility: System controllability test for loss of chemical reaction

The Japan Atomic Energy Agency has been planning the demonstration test of hydrogen production with the High Temperature Engineering Test Reactor (HTTR). In a HTTR hydrogen production system (HTTR-H2), it is required to control a primary helium temperature within an allowable value at a reactor inlet to prevent a reactor scram. A cooling system for a secondary helium with a steam generator (SG) and a radiator is installed at the downstream of a chemical rector in a secondary helium loop in order to mitigate the thermal disturbance caused by the hydrogen production system. Prior to HTTR-H2, the simulation test with a mock-up test facility has been carried out to establish the controllability on the helium temperature using the cooling system against the loss of chemical reaction. It was confirmed that the fluctuations of the helium temperature at chemical reactor outlet, more than 200 K, at the loss of chemical reaction could be successfully mitigated within the target of ±10 K at SG outlet. A dynamic simulation code of the cooling system for HTTR-H2 was verified with the obtained test data.     

Effect of timing of granulocyte-colony stimulating factor administration on leukopenia induced by systemic chemotherapy in patients with non-small-cell lung cancer--multi-center randomized crossover study

Sixty-six chemotherapy-naive patients with non-small-cell carcinoma of the lung were given two courses of systemic chemotherapy consisting of mitomycin C, vindesine, and cisplatin. The effect of the timing of administration of grannulocyte colony-stimulating factor (G-CSF) on the incidence of neutropenic fever, the nadir leukocyte count, the duration of neutropenia ( < or = 1000/mm3), and the time needed for recovery from neutropenia was studied. Patients were assigned at random to begin receiving G-CSF (50 microns/m2, subcutaneously) either when the leukocyte count was less than or equal to 1000/mm3 (group I) or when it was between 1000/mm3 and 2000/mm3 (group II), in a crossover fashion. The nadir leukocyte count was lower in group I than in group II (859/mm3 and 1215/mm3, respectively). The duration of leukopenia (defined as a leukocyte count less than or equal to 1000/mm3) was greater in group I than in group II (1.5 days and 0.8 day, respectively), as was the time needed for recovery to a leukocyte count of 2000/mm3 (1.9 days and 1.6 days, respectively) (p < 0.05). No differences were found in the incidence of neutropenic fever (group I: 44%, group Ii: 45%), in the duration of fever (group I: 2.3 days, group II: 2.8 days), or in the duration of G-CSF use (group I: 6.3 days, group II: 6.8 days). There were no treatment-related deaths in either group. We conclude that when this type of combination chemotherapy is given for non-small-cell carcinoma of the lung, administration of G-CSF can be postponed without clinical problems until the leukocyte count is less than of equal to 1000/mm3.     

Angiotensin-II-induced hypertension chemotherapy: evaluation of hepatic blood flow with oxygen-15 PET

We quantitatively measured blood flow in liver parenchyma and hepatic tumors in two patients using 15O-carbon dioxide (steady state) and 15O-water (dynamic) PET imaging. Images were acquired before and during administration of angiotensin-II to achieve a hypertensive state. Blood flow in the hepatocellular carcinoma was greater than that of the parenchyma. Blood flow in the colon metastasis was similar to that in the parenchyma and lower in the center than in the periphery. During a hypertensive state induced by angiotensin II, blood flow in both the primary and secondary liver tumors did not change, while blood flow in the liver parenchyma decreased. As a result, there was a relative increase in tumor blood flow during the hypertensive state on PET images. Furthermore, blood flow to the spleen decreased to 55% of baseline during the hypertensive state. These findings suggest that hypertensive cancer chemotherapy may protect normal tissue. Furthermore, PET imaging may be able to predict the efficacy of hypertensive cancer chemotherapy in the patients with liver tumors.     

Induction of lymphocytes cytotoxic to oral epithelial cells by Streptococcus mitis superantigen

The preparation of a superantigenic fraction F-2 from the culture supernatant of Streptococcus mitis 108, a fresh isolate from human tooth surfaces, was reported previously. Now, to determine the possible pathogenic role of the superantigen in oral mucosal diseases, we examined the cytotoxic effects of human peripheral blood T-cells activated with F-2 on human oral epithelial cells. T-cells activated with F-2 were cytotoxic to the human squamous carcinoma HO-1-N-1 cells derived from the oral mucosa, similar to those activated with Staphylococcus aureus enterotoxin B (SEB). This cytotoxic effect was increased in a dose-dependent manner by the addition of the respective stimulant, F-2 or SEB, to the cytotoxic assay system. F-2 endowed mainly CD8+ T-cells with cytotoxic activity. Pretreatment with human interferon gamma increased the sensitivity of the HO-1-N-1 cells to the cytotoxic effects of F-2-activated T-cells. The F-2-activated T-cells were also cytotoxic to human keratinocytes derived from gingiva. There was no correlation between the degree of cytotoxicity and the levels of tumor necrosis factor alpha in co-cultures of F-2-activated T-cells and HO-1-N-1 cells. A double-chamber plate experiment revealed no cytotoxic effects when the F-2-activated T-cells were separated from the HO-1-N-1 cells. Supernatants of the co-cultures of target and effector cells were not cytotoxic to HO-1-N-1 cells. These findings suggest that the cytotoxic effects of the F-2-activated T-cells on HO-1-N-1 cells were mediated not by soluble factors but by the direct interaction between the activated T-cells and the target cells. The cytotoxicity of the F-2-activated T-cells against HO-1-N-1 cells was markedly inhibited by monoclonal antibodies (MAbs) against CD11a and CD54, but was only slightly inhibited by MAbs against human leukocyte antigen (HLA)-DR and CD2. Thus, the interaction between lymphocyte-function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) was crucial for the F-2-dependent T-cell-mediated cytotoxicity against oral epithelial cells, while HLA-DR and CD2 molecules are not necessarily involved in the cytotoxicity observed.     

Present status and practical issues on dosimetry for the lens of the eye at JAEA MOX fuel facilities

ABSTRACT

At Japan Atomic Energy Agency (JAEA) MOX fuel facilities, a worker usually wears a protective lead apron; therefore, the dose to the lens of the eye (lens dose) outside the apron is higher than that to the torso. To estimate the potential impact on the current facility operation of the International Commission of Radiological Protection (ICRP)-proposed lens dose limit reduction from 150 mSv/y to average 20 mSv/y, the authors carried out an analysis on the past dose records for the workers over the last 18 years. Of a total of 4,312 workers’ records analyzed, two workers’ annual lens doses exceeded the lowered limit of 20 mSv (23.3 mSv and 20.7 mSv), although the maximum effective dose was below 10 mSv in each case. These compiled dose data reveal that in the glovebox and related operations the lens dose will be a limiting factor in radiological control under the newly lowered dose limit. To ensure that the number of workers with an annual lens dose greater than 15 mSv (approximately 0.6% of the workers) is kept to a minimum, the implementation of an administrative control level for the lens dose is considered.     

Thermal and mechanical properties of hydrides of Zr–Hf alloys

Polycrystalline bulk samples of δ-phase Hf hydrides with various Zr contents were prepared and their high-temperature stability and thermal and mechanical properties were investigated. The phase structure was examined between room temperature and 973 K using high-temperature X-ray diffraction and thermogravimetric–differential thermal analysis. From room temperature to 673 K, the coefficient of linear thermal expansion, specific heat capacity, and thermal conductivity were evaluated. The Vickers hardness and sound velocity were measured at room temperature, and the elastic modulus was evaluated. The effect of the Zr content on the high-temperature stability and the thermal and mechanical properties of Hf hydrides was studied.     

Verification analysis of thermoluminescent albedo neutron dosimetry at MOX fuel facilities

Radiation workers engaging in the fabrication of MOX fuels at the Japan Atomic Energy Agency-Nuclear Fuel Cycle Engineering Laboratories are exposed to neutrons. Accordingly, thermoluminescent albedo dosemeters (TLADs) are used for individual neutron dosimetry. Because dose estimation using TLADs is susceptible to variation of the neutron energy spectrum, the authors have provided TLADs incorporating solid-state nuclear tracks detectors (SSNTDs) to selected workers who are routinely exposed to neutrons and have continued analysis of the relationship between the SSNTD and the TLAD (T/R(f)) over the past 6 y from 2004 to 2009. Consequently, the T/R(f) value in each year was less than the data during 1991-1993, although the neutron spectra had not changed since then. This decrease of the T/R(f) implies that the ratio of operation time nearby gloveboxes and the total work time has decreased.     

Measurement of the 2-dimensional electric field vector indielectric liquids

A new measurement technique for two-dimensional electric field vectors (electric field intensity and its direction) in liquid dielectrics has been developed in this study. The theoretical equation for measuring the electrical field vector is derived for the optical system which consists of a He-Ne laser, polarizer, quarter-wave plate, test cell with nonuniform electric field, nonpolarizing beam splitter, two analyzers and two photo detectors. The effectiveness of the technique is confirmed by comparing the theoretical values and experimental results. Furthermore, the nonuniform electric field vector distributions of the transformer oil in a compound insulation system of liquids and solids are measured