Interferon regulatory factor 7 (IRF7) has an essential role in the production of type I interferon. Although recent studies detected association of a single nucleotide polymorphism (SNP) rs4963128 in ...PHD and ring finger domains 1 (PHRF1)/KIAA1542, located closely to IRF7, and IRF7 rs1131665 (glutamine (Gln) 412 arginine (Arg)) with systemic lupus erythematosus (SLE), causal variants have not been established. In this study, we resequenced exons and introns of IRF7 to screen for all common polymorphisms, and examined whether they were associated with SLE in 416 Japanese patients with SLE and 505 healthy controls. We also tested whether the association of PHRF1 rs4963128 with SLE was replicated in a Japanese population. None of the IRF7 polymorphisms was associated with SLE. PHRF1 rs4963128T was not significantly associated with occurrence of SLE either; however, this allele was significantly increased in SLE with anti-Sm antibodies (6.8%) as compared with healthy controls (3.1%, P = 0.014, odds ratio OR 2.31) and SLE without anti-Sm antibodies (3.3%, P =0.041, OR 2.12). This allele was also increased in SLE with renal disorder (5.1%) as compared with those without renal disorder (2.4%, P = 0.047, OR 2.17). These results confirmed recently reported association of PHRF1 rs4963128T with anti-Sm antibody positive SLE in African-American populations, and supported the role of PHRF1-IRF7 region in the genetics of SLE.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Interferon regulatory factor 5 (IRF5) and signal transducer and activator of transcription 4 (STAT4) are shared susceptibility genes for various autoimmune diseases. In this study, we investigated ...whether these genes also contribute to susceptibility to anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in a Japanese population. A case-control study was carried out on IRF5 rs10954213 and STAT4 rs7574865 in 232 Japanese myeloperoxidase (MPO)-ANCA-positive AAV patients, including 177 microscopic polyangiitis and 710 healthy controls. IRF5 rs10954213G was significantly increased in MPO-ANCA-positive AAV (additive model, P=0.023, odds ratio=1.27, 95% confidence interval=1.03-1.57). The risk allele was previously shown to be associated with lower mRNA level of IRF5. On the other hand, significant association of STAT4 rs7574865T with AAV was not detected. These observations suggested that IRF5 may contribute to susceptibility to MPO-ANCA-positive AAV in a Japanese population.
In human serum, a portion of homocysteine (Hcy) exists as an N-linked form to the epsilon-amino group of protein lysine residues. N-homocysteinylated proteins differ structurally and functionally ...from native proteins. The present study strives to develop detection and potential semi-quantification methods for N-homocysteinylated apolipoprotein AI (N-Hcy-apoAI) in human serum.
Serum treated with or without cysteamine was supplied to isoelectric focusing (IEF) followed by an immunoblot using an anti-apoAI antibody. Cysteamine treatment increased the isoelectric point for N-Hcy-apoAI, but not for unmodified apoAI, due to the presence of -SH group(s) derived from Hcy and the absence of a cysteine residue in the apoAI molecule. N-Hcy-apoAI was semi-quantified from the scanned immunoblot pattern via a computer.
After cysteamine treatment, N-Hcy-apoAI in the serum was identified by IEF at the position with a higher pI value compared with intact apoAI. The reproducibility (between assays) of the semi-quantification method was 19.1% CV (coefficient of variation) for an average ratio 5.9% of N-Hcy-apoAI to the whole apoAI in the serum. Approximately 1.0-7.4% of apoAI was N-homocysteinylated in the serum obtained from 27 healthy subjects. Neither the ratio of N-Hcy-apoAI nor its concentration, calculated by total apoAI concentration, indicated correlation with the so-called total (free and S-linked) Hcy concentration.
We directly found that a portion of apoAI in the serum undergoes homocysteinylation in an N-linkage manner, and used this to develop a potential semi-quantification method for N-Hcy-apoAI.
A new electron-emitting device operating in completely passive manner has been developed to prevent spacecraft charging and discharging. It is named as electron-emitting film (ELF) for spacecraft ...charging mitigation. This emitter (ELF) utilizes the field enhancement at the triple junction formed at the interface where metal and insulator are met and exposed to vacuum. ELF emits prebreakdown emission current that might lead to arcing at the triple junction. Hence, it balances the input and output currents to the spacecraft during substorm. After ensuring the robustness of this ELF against ground handling and in-orbit contamination, laboratory experiment confirmed continuous electron emission for 100 accumulated hours to assure the endurance. In this paper, its durability against high-energy electron and proton irradiation equivalent to ten solar years in GEO is reported. Effect of heat cycling (-150 °C-100 °C) and vacuum ultraviolet irradiation in GEO on this emitter is also completed. Postemissions of this ELF confirm the durability under those harsh space environments.
Abstract Metastasis of malignant tumors to the oral cavity is rare. The authors report a case of thyroid carcinoma with mandibular osteoblastic metastasis. An 83-year-old female presented with lower ...jaw swelling and pain. An elastic hard subcutaneous mass was observed in the median mandible. X-ray images confirmed a tumor lesion with periosteal reaction spreading radially from the mandible. A biopsy revealed nests of large, polygonal tumor cells growing in a supporting fibrovascular framework. The patient's anamnesis included thyroid carcinoma with lung metastasis, 2 years ago, treated by total enucleation of the thyroid and excision of the superior lobe of the left lung. Biopsy, primary and metastatic tumor samples all tested positive for thyroglobulin, suggesting a thyroid follicular epithelial origin. Mandibular metastasis of poorly differentiated carcinoma of the thyroid gland was diagnosed. Consent for further treatment was not obtained. The patient died 1 year and 7 months later.
A series of spacecraft charging analyses was carried out for large GEO satellites using Multi-Utility Spacecraft Charging Analysis Tool. The purpose was to derive the number of electrostatic ...discharges expected for 15 years in orbit, which would be used as the basis of the number of primary electrostatic discharges (ESDs) to be used in future solar cell coupon ESD tests. The combinations of GEO plasma parameters (electron density, proton density, electron energy, and proton energy) that have a high probability of occurrence have been identified first. For each of those plasma parameters, a charging analysis was done. In the simulation, the time for the differential voltage between solar array cover glass and the spacecraft chassis to reach the ESD inception threshold was calculated. The results indicate that, for a typical GEO satellite, the expected number of ESDs in 15 years is on the order of 10 000, agreeing well with the previous work where another satellite was simulated by NASCAP/GEO.
Anti-glucose-6-phosphate isomerase (GPI) antibodies from K/BxN mice directly induce arthritis; however, the transfer of these antibodies from mice with GPI-induced arthritis does not induce ...arthritis. CD4⁺ T cells play an important role in the induction and effector phase in this model; however, the roles of B cells and immunoglobulins (Igs) have not been elucidated. We investigated the roles of B cells and Igs in GPI-induced arthritis by using adoptive transfer system into SCID mice. Transfer of splenocytes of male DBA/1 mice immunized with GPI into SCID mice induced arthritis on day 6 in the latter, in association with the production of anti-GPI antibodies. Co-localization of C3 and IgG on the articular surface was identified in arthritic SCID mice. Inoculation of IgG (or anti-GPI antibodies) and CD19⁺-depleted splenocytes from arthritic DBA/1 mice induced arthritis in SCID mice, but not CD19⁺-depleted or CD4⁺-depleted splenocytes from DBA/1 mice. In vitro analysis of cytokine production by splenocytes from DBA/1 arthritic mice demonstrated production of large amounts of tumour necrosis factor (TNF)-α and interleukin (IL)-6 in an antigen-specific manner (P < 0·01), and production was dominated by CD19⁺-depleted than CD4⁺-depleted splenocytes (P < 0·05). Addition of IgG from DBA/1 arthritic mice to the culture enhanced TNF-α but not IL-6 production, and this effect was blocked by anti-Fcγ receptor antibody. In vivo analysis of neutralization with TNF-α protected arthritis completely in SCID mice. Our results highlight the important role of B cells in GPI-induced arthritis as autoantibody producers, and these autoantibodies can trigger joint inflammation in orchestration with inflammatory cytokines, especially TNF-α.
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