Hydrogen-bond-assisted isotactic-specific radical polymerization of N-vinyl-2-pyrrolidone with tartrate additives in toluene at low temperatures : high-resolution 1H NMR analysis

A diethyl L-tartrate (L-EtTar)-assisted radical polymerization of N-vinyl-2-pyrrolidone has been developed as the first reported example of the synthesis of isotactic-rich poly(N-vinyl-2-pyrrolidone) (PVP). The addition of L-EtTar in toluene at temperatures of –40°C and lower led to a significant increase in the polymer yield by one order of magnitude compared with the reaction in the absence of L-EtTar. Decreasing the polymerization temperature led to increases in the isotacticity of the PVP, with the mm triad reaching 66.4% at −93 °C. 1H NMR measurement at 920 MHz was conducted to establish a reliable strategy for quantifying the triad tacticities. High-temperature NMR measurements at 250 °C were performed using a specially-designed NMR probe, which led to dramatic narrowing of the 1H line width

High TC ferromagnetism in diluted magnetic semiconducting GaN:Mn films

Wurtzite GaN:Mn films on sapphire substrates were successfully grown by use of the molecular beam epitaxy (MBE) system. The film has an extremely high Curie temperature of around 940 K, although the Mn concentration is only about 3 ~ 5 %. Magnetization measurements were carried out in magnetic fields parallel to the film surface up to 7 T. The magnetization process shows the coexistence of ferromagnetic and paramagnetic contributions at low temperatures, while the typical ferromagnetic magnetization process is mainly observed at high temperatures because of the decrease of the paramagnetic contributions. The observed transport characteristics show a close relation between the magnetism and the impurity conduction. The double exchange mechanism of the Mn-impurity band is one of the possible models for the high-TC ferromagnetism in GaN:Mn.Comment: 20 pages, 4 figures, submitted to Physica

Japan College of Rheumatology 2009 guidelines for the use of tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, in rheumatoid arthritis

The introduction of biological agents targeting tumor necrosis factor-alpha (TNF-α) has brought about a paradigm shift in the treatment of rheumatoid arthritis (RA). Although these anti-TNF agents have excellent efficacy against RA, a substantial number of patients still show inadequate responses. In Western countries, such patients are already being treated with new classes of antirheumatic drugs such as abatacept and rituximab. Tocilizumab (TCZ) is a humanized monoclonal antibody developed in Japan against the human interleukin-6 (IL-6) receptor. TCZ does not only alleviate the signs and symptoms of RA but also seems to prevent progressive bone and joint destruction. However, there is a concern that TCZ might increase the risk of adverse events such as infections since IL-6 plays a pivotal role in the immune system. Calculating the relative risks of specific adverse outcomes with TCZ use remains difficult, due to insufficient patient numbers enrolled in clinical trials to date. This review presents tentative guidelines for the use of TCZ for RA patients prepared by the Japan College of Rheumatology and based on results of clinical trials in Japan and Western countries. The guidelines are intended as a guide for postmarketing surveillance and clinical practice, and will be revised periodically based on the surveillance

Identification of baseline gene expression signatures predicting therapeutic responses to three biologic agents in rheumatoid arthritis: a retrospective observational study

Ranked gene list by GSEA (TCZ analysis). (XLSX 984 kb

Effects of 3-styrylchromones on metabolic profiles and cell death in oral squamous cell carcinoma cells

Abstract4H-1-benzopyran-4-ones (chromones) are important naturally-distributing compounds. As compared with flavones, isoflavones and 2-styrylchromones, there are only few papers of 3-styrylchromones that have been published. We have previously reported that among fifteen 3-styrylchromone derivatives, three new synthetic compounds that have OCH3 group at the C-6 position of chromone ring, (E)-3-(4-hydroxystyryl)-6-methoxy-4H-chromen-4-one (compound 11), (E)-6-methoxy-3-(4-methoxystyryl)-4H-chromen-4-one (compound 4), (E)-6-methoxy-3-(3,4,5-trimethoxystyryl)-4H-chromen-4-one (compound 6) showed much higher cytotoxicities against four epithelial human oral squamous cell carcinoma (OSCC) lines than human normal oral mesenchymal cells. In order to further confirm the tumor specificities of these compounds, we compared their cytotoxicities against both human epithelial malignant and non-malignant cells, and then investigated their effects on fine cell structures and metabolic profiles and cell death in human OSCC cell line HSC-2. Cytotoxicities of compounds 4, 6, 11 were assayed with MTT method. Fine cell structures were observed under transmission electron microscope. Cellular metabolites were extracted with methanol and subjected to CE-TOFMS analysis. Compounds 4, 6, 11 showed much weaker cytotoxicity against human oral keratinocyte and primary human gingival epithelial cells, as compared with HSC-2, confirming their tumor-specificity, whereas doxorubicin and 5-FU were highly cytotoxic to these normal epithelial cells, giving unexpectedly lower tumor-specificity. The most cytotoxic compound 11, induced the mitochondrial vacuolization, autophagy suppression followed by apoptosis induction, and changes in the metabolites involved in amino acid and glycerophospholipid metabolisms. Chemical modification of lead compound 11 may be a potential choice for designing new type of anticancer drugs

Open Abdominal Management Among Non-Trauma Patients: The Appropriate Duration and a New Clinical Index

Purpose Despite widespread adoption of open abdominal management (OAM), there is currently no threshold criterion for OAM duration for non-trauma patients. Moreover, there is a positive relationship between morbidity and the duration of OAM, but an uncertain relationship with patients’ age. Therefore, a novel clinical index for the duration of open abdominal management (IDOM) was developed based on the patient’s age and risk of severe complications following OAM to indicate the maximum tolerable number of days of OAM based on the individual’s age. The utility of this new index was evaluated. Methods This retrospective study included 65 non-trauma patients managed with an open abdomen (OA) from August 2015 to August 2018. The IDOM was developed based on the patient’s age. The result indicated the maximum number of OA days. Patients’ demographic and operative variables were examined and patient data was assigned to one of two groups according to whether the actual number of OA days was above or below the calculated IDOM. Prevalence of complications between these groups was compared. Measures of validity were employed to assess the utility of the IDOM for patient complications. Results Sixty-five patients were included. The above-the calculated IDOM group exhibited a significantly longer OA and higher rates of wound complications and postoperative respiratory complications compared with the below the calculated IDOM group. The IDOM predicted the incidence of OA-related complications with a sensitivity of 72.4%, and a specificity of 80.6%. Conclusion The IDOM is a potentially useful tool for appropriate duration at the outset of OA

Exploratory classification of clinical phenotypes in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis using cluster analysis

A novel patient cluster in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may be identified in Japan. We performed multiple correspondence and cluster analysis regarding 427 clinically diagnosed AAV patients excluding eosinophilic granulomatosis with polyangiitis. Model 1 included the ANCA phenotype, items of the Birmingham Vasculitis Activity Score, and interstitial lung disease; model 2 included serum creatinine (s-Cr) and C-reactive protein (CRP) levels with model 1 components. In seven clusters determined in model 1, the ANCA-negative (n=8) and proteinase 3-ANCA-positive (n=41) groups emerged as two distinct clusters. The other five myeloperoxidase-ANCA-positive clusters were characterized by ear, nose, and throat (ENT) (n=47); cutaneous (n=36); renal (n=256), non-renal (n=33); and both ENT and cutaneous symptoms (n=6). Four clusters in model 2 were characterized by myeloperoxidase-ANCA negativity (n=42), without s-Cr elevation (1.3 mg/dL) with high CRP (>10 mg/dL) (n=71), or s-Cr elevation (>= 1.3 mg/dL) without high CRP (<= 10 mg/dL) (n=157). Overall, renal, and relapse-free survival rates were significantly different across the four clusters in model 2. ENT, cutaneous, and renal symptoms may be useful in characterization of Japanese AAV patients with myeloperoxidase-ANCA. The combination of s-Cr and CRP levels may be predictive of prognosis