Opioid peptide participates in post-tetanic twitch inhibition in guinea pig isolated ileum

Phospholipase A2 (PLA2)-catalysed liberation of arachidonic acid is the rate-limiting step in the generation of the lipid mediators prostaglandins and leukotrienes. PLA2 regulation thus represents a pivotal mechanism in the pathogenesis of inflammation. In this study we investigated the effects of TNF alpha and IL-1 alpha on PLA2 activity in cultured murine keratinocytes. Starting 18 h after stimulation, PLA2 activity increased significantly by about 250-320%) in the supernatants and in the cell pellets. This effect was completely inhibited either by preincubation of the cells with dexamethasone 48 h before stimulation or by coincubation with actinomycin D. PLA2 activity detected in the supernatants was blocked by reduction with dithiothreitol, whereas the PLA2 activity in the pellets was dithiothreitol-resistant. We conclude that in murine keratinocytes IL-1 alpha induce de novo synthesis and release of a secretory PLA2 and the induction of a different PLA2 activity in the cytosol. These findings indicate a crucial link between early cytokine effects and the initiation of the lipid mediator cascade in keratinocytes. The observation that PLA2 induction could be completely inhibited by preincubation with dexamethasone allows new insights into the mechanism of steroid effects on epidermal inflammation and renders PLA2 regulation an interesting therapeutic target.     

Control of ammonia and odors in animal houses by a ferroelectricplasma reactor

The objective of this study was to develop an electric air-cleaning system for animal houses to control noxious gases and odors. An AC-powered ferroelectric packed-bed plasma reactor was tested for its ability to decompose ammonia and odors in the air. Four important parameters that affect reactor performance were investigated: gas residence time in the reactor (four test levels, 0.2 to 1.3 s), power voltage (six levels, 0 to 15 kV), power frequency (two levels, 60-Hz and 18-kHz), and initial ammonia concentration (three levels, 21, 27 and 55 ppm). Up to 95% ammonia decomposition efficiencies were obtained under a combination of test conditions. The packed-bed plasma reactor was effective in decomposing odors in the air taken from a swine house     

Development of kA-class alternating current superconducting conductors and fabrication of a prototype coreless superconducting autotransformer

Recently, multifilamentary superconducting wires with very low ac losses have been produced and practical applications will now be considered. To realize actualsize power machines and apparatuses, it is necessary to develop 1 - 10 kA ac conductors. However, the critical currents of multifilamentary wires at 1 T are several tens of A, and therefore it is necessary to use multistrand conductors consisting of several tens or several hundreds of strands. Such conductors sometimes show ac current degradation because of such factors as (1) nonuniform current distribution, (2) wire motion, (3) temperature increase, (4) longitudinal magnetic field effect, etc. Formerly, a coreless transformer was considered unpractical because of its large exciting current. However, Yamamoto and others proposed that a coreless superconducting transformer could be used as a stepdown autotransformer at the receiving side, utilizing its large exciting current as the reactive power source to cancel the charging current of an underground transmission line or UHV line, and therefore the shunt reactors could be eliminated. In this paper, development of ac-superconducting conductors aimed at prevention of current degradation are discussed, as well as quench test results of two small coils made with these conductors. In these conductors, low ac low strands with ultrafine NbTi filaments are twisted around a central bundle of stainless steel wires. One of the coils has been designed as a model coreless autotransformer, and its test result is also described.     

Primary human immunodeficiency virus type 1 viremia and central nervous system invasion in a novel hu-PBL-immunodeficient mouse strain

We established four new mouse strains with defective T and B cells as well as defects in innate immunological reactions using an NK cell depletion antibody and showed that all mutant mouse strains efficiently received human peripheral blood leukocyte (PBL) engraftment (hu-PBL-scid mice). Higher levels of human immunodeficiency virus type 1 (HIV-1) replication were observed in these new hu-PBL-scid mice than in conventional hu-PBL-C.B-17-scid mice. In one particular strain, hu-PBL-NOD-scid mice, high levels of HIV-1 viremia (more than 10(6) 50% infectious doses per ml) were detected after infection with HIV-1. The plasma viral load was about 100 to 1,000 times higher than that observed in other hu-PBL-scid mice infected with HIV-1. Although high-level viremia did not correlate with the total amount of HIV-1 RNA in cells from infected mice, high levels of free virions were detected only in hu-PBL-NOD-scid mice. HIV-1 viremia induced systemic HIV-1 infection involving the liver, lungs, and brain. PCR in situ hybridization confirmed that HIV-1-infected cells invaded the brain tissue of the hu-PBL-NOD-scid mice. Our results suggest that the genetic background, including innate immunity, is critical in the development of primary HIV-1 viremia and subsequent central nervous system invasion with HIV-1. The hu-PBL-NOD-scid mouse represents a useful model for the study of the pathogenesis of HIV-1 in vivo, especially brain involvement, and therapy of primary HIV-1 viremia.     

Formation and Microstructure of Carbon-Containing Oxide Scales by Oxidation of Single Crystals of Zirconium Carbide

The isothermal oxidation of ZrC single crystals with (100) orientation was carried out at temperatures of 500°, 550°, and 600°C at an oxygen pressure of 2.6 kPa for times up to 240 h. A polished cross section of the oxidized crystal was observed by backscattered electron imaging in a scanning electron microscope. Quantitative chemical analysis for Zr, O, and C and their elemental profiles by the linescan method in the ZrC and oxide scale were performed by wavelength dispersive X-ray microanalysis. A thin foil of a crystal oxidized at 600°C was examined by transmission electron microscopy. It was found that the oxide scale was divided into two regions, zones 1 and 2, which contained 14 to 23 and 7 to 10 at. % carbon, respectively. Zone 1 exhibited an almost compact, pore-free matrix of c -ZrO₂. In zone 2, some growth and aggregation of the c -ZrO₂ occurred, producing 5- to 20-nm-sized particles between which carbon should have been present. The thickness of zone 1 increased parabolically up to 240 h at 500°C and probably in an early period at 550° and 600°C, reaching a constant (about 2 (μm), in contrast to the thickness of zone 2, which increased linearly with time.     

Complement C5a anaphylatoxin fragment causes apoptosis in TGW neuroblastoma cells

Human neuroblastoma TGW cells express a C5a anaphylatoxin receptor-like molecule termed neuronal C5a receptor. A C5a-receptor fragment peptide (termed PR226-multiple antigenic peptide) can induce rapid apoptosis in TGW cells via neuronal C5a receptor-associated signal transduction pathways. In order to analyse role of activated complement system in neurodegeneration, TGW cells were exposed to an oligomer form of a C5a fragment (amino acids: 37-53) peptide termed PL37-multiple antigenic peptide. Upon treatment with PL37-multiple antigenic peptide, an increased nuclear c-fos expression was shown within 30 min. DNA fragmentation, a hallmark of apoptosis, was noted within 4 h. Extracellular administration of 100 nM PL37-multiple antigenic peptide evoked inward calcium current pulses. At higher doses (0.5 microM-1 microM), PL37-multiple antigenic peptide evoked higher current pulses, followed by an irreversible, high inward current. To exert its apoptotic effect, PL37-multiple antigenic peptide utilizes a pertussis toxin-sensitive signal transduction pathway associated with the neuronal C5a receptor. Activation of the complement system and therefore release of C5a has already been reported in Alzheimer's disease. In addition, the presence of the Kunitz-type proteinase inhibitors indicates an impaired protease function and a possible abnormal fragmentation of C5a anaphylatoxin. Our data suggest that neurons expressing neuronal C5a receptor are more vulnerable to the apoptosis associated with the neuronal C5a receptor and the possibility that abnormal activation of C5a receptor and C5a anaphylatoxin fragments might be involved in the pathogenesis of Alzheimer's disease.     

Plastic film carbon electrodes: enzymatic modification for on-line, continuous, and simultaneous measurement of lactate and glucose using microdialysis sampling

Ring and split-disk plastic film carbon electrodes (PFCEs) were fabricated for use in thin-layer radial flow cells which were coupled to a microdialysis sampling system. PFCEs, were initially coated with osmium poly(vinylpyridine) redox polymer horseradish peroxidase (Os-gel-HRP). Then a second coat of oxidase enzyme was applied to produce enzyme bilayer (oxidase/Os-gel-HRP) PFCEs which were subsequently over-coated with cellulose acetate for use in the determination of glucose or lactate at 0 mV (vs Ag/AgCl). Split-disk electrode geometry enabled different oxidase enzymes to be immobilized on each half of a split-disk, Os-gel-HRP-coated, PFCE to facilitate the electrochemically independent yet continuous on-line determination of these two analytes from a single dialysate. In continuous-flow experiments, cellulose acetate overcoated oxidase/Os-gel-HRP cast-coated PFCEs were quick to stabilize background current and displayed linear and sensitive responses to substrates. The effect of ascorbic acid was minimal and cross talk between partner split-disk electrodes was demonstrated to be acceptable for in vivo applications. The utility of this analytical system is demonstrated by the quantitative on-line continuous assay of changes in dialysate striatal extracellular glucose and lactate from a conscious rat during (a) local stimulation of neurons by perfusion with the depolarizing agent, Veratridine, and (b) physical restraint.     

A rare case of a thyrotropin-secreting pituitary tumor which responded to methimazole

A 52-year-old Japanese male complained of palpitations and excessive sweating. He showed evidence of hyperthyroidism, but without suppression of the serum thyroid-stimulating hormone (TSH). On admission, the serum level of the alpha-subunit of TSH was elevated, but tests for thyroid autoantibodies were negative. The TSH response to thyrotropin-releasing hormone (TRH) was blunted. Imaging studies revealed a pituitary tumor 2 cm in diameter. Administration of methimazole lowered the serum levels of thyroid hormones, and elevated the serum level of TSH. These findings led to the diagnosis of a thyrotropin-secreting pituitary tumor. Immunohistochemical analysis and electron microscopic findings verified the diagnosis.     

Effects of buprenorphine and Ro 15-4513 on delayed death and brain beta-endorphin levels in rats treated with cocaine or cocaine-ethanol

The present study was aimed at elucidating the relationship between brain beta-endorphin, which was estimated by the immunofluorescence method, and fatal drug toxicities due to cocaine and combined cocaine-ethanol administration, including the late fatal toxicities clinically noted. beta-endorphin is an endogenous opioid peptide, and its secretion has been suggested to be influenced by physiological stresses. Furthermore, since protection against these fatal toxicities has been previously reported to be provided by buprenorphine (a ligand for opioid receptors) and Ro 15-4513 (a ligand for benzodiazepine receptors), this study also focused on the relationship between the effects of these two ligands and the changes in brain beta-endorphin immunoreactivity. In the fatal toxicity study, a toxic dose (75 mg/kg, i.p.) of cocaine combined with and without ethanol (3 g/kg, i.p.) was administered to the rats, with and without buprenorphine (0.25, 0.5, 1 mg/kg, i.p.) or Ro 15-4513 (5, 10, 15 mg/kg, i.p.). All of the deaths that occurred in these animals were divided into two groups: early deaths with early toxic symptoms in which the drugs were detected in the tissue samples, and late deaths with late toxic symptoms in which no drugs were detected in the samples. Without the administration of buprenorphine or Ro 15-4513, the frequency of late deaths was higher in the cocaine group as compared to the cocaine-ethanol group. The total mortality rate was effectively attenuated by treatment with 0.25 mg/kg buprenorphine or 10 mg/kg Ro 15-4513. Following treatment with 1 mg/kg buprenorphine or 15 mg/kg Ro 15-4513, the frequency of late deaths was significantly enhanced in the cocaine group. The brain and liver cocaethylene concentrations were also attenuated in those groups in which the total mortality rates were attenuated. In the brain beta-endorphin immunoreactivity study, the number of beta-endorphin immunoreactive nerve cells at the arcuate nucleus was counted at 3 minutes or 24 hours after the drug treatment. At 3 minutes after the drug treatment, the number of weakly immunoreactive cells with photographic light absorption values greater than 50% was enhanced in the groups in which the frequency of late deaths had been increased. In the cocaine-ethanol groups treated with buprenorphine or Ro 15-4513, this enhancement of weakly immunoreactive cells was observed when the total mortality rate was increased, regardless of the type of death. At 24 hours after the drug treatment (50 mg/kg cocaine), an enhancement of the weakly immunoreactive cells only was observed in all of the groups in which the occurrence of toxicities had been enhanced, regardless of the type of toxicity. Therefore, it can be concluded that the enhancement of total brain beta-endorphin immunoreactivity was closely correlated with the increase in the frequency of total fatal toxicities, and that the enhancement of weakly immunoreactive cells was closely correlated with the increase in the frequency of delayed fatal toxicities.     

Raman characterization of lattice-matched GaInAsN layers grown on GaAs (0 0 1) substrates

First systematic Raman scattering characterization for the nearly lattice-matched GaInAsN layers has been discussed to investigate the local structural changes as the In and the N compositions increase. It has been found that the formation of the spontaneously ordered clusters in the GaInNAs layers strongly depends on the In incorporation, and the degradation mechanism of the crystal quality of GaInAsN with the high In and N compositions may be completely different from the GaAsN systems.