Decoding cellular deformation from pseudo-simultaneously observed Rho GTPase activities.

Limitations in simultaneously observing the activity of multiple molecules in live cells prevent researchers from elucidating how these molecules coordinate the dynamic regulation of cellular functions. Here, we propose the motion-triggered average (MTA) algorithm to characterize pseudo-simultaneous dynamic changes in arbitrary cellular deformation and molecular activities. Using MTA, we successfully extract a pseudo-simultaneous time series from individually observed activities of three Rho GTPases: Cdc42, Rac1, and RhoA.

[Determination of Flufenacet and Its Metabolites in Agricultural Products by LC-MS/MS].

A simultaneous analytical method based on LC-MS/MS was developed for the determination of flufenacet and its metabolites, [(4-fluorophenyl)(1-methylethyl) amino]oxo-acetic acid and [N-(4-fluorophenyl)-N-(1-methylethyl) acetamide]-2-sulfinylacetic acid, in agricultural products. The compounds were extracted from samples with methanol. The crude extracts were purified using Bond Elut C18 and InertSep GC/PSA, then determined by LC-MS/MS.

Prodromal signs and symptoms of serious infections with tocilizumab treatment for rheumatoid arthritis: Text mining of the Japanese postmarketing adverse event-reporting database.

Objective: To search for signs and symptoms before serious infection (SI) occurs in tocilizumab (TCZ)-treated rheumatoid arthritis (RA) patients.

Methods: Individual case safety reports, including structured (age, sex, adverse event [AE]) and unstructured (clinical narratives) data, were analyzed by automated text mining from a Japanese post-marketing AE-reporting database (16 April 2008-10 April 2015) assuming the following: treated in Japan; TCZ RA treatment; ≥1 SI; unable to exclude causality between TCZ and SIs.

Results: The database included 7653 RA patients; 1221 reports met four criteria, encompassing 1591 SIs.

Effectiveness and safety of tocilizumab in achieving clinical and functional remission, and sustaining efficacy in biologics-naive patients with rheumatoid arthritis: The FIRST Bio study.

Objective: To evaluate effectiveness and safety of tocilizumab (TCZ) in biologic-naive Japanese patients with rheumatoid arthritis (RA) in real-world settings, and to analyze the relationship between disease duration and clinical outcomes.

Methods: The FIRST Bio study was a postmarketing surveillance study of intravenous TCZ in biologics-naive patients who had a prior inadequate response or were intolerant to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD). Effectiveness, safety, and concomitant csDMARD administration were assessed.

Retreatment efficacy and safety of tocilizumab in patients with rheumatoid arthritis in recurrence (RESTORE) study.

Objectives: To evaluate the safety and efficacy of retreatment with tocilizumab (TCZ) in patients who had participated in the DREAM study (Drug free remission/low disease activity after cessation of tocilizumab [Actemar] monotherapy study) and had experienced loss of efficacy.

Methods: Patients were retreated with TCZ or other disease modifying antirheumatic drugs (DMARDs). Disease activity was measured using the 28-joint disease activity score (DAS28) for 12 weeks.

Drug free REmission/low disease activity after cessation of tocilizumab (Actemra) Monotherapy (DREAM) study.

Objectives: To investigate the duration of remission and low disease activity (LDA) after cessation of tocilizumab (TCZ) treatment in rheumatoid arthritis patients who showed remission or LDA as assessed by DAS28 in response to preceding TCZ monotherapy, and to explore the factors contributing to prolonged efficacy duration.

Methods: Disease activity was monitored for 56 weeks. The rate of continued efficacy was estimated by Kaplan-Meier curves.

Chemical propulsion using ionic liquids.

Chemical propulsion generates motion by directly converting locally stored chemical energy into mechanical energy. Here, we describe chemically driven autonomous motion generated by using imidazolium-based ionic liquids on a water surface. From measurements of the driving force of a locomotor loaded with an ionic liquid and observations of convection on the water surface originating from the ionic liquid container of the locomotor, the driving mechanism of the motion is found to be due to the Marangoni effect that arises from the anisotropic distribution of ionic liquids on the water surface.

Assessment of the validity of the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) as a disease activity index of rheumatoid arthritis in the efficacy evaluation of 24-week treatment with tocilizumab: subanalysis of the SATORI study.

As tocilizumab (TCZ) greatly inhibits inflammatory markers, methods of evaluating rheumatoid arthritis (RA) disease activity that include inflammatory markers may overestimate the effect of TCZ treatment. We have evaluated the impact of inflammatory markers on the efficacy of TCZ by comparing the efficacy indicated by the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) with that indicated by the clinical and simplified disease activity indexes (CDAI and SDAI, respectively) and the American College of Rheumatology (ACR) core set criteria in a double-blind study of TCZ-the SATORI study. The Spearman correlation coefficient between DAS28-ESR and CDAI was comparable between that at week 24 and that at baseline [correlation coefficient at baseline and week 24 was 0.

Safety and efficacy profiles of tocilizumab monotherapy in Japanese patients with rheumatoid arthritis: meta-analysis of six initial trials and five long-term extensions.

We present safety and efficacy data from Japanese clinical studies on monotherapy with tocilizumab (TCZ), a humanized anti-interleukin 6 receptor monoclonal antibody, in which 601 patients with moderate to severe rheumatoid arthritis, with a total of 2188 patient-years (pt-yr) exposure, were enrolled. The median treatment duration was 3.8 years.

Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease.

Interleukin-6 (IL-6) plays pathologic roles in immune-inflammatory diseases such as rheumatoid arthritis (RA) and Castleman disease. By inhibiting IL-6 receptors (IL-6Rs), tocilizumab (a humanized anti-IL-6R antibody) ameliorates the symptoms of these diseases and normalizes acute-phase proteins, including C-reactive protein (CRP). We found that tocilizumab treatment increased serum levels of IL-6 and soluble IL-6R (sIL-6R).

Toxicity, pharmacokinetics, and dose-finding study of repetitive treatment with the humanized anti-interleukin 6 receptor antibody MRA in rheumatoid arthritis. Phase I/II clinical study.

Objective: To evaluate the safety and pharmacokinetics of multiple infusions of a humanized anti-interleukin-6 (IL-6) receptor antibody, MRA, in patients with rheumatoid arthritis (RA).

Methods: In an open label trial, 15 patients with active RA were intravenously administered 3 doses (2, 4, or 8 mg/kg) of MRA biweekly for 6 weeks, and pharmacokinetics were assessed. Patients continued on MRA treatment for 24 weeks, and were then assessed for safety and efficacy.

Polyglutamation of a novel antifolate, MX-68, is not necessary for its anti-arthritic effect.

N-[[4-[(2,4-diaminopteridin-6-yl)methyl]-3,4-dihydro-2H-1,4-benzothiazin-7-yl]-carbonyl]-L-homoglutamic acid (MX-68), a derivative of methotrexate, was chemically designed to resist polyglutamation and to have a high affinity for dihydrofolate reductase, in an attempt to reduce the side effects of methotrexate. We confirmed that MX-68 did not undergo polyglutamation and investigated the pharmacological activities of MX-68 compared with methotrexate. (1) In vitro: MX-68 inhibited the activity of dihydrofolate reductase to the same degree as methotrexate-tetraglutamate.