Identification of Tumor Suppressive Genes Regulated by miR-31-5p and miR-31-3p in Head and Neck Squamous Cell Carcinoma

We identified the microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC) tissues by RNA sequencing, in which 168 miRNAs were significantly upregulated, including both strands of the miR-31 duplex (miR-31-5p and miR-31-3p). The aims of this study were to identify networks of tumor suppressor genes regulated by miR-31-5p and miR-31-3p in HNSCC cells. Our functional assays showed that inhibition of miR-31-5p and miR-31-3p attenuated cancer cell malignant phenotypes (cell proliferation, migration, and invasion), suggesting that they had oncogenic potential in HNSCC cells. Our in silico analysis revealed 146 genes regulated by miR-31 in HNSCC cells. Among these targets, the low expression of seven genes (miR-31-5p targets: CACNB2 and IL34; miR-31-3p targets: CGNL1, CNTN3, GAS7, HOPX, and PBX1) was closely associated with poor prognosis in HNSCC. According to multivariate Cox regression analyses, the expression levels of five of those genes (CACNB2: p = 0.0189; IL34: p = 0.0425; CGNL1: p = 0.0014; CNTN3: p = 0.0304; and GAS7: p = 0.0412) were independent prognostic factors in patients with HNSCC. Our miRNA signature and miRNA-based approach will provide new insights into the molecular pathogenesis of HNSCC.     

Voltage-dependent calcium channel promoter restores baroreflex sensitivity in conscious dogs with heart failure

BACKGROUND: The aim of this study was to determine the mechanism by which the calcium channel promoter BAY y 5959 affects the control of heart rate and baroreflex sensitivity in conscious dogs with pacing-induced heart failure (HF). METHODS AND RESULTS: We compared responses to BAY y 5959, which increases inotropy and decreases chronotropy, with those to norepinephrine (NE), which coincidentally exerts the same directional effects on inotropy and chronotropy, albeit through different mechanisms, in the presence and absence of ganglionic blockade both in control and in HF. Both BAY y 5959 and NE elicit direct effects on the heart and indirect effects through activation of reflexes, primarily the sinoaortic baroreceptor reflex. BAY y 5959 still reduced heart rate in dogs with arterial baroreceptor denervation, but not after ganglionic blockade. HF induced classic catecholamine desensitization to the inotropic effects of NE and blunted reflex bradycardia. In contrast, inotropic responses to BAY y 5959 were preserved in HF. Surprisingly, the autonomically mediated bradycardia induced by BAY y 5959 was also preserved in HF. Baroreflex sensitivity was assessed in control and in HF by pulse interval-systolic arterial blood pressure (PI/SAP) slopes constructed in response to pharmacological alterations in arterial pressure. HF depressed the PI/SAP slope from 11.5+/-1.3 to 4.8+/-0.9 ms/mm Hg, but during BAY y 5959 infusion in HF, the PI/SAP slope was restored to 24.1+/-5.2 ms/mm Hg. To assess central versus peripheral actions of BAY y 5959, the agent was infused with intra-carotid artery perfusion at a low dose, which acted centrally but did not have an effect peripherally. Under these conditions, it still decreased heart rate and restored baroreflex sensitivity (PI/SAP slope, 12.7+/-2.8 ms/mm Hg). CONCLUSIONS: Thus, the calcium promoter restores arterial baroreflex sensitivity in HF. Based on intra-carotid artery experiments, this occurs through a central nervous system and vagal mechanism.     

A Consensus Protocol over Noisy Two‐Layered Networks with Cooperative and Antagonistic Interactions

This study is concerned with the consensus problems of multi‐agent systems with cooperative and antagonistic noisy interactions described by two‐layered network. That is, each agent is simultaneously influenced by the force of attraction and repulsion between each neighboring agents in cooperative and antagonistic layers. A distributed algorithm for achieving the consensus in a probabilistic sense is proposed and its sufficient conditions are clarified. The conditions tell us rigorous stopping rules which enable us to know the number of iterations that achieves consensus within a prespecified accuracy and probability. Some applications of consensus problems with cooperative and antagonistic interactions are shown through numerical examples.     

Induction of alloantigen-specific T cell tolerance through the treatment of human T lymphocytes with wortmannin

Signaling through the CD28 molecule on T cells by its natural ligand, B7, on APCs has recently been shown to require the presence of an active phosphatidylinositol 3-kinase pathway to mediate some of its costimulatory activities (1-7). Using the phosphatidylinositol 3-kinase inhibitor, wortmannin (WN) (8), on human and murine T cells, we have inhibited B7-1-mediated T cell activation and induced Ag-specific tolerance. The addition of WN and/or the B7-1 antagonist, CTLA4Ig, to primary human T cell cultures stimulated with B7-1-transfected allogeneic melanoma cell lines inhibited the generation of alloantigen-specific proliferative and cytolytic responses in vitro. Subsequent examination of these WN- and CTLA4Ig-treated primary T cell cultures revealed that these lymphocyte populations were tolerized to rechallenge with the priming alloantigens in secondary cultures in the absence of additional inhibitor(s). However, reactivity to a third party allogeneic stimulator remained intact. This WN-induced tolerance was reversed by the addition of high dose IL-2, but not IL-4 or IL-7, to the primary cultures, indicating that T cell anergy, not deletion, was responsible for this phenomenon. In vivo studies using a murine graft-vs-host disease (GVHD) model demonstrated that WN treatment of allogeneic donor lymphocytes in vitro failed to generate a significant GVHD in irradiated mouse recipients compared with control allogeneic donor lymphocytes. These findings suggest potentially novel therapeutic strategies for the prevention of GVHD.     

Antibacterial actin of vinegar against food-borne pathogenic bacteria including Escherichia coli O157:H7 (Part 2). Effect of sodium chloride and temperature on bactericidal activity

Bactericidal effects of various kinds of AWASEZU (processed vinegar, 2.5% acidity) on food-borne pathogenic bacteria including Escherichia coli O157:H7 and other bacteria were examined. the order of bactericidal activities was NIHAIZU (3.5% NaCl was added) > SANBA-IZU (3.5% NaCl and 10% sucrose were added) > plain vinegar (spirit vinegar) > AMAZU (10% sucrose was added). This indicates that their activities were enhanced by the addition of sodium chloride and suppressed by the addition of sugar. On the other hand, when soy sauce was used instead of sodium chloride, the order of bactericidal activities was plain vinegar > AMAZU > NIHAIZU > SANBAIZU. This is mainly because their activities were suppressed by the increase in the pH value. The effect of sodium chloride (0.01-15%) and temperature (10-50 degrees C) on bactericidal activities against E. coli O157:H7 in spirit vinegar (0.5-2.5% acidity) was further examined. When vinegar was used in combination with sodium chloride, predominant synergism on the bactericidal activity was observed. Their activities were markedly enhanced by the addition of sodium chloride in proportion to the concentration. In addition to this, at higher temperatures spirit vinegar killed bacteria much more rapidly. It should be noted that the bactericidal activity of spirit vinegar was extremely enhanced by the combined use of the addition of sodium chloride and the rise of temperature. For example, in 2.5% acidity vinegar, the time required for 3 log decrease in viable cell numbers at 20 degrees C was shortened to 1/140-fold by the addition of 5% sodium chloride, shortened to 1/51-fold by the rise of the reaction temperature at 40 degrees C, and shortened to 1/830-fold; 0.89 minutes by both the addition of 5% sodium chloride and the rise of temperature at 40 degrees C. In order to propose the methods to prevent food poisoning by bacterial infection, bactericidal activities of vinegar solution containing sodium chloride on cooking tools and raw vegetables were examined. Vinegar solution (1-2% acidity, 3-7% NaCl) produced more than 3 log decrease in viable cell numbers of E. coli O157:H7 on the surface of cutting board, and cabbage and cucumber at 20-50 degrees C. These results suggested that the treatment with vinegar solution containing sodium chloride may be one of the useful methods to prevent food poisoning.     

A study of virulence factors produced by MRSA strains isolated from blood samples

Toxic shock syndrome toxin-1 (TSST-1) and enterotoxins are important virulence factors produced by Staphylococcus aureus. It is reported that these toxins are associated with septic shock and toxic shock syndrome. We investigated the toxin production and coagulase types of 701 MRSA strains isolated in Sasebo City General Hospital between 1994 and 1996 TSST-1 or/and enterotoxins were detected in 67% of all MRSA strains, and those were detected in 88% of MRSA strains isolated from blood samples. 45% of all MRSA strains produced both TSST-1 and enterotoxin C, and 70% of MRSA strains obtained from blood produced those toxins. Frequency of TSST-1 or/and enterotoxin production by MRSA strains isolated from blood samples was significantly higher than that by MRSA strains isolated from urine and pharynx (p < 0.05), and frequency of both TSST-1 and enterotoxin C production by MRSA isolates from blood was significantly higher than that by MRSA strains isolated from pharyngeal sample (p < 0.05). This study indicated that investigation of virulence factors produced by MRSA might give the useful information on prevention and treatment of MRSA infection.     

A comprehensive economic analysis of biomass gasification systems

This paper presents a comprehensive economic analysis of biomass gasification systems. There has recently been interest in promoting biomass energy systems in Japan's domestic sector. However, there are problems in achieving this project. The costs of plant construction are very high compared with conventional plants. Accordingly, the unit costs of electricity will be increased to levels comparable with those of other environmental energy systems. Copyright © 2004 Wiley Periodicals, Inc. In this paper, biomass energy systems using woody biomass are proposed from the viewpoint of successful environmental business. Biomass integrated gasification combined cycle (BIGCC) plants operated by independent power producers and biomass gasification cogeneration (BGCGS) plants in sawmills or asphalt‐concrete production factories have the potential for implementation in the near future. Our analysis concludes that the systems proposed in this paper provide the following outcomes with subsidies: (1) the generating cost of BIGCC ranges from 15.1 to 36.6 yen/kWh, (2) the generating cost of BGCGS ranges from 2.6 to 32.2 yen/kWh, and (3) the cost reduction of BGCGS products in asphalt factories amounts to about 60 million yen per year. © 2005 Wiley Periodicals, Inc. Electr Eng Jpn, 153(3): 52–63, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.20089     

Low superoxide dismutase activity in schizophrenic patients with tardive dyskinesia

BACKGROUND: Tardive dyskinesia (TD) is a therapy-resistant adverse effect of neuroleptics. Although the exact pathophysiology of TD is unknown, oxygen radicals have been speculated to play a role in TD based on several lines of evidence. Superoxide dismutase (SOD) is a key enzyme which scavenges oxygen radicals. The authors investigated the association between erythrocyte SOD activity and TD. METHODS: Erythrocyte SOD activities were measured, blinded as to the presence or absence of TD. In 30 patients with schizophrenia who had been on typical neuroleptics for more than 10 years. TD severity was independently assessed, using the abnormal involuntary movement scale (AIMS), by two raters. RESULTS: There was a significant decrease in erythrocyte SOD activity in the definite TD group (N = 10) as compared with the no TD (N = 8) and questionable TD (N = 12) groups. Erythrocyte Cu,Zn-SOD activities correlated with AIMS scores. CONCLUSIONS: Patients with TD had low SOD activities as compared to those without TD. As a causal link between SOD activity and TD was not established in this study, larger prospective studies are warranted to determine whether patients with low SOD activity are susceptible to neuroleptic-induced TD.     

Quantitation of hepatitis G virus RNA in allogeneic bone marrow transplant recipients. Stem Cell Transplantation Team

In thermolysin, tryptophan 115 seems to be at the S2 subsite. Trp-115 was replaced with tyrosine, phenylalanine, leucine, and valine during site-directed mutagenesis in order to evaluate the role of Trp-115 in the proteolytic activity of thermolysin. The mutant enzymes with Tyr-115 or Phe-115 had as much proteolytic activity as the wild-type enzyme, but the other two mutant enzymes had no activity. We found earlier that the substitution of Trp-115 with alanine, glutamic acid, lysine, and glutamine causes the enzyme to lose all activity, so an aromatic amino acid at position 115 seems to be essential for thermolysin.