A cryopreservation method of human peripheral blood mononuclear cells for efficient production of dendritic cells

We studied whether inducers of cell differentiation alone could have cytotoxic effect on the promonocytic U937 and Mono Mac 6 cells in vitro. The cells were incubated with standard differentiating doses of interferon (IFN)-gamma, dibutyryl cAMP (Bt2cAMP) or the phorbol ester phorbol-12-myristate-13-acetate (PMA), with or without lipopolysaccharide (LPS), and both protein synthesis and viability were examined. In both U937 and Mono Mac 6 cells the incorporation of [3H]leucine was significantly reduced after PMA plus LPS stimulation, but not after IFN-gamma stimulation, when compared with controls. For U937 cells there was also reduced incorporation after Bt2cAMP stimulation. Trypan blue exclusion experiments and the number of cells remaining in the cultures indicated that Bt2cAMP-, PMA- and/or LPS-stimulated, but not IFN-gamma-stimulated, cells were less viable than unstimulated U937 or Mono Mac 6 cells. The results suggest that Bt2cAMP, PMA and LPS, but not IFN-gamma, are cytotoxic towards promonocytic cancer cell lines in vitro.     

Framework for Performance-Based Design of Building Structures

Abstract:   This article proposes a new framework for performance-based design (PBD) of building structures. This framework was proposed under the 3-year Japanese Government Comprehensive Research and Development Project on "Development of a New Engineering Framework for Building Structures" launched in the fiscal year of 1995. The primary objective of the project is to create a system in which the performance of buildings is clearly stated, and consumers, that is, occupants, are well informed of how their buildings will perform and how much it will cost to maintain their performance. The framework emphasizes the establishment of target performance, the performance evaluation, and the performance statement as the main three elements. It also stresses that an institutional framework and support systems need to be provided to enable PBD to be practiced efficiently. The implementation of the proposed framework is also expected to promote engineering innovation, progress in building engineering, and globalization. The new framework will also bring other benefits, such as improved design techniques, greater design flexibility, and international harmonization. It is also important for building structural performance to become one of the most important indexes for consumers to define a building's value. The Japanese building code was changed to the performance-based code, based in the clear and comprehensive manner proposed in this article. In the United States, "Vision 2000" ( SEAOC, 1995 ) was published, then many research activities were conducted simultaneously.     

Molecular biological background of FAP and HNPCC, and treatment strategies of both diseases depend upon genetic information

Recent advancement of molecular biology disclose responsible genes of FAP(familial adenomatous polyposis) and HNPCC(hereditary non polyposis colorectal cancer). Gardner Syndrome is now categorized as subtype of FAP. Turcot Syndrome is now known as a heterogeneous disease. Turcot Syndrome caused by APC gene develops medulloblastoma and Turcot Syndrome caused by mismatch repair gene develops glioblastoma. Because of the discovery of APC gene, the presymptomatic diagnosis of asymptomatic gene carriers are now available and preventive surgery can be planned. FAP patients with mutated APC gene between codon 1250 and 1464 shows severe phenotype. It is known that FAP patient whose APC gene mutation locates at codon 1309 develops cancer 10 years earlier in comparison to the rest of the cases. Consequently risky rectal mucosa should be removed in this group of patients. As for HNPCC, presymptomatic diagnosis is still not possible because the penetrance rate has not been estimated yet and some additional responsible genes are expected to be discovered. Replication error, mutator phenotype of mismatch repair gene is useful indicator to predict second primary cancers. When the patient in a HNPCC family develops adenoma with microsatellite mistability, preventive colectomy might be one of the surgical option with the informed consent of the patient.     

Potent inhibition of HIV type 1 replication by an antiinflammatory alkaloid, cepharanthine, in chronically infected monocytic cells

Cepharanthine is a biscoclaurine alkaloid isolated from Stephania cepharantha Hayata and has been shown to have antiinflammatory, antiallergic, and immunomodulatory activities in vivo. As several inflammatory cytokines and oxidative stresses are involved in the pathogenesis of HIV-1 infection, we investigated the inhibitory effects of cepharanthine on tumor necrosis factor alpha (TNF-alpha)- and phorbol 12-myristate 13-acetate (PMA)-induced HIV-1 replication in chronically infected cell lines. Two chronically HIV-1-infected cell lines, U1 (monocytic) and ACH-2 (T lymphocytic), were stimulated with TNF-alpha or PMA and cultured in the presence of various concentrations of the compound. HIV-1 replication was determined by p24 antigen level. The inhibitory effects of cepharanthine on HIV-1 long terminal repeat (LTR)-driven gene expression and nuclear factor kappaB (NF-kappaB) activation were also examined. Cepharanthine dose dependently inhibited HIV-1 replication in TNF-alpha- and PMA-stimulated U1 cells but not in ACH-2 cells. Its 50% effective and cytotoxic concentrations were 0.016 and 2.2 microg/ml in PMA-stimulated U1 cells, respectively. Cepharanthine was found to suppress HIV-1 LTR-driven gene expression through the inhibition of NF-kappaB activation. These results indicate that cepharanthine is a highly potent inhibitor of HIV-1 replication in a chronically infected monocytic cell line. Since biscoclaurine alkaloids, containing cepharanthine as a major component, are widely used for the treatment of patients with various inflammatory diseases in Japan, cepharanthine should be further pursued for its chemotherapeutic potential in HIV-1-infected patients.     

Development of systems reliability analysis code SECOM-2 for seismic PSA

An integrated code system SECOM-2, developed at the Japan Atomic Energy Research Institute (JAERI), has the following functions for systems reliability analysis in seismic probabilistic safety assessments (PSAs): (1) calculation of component failure probability, (2) extraction of minimal cut sets (MCSs) from a given fault tree (FT), (3) calculation of frequencies of accident sequences and core damage, (4) importance analysis with several measures with consideration of unique parameters of seismic PSAs, (5) sensitivity analysis, and (6) uncertainty analysis. This paper summarizes the special features of SECOM-2 to perform the analyses mentioned above. At JAERI, using an integrated FT which represents seismically induced core damage due to all initiating events as a system model to calculate core damage frequency of a nuclear power plant, SECOM-2 can calculate conditional point estimate probabilities of system failures, losses of safety functions, and core damage as a function of earthquake motions. The point estimate is computed by a method which gives an exact numerical solution using the Boolean arithmetic model method. As for consideration of correlation of component failure, which has been an important issue in seismic PSAs, a new technique based on direct FT quantification by a Monte Carlo simulation is being added to SECOM-2. Adding this technique, the core damage frequency can be calculated not only with the upper bound approximation based on MCSs but also with a near exact solution taking into account the correlation among all components. This paper also presents the preliminary results of a seismic PSA of a generic BWR plant in Japan performed at JAERI to demonstrate the functions of the SECOM-2 code.     

MST-16, a novel derivative of bis(2,6-dioxopiperazine), synergistically enhances the antitumor effects of anthracyclines

OBJECTIVE: The aim of this study was to evaluate whether toluene, like many other organic solvents and solvent mixtures, could impair color vision. SUBJECTS AND METHODS: We investigated color vision impairment in three groups of workers, two groups occupationally exposed to toluene and a nonexposed group. The first exposed group, group E1, comprised 41 workers (median value of toluene in air 35.00 ppm, range 11.3-49.3 ppm) and the second exposed group, group E2, comprised 32 subjects (median value of toluene in air 156.00 ppm, range 66.0-250.0 ppm). The nonexposed group, group NE, comprised 83 subjects. Color vision was evaluated by the Lanthony D-15 desaturated test according to Verriest's classification: type I, loss in the red-green range; type II, loss in the blue-yellow and red-green ranges, and type III, loss in the blue-yellow range. Subjects were classified as dyschromates if specific acquired loss was determined in at least one eye. In both exposed groups, exposure was evaluated by measurement of the concentration of toluene in the ambient air and in the blood. In group E2, level of hippuric acid and orthocresol in urine after the work shift were also determined. The Mann-Whitney U-test, t-test, chi 2-test, and Spearman's rank correlation and multiple regression analysis were used for statistical analysis. RESULTS: Type III dyschromatopsia was detected in all groups examined: 26.6% of the workers in group NE, 31.7% of those in group E1, and 50% of those in group E2. As many as 15.6% of the workers in group E2, 4.8% of those in group E1, and only 1.2% of those in group NE had type II dyschromatopsia. A statistically significant difference in the prevalence of total dyschromatopsia (type III + type II) was established among the three examined groups together (chi 2 = 14.13; df = 2; P < 0.01), between group E2 and group E1 (chi 2 = 4.96; P < 0.05), and between group E2 and group NE (chi 2 = 12.50; P < 0.005), whereas no significant difference was found between groups E1 and NE. Type III dyschromatopsia was significantly correlated with age in group NE (P < 0.01) and in group E1 (P < 0.005). In group E2, both type II (P < 0.05) and type III dyschromatopsia correlated with toluene in ambient air and with the duration of exposure to toluene (both P < 0.005). In group E2, total dyschromatopsia correlated significantly with toluene in ambient air and in blood (both P < 0.05) as well as with hippuric acid in urine after the work shift (P < 0.001). CONCLUSION: This study suggests that toluene can impair color vision.     

Improvement of bond strength of BPDA‐PDA‐type polyimide film by corona discharge treatment

Aromatic polyimide film composed of biphenyl tetracarboxylic acid dianhydride (BPDA) and p‐phenylene diamine (PDA) is a very stable polymer at high temperatures and very useful for the electronics industry. Bonding properties were improved by corona discharge treatment of this film. The chemical modification method was applied for generated functional groups, that is, carboxylic, hydroxyl, and amino groups in the gas phase, and the quantity of these functional groups was determined by X‐ray photoelectron spectroscopy. The functional groups increased with corona energy, leveling off at a specific corona energy. The bond strength of the copper foil/adhesive/polyimide film was determined. The relationship between bond strength and functional group content was analyzed by multivariate analysis. Bond strength could be sufficiently correlated with functional group quantity. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 3403–3408, 2006