An Anti-apoptotic Role of NF-κB in TNFα-induced Apoptosis in an Ameloblastoma Cell Line

AbstractNuclear factor-κB (NF-κB) is involved in the promotion of cell survival in a variety of cell types. The present study focused on the role of NF-κB in TNFα-induced apoptosis in an ameloblastoma. Immunohistochemical staining revealed p65 NF-κB protein to be expressed in ameloblastoma tissues. Furthermore, immunoblotting and immunocytochemistry analyses showed that the stimulation of TNFα in an ameloblastoma cell line (AM-1) induced p65 NF-κB translocation from the cytoplasm to the nucleus, indicating NF-κB activation. These findings were confirmed by an NF-κB luciferase reporter assay, which detected enhanced NF-κB transcription activity of AM-1 cells by TNFα stimulation. Moreover, pretreatment with SN50, a nuclear translocation inhibitor, prior to TNFα stimulation, effectively inhibited TNFα-induced NF-κB activation in AM-1 cells. In order to reveal the role of NF-κB activation during TNFα-induced apoptosis in AM-1 cells, an apoptosis assay was performed, and showed that the potential of TNFα in inducing apoptosis in AM-1 cells was significantly elevated by inhibiting the NF-κB activation. These results suggest that NF-κB plays an anti-apoptotic role in TNFα-induced apoptosis in AM-1 cells

2001-GT-0083 DEVELOPMENT OF DRY LOW-NOX COMBUSTOR FOR 300 KW CLASS GAS TURBINE APPLIED TO CO-GENERATION SYSTEMS

ABSTRACT A 300 kWe class gas turbine which has a two-shaft and simple-cycle has been developed to apply to co-generation systems. The gas turbine engine is operated in the range of about 30% partial load to 100% load. The gas turbine combustor requires a wide range of stable operations and low NOx characteristics. A double staged lean premixed combustor, which has a primary combustion duct made of Si 3 N 4 ceramics, was developed to meet NOx regulations of less than 80 ppm (corrected at 0% oxygen). The gas turbine with the combustor has demonstrated superior low-emission performance of around 40 ppm (corrected at 0% oxygen) of NOx, and more than 99.5% of combustion efficiency between 30% and 100% of engine load. Endurance testing has demonstrated stable high combustion performance over 3,000 hours in spite of a wide compressor inlet air temperature (CIT) range of 5 to 35 degree C.. While increasing the gas generator turbine speed, the flow rate of primary fuel was controlled to hold a constant equivalence ratio of around 0.5 in the CIT range of more than 15 C. The output power was also decreased while increasing the CIT, in order to keep a constant temperature at the turbine inlet. The NOx decreases in the CIT range of more than 15 C. On the other hand, the NOx increases in the CIT range of less than 15 C when the output power was kept a constant maximum power. As a result, NOx emission has a peak value of about 40 ppm at 15 C

Utility of movement disorder society-unified Parkinson's disease rating scale for evaluating effect of subthalamic nucleus deep brain stimulation

BackgroundThe Movement Disorders Society (MDS)-Unified Parkinson's Disease Rating Scale (UPDRS) is increasingly used to assess motor dysfunction before and after subthalamic nucleus deep brain stimulation (STN-DBS).ObjectivesWe, therefore, investigated whether the MDS-UPDRS can detect longitudinal changes in motor function after STN-DBS in the same way as UPDRS.MethodsWe examined 21 patients with Parkinson's disease (PD) (mean age 59.2 ± 10.6 years, mean disease duration 12.0 ± 3.0 years) who underwent STN-DBS and whose motor functions were assessed by the UPDRS and MDS-UPDRS before, 3 months after, and 1 year after STN-DBS. We then evaluated the consistency between the scores of Parts II and III of the UPDRS and MDS-UPDRS during the off phase using Lin's concordance coefficient (LCC) and a Bland-Altman plot.ResultsThe scores of Parts II and III of both the UPDRS and MDS-UPDRS were significantly decreased 3 months and 1 year after STN-DBS during the off phase. Scores of the UPDRS and MDS-UPDRS showed significant positive correlations before and after STN-DBS. We calculated estimated MDS-UPDRS scores from the UPDRS scores using a regression line and calculated the LCC between the MDS-UPDRS and the estimated MDS-UPDRS scores. The LCC value was 0.59–0.91, which suggests a relatively high consistency between the UPDRS and MDS-UPDRS. The Bland-Altman plot showed that differences between both scores were basically within ±1.96 standard deviations of the difference.ConclusionThe present preliminary study indicated that the utility of the MDS-UPDRS in evaluating motor function before and after STN-DBS demonstrates its potential equivalency to the UPDRS

Elevated β-catenin pathway as a novel target for patients with resistance to EGF receptor targeting drugs

There is a high death rate of lung cancer patients. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective in some lung adenocarcinoma patients with EGFR mutations. However, a significant number of patients show primary and acquire resistance to EGFR-TKIs. Although the Akt kinase is commonly activated due to various resistance mechanisms, the key targets of Akt remain unclear. Here, we show that the Akt-β-catenin pathway may be a common resistance mechanism. We analyzed gene expression profiles of gefitinib-resistant PC9M2 cells that were derived from gefitinib-sensitive lung cancer PC9 cells and do not have known resistance mechanisms including EGFR mutation T790M. We found increased expression of Axin, a β-catenin target gene, increased phosphorylation of Akt and GSK3, accumulation of β-catenin in the cytoplasm/nucleus in PC9M2 cells. Both knockdown of β-catenin and treatment with a β-catenin inhibitor at least partially restored gefitinib sensitivity to PC9M2 cells. Lung adenocarcinoma tissues derived from gefitinib-resistant patients displayed a tendency to accumulate β-catenin in the cytoplasm. We provide a rationale for combination therapy that includes targeting of the Akt-β-catenin pathway to improve the efficacy of EGFR-TKIs

Criterion and Construct Validity of the CogState Schizophrenia Battery in Japanese Patients with Schizophrenia

BACKGROUND: The CogState Schizophrenia Battery (CSB), a computerized cognitive battery, covers all the same cognitive domains as the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery but is briefer to conduct. The aim of the present study was to evaluate the criterion and construct validity of the Japanese language version of the CSB (CSB-J) in Japanese patients with schizophrenia. METHODOLOGY/PRINCIPAL FINDINGS: Forty Japanese patients with schizophrenia and 40 Japanese healthy controls with matching age, gender, and premorbid intelligence quotient were enrolled. The CSB-J and the Brief Assessment of Cognition in Schizophrenia, Japanese-language version (BACS-J) were performed once. The structure of the CSB-J was also evaluated by a factor analysis. Similar to the BACS-J, the CSB-J was sensitive to cognitive impairment in Japanese patients with schizophrenia. Furthermore, there was a significant positive correlation between the CSB-J composite score and the BACS-J composite score. A factor analysis showed a three-factor model consisting of memory, speed, and social cognition factors. CONCLUSIONS/SIGNIFICANCE: This study suggests that the CSB-J is a useful and rapid automatically administered computerized battery for assessing broad cognitive domains in Japanese patients with schizophrenia

Characterization of pullulanase (PUL)-deficient mutants of rice (Oryza sativa L.) and the function of PUL on starch biosynthesis in the developing rice endosperm

Rice (Oryza sativa) allelic sugary1 (sug1) mutants defective in isoamylase 1 (ISA1) accumulate varying levels of starch and phytoglycogen in their endosperm, and the activity of a pullulanase-type of a debranching enzyme (PUL) was found to correlate closely with the severity of the sug1 phenotype. Thus, three PUL-deficient mutants were generated to investigate the function of PUL in starch biosynthesis. The reduction of PUL activity had no pleiotropic effects on the other enzymes involved in starch biosynthesis. The short chains (DP ≤13) of amylopectin in PUL mutants were increased compared with that of the wild type, but the extent of the changes was much smaller than that of sug1 mutants. The α-glucan composition [amylose, amylopectin, water-soluble polysaccharide (WSP)] and the structure of the starch components (amylose and amylopectin) of the PUL mutants were essentially the same, although the average chain length of the B2-3 chains of amylopectin in the PUL mutant was ∼3 residues longer than that of the wild type. The double mutants between the PUL-null and mild sug1 mutants still retained starch in the outer layer of endosperm tissue, while the amounts of WSP and short chains (DP ≤7) of amylopectin were higher than those of the sug1 mutant; this indicates that the PUL function partially overlaps with that of ISA1 and its deficiency has a much smaller effect on the synthesis of amylopectin than ISA1 deficiency and the variation of the sug1 phenotype is not significantly dependent on the PUL activities