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A search for an immunomodulating agent from mycobacteria was carried out usingMycobacterium leprae. The antigenicity of each fraction of the bacterial membrane, which contains the most antigenic components ofM. leprae, was assessed by using sera from paucibacillary leprosy. N-terminal sequencing of the serum-reactive protein and functional assessment of the membrane fractions using monocyte-derived dendritic cells (DCs) identified major membrane protein II (MMP-II) as one of the efficient T-cell-activating candidates. Purified MMP-II stimulated DCs from healthy individuals to produce interleukin-12 p70 and up-regulated the surface expression of major histocompatibility complex class I and II, CD86, and CD83 molecules. Also, there was an increase in the percentage of CD83+cells in the DC population. Furthermore, MMP-II-pulsed DCs expressed their derivatives on their surfaces. Using Toll-like receptor 2 (TLR-2)-dependent receptor constructs, we found that TLR-2 signaling was involved in DC maturation induced by MMP-II. Taken together, MMP-II can be recognized as an immunomodulating protein in terms of activation of antigen-presenting cells and innate immunity.

Dans le cadre du controle avance de la lepre au Pakistan ou le programme de l'Organisation Mondiale de la Sante a atteint son but d'elimination en 1996, nous avons mene une etude d'epidemio-surveillance des patients seropositifs contre Mycobacterium leprae, de leurs contacts et des souches resistantes de M. leprae aux medicaments. Nous avons mesure les niveaux d'anticorps anti-PGL-I dans le serum de patients lepreux et des personnes en contact avec ces derniers afin d'effectuer une detection precoce de l'infection par M. leprae. Parmi 34 patients actuellement sous traitement, 4 patients lepromateux etaient positifs a l'examen serologique, et 6,8 a 23,7 pour cent des personnes en contact, soit professionnel, soit domestiques, furent seropositifs. De plus, 3 cas (1,2%) presentaient un titre eleve. La resistance a la dapsone et la rifampicine furent evaluees pour la surveillance des souches resistantes de M. leprae. Quatre des 18 echantillons positifs par PCR presentaient des mutations du gene folP et, parmi 10 echantillons positifs par PCR, une avait une mutation du gene rpoB. Ces resultats indiquent que l'analyse serologique des contacts proches de patients hanseniens pourrait bien etre utile pour decouvrir les individus a haut risque et qu'il existe des souches de M. leprae resistantes aux medicaments chimiotherapeutiques au Pakistan.

In this study, we investigated the role of serum amyloid A protein (SAA) in the production of interleukin-6 (IL-6) using rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). Recombinant SAA stimulation induced the production of pro-inflammatory cytokine, IL-6, from RA-FLS. The signaling events induced by SAA included the activation of the mitogen-activated protein kineases, p38 and JNK1/2 and the activation of nuclear factor-kappa B (NF-kappaB). Inhibitor studies have shown SAA-induced IL-6 production to be down-regulated by NF-kappaB inhibition and partially inhibited by p38 or JNK inhibitors. Our findings demonstrate that SAA is a significant inducer of IL-6, which is critically involved in RA pathogenesis.

We examined the effects of intraplantar (i.pl.) administration of NaHS, an H2S donor, known to cause T-type Ca2+ channel (T-channel)-dependent mechanical hyperalgesia, on responsiveness to electric stimulation with 5, 250 and 2000 Hz sine waves (SW) that selectively excites C, Aδ and Aβ fibers, respectively. NaHS, given i.pl., caused behavioral hypersensitivity to SW stimulation at 5 Hz, but not 250 or 2000 Hz, in rats. NaHS also enhanced phosphorylation of spinal ERK following 5 Hz SW stimulation. Three distinct T-channel blockers abolished the NaHS-induced behavioral hypersensitivity to 5 Hz SW stimulation. Thus, H2S selectively sensitizes C-fiber nociceptors via T-channels.

Objective: The objective of this study is to determine the factors associated with time spent performing housework/childcare by fathers of children under 12 years of age (preschool and elementary school children) in Japan. Methods: An online survey of employees and employers was conducted in 2017. Of the 7,796 total responses to the survey, those of 621 fathers of children aged 0–12 years were analyzed. Participants were divided into two groups: fathers of children aged 0–6 years, and fathers of children aged 7–12 years. Multiple logistic regression analysis was performed on the items for which there was a significant intergroup difference, setting time spent performing housework as the dependent variable and the survey items as the independent variables. Results: For fathers of children aged 0–6 years, working 40 hours or less per week and commuting for one hour or less were associated with more time spent performing housework/childcare. For fathers of children aged 7–12 years, working less than 40 hours a week, working from home more than once a week, and having spouses with full-time jobs were associated with more time spent performing housework/childcare. Conclusion: This study revealed the factors associated with the time spent by fathers of children under 12 in performing housework/childcare. As several of these factors cannot be altered by the fathers’ efforts alone, companies and society in general must endeavor to improve work styles to better suit the habits and preferences of fathers. This will promote work–life balance and create better family relationships.

Significant amino acid sequence homology in two regions of Vargula hilgendorfii to one in apoaequorin was reported. The intra-amino acid homology in Vargula luciferase between residues 81-312 and 321-540 was 19.3%, and each of this intra-homologous region contained the region homologous to apoaequorin. In order to prove the possibility that only one of the homologous regions is sufficient for luminescence, we have produced a chimeric protein comprising of only the N-terminal homologous region of Vargula luciferase fused to protein A. Comparison of the luminescence of this truncate luciferase indicated that there was 38.5% retention in the bioluminescence of luciferase when compared to that of the mature form of luciferase. This fact may have interesting implications for further study of engineering luciferase.

The use of the mobile internet has been increasing rapidly around the world, presenting high hopes for new business opportunities. However, only a few studies have been conducted to identify e-business implications of the mobile internet, even though it is one of the crucial factors in realising the potential of the mobile internet. Furthermore, the unique characteristics of local telecommunication markets along with the increasing trend for global e-business have led to a growing need for cross-national studies on the mobile internet. This study aims at investigating e-business implications of the mobile internet from a customer perspective across different countries. To investigate the cross-national differences of the mobile internet, simultaneous online surveys using an identical questionnaire were conducted in Hong Kong, Japan and Korea. Results from the online survey in the three countries yielded the following findings. First, adoption patterns for the mobile internet were different across the three countries. Second, customers' perceptions of the importance of the mobile internet, and their willingness to pay for mobile internet services, differed significantly across different countries. Finally, customers' preferred services in mobile internet businesses also differed across the three countries. This paper concludes with the implications of the results of the study for mobile service providers and policy makers.

Background Heparin-induced thrombocytopenia (HIT) is a thromboembolic complication that can occur with unfractionated heparin (UFH) or low molecular weight heparin (LMWH). Our objective was to determine and compare the incidence of IgG-class HIT antibodies in patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) with different antithrombotic prophylaxis therapies and their contributions to the occurrence of venous thromboembolism (VTE). Methods A prospective observational study was performed for 374 Japanese patients undergoing THA or TKA to determine the incidence of VTE. IgG-class anti-PF4/heparin antibodies were measured using IgG-specific EIA before and after the operation. Results In the clinical outcome, the incidence of symptomatic deep vein thrombosis (DVT) was 15.0% (56/374, TKA; 35, THA; 21) and pulmonary emboli (PE) were not observed. The total seroconversion incidence of IgG-class PF4/heparin antibodies was 19.8% (74/374). The seroconversion incidence of IgG-class PF4/heparin antibodies was higher in patients receiving UFH (32.7%) compared to those receiving LMWH (9.5%) or fondaparinux (14.8%). Furthermore, the seroconversion incidence was significantly higher in patients undergoing TKA compared to those undergoing THA. Based on multivariate analysis, seroconversion of the IgG-class PF4/heparin antibodies was independent a risk factor for symptomatic DVT. Conclusion Our findings show that the seroconversion of IgG-class anti-PF4/heparin antibodies differed with various anti-thrombotic prophylaxis therapeutics and was associated with the risk of DVT in a subset of patients undergoing total joint arthroplasty (TKA and THA).

Background The new JAK3 inhibitor, CP690,550, has shown efficacy in the treatment of rheumatoid arthritis. The present study was undertaken to assess the effects of CP690,550 on cytokine production and cellular signaling in human CD4+ T cells. Results CD4+ T cells produced IL-2, IL-4, IL-17, IL-22 and IFN-γ in following stimulation with a CD3 antibody. At the optimal concentration, CP690,550 almost completely inhibited the production of IL-4, IL-17, IL-22 and IFN-γ from these activated CD4+ T cells, but only had marginal effects on IL-2 production. Moreover CP690,550 inhibited anti-CD3-induced phosphorylation of STAT1, STAT3, STAT4, STAT5, and STAT6, but not the TCR-associated phosphorylation of ZAP-70. Conclusions Therefore, CP690,550-mediated modification of the JAK/STAT pathway may be a new immunosuppressive strategy in the treatment of autoimmune diseases.

Introduction Interleukin (IL)-6-type cytokines exert their effects through activation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling cascade. The JAK/STAT pathways play an important role in rheumatoid arthritis, since JAK inhibitors have exhibited dramatic effects on rheumatoid arthritis (RA) in clinical trials. In this study, we investigated the molecular effects of a small molecule JAK inhibitor, CP690,550 on the JAK/STAT signaling pathways and examined the role of JAK kinases in rheumatoid synovitis. Methods Fibroblast-like synoviocytes (FLS) were isolated from RA patients and stimulated with recombinant oncostatin M (OSM). The cellular supernatants were analyzed using cytokine protein chips. IL-6 mRNA and protein expression were analyzed by real-time PCR method and ELISA, respectively. Protein phosphorylation of rheumatoid synoviocytes was assessed by Western blot using phospho-specific antibodies. Results OSM was found to be a potent inducer of IL-6 in FLS. OSM stimulation elicited rapid phosphorylation of STATs suggesting activation of the JAK/STAT pathway in FLS. CP690,550 pretreatment completely abrogated the OSM-induced production of IL-6, as well as OSM-induced JAK/STAT, and activation of mitogen-activated kinases (MAPKs) in FLS. Conclusions These findings suggest that IL-6-type cytokines contribute to rheumatoid synovitis through activation of the JAK/STAT pathway in rheumatoid synoviocytes. Inhibition of these pro-inflammatory signaling pathways by CP690,550 could be important in the treatment of RA.