Search

Negative charged sites in the normal rabbit articular cartilage were investigated using cationic colloidal iron methods. In light microscopy of the cartilage stained with the colloidal iron at pH 1.5, a distinct Prussian blue reaction was observed in the pericellular matrix, and a weak blue reaction in the territorial and interterritorial matrices. At pH 7.0, a diffuse Prussian blue reaction was observed in the pericellular and interterritorial matrices. Digestion with chondroitinase ABC, hyaluronidase and keratanase could not erase the Prussian blue reaction. However, the sections digested with collagenase followed by chondroitinase ABC showed significant elimination of the Prussian blue reaction. Electron microscopy of ultrathin sections stained with the colloidal iron at pH 1.5 revealed that the cationic colloid particles were deposited abundantly in the pericellular matrix and dotted along collagen fibrils in the territorial and interterritorial matrices. The present results suggest that negatively charged sites in the articular cartilage derive mostly from chondroitin sulfate, whose proteoglycans firmly bind to collagen fibrils. Such an ultrastructure may maintain the electrostatic microenvironment in the collagen plexus, holding much water in the cartilage matrix, and also producing biomechanical properties such as tensile strength and elasticity of the cartilage.

Successful treatment was achieved for a patient with superior mesenteric artery thromboembolism concomitant with bilateral renal artery thromboembolism. Thrombi of the three vessels were lysed simultaneously with a three-catheter technique using short-term, high-dose urokinase followed by overnight infusion with low-dose urokinase.

Real-time observation of the high temperature interface between silicon carbide (SiC) and liquid alloy is indispensable to optimize the conditions for producing high quality SiC crystals by the solution growth method. In this work, real-time observation of the interface was established by using the interference observation to measure the height profile of the interface. The temperature dependence of the refractive index of 4H-SiC was measured up to 1773 K. The height measurement was then carried out for the SiC/alloy interface at 1573 K. From interference observation, bunched step heights of less than 10 nm were measured. The developed technique was applied for the real-time observation of dissolution behavior of SiC into molten Fe-Si alloy at 1573 K. The dissolution kinetics was discussed in terms of carbon mass transfer in the solution and interfacial reaction.

Background: A widespread downregulation of microRNAs is commonly observed in human cancers and is involved in cellular transformation and tumorigenesis. Because we previously reported that microRNA functions are inhibited under various kinds of cellular stresses including inflammatory cytokines in vitro, we hypothesized that chronic inflammation in vivo may also cause chronic functional impairment of microRNAs, which mimics a global reduction of microRNA abundance, resulting in a causal role in inflammation-associated tumorigenesis. Methods & Results: 1) To examine this hypothesis, we first confirmed the functional impairment of microRNAs under inflammatory stimuli in vitro using artificial reporter constructs. The derepression of microRNA-targeting reporter activities by inflammatory stimuli could also be observed using reporter constructs containing natural 3’UTR sequences of c-myc and Lin28B genes, which are targeted by endogenous let-7. 2) Next, we constructed reporter transgenic mice bearing CMV-promoter driven GFP construct carrying target sequences of microRNAs in its 3’UTR, and monitored the changes of microRNA functions in vivo during the course of a Dextran Sulfate Sodium (DSS) induced colitis-associated colon tumor model. The expression levels of GFP were significantly increased during colitis, suggesting that microRNA functions were impaired during the chronic inflammation in vivo. The expression levels of microRNA-target oncogenes such as c-myc and Lin28B in the colonic mucosa were indeed upregulated. 3) Lastly, to determine the consequences of the global functional impairment of microRNAs during the colitis, we examined Dicer-deficient mice, which have globally low levels of microRNA expression and may mimic the functional impairment of global microRNAs induced by chronic inflammation described above. As expected, Dicer deficient mice were more liable to have the colitis-associated tumors. This indicates that the global decrease of microRNAs leads to oncogenesis, suggesting that the functional impairment of global miRNAs during chronic inflammation can also be a cause of the inflammation-associated carcinogenesis. Conclusion: In conclusion, we propose a novel concept that the attenuation of global microRNA functions by chronic inflammation is the cause of inflammation-associated tumorigenesis. Citation Format: Takeshi Yoshikawa. Functional impairment of microRNAs induced by chronic inflammation is the cause of inflammation-associated colon tumorigenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2866. doi:10.1158/1538-7445.AM2013-2866

Nuclear factor κB (NF-κB) is a transcriptional factor that regulates a set of genes that are critical to many cellular biological processes, including liver tumorigenesis. MicroRNAs (miRNAs) are small non-coding RNAs that regulate specific target gene expression.To determine the miRNAs which are involved in regulating NF-κB activation in the liver, we screened for 60 kinds of miRNAs expressing in hepatocytes that can modulate NF-κB activation. We identified that miRNA-140 suppressed NF-κB activation significantly.Because miRNA-140 dysfunction was frequently observed in human hepatocellular carcinomas, it was hypothesized that the impairment of miRNA-140 function may be involved in hepatocarcinogenesis through NF-κB activation. Nuclear receptor interacting protein 1 (NRIP1) which is coactivator of NF-κB was identified as a target of miRNA-140 and the increased NRIP1 in hepatocellular carcinoma cells this led to enhanced NF-κB activation and hepatocarcinogenesis. MiRNA-140 knockout mice were indeed prone to hepatocarcinogenesis and had a phenotype similar to results in vitro. These results indicate that miRNA-140 acts as a liver tumor suppressor and the impairment of miRNA-140 function may also lead to hepatocarcinogenesis. Citation Format: Akemi Takata, Motoyuki Otsuka, Takeshi Yoshikawa, Takahiro Kishikawa, Motoko Ohno, Haruhiko Yoshida, Kazuhiko Koike. MicroRNA-140 dysfunction leads to hepatocarcinogenesis through NF-κB activation by impairing the regulation of NF-κB coactivator. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3059. doi:10.1158/1538-7445.AM2013-3059

Introduction Bone metastasis is one of the most common complications in clinical intractable castration-resistant prostate cancer (CRPC) and advanced prostate cancer period. The invasion ability of cancer cells was thought to have important relationship with the potential of cancer metastasis. EP4 receptor is overexpressed in several cancers, and enhanced EP4 receptor signaling has been previously shown to correlate with the invasion of several different cancer types. In present study, we found that EP4 antagonist can in vitro suppress the invasion phenotype abilities of CRPC PC3 cells, LNCaP cells with EP4 overexpressed which have the tendency to castration-resistance and in vivo suppress the CRPC bone metastasis animal models. Materials and methods Materials In vitro: PC3 cell and LNCaP cell in vivo: PC3/Luc cell. EP4-specific antagonist: ONO-AE3-208 Methods RNA interference was used to stably transfected EP4 to LNCaP with the pcDNA3.1-EP4, so as to be the LNCaP with vector control (LNCaP-mock) and LNCaP with EP4 overexpressed (LNCaP/EP4+) as described in our previous article. Effect on cell proliferation was determined firstly by the MTT assay. Transwell invasion assay was used to in vitro examine the metastasis abilities of PC3 cells, LNCaP cells, LNCaP/EP4+ and all after EP4 antagonist affected. Cells with ONO-AE3-208 at the final concentration of 0.1μmol/L, 1μmol/L and 10μmol/L were administrated to be the experimental group. To observe the effect of EP4 antagonist on the bone metastasis of prostate cancer in vivo, PC3/Luc cells were inoculated into the left cardiac ventricle of 5-week-old male nude mice. The mice developed osteolytic lesions with a mean endpoint at 52±7 days.To assess whether EP4 antagonist suppresses bone metastasis, ONO-AE3-208 (10 mg/kg/d) was given to the animals 5 days a week I.p. which the same volume of DDW was given as the control.To detect PC3 cell dissemination, bioluminescent imaging (BLI) was applied using a cooled CCD camera. We evaluated the efficacy of ONO-AE3-208 by measuring the photon counts of the metastatic lesions in the mandible and both hip joints in a blinded manner. Results The invasion assay showed that ONO-AE3-208 can inhibit the invasive abilities of both PC3 and LNCaP/EP4+ in a dose-dependent manner (p < 0.01). In animal experiment, metastatic bone lesions in the control group progressed while the photon emission was significantly suppressed in the ONO-AE3-208 treatment group during the observation period from day 28 every 7 days (p < 0.01). Conclusion We demonstrated that EP4 antagonist can in vitro inhibit the invasive abilities of CRPC PC3 and LNCaP/EP4+ cells. The administration of it can also suppress the bone metastasis of CRPC in vivo. Citation Format: Song Xu, Takayuki Goto, Takeshi Yoshikawa, Zhengyu Zhang, Liming Wang, Naoki Terada, Osamu Ogawa. EP4 antagonist suppresses bone metastasis in prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2813. doi:10.1158/1538-7445.AM2013-2813

MiRNA expression profile of human cancers has been characterized by an overall miRNA downregulation. While the causes include a transcriptional silencing and a failure of miRNA maturation, another possibility is that the deregulation of the machinery components for executing miRNA function also may cause similar consequences. Then, we screened the protein expression levels of the established members of the miRNA-containing ribonucleoproteins (Dicer, Ago2, TRBP2, DDX20 also known as Gemin3, and Gemin4) in various organ cancers by immunohisotchemistry. We detected reduced expression of DDX20 only in hepatocellular carcinoma tissues, while the levels of other genes were not drastically changed. We show that DDX20 suppresses NF-κB activity through regulating a subset of miRNA function. A microRNA library screen revealed that miR-140-3p and miR-22 suppress NF-κB activation by targeting the expression of NRIP1 and NCOA1, both are coactivators of NF-κB. However, in DDX20 deficient cells, this suppressive effect was lost, leading to NF-κB activation, a key regulator of hepatocarcinogenesis. In addition, DDX20 knockdown indeed induced cell transformation, revealed by a sphere-forming assay. These results indicate that DDX20 deficiency enhances NF-κB activity by impairing the NF-κB-suppressive action of microRNAs, and suggest that deregulation of the microRNA machinery may be one of the mechanisms of oncogenesis in liver cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3978. doi:10.1158/1538-7445.AM2011-3978

The remarkable SME is induced above glass transition temperature (Tg) by the transition volume change on Zr-5at%Ni-9at%Al-30at%Cu glassy alloy. The shape memory metallic glass is a new concept of the actuator applicable for hard-irradiated environment such as in fusion reactor.

In this paper, we describe the use of liquid Fe–Si alloy as the solvent for the solution growth of silicon carbide (SiC). Iron was chosen owing to the high solubility of carbon in molten iron. The crystal growth of SiC from Fe–40 mol % Si solvent on a seed crystal wafer of 6H- or 4H-SiC was carried out at 1,623–1,723 K using induction heating. The growth rate of SiC was obtained to be 90–260 µm/h. Furthermore, Raman spectroscopy revealed homo epitaxial growth on both 6H- and 4H-SiC under the experimental conditions used. Thus, the Fe–Si solvent was found to be effective for the rapid solution growth of SiC.

To respond to demands while reducing inventories, the Kanban control system (KCS) has been developed as a typical system for just-in-time production system. The original KCS has been revised to adaptive KCS by Tardif and Maaseidvaag (2001). However, in the adaptive KCS, how to adjust the number of Kanbans at each stage has never been considered. This paper proposes two types of adaptive KCS for two-stage production lines according to the difference of adjusting the number of Kanbans at each stage. A queuing-network model of the two types of adaptive KCSs is developed, and the performance is analysed and compared with each other by using Markov analysis. Numerical calculations are conducted to investigate the influence of the processing rate and cost parameters on the performance measures. The results show the advantages of each system over the other.

Epidemiologic evidence suggests that the risk of developing skin cancer is higher in certain geographic regions where sunlight is excessive. Even in such high risk regions, two distinct populations of long-term residents exist: people with, and people without skin cancer. We have compared the quantitative lifetime sunlight exposure between 11 nonmelanoma skin cancer patients who have lived in South Florida for 23.7 +/- 5.1 years and 9 age-matched normal, healthy individuals who have lived in South Florida for 23.4 +/- 4.1 years. An estimation of personal cumulative sunlight exposure was determined for each subject from data collected through detailed interviews. We found that there was no detectable, significant quantitative difference in cumulative sunlight exposure during life between these two groups. Because these individuals had previously been phenotyped for the effects of ultraviolet-B (UVB) radiation on induction of contact hypersensitivity, our results suggest that UVB-susceptibility may be a better indicator of skin cancer risk than cumulative lifetime sunlight exposure. Thus, although there is little doubt that sunlight exposure is an important factor in the development of skin cancer, our results emphasize the importance of host genetic factors in the pathogenesis of this disease.

Abstract 1926 Poster Board I-949 Purpose: Diffuse large B cell lymphoma (DLBCL) is a heterogeneous entity, with patients exhibiting a wide range of outcomes. The introduction of rituximab to CHOP (R-CHOP) has significantly altered improvement in survival. This raises concern regarding the utility of previously identified prognostic factors. Before rituximub era, some investigators have suggested that serum levels of some cytokines and their soluble receptors might reflect tumor growth and host tumor responses. Interleukin-18 (IL-18), originally designated as an interferon (IFN)-gamma inducing factor, is a cytokein which stimulates cytotoxic NK cell activity and T cells to produce IFN-gamma, IL-2, and GM-CSF. Increased IL-18 serum levels have been found in patients with some hematopoietic neoplasms. IL-18 is also immunostimulatory cytokine with antitumor activity in preclinical models, and a phase I study of recombinant human IL-18 was done to patients with advanced cancer. We have previously reported that IL-18 was strong prognostic factor in aggressive lymphoma patients who received CHOP without rituximab (ASH 2004, abstract #4543). The aim of the present study is to re-assess the prognostic significance of serum IL-18 in DLBCL treated with rituximab, and we also assessed IL-18 with subtype of DLBCL, GCB type and non GCB type. Meterials and methods: Consecutive 154 previously untreated patients with DLBCL prospectively participated in this study between 2002 and 2008. The patients were treated with 6-8 cycles of R-CHOP or R-THP (pirarubicin) -COP regimens. There was no difference with CHOP and THP-COP in our recent prospective randomized study (Tsurumi H et. al. JCRCO 2004). Serum IL-18 was determined by ELISA, and we classified subgroups of DLBCL according to Hans et al. Results: In all patients with DLBCL, the mean ± SD of serum IL-18 level was 829.5±1280.8 pg/ml (range 56 - 8697.5) with a median of 415.8 pg/ml. Various poor prognostic features, such as poor PS, many extranodal sites, advanced disease (CS III/IV) increased LDH and elderly people were strongly associated with a high serum IL-18 levels. The median serum IL-18 levels of the different IPI risk groups were as follows: 201pg/ml for the L risk; 361pg/ml for the LI risk; 440pg/ml for the HI risk; 691pg/ml for the H risk, respectively (P Conclusion: These results suggest that, in even rituximab era, a high serum IL-18 level predicts a poor prognosis of DLBCL and may be a useful biomarker for selecting appropriate treatment. Upfront high dose chemotherapy might be well indicated for non-GCB type DLBCL patients with serum high IL-18. Disclosures: No relevant conflicts of interest to declare.

Abstract 2924 Poster Board II-900 Introduction : Indoleamine 2,3-dioxygenase (IDO) is an enzyme that degrades the essential amino acid tryptophan along the kynurenine pathway. Pro-inflammatory cytokines, such as IFN-g, induce IDO during the inflammatory response in many human cell types. The induction of IDO is synergistic in the presence of TNF-a, IL-1 or IL-6, and might be mediated by a signaling pathway from NF-κB and/or MAPKs. Furthermore, some metabolites derived from tryptophan by IDO, such as L-kynurenine, block antigen-driven specific T-cell proliferation and induce T-cell death. Thus, IDO activity might play an important role in regulation of the immune response exerted by antigen presenting cells and also provide transformed cells with a potent tool to help escape from assault by the immune system. Indeed, we have previously reported that high serum L-kynurenine level is associated with poor prognosis of diffuse large B-cell lymphoma (DLBCL) (ASH 2008 abstract 2812). Here, we investigated the IDO expression of patients with DLBCL. Patients and methods : The study protocol comprised a prospective, consecutive entry design that was approved by our Institutional Review Board. We investigated 119 patients between December 2003 and June 2008 who were histologically diagnosed with DLBCL according to the WHO classification. We performed immunohistochemical (IHC) analysis for IDO expression by mouse anti-human IDO monoclonal antibody. Patients aged Results : The median age was 65.2 year (range, 24 - 88 y) and the median follow-up was 22.9 month (range, 0.60 – 55.4 mo). The IDO expression patterns were classified into 3 categories; diffuse positive, focal positive and negative patterns. The diffuse positive IDO expression in tumor tissue was found in 38 cases (32%). The focal positive and negative expression of IDO was 16 cases (13.4%) and 65 cases (54.6%), respectively. The diffuse IDO positive cells were lymphoma cells and the focal IDO positive cells were dendritic cells (DC) confirmed by IHC analysis. The CR rates of patients with diffuse positive IDO expression, focal positive and negative were 55.3%, 62.5% and 83.1%, respectively (P Discussion : A poor prognosis of patients with positive IDO expression might suggest that local immunity in tumor tissue is depressed by increasing L-kynurenine levels. Hence, IDO expression contributes to refractory to chemotherapy for DLBCL. Interestingly, expression pattern of IDO was significantly related with response to the treatment and prognosis of DLBCL. In conclusion, IDO activity might play an important role in DLBCL and the cells which express IDO are important for the response to treatment and prognosis of this malignancy. IDO, therefore, might be a candidate of therapeutic targets for DLBCL patients who are resistance to chemotherapy. Disclosures: No relevant conflicts of interest to declare.

Published under licence in Journal of Physics: Conference Series by IOP Publishing Ltd., Solid-liquid interfacial energies in alloys are important properties for the process design of materials production such as casting and crystal growth. Inadequate information exists on solid-liquid interfacial energies. Our aim for this study was thus to establish a method to measure solid-liquid interfacial energies in alloys from equilibrium interfacial shapes of solid-liquid-gas phases. Experiments were carried out on Cu-B and Ag-Bi systems where copper and silver were treated as solid phases, respectively. Since the determined values for solid-liquid interfacial tensions for both systems agreed with reported values or estimated values, it was clarified that solid-liquid interfacial energies can be measured by observing the interfacial shape.

Published under licence in Journal of Physics: Conference Series by IOP Publishing Ltd., The authors have applied hydrothermal reactions to develop recycling processing of slag or glass. As an example, under hydrothermal conditions such as 200～300oC and 30～40MPa with H2O, powders made of glass can be sintered to become solidified glass materials containing about 10mass% H2O. When the glass containing H2O is heated again under normal pressure, the glass expands releasing H2O to make porous microstructure. H2O starts to emit just above the glass transition temperature. Therefore, when we have a glass with low glass transition temperature, we can make low temperature foaming glass. The SiO2-Na2O-B2O3 glass is a candidate to be such a foaming glass. In this paper, we describe our recent trial on the fabrication of the low temperature foaming glass by using hydrothermal reaction.

Published under licence in Journal of Physics: Conference Series by IOP Publishing Ltd., Fe-Si melt is a candidate for use as an alloy solvent for rapid liquid phase growth of SiC because of the high solubility of carbon in molten iron. In this work, the equilibrium phase relationship between SiC and the liquid phase of the Fe-Si-C system was investigated at 1523 K by the phase equilibration technique, and was further studied with the thermodynamic calculation. It was found that Fe- 36 mol% Si melt equilibrates with SiC at the temperature and possesses the higher carbon solubility than silicon-based melt. The first trial of the SiC crystal growth experiment was then carried out with Fe- 36 mol% Si melt by means of temperature difference method, and formation of SiC layer was obtained on the graphite substrate. Accordingly, it was found possibility for rapid growth of SiC by the solvent growth method with Fe- 36 mol% Si melt.

Background: Indoleamine 2,3-dioxygenase (IDO) exerts powerful immunomodulatory effects through its enzymatic activity that leads to catabolism of the essential amino acid L-tryptophan. Pro-inflammatory cytokines such as IFN-g induce IDO during the inflammatory response in many human cell types. The induction of IDO is synergistic in the presence of TNF-a, IL-1 or IL-6, and might be mediated by a signaling pathway from NF-kB and/or MAPKs. Furthermore, some metabolites derived from tryptophan generated by IDO such as L-kynurenine, block Ag-driven specific T-cell proliferation and induce T-cell death. Increments in IDO activity correlate with tumor progression in various malignancies. Therefore, IDO activity might play an important role in regulation of the immune response exerted by antigen presenting cells and also provide transformed cells with a potent tool to help escape from assault by the immune system. The activity of IDO can be estimated by measuring the serum concentration of kynurenine. Here, we investigated the relevance of L-kynurenine as a prognostic factor for DLBCL with R-CHOP therapy. Patients and methods: The study protocol comprised a prospective, consecutive entry design that was approved by our Institutional Review Board. We investigated 75 patients between December 2002 and March 2007 who were histologically diagnosed with DLBCL according to the WHO classification. We measured L-kynurenine by high-performance liquid chromatography using a spectrophotometric or a fluorescence spectrometric detector. Patients aged Results: The median age was 68 y (range, 24 – 82 y) and the median follow-up was 20.6 mo (range, 0.6 – 42.3 mo). The median serum L-kynurenine level was 1.575 mM (range, 0.537 – 9.588). We found no significant correlations between L-kynurenine and gender, LDH, or sIL-2R. However, L-kynurenine significantly correlated with age (r = 0.279, P Discussion: The increase in serum L-kynurenine levels is thought to be caused by enhanced L-TRP catabolism, which inhibits tumoral local immunity. The result of a poor prognosis among patients with high L-kynurenine levels suggests that depressed local immunity due to enhanced IDO activity contributes to DLBCL becoming refractory to treatment.

Background: A combination of rituximab and CHOP (R-CHOP) is currently the standard treatment for diffuse large B-cell lymphoma (DLBCL). We previously reported the utility of THP-COP regimen consisted of cyclophosphamide (CPA), pirarubicin (tetrahydropyranyl adriamycin: THP), vincristine (VCR), and prednisolone (PSL) in patients with DLBCL (Tsurumi H. et al. Hematol Oncol 2007). THP, a derivative of doxorubicin (DOX), is another anthracycline that has been reported to be less cardiotoxic than DOX. We conducted this phase II study to verify untreated patients with CD20 positive DLBCL. Patients and Methods: The primary objective was to assess the efficacy of R-THP-COP with response rates. Secondary objectives were to assess the overall survival and drug safety. The study was conducted with local ethics committee approval, and all patients gave written, informed consent prior to enrollment. Adverse effects were graded according to the National Cancer Institute Common Toxicity Criteria version 2.0. Over 18 were eligible for inclusion in the study if they had a diagnosis of untreated CD20 positive DLBCL. DLBCL was confirmed by biopsy. All patients had DLBCL at clinical stage (CS) II, III, or IV. Patients aged Results: A total of 100 patients (55 males and 45 females) were enrolled in the study between December 2003 and December 2006. The median age was 59 years (range 24 – 69) in young patients (n = 48), and 75 years (range 70 – 83) in elderly patients (n = 52). 44 (92%) reached CR or CRu in young patients and 33 (63%) in elderly patients. Median follow-up was 29.4 months. The OS rate was 80.8 % after 3 years in young patients and 69.9% in elderly patients. The PFS rate was 74.7% after 3 years and 61.0% in elderly patients. OS rates did not differ significantly in accordance with IPI. There were 16 (35%), 35 (78%) and 7 (15%) patients who developed grade 3 or 4 anemia, neutropenia and thrombocytopenia in young patients, respectively. There were 12 (29%), 35 (85%) and 6 (14%) patients who developed grade 3 or 4 anemia, neutropenia and thrombocytopenia in elderly patients, respectively. Non-hematologic adverse effects were tolerable. Treatment regimen-related death was not observed in this study. Discussion: In this study, the efficacy, feasibility, and toxicity of the THP-COP regimen was not inferior to those previously reported for CHOP. The CR rate was 92%, this CR rate was not inferior to our previous study and other previous reported studies. About the survival rate, the 3-year OS in our R-THP-COP regimen for patients with DLBCL was equal to or higher than that of our previous study. We concluded that R-THP-COP regimen in not inferior to R-CHOP about curative effect at least. About the safety, it is not thought that the R-THPCOP regimen has more adverse events than the R-CHOP regimen either. The results of our clinical trial prove that it is worth performing the randomized trial of the R-THP-COP regimen and the R-CHOP regimen as phase III trial. We designed this phase III trial and the trial is ongoing.

Normal, healthy human volunteers and patients with proved history of non-melanoma skin cancer have been tested for their capacity to develop contact hypersensitivity to dinitrochlorobenzene (DNCB) following exposure of buttock skin to acute, low-dose ultraviolet B (UVB) radiation. Using a radiation protocol that achieves virtually complete depletion of normal-appearing Langerhans cells from irradiated skin, it was learned that approximately 60% of healthy volunteers developed vigorous contact hypersensitivity (CH) when 2000 micrograms DNCB was painted on the irradiated site. These individuals were designated UVB-resistant, and were distinguished from other individuals, designated UVB-susceptible, who failed to develop contact hypersensitivity following an identical treatment protocol. It was then discovered that virtually all (92%) skin cancer patients exposed to UVB and DNCB failed to develop CH, i.e., were UVB-susceptible. In subsequent experiments, epicutaneous application of 2000 micrograms DNCB to unirradiated skin of UVB-susceptible individuals revealed a further distinction between normal persons and skin cancer patients. Approximately 45% of the latter (and none of the former) remained unresponsive (failed to develop contact hypersensitivity following this second attempt at sensitization), implying that they had been rendered immunologically tolerant. These tolerant individuals responded normally to the unrelated hapten, diphencyprone. We conclude that human beings resemble inbred strains of laboratory mice in that some individuals are UVB-susceptible, whereas others are UVB-resistant. Because the incidence of UVB-susceptibility was significantly higher in skin cancer patients, and as specific unresponsiveness could be demonstrated only in these patients, we propose that UVB-susceptibility, as we define it in this hapten system, may be a risk factor for the development of skin cancer.

The solid solubilities of aluminum in silicon in the temperature range of 1016-1622 K have been measured by introducing aluminum into solid silicon by passing a molten silicon-aluminum zone through single crystalline silicon with temperature gradient zone melting method. The maximum solubility was found to be 4.3 X 10 -4 in molar fraction around 1450 K. The activity coefficient of aluminum in solid silicon at infinite dilution relative to the pure solid state was determined as RT In γ 0 Al(s) = 93200(±1000) - 14.5(±0.8)T (J/mol) (1016-1622 K).

The characteristics of a multichannel arc gap are investigated experimentally in the voltage range of less than 45 kV using a ferrite sharpener. The gap comprises 12 or 24 steel needle electrodes and a brass rod electrode. We examined the characteristics of the number of arc channels when the following parameters were changed independently: (1) rise rate of voltage pulse applied to the gap, (2) length of feeders which transmit voltage pulse from the ferrite sharpener to each needle electrode, (3) gap length, (4) kind and pressure of intergap gas and (5) with and without UV irradiation.

We report an ultraviolet B (UVB) protocol that achieves essentially complete depletion of Langerhans cells (LC) from human skin, while leaving the skin clinically intact. Sixteen human volunteers of skin types II and III were exposed to 144 mJ/cm2 of UVB each day for 4 successive days, on a 2-cm-diameter circle of buttock skin. In each case the irradiated skin showed redness and mild edema but no vesiculation or ulceration. One hour after the last exposure a 4-mm punch biopsy was taken from the center of the irradiated site. The epidermal sheet from each sample was separated and exposed to CD-1 antibody (12 samples) or HLA-DR antibody (4 samples) and the density of LC was assessed by immunofluorescence light microscopy. In each case the epidermal LC population was severely depleted to less than 20 cells/mm2, from a baseline of approximately 565 cells/mm2, and in many cases no morphologically normal LC remained. This simple protocol thus provides intact human skin completely depleted of LC. Such skin will provide an appropriate model for the in vivo study of the immune function in human skin deprived of its epidermal antigen-presenting capacity.

The aim of this study was to isolate algicidal bacteria so as to control harmful cyanobacterium Microcystis aeruginosa (M. aeruginosa) blooms using biological methods. Nine bacterial strains were isolated to inhibit the growth of M. aeruginosa, among which the MaI11-5 bacterial strain exhibited remarkable algicidal activity against M. aeruginosa cells during the test. Based on the 16S rDNA analysis, the isolated MaI11-5 was identified as Pedobacter sp. through morphology and homology research. The results of cocultivation of the cyanobacteria with MaI11-5 algicidal isolates showed obvious algicidal activity against cyanobacterial cells. The algicidal effect of MaI11-5 exceeded 50% after two days, exceeded 70% after four days, and reached 80% after seven days. The observation results with a scanning electron microscope showed that the cyanobacterial cells aggregated and produced mucous-like substances when cocultivated with the algicidal bacteria. The results indicated that the MaI11-5 bacterial strain may possess a novel function for controlling harmful blooms and further studies will provide new insights into its role in water environment.

The incidence of skin cancers of the basal and squamous cell types is extremely low among genetically black-skinned human beings, whereas these types of skin cancers are common among Caucasians, especially those who live in geographic areas of high sun exposure. Ultraviolet B light (UVB) is thought to be the primary oncogenic agent in sunlight. We have recently demonstrated that acute, low-dose exposure of Caucasian skin to UVB impairs the induction of contact hypersensitivity to dinitrochlorobenzene (DNCB) in approximately 40% of normal individuals. Importantly, this trait--termed UVB susceptibility--was found to be a characteristic of virtually 100% of patients with a history of biopsy-proved skin cancer, implying that UVB susceptibility may be a risk factor for this disease. Because melanin pigment is thought to be protective of some of the deleterious effects of UVB radiation, we have examined the capacity of a low-dose regimen of UVB to alter induction of contact hypersensitivity in individuals with genetically melanized or heavily tanned skin. Our results indicate that UVB radiation depletes heavily pigmented skin of Langerhans cells, just as it does in Caucasian skin. Moreover, UVB-susceptibility exists as a polymorphic trait in individuals with genetically determined black skin, as well as in individuals with heavily tanned skin, and the incidence of this trait is similar to that found among normal Caucasian subjects. Thus, melanin does not appear to protect against the deleterious effects of an acute, low-dose regimen of UVB on induction of cutaneous immunity, and the UVB susceptibility trait is equally well-represented in both black- and Caucasian-skinned individuals. We conclude that although UVB susceptibility may function as a risk factor for skin cancer in Caucasians, it does not function similarly in black-skinned human beings, probably because melanin effectively protects against the mutagenic properties of UVB radiation.

Tellurium is added to sulfur free-cutting steel in order to improve its machinability by inclusion control. However, the thermodynamic properties of the steel and inclusions have not yet been studied. In the present work, the dissolution of tellurium into steel was investigated. First, the equilibrium Te2(g) partial pressure of solid tellurium was determined at 663–693 K by the transpiration method. The equilibration of molten iron under a controlled tellurium partial pressure, prepared by the transpiration method, was then performed at 1823 K. An approximately linear relationship between the tellurium content of the molten iron and the partial pressure of Te(g) was found at mass% Te < 0.01.

Removal of boron is one of the major problems on the purification of silicon for solar cells. In order to clarify the possibility of its removal by acid leaching with calcium addition, the effect of calcium on thermodynamic properties of boron in molten silicon was studied. The interaction parameter between boron and calcium in molten silicon was determined as the negative value e Ca B = -3.08 ± 0.84 at 1723K and the practical leaching treatment was found to promote the removal ratio of boron up to 40% when 6.2% of calcium was contained in molten silicon.

A process for the recycling of wasted optical fiber is proposed in this work. By reducing optical fiber, which consists of highly purified silica with a plastic coating, high-purity silicon is obtained. For the preliminary approach for this purpose, the reduction of the silica inside the optical fiber into silicon was carried out using an arc-plasma furnace. As a result, silicon was formed without the addition of carbon as a reducing agent. However, because the coating material was thermally decomposed and gasified in the early stage of the reaction, the quantity of carbonaceous compounds present as the reductant was deficient, resulting in the formation of silicon carbide or silicon monoxide as byproducts. Further addition of carbon showed no significant effect on the yield of silicon but increased the amount of silicon carbide. In contrast, the silicon carbide was found to improve the yield of silicon when it was recycled back into the reactant medium with the unreacted optical fiber.