Although matrix metalloproteinases (MMPs) are thought to be involved in the invasion and metastasis of a variety of malignant tumors, including human hepatocellular carcinoma (HCC), the mechanisms ...for the expression of MMPs in HCC are not known. To understand the mechanism(s) of MMP expression, the expression of matrilysin (MMP-7) and several genes of the Ets transcription factor family was investigated in human HCC and hepatoma-derived cell lines. The role of Ets-1 gene expression in HCC was also studied. Analysis by semiquantitative reverse transcription-PCR revealed that MMP-7 and Ets-1 are overexpressed and closely associated in HCC. To clarify the role of Ets-1, hepatoma cells were transduced with human Ets-1 or targeted with the Ets-1-specific antisense oligonucleotides. Cells stably transduced with the Ets-1 gene showed increased MMP-7 expression compared to parental and mock-transfected cells. Cells targeted with Ets-1-specific antisense oligonucleotides showed reduced expression of MMP-7. Cotransfection of cells with a MMP-7 promoter-reporter gene plasmid and an Ets-1 expression vector yielded an increase in MMP-7 promoter activity in an Ets-1-responsive element-dependent manner. Taken together, these data suggested that the Ets-1 oncogene is up-regulated and involved in the overexpression of MMP-7 in human HCC and may contribute to the progression of HCC.
This paper focuses on the effects of the interface between epoxy resin and nano- or micro-scale silica filler. Experiments were carried out on epoxy resin containing nano- or micro-scale silica ...fillers (nano-composite or micro-composite) to investigate the effects of the epoxy/filler interface on the properties of water absorption, electrical insulation and fracture toughness. The results indicated that epoxy/silica filler interface has an impact on the properties of the nano- and micro-composites. Nano-composites were shown to have higher water absorption than micro-composites because water accumulated over a larger interface area. Moreover, the nano-composites with interfaces treated with a silane coupling agent showed insulation breakdown properties and fracture toughness superior to those of the base epoxy resin and the micro-composites. The chemical bonding by the silane coupling agent at the epoxy/nano-scale silica filler interface played a more important role in water absorption and insulation breakdown properties than for the micro-scale silica filler. The filler size reduction to nano-scale needs appropriate interface treatment because of its tremendously large interface area. In addition, belt-shaped area models demonstrated the improvement of insulation breakdown properties and fracture toughness from the viewpoint of encountering frequency between electrical treeing or initial cracking and fillers. It is assumed that an increase in encountering frequency prevents treeing or cracking from propagating efficiently and thus improves insulation breakdown properties and fracture toughness in the nano-composite.
We directly observed laser shock-induced, anomalous elastic compression of highly oriented pyrolyticgraphite (HOPG) and subsequent phase transition to lonsdaleite at a longitudinal stress of ~30 GPa ...usingan X-ray Free Electron Laser (XFEL). The observed phase transition is diffusionless and most likelyrelaxes a strong shear stress in the highly elastically compressed lattice. Our experimental results showthat this diffusionless transformation depends on the mosaic spread of Highly Oriented PyrlolyticGraphite (HOPG) samples.
A 68-year-old man was admitted with acute renal failure caused by cholesterol embolization after undergoing carotid artery stenting. Hemodialysis therapy (HD) was immediately required because of ...uremia, using nafamostat mesilate as an anticoagulant for HD. However, blue toes and gangrene of the feet worsened. To prevent use of anticoagulants and stabilize BP, HD was changed to peritoneal dialysis (PD). After starting PD, blue toes and gangrene improved markedly. Residual renal function also partially recovered. Although BP was unstable during HD, stability of BP and avoidance of anticoagulants during PD therapy might have contributed to the good results.
The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of ...schizophrenia in Japan. We used a high-density single-nucleotide–polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (
LOD=
3.39) and suggestive evidence of linkage to 14q11.2 (
LOD=
2.87), 14q11.2-q13.2 (
LOD=
2.33), and 20p12.1-p11.2 (
LOD=
2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study—which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent—indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The American Society of Hematology guidelines recommend rituximab as second-line treatment, as well as splenectomy and thrombopoietin receptor agonists (TPO-RAs), for chronic immune thrombocytopenia ...(ITP). However, rituximab has not been approved for the treatment of chronic ITP in Japan. To establish chronic ITP as a new indication for rituximab, we conducted an investigator-initiated clinical trial to clarify the efficacy and safety of rituximab for Japanese patients with ITP.
This study was designed as a single-arm, multicenter phase III study. Patients diagnosed with chronic ITP who were previously treated with at least one therapy for ITP and whose platelet count was ≤ 30,000/μL were included. Patients with a past history or current hepatitis B virus, hepatitis C virus or HIV infection, who were treated with splenectomy within 12 weeks or with TPO-RA within 4 weeks were excluded. Rituximab at a dose of 375 mg/m2was intravenously infused once weekly for 4 weeks. Patients were premedicated with acetaminophen, restamin and hydrocortisone to prevent infusion reactions. Platelet counts, bleeding symptoms, and B lymphocyte counts were observed once monthly following the protocol. The primary endpoint was the proportion of patients whose platelet count was ≥ 50,000/μL 24 weeks after treatment with rituximab.
Between October 2011 and January 2013, 26 patients were enrolled in this study from 10 hospitals in Japan. Median age of the patients was 40 years and 89% were female. Baseline platelet counts were 23,000/μL. Median interval from diagnosis of ITP to commencing rituximab therapy was 5.9 years. Previous treatment of ITP was corticosteroids (69%), splenectomy (15%), TPO-RA (27%) and intravenous immunoglobulins (39%). At baseline, 58% of patients had some bleeding symptoms. Median number of previous ITP treatments was two. All patients completed the study. At 24 weeks after treatment, 30.8% (95% CI: 14.3–51.8%) of patients achieved platelet counts > 50,000/μL. Seven of eight responders demonstrated improvement until 8 weeks. Platelet count was significantly increased compared with baseline (P<0.001). No unknown severe adverse events were observed. Subgroup analyses showed that ITP duration was numerically associated with the efficacy rate (46% vs 15% for duration< median vs ≥ median, respectively). Bleeding symptoms measured with the WHO bleeding scale were improved compared with baseline.
We demonstrated the efficacy and safety of rituximab in Japanese patients with chronic ITP. The response rate was similar to that in previous reports in the US and Europe. We plan to propose that the Japanese government approve chronic ITP as a new indication for rituximab.
Miyakawa:Fuji film: Consultancy; Alexion pharmaceuticals: Honoraria; GlaxoSmithKline: Consultancy, Honoraria; KyowaHakkoKirin: Consultancy, Honoraria; Shire: Honoraria. Off Label Use: rituximab, clinical trial. Nishiwaki:Chugai pharmaceutical: Research Funding; Zenyaku Kogyo: Research Funding. Higashihara:Alexion: Honoraria; Asahi Kasei Pharma: Honoraria; Janssen pharma: Honoraria, Research Funding; Takeda: Honoraria; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Shionogi: Honoraria, Research Funding; Nippon Shinyaku: Honoraria, Research Funding; GlaxoSmithKline: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Chugai: Honoraria, Research Funding; KyowaHakkoKirin: Honoraria, Research Funding; Boehringer-Ingeheim: Honoraria; Daiichi Sankyo: Honoraria; Yakurt: Honoraria; Astellas: Research Funding; Pfizer: Research Funding; Teijin: Research Funding; Meiji Seika pharma: Research Funding; Venesis: Research Funding; Baxter: Research Funding; Torii pharmaceutical: Research Funding; Bristol-Myers Squibb: Research Funding; Dainippon Sumitomo: Research Funding; Taiho: Research Funding; Taisho Tomiyama: Research Funding; MSD: Research Funding. Nishikawa:Daiichi-Sankyo: Research Funding. Ozaki:Chugai pharmaceutical: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Kyowa Hakko Kirin: Honoraria. Kanakura:Alexion Pharmaceuticals: Research Funding, Speakers Bureau. Okamoto:Novartis : Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; GlaxoSmithKlein: Honoraria, Research Funding; KyowaHakkoKirin: Honoraria, Research Funding; Chugai: Honoraria, Research Funding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Junctional adhesion molecule (JAM) is a member of the immunoglobulin superfamily (IgSF) expressed in tight junctions of epithelial cells and endothelial cells, and implicated in transendothelial ...migration of leukocytes. Recently, JAM is reported to be constitutively expressed on circulating monocytes, neutrophils, lymphocytes subsets, and platelets. However, the role of JAM is not known. Here, we examined how phosphorylaton of JAM is regulated upon platelet activation. Phosphorylation of JAM was induced by thrombin, collagen, but not by ADP. The phosphorylated amino acids were shown to be serine residues by phosphoamino acid analysis. Inhibition of JAM's phosphorylation by PKC inhibitors and Ca++ chelator suggests the involvement of conventional types of PKCs. By in vitro kinase assays, we demonstrated that JAM could be directly phosphorylated by cPKCs. We also demonstrated phosphorylation of Ser 284, a putative PKC phosphorylation site, by immunoblotting with anti-phosphoserine-JAM antibody in thrombin-stimulated platelets. In addition to the phosphorylation, JAM seemed to form clusters at several sites of cell–cell contact in aggregated platelets by immunoelectron microscopic study. We speculate that JAM may be directly phosphorylated by cPKC(s)upon platelet activation and that the phosphorylationmight be involved in platelet activation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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