In vivo metabolism of the vitamin D analog, 22-oxacalcitriol: evidence for side-chain truncation and 17-hydroxylation

After intravenous administration of the vitamin D3 analog, 22-oxacalcitriol (OCT), to normal rats plasma metabolites were investigated by HPLC, GC-MS and LC-MS. Five side-chain oxidation metabolites, 24R(OH)OCT, 24S(OH)OCT, (25R)-26(OH)OCT, (25S)-26(OH)OCT and 24oxoOCT, were identified by comparison with the corresponding synthetic compounds. These side-chain oxidation metabolites were similar to those of calcitriol [1alpha,25(OH)2 vitamin D3] described previously. Besides these five metabolites, two unique side-chain cleavage metabolites, 20S(OH)-hexanor-OCT and 17,20S(OH)2-hexanor-OCT, were identified as main metabolites in plasma by GC-MS and LC-MS using a specific chemical reaction. Our studies suggest that OCT is extensively metabolized and circulates in blood as a number of metabolites as well as unchanged OCT. This metabolism includes both unique pathways of C23-O22 cleavage and 17-hydroxylation, in addition to the side-chain oxidation metabolites similar to those of 1alpha,25-(OH)2D3.     

Family M42 aminopeptidase from the syntrophic bacterium Symbiobacterium thermophilum: characterization using recombinant protein

The chromosomal DNA of the syntrophic thermophile Symbiobacterium thermophilum contains open reading frames of the genes encoding family M42 aminopeptidases, Pep1079, Pep1080, and Pep1081. To characterize these peptidases, the genes were cloned into Escherichia coli and overexpressed. Our experiments using the recombinant proteins confirmed that Pep1079, Pep1080, and Pep1081 are components of arginyl or lysinyl aminopeptidases that require Co2+ for enzymatic activity. Coexistence of Pep1079 and Pep1080 is necessary for expressing high peptidase activity. Pep1081 enhances the activity of Pep1079 and Pep1080.     

A 99-mm2 0.7-W single-chip MPEG-2 422P@ML video, audio,and system encoder with a 64-Mb embedded DRAM for portable 422P@HLencoder system

A scalable single-chip 422P@ML MPEG-2 video, audio, and system encoder LSI for portable 422P@HL system is described. The encoder LSI is implemented using 0.13-μm embedded DRAM technology. It integrates 3-M logic gates and 64-Mb DRAM in an area of 99-mm². The power consumption is suppressed to 0.7 W by adopting a low-power DRAM core. It performs real-time 422P@ML video encoding, audio encoding, and system encoding with no external DRAM. Furthermore, the encoder LSI realizes a 422P@HL video encoder with multichip configuration, due to its scalable architecture. This results in a PC-card size 422P@HL encoder for portable HDTV codec system     

Reconstitution of a functional interleukin (IL)-7 receptor demonstrates that the IL-2 receptor gamma chain is required for IL-7 signal transduction

The interleukin (IL)-2 receptor gamma chain has recently been shown to be a component of the IL-7 and IL-4 receptors. Using a transient transfection assay and the trans-activation of reporter gene constructs which are under the control of cytokine-responsive promoter elements, we have studied signal transduction through the IL-7 receptor (IL-7R). The reporter gene expression was not stimulated by receptors that contained the cytoplasmic domain of the IL-7R, either as intact IL-7R or as part of a chimeric receptor. However, co-expression of the IL-7R with the IL-2 receptor gamma chain was able to stimulate gene activation. For maximal stimulation the intact cytoplasmic domains of each chain was required.     

High air stability of threshold voltage on gate bias stress in pentacene TFTs with a hydroxyl-free and amorphous fluoropolymer as gate insulators

We investigated the air stabilities of threshold voltages (V_th) on gate bias stress in pentacene thin-film transistors (TFTs) with a hydroxyl-free and amorphous fluoropolymer as gate insulators. The 40-nm-thick thin films of spin-coated fluoropolymer had excellent electrical insulating properties, and the pentacene TFTs exhibited negligible current hysteresis, low leakage current, a field-effect mobility of 0.45 cm²/Vs and an on/off current ratio of 3 × 10⁷ when it was operated at −20 V in ambient air. After a gate bias stress of 10⁴ s, a small V_th shift below 1.1 V was obtained despite non-passivation of the pentacene layer. We have discussed that the excellent air stability of V_th was attributed to the insulator surface without hydroxyl groups.     

A novel mutant gammac chain from a patient with typical phenotype of X-linked severe combined immunodeficiency (SCID) has partial signalling function for mediating IL-2 and IL-4 receptor action

Mutations of the common gamma (gammac) chain result in X-linked SCID (X-SCID), which is characterized by the reduction in number or absence of peripheral blood T cells and natural killer (NK) cells, with retention of normal numbers of B cells. In the present study we describe a novel mutant gammac chain of an X-SCID patient with a typical X-SCID phenotype. This mutant receptor subunit is able to associate with Jak3 to transduce a weak signal. The Jak3-specific action is demonstrated by the induction of gene expression through the haematopoietin receptor response element (HRRE) by IL-2 and IL-4 in the experimental model of transiently transfected hepatoma cells over-expressing Jak3. This result suggests that a threshold in the gammac-Jak3 interaction determines the X-SCID phenotype.     

Functional role of interleukin-4 (IL-4) and IL-7 in the development of X-linked severe combined immunodeficiency

Dextromethorphan (DEM)-mediated N-methyl-D-aspartate receptor blockade may result from an action of unchanged DEM or its active metabolite, dextrorphan (DOR). In humans, DEM is metabolized into DOR by the polymorphic enzyme CYP2D6. We therefore investigated the impact of quinidine (Qd), a selective inhibitor of CYP2D6, on DEM disposition and the contribution of CYP2D6 phenotype on DEM antinociceptive and neuromodulatory effects. Using a randomized, double-blind, crossover, placebo-controlled design, healthy volunteers (n = 7) received Qd (50 mg Qd sulfate orally) or a placebo and, 12 h later, either DEM (50 mg DEM hydrobromide orally) or a placebo. DEM and DOR pharmacodynamics were assessed for their antinociceptive and neuromodulatory effects. Antinociceptive effects were assessed over 4 h by subjective pain threshold and RIII nociceptive reflex (RIII) monitoring. Neuromodulatory effects were studied using the primary and secondary hyperalgesia induced by the topical application of capsaicin. Two of seven subjects were genotypic CYP2D6 PM. Pretreatment of EM by Qd suppressed DOR formation and increased the plasma level of DEM to the levels of poor metabolizers. In poor metabolizers, DEM induced a significant increase in objective (+45%) and subjective (+35%) pain thresholds. In extensive metabolizers, only a slight and short-lasting increase in the subjective threshold was observed, whereas no effect was seen on the objective threshold. DEM modulates secondary hyperalgesia compared with DOR. The CYP2D6 phenotype affects the disposition of DEM and the production of the active metabolite DOR. The impact of the CYP2D6 phenotype is of major importance for the spinal antinociceptive and neuromodulatory effects of DEM.     

Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genes

Interleukins-2 and -15 (IL-2 and IL-15) are cytokines with overlapping but distinct biological effects. Their receptors share two subunits (the IL-2R beta and -gamma chains) that are essential for signal transduction. The IL-2 receptor requires an additional IL-2-specific alpha subunit for high affinity IL-2 binding. Recently, a murine IL-15-specific alpha subunit was identified, cloned, and shown to be structurally related to IL-2R alpha. However, the murine IL-15R alpha alone bound IL-15 with a 1000-fold higher affinity than that seen with IL-2R alpha and IL-2. We now extend these studies into the human system with the isolation of three differentially spliced human IL-15R alpha variants that are all capable of high affinity binding of IL-15. The cytoplasmic domain of IL-15R alpha, like that of IL-2R alpha, is dispensable for mitogenic signaling, suggesting that the primary role of the alpha chains is to confer high affinity binding. At high concentrations, IL-15, like IL-2, is able to signal through a complex of IL-2R beta and -gamma in the absence of the alpha subunit. Furthermore, the IL15RA and IL2RA genes have a similar intron-exon organization and are closely linked in both human and murine genomes. However, the distribution of expression of the IL-15R alpha is much wider than that of the IL-2R alpha, suggesting a broader range of cellular targets for IL-15.     

A 0.8-μm BiCMOS ATM switch on an 800 Mb/s asynchronous bufferedbanyan network

An experimental element switch LSI for asynchronous transfer mode (ATM) switching systems was realized using 0.8-μm BiCMOS technology. The element switch transfers cells asynchronously when used in a buffered banyan network. Three key features of the element switch architecture are CASO buffers to increase the throughput, a synchronization technique called SCDB (synchronization in a clocked dual port buffer) to make possible asynchronous cell transmission on the element switches with simple hardware, and an implementation technique for virtual cut through, called CELL-BYPASS, which lowers the latency. An implementation of elastic store is proposed to achieve high-speed synchronization with simple hardware. The element switch LSI adopts an emitter-coupled-logic (ECL) interface. The maximum operation frequency of the element switch LSI is 200 MHz (typical)     

Effect of MgO and SO3 on the Impurity Concentration in Alite in Portland Cement Clinker

MgO in clinker promotes the stable growth of alite in favor of the occurrence of M ₃. Mg ions go into solid solution in alite by simply replacing the Ca-sites in the structure. While the concentration of Mg in alite increases in proportion to the amount of MgO in the clinker, the concentration of Al, Fe, and Ti in alite remains constant. It is thus the Mg ions occupying the Ca-sites that give rise to the occurrence of M ₃ at ambient temperature. By contrast, SO₃ encourages the growth instability of alite. The concentration of impurity elements in alite tends to increase with increasing amount of SO₃ in clinker. This is most remarkable for Al and seems closely connected with the occurrence of M ₁ at ambient temperature. The presence of S was clearly recognized in alite.