Retrospective clinical study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis management group in Japan: one-year clinical outcomes (RECONFIRM-2)

Biologics targeting TNF have brought about a paradigm shift in the treatment of rheumatoid arthritis (RA) and infliximab, anti-TNF-α chimeric monoclonal antibody, was marketed in 2003 in Japan. We previously reported on the RECONFIRM study, a retrospective clinical study on the efficacy of infliximab therapy in a RA management group in Japan, where we evaluated the clinical response after 22 weeks of the therapy in 258 patients. The study reported here was aimed at reconfirming the clinical efficacy of the infliximab therapy and demographic factors related to the efficacy over a 54-week study period in 410 RA patients in the same study group. Infliximab was infused according to the domestically approved method, and the clinical response was evaluated following 54 weeks of infliximab therapy using the European League Against Rheumatism (EULAR) response criteria. Disease activity was assessed by DAS28-CRP (Disease Activity Score including a 28-joint count/C-reactive protein). Infliximab was discontinued in 24.4% of the 410 patients at 54 weeks and 9.3% and 8.1% discontinued the therapy due to adverse events and inefficiency, respectively. Average DAS28-CRP decreased from 5.5 at week 0 to 3.1 at week 54 after the therapy. Patients in remission and those showing low-, moderate-, and high-disease activity changed from 0.0, 1.0, 9.0 and 90.0%, respectively, at the start of the study to 27.6, 11.7, 34.4 and 26.3%, respectively, at week 54. Younger age, RF-negativity and low scores of DAS28-CRP showed significant correlations with remission at week 54. EULAR response criteria—good, moderate, and no response to infliximab—were 37.0, 41.7 and 21.2%, respectively. In conclusion, we reconfirmed the clinical efficacy of infliximab and demographic factors related to the efficacy over a 54-week study period in 410 Japanese patients with RA using DAS28-CRP and EULAR response criteria

Efficacy and tolerability of tocilizumab in rheumatoid arthritis patients seen in daily clinical practice in Japan: results from a retrospective study (REACTION study)

Tocilizumab, a humanized monoclonal antibody to the interleukin 6 (IL-6) receptor, was approved for use as rheumatoid arthritis (RA) therapy in Japan in 2008, but its efficacy and tolerability in daily practice has not yet been reported. We report the results of a multicenter retrospective study on the efficacy and safety of tocilizumab involving all patients (n = 229) who were started on tocilizumab therapy at three rheumatology institutes in Japan from April 2008 through to March 2009. Tocilizumab was infused every 4 weeks at a dose of 8 mg/kg according to the drug labeling. Among the 229 patients, 55% concomitantly received methotrexate (MTX) and 63% had previously received anti-tumor necrosis factor (TNF) therapy. Average disease activity score (DAS) 28 of all 229 patients significantly decreased from 5.70 to 3.25 after 24 weeks of therapy. A European League Against Rheumatism (EULAR) good response and DAS28 remission was achieved in 57.4 and 40.7% of the patients, respectively, at 24 weeks. White blood cell counts significantly decreased and liver enzymes and total cholesterol slightly but significantly increased; however, liver enzyme levels did not increase in patients without MTX. Tocilizumab was discontinued in 47 cases (20.5%) due to lack of efficacy (5.2%), adverse events (11.4%), and other reasons (3.9%). The overall retention rate at 24 weeks was 79.5%. Based on these results, we conclude that tocilizumab therapy in daily rheumatology practice appears to be highly efficacious and well tolerated among active RA patients, including the anti-TNF therapy-refractory population. Tocilizumab infusion is therefore applicable not only as an alternative approach for anti-TNF therapy-resistant patients, but also as primary biologic therapy for active RA patients

Regulation of hepatitis C virus secretion by the Hrs-dependent exosomal pathway

AbstractThe molecular mechanisms of assembly and budding of hepatitis C virus (HCV) remain poorly understood. The budding of several enveloped viruses requires an endosomal sorting complex required for transport (ESCRT), which is part of the cellular machinery used to form multivesicular bodies (MVBs). Here, we demonstrated that Hrs, an ESCRT-0 component, is critical for the budding of HCV through the exosomal secretion pathway. Hrs depletion caused reduced exosome production, which paralleled with the decrease of HCV replication in the host cell, and that in the culture supernatant. Sucrose-density gradient separation of the culture supernatant of HCV-infected cells revealed the co-existence of HCV core proteins and the exosome marker. Furthermore, both the core protein and an envelope protein of HCV were detected in the intraluminal vesicles of MVBs. These results suggested that HCV secretion from host cells requires Hrs-dependent exosomal pathway in which the viral assembly is also involved

Association of dengue virus type-specific IgG on platelets is specific for the acute phase in an imported Japanese patient with secondary dengue 2 virus infection

The mechanism of thrombocytopenia in dengue virus infection remains unknown. We report herein an imported case of a 21-year-old male Japanese with dengue fever caused by secondary dengue 2 virus infection. The thrombocytopenia detected around the day of defervescence was associated with an increased level of plateletassociated IgG (PAIgG). The eluate from the platelets during the acute phase of this case contained an increased activity of anti-dengue virus 2 IgG, while the eluate from platelets during the convalescent phase contained a low level of anti-dengue 2 IgG. These findings suggest the transient formation of PAIgG involving anti-dengue 2 virus IgG during the acute phase of secondary dengue 2 virus infection

Effectiveness of the SA 14-14-2 Live-Attenuated Japanese Encephalitis Vaccine in Myanmar

Myanmar is an endemic country for the Japanese encephalitis virus (JEV), and the SA-14-14-2 live-attenuated JEV vaccine was first introduced as a catch-up vaccination campaign in 2017. To determine the effectiveness of vaccination by means of neutralizing antibody titers against JEV, a cross-sectional descriptive study was conducted among five to 15-year-old monastic school children in Mandalay, Myanmar. A total of 198 students who had received vaccines were recruited, and single-time investigation of anti-JEV IgG and neutralizing antibodies against wild-type JEV were determined using anti-JEV IgG ELISA and plaque reduction neutralization tests (PRNT50). All students 100% (198/198) showed positive results on the anti-JEV IgG ELISA, and 87% (172/198) of the students had neutralizing antibodies against JEV six months after immunization. The geometric mean titers of both IgG antibodies and neutralizing antibodies increased with the participants’ age groups, and statistically significant differences in anti-JEV IgG titers were noted across age groups. In this study, we could not investigate the persistence of neutralizing antibodies as only single-time blood collection was done. This study, which is the first report of JEV vaccination among children in Myanmar, showed similar neutralizing antibody production rates among vaccinated individuals as did studies in other countries

Involvement of NMDAR2A tyrosine phosphorylation in depression‐related behaviour

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102200/1/embj2009300-sup-0001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102200/2/embj2009300.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102200/3/embj2009300-sup-0003.pd