Hemophagocytic syndrome in five patients with Epstein-Barr virus negative B-cell lymphoma

BACKGROUND: The recent recognition of the association of Epstein-Barr virus (EBV) with T-cell/natural killer cell (T/NK-cell) lymphoma has documented that particular types of EBV-containing T/NK-cell lymphoma are frequently complicated by hemophagocytic syndrome (HPS). This observation suggests that both EBV and proliferating T/NK-lymphoma cells play significant roles in the development of HPS. Cytokines released from neoplastic T cells are presumed to account for the activation of macrophages, which is followed by a complex cascade of cytokine production, resulting in full-blown HPS. Five patients with B-cell lymphoma complicated by HPS were studied for elevated serum cytokines, the association of EBV, and CD25 expression of lymphoma cells; the aim of this study was to verify whether the mechanisms of HPS development hypothesized for T/NK-cell lymphoma also operate in B-cell lymphoma. METHODS: Sera were analyzed for the presence of inflammatory and immunoregulatory cytokines. Flow cytometry, immunohistology (IH), in situ hybridization (ISH), polymerase chain reaction (PCR), and Southern blot analysis were performed using bone marrow aspirates, biopsy specimens, and autopsy specimens. RESULTS: Immunophenotypic and Southern blot studies verified that the lymphoma cells of all five patients were of B-cell lineage. Bone marrow aspirates demonstrated histiocytosis with extensive hemophagocytic activity. Marked elevation of serum cytokines and expression of CD25 were observed in all five patients. However, the results of PCR, ISH using EBER1 probe, and IH for latent membrane protein indicated that these lymphoma cells were free of EBV infection. CONCLUSIONS: In patients with B-cell lymphoma, EBV infection is not necessarily required for the initiation of HPS. In this article, the pathogenesis of HPS assumed to be operative in B-cell lymphoma is discussed with reference to T/NK-cell lymphoma complicated by HPS.     

A New Hybrid Phosphine Ligand for Palladium‐Catalyzed Amination of Aryl Halides

A new hybrid phosphine was designed. The phosphine combines two common structural characteristics found among the effective phosphine ligands reported recently, namely, three tert‐alkyl substituents binding to the phosphorus and an aryl group at an appropriate position. A hybrid phospine/palladium system is versatile and effective for the coupling reaction of various aryl halides with primary and secondary amines including carbazole.     

Motion control of electric vehicles and prospects of supercapacitors

Novel motion control techniques for electric vehicles (EVs) on the basis of the quick torque generation in these vehicles have been developed at the Hori Laboratory. Because EVs are powered by electric motors, they have three major advantages: (i) motor torque generation is quick and accurate, (ii) a motor can be attached to each wheel, and (iii) motor torque can be estimated precisely. These advantages enable us to (i) easily realize high-performance antilock braking systems and traction control systems with minor feedback control of each wheel, (ii) control chassis motion, for example, direct yaw control, and (iii) estimate road surface condition. We have developed test vehicles and confirmed the effectiveness of the proposed methods. Recently, we have manufactured small EVs that are powered only by supercapacitors. Supercapacitors have long operating life, large current density, and are environmental friendly. Furthermore, their energy level can be estimated from their terminal voltage. Because EVs powered by supercapacitors can run for more than 20 min by charging only for 30 s, recharging EVs will not be a major problem. In the future, EVs will be recharged via contactless power transfer. Copyright © 2009 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.     

Structure-Based Design,Synthesis, and Biological Evaluation of Imidazo[4,5-b]Pyridin-2-one-Based p38 MAP Kinase Inhibitors: Part 2

We identified novel potent inhibitors of p38 mitogen-activated protein (MAP) kinase using a structure-based design strategy, beginning with lead compound, 3-(butan-2-yl)-6-(2,4-difluoroanilino)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one ( 1 ). To enhance the inhibitory activity of 1 against production of tumor necrosis factor-α (TNF-α) in human whole blood (hWB) cell assays, we designed and synthesized hybrid compounds in which the imidazo[4,5-b]pyridin-2-one core was successfully linked with the p-methylbenzamide fragment. Among the compounds evaluated, 3-(3-tert-butyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)-4-methyl-N-(1-methyl-1H-pyrazol-3-yl)benzamide ( 25 ) exhibited potent p38 inhibition, superior suppression of TNF-α production in hWB cells, and also significant in vivo efficacy in a rat model of collagen-induced arthritis (CIA). In this paper, we report the discovery of potent, selective, and orally bioavailable imidazo[4,5-b]pyridin-2-one-based p38 MAP kinase inhibitors.     

Construction of Cellulose Binding Domain Fusion FMN-Dependent NADH-Azoreductase and Glucose 1-Dehydrogenase for the Development of Flow Injection Analysis with Fusion Enzymes Immobilized on Cellulose

The cellulose binding domain (CBD) of cellulosome-integrating protein A from Clostridium thermocellum NBRC 103400 was genetically fused to FMN-dependent NADH-azoreductase (AZR) and glucose 1-dehydrogenase (GDH) from Bacillus subtilis. The fusion enzymes, AZR-CBD and CBD-GDH, were expressed in Escherichia coli Rosetta-gami B (DE3). The enzymes were purified from cell-free extracts, and the specific activity of AZR-CBD was 15.1 U/mg and that of CBD-GDH was 22.6 U/mg. AZR-CBD and CBD-GDH bound strongly to 0.5 % swollen cellulose at approximately 95 and 98 % of the initial protein amounts, respectively. After immobilization onto the swollen cellulose, AZR-CBD and CBD-GDH retained their catalytic activity. Both enzymes bound weakly to 0.5 % microcrystalline cellulose, but the addition of a high concentration of microcrystalline cellulose (10 %) improved the binding rate of both enzymes. A reactor for flow injection analysis was filled with microcrystalline cellulose-immobilized AZR-CBD and CBD-GDH. This flow injection analysis system was successfully applied for the determination of glucose, and a linear calibration curve was observed in the range of approximately 0.16–2.5 mM glucose, with a correlation coefficient, r, of 0.998.     

Growth of β-Ga2O3 nanocolumns crossing perpendicularly each other on MgO (1 0 0) surface

β-Ga₂O₃ nanocolumns straightened and crossed perpendicularly each other were deposited on MgO (1 0 0) substrate by vapor phase transport method. Growth of the nanocolumns was examined at steps of 1000, 1050, and 1200 °C in elevation of source-boat temperature. We have drawn out the substrate from deposition-tube at each source-boat temperatures of 1000, 1050, and 1200 °C. Scanning electron microscopy of the sample with source-boat temperature of 1200 °C demonstrated that the straightened and elongated nanocolumns are crossing perpendicularly each other. Typical lengths of the nanocolumns were in the range of several hundreds nanometers below 1050 °C, and those of 1200 °C were in the range of ten to fifteen hundreds nanometers. Diameters of the nanocolumns stayed in the range of few hundreds nanometers, notwithstanding variation of the source temperature. X-ray diffraction and transmission electron microscopy with energy dispersive X-ray spectroscopy revealed that the nanocolumns are monoclinic β-Ga₂O₃ crystal, and the (4 0 0) plane of β-Ga₂O₃ nanocolumns is parallel to the (1 0 0) plane of MgO substrate.     

Manufacture of organic transistors on large‐area flexible substrate using direct imaging exposure system by wet process suitable for roll‐to‐roll production

Organic thin‐film transistors (OTFTs) can be fabricated via a wet process and have exceptionally high flexibility. Therefore, production using the roll‐to‐roll (RtoR) method is expected. We succeeded in developing a new OTFT wet fabrication process adaptable to the RtoR process. Utilizing the electroless plating method for wiring formation, all materials can be formed in a wet process and can be patterned using the photolithography process. In addition, we succeeded in fabricating OTFT on an A4‐type flexible substrate using RtoR direct imaging exposure system.     

Cell surface protein engineering for high-performance whole-cell catalysts

Cell surface protein engineering facilitated by accumulation of information on genome and protein structure involves heterologous production and modification of cell surface proteins using genetic engineering, and is important for the development of high-performance whole-cell catalysts. In this field, cell surface display is a major technology by exposing target proteins, such as enzymes, on the cell surface using a carrier protein. The target proteins are fused to the carrier proteins that transport and tether them to the cell surface, as well as to a secretion signal. This paper reviews cell surface display systems for prokaryotic and eukaryotic cells from the perspective of carrier proteins, which determine the number of displayed molecules, and the localization, size, and direction (N- or C-terminal anchoring) of the passengers. We also discuss advanced methods for displaying multiple enzymes and a new method for the immobilization of whole-cell catalysts using adhesive surface proteins.

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