Expression and function of inducible co-stimulator in patients with systemic lupus erythematosus: possible involvement in excessive interferon-γ and anti-double-stranded DNA antibody production

Inducible co-stimulator (ICOS) is the third member of the CD28/cytotoxic T-lymphocyte associated antigen-4 family and is involved in the proliferation and activation of T cells. A detailed functional analysis of ICOS on peripheral blood T cells from patients with systemic lupus erythematosus (SLE) has not yet been reported. In the present study we developed a fully human anti-human ICOS mAb (JTA009) with high avidity and investigated the immunopathological roles of ICOS in SLE. JTA009 exhibited higher avidity for ICOS than a previously reported mAb, namely SA12. Using JTA009, ICOS was detected in a substantial proportion of unstimulated peripheral blood T cells from both normal control individuals and patients with SLE. In CD4(+)CD45RO(+ )T cells from peripheral blood, the percentage of ICOS(+ )cells and mean fluorescence intensity with JTA009 were significantly higher in active SLE than in inactive SLE or in normal control individuals. JTA009 co-stimulated peripheral blood T cells in the presence of suboptimal concentrations of anti-CD3 mAb. Median values of [(3)H]thymidine incorporation were higher in SLE T cells with ICOS co-stimulation than in normal T cells, and the difference between inactive SLE patients and normal control individuals achieved statistical significance. ICOS co-stimulation significantly increased the production of IFN-γ, IL-4 and IL-10 in both SLE and normal T cells. IFN-γ in the culture supernatants of both active and inactive SLE T cells with ICOS co-stimulation was significantly higher than in normal control T cells. Finally, SLE T cells with ICOS co-stimulation selectively and significantly enhanced the production of IgG anti-double-stranded DNA antibodies by autologous B cells. These findings suggest that ICOS is involved in abnormal T cell activation in SLE, and that blockade of the interaction between ICOS and its receptor may have therapeutic value in the treatment of this intractable disease

Hydrogen effects in hydrofluorocarbon plasma etching of silicon nitride: Beam study with CF+, CF2+, CHF2 +, and CH2F+ ions

Tomoko Ito and Kazuhiro Karahashi, Journal of Vacuum Science & Technology A 29, 050601 (2011) https://doi.org/10.1116/1.361098

Analysis of multiparous couples' perceptions of husbands' supportiveness for their wives' satisfaction during pregnancy

This study was conducted to clarify the differences and commonalities in perceptions regarding husbands’supportiveness for their wives’satisfaction during pregnancy between husbands and wives with older children. This report also discusses the effect of nursing care that enhances the supportiveness provided by husbands during their wives’pregnancy. Semi-structured interviews were conducted with two multiparous couples during pregnancy. All interviews were transcribed and a qualitative inductive analysis was performed using Berelson's Content Analysis methods. The following five categories were identified regarding the husbands' supportiveness during their multiparous wives' pregnancy:［Increased consciousness of parenthood toward the unborn baby];［Empathy regarding wife’s physical and mental health arising from the previous pregnancy and childbirth , and addition of a new baby]; [Support with housework to show empathy for the multiparous wife]; [Care of older children to show empathy ofr the multiparous wife]; [Akjustment of roles in the parenting older children.] From the discussion about the common and different perceptions between multiparous couples, the following suggestion emerges. Nursing care should focus on enhancing the intimacy of a couple, strengthening the family system, increasing consciousness of parenthood toward an unborn baby, and adjusting the role in the parenting of older children

A Novel Membrane Protein That Is Transported to Protein Storage Vacuoles via Precursor-Accumulating Vesicles

A novel protein, MP73, was specifically found on the membrane of protein storage vacuoles of pumpkin seed. MP73 appeared during seed maturation and disappeared rapidly after seed germination, in association with the morphological changes of the protein storage vacuoles. The MP73 precursor deduced from the isolated cDNA was composed of a signal peptide, a 24-kD domain (P24), and the MP73 domain with a putative long α-helix of 13 repeats that are rich in glutamic acid and arginine residues. Immunocytochemistry and immunoblot analysis showed that the precursor-accumulating (PAC) vesicles (endoplasmic reticulum–derived vesicles responsible for the transport of storage proteins) accumulated proMP73, but not MP73, on the membranes. Subcellular fractionation of the pulse-labeled maturing seed demonstrated that the proMP73 form with N-linked oligosaccharides was synthesized on the endoplasmic reticulum and then transported to the protein storage vacuoles via PAC vesicles. Tunicamycin treatment of the seed resulted in the efficient deposition of proMP73 lacking the oligosaccharides (proMP73ΔΨ) into the PAC vesicles but no accumulation of MP73 in vacuoles. Tunicamycin might impede the transport of proMP73ΔΨ from the PAC vesicles to the vacuoles or might make the unglycosylated protein unstable in the vacuoles. After arrival at protein storage vacuoles, proMP73 was cleaved by the action of a vacuolar enzyme to form a 100-kD complex on the vacuolar membranes. These results suggest that PAC vesicles might mediate the delivery of not only storage proteins but also membrane proteins of the vacuoles