A case of planned pregnancy with an interruption in infliximab administration in a 27-year-old female patient with rheumatoid-factor-positive polyarthritis juvenile idiopathic arthritis which improved after restarting infliximab and methotrexate

We report a 27-year-old case of juvenile idiopathic arthritis (JIA) having been stopped infliximab during pregnancy. She was safely treated by infliximab therapy with premedications for preventing infusin reactions after her delivery, and then improved in the same manner as when she had been treated with infliximab therapy before pregnancy. As a result, it remains unclear whether or not we can use infliximab to control disease activities during pregnancy. In addition, it is also important to clarify whether or not premedications should be used when resuming infliximab treatment in such patients after pregnancy. These problems still remain controversial. More definitive data are needed in order to allow rheumatologists to better select the optimal TNF-alpha inhibitor therapy when treating pregnant JIA patients.     

Skin Irritation to Glass Wool or Continuous Glass Filaments as Observed by a Patch Test among Human Japanese Volunteers

Glass wool and continuous glass filaments have been used in industry. We examined the irritability of those among Japanese. A patch test was performed on 43 volunteers for the followings: glass wool for non-residential use with and without a urea-modified phenolic resin binder, that for residential use with and without the binder, and continuous glass filaments with diameters of 4, 7, 9, and 13 µm. Materials were applied to an upper arm of each volunteer for 24 h. The skin was observed at 1 and 24 h after the removal. At 1 h after removal, slight erythema was observed on the skin of a woman after the exposure to glass wool for residential use without the binder. Erythema was observed on the skin of another woman at 1 h after a 24-h exposure to glass wool for non-residential use without the binder. There were no reactions at 24 h after the removal. The low reactions in the patch test suggested that the irritability caused by glass wool, irrespective of a resin component, could be induced mechanically, and that the irritability caused by continuous glass filaments with resin could be slight and either mechanical or chemical.     

Efficient Activation of Human T Cells of Both CD4 and CD8 Subsets by Urease-Deficient Recombinant Mycobacterium bovis BCG That Produced a Heat Shock Protein 70-M. tuberculosis-Derived Major Membrane Protein II Fusion Protein

For the purpose of obtaining Mycobacterium bovis bacillus Calmette-Guérin (BCG) capable of activating human naive T cells, urease-deficient BCG expressing a fusion protein composed of Mycobacterium tuberculosis-derived major membrane protein II (MMP-II) and heat shock protein 70 (HSP70) of BCG (BCG-DHTM) was produced. BCG-DHTM secreted the HSP70-MMP-II fusion protein and effectively activated human monocyte-derived dendritic cells (DCs) by inducing phenotypic changes and enhanced cytokine production. BCG-DHTM-infected DCs activated naive T cells of both CD4 and naive CD8 subsets, in an antigen (Ag)-dependent manner. The T cell activation induced by BCG-DHTM was inhibited by the pretreatment of DCs with chloroquine. The naive CD8⁺ T cell activation was mediated by the transporter associated with antigen presentation (TAP) and the proteosome-dependent cytosolic cross-priming pathway. Memory CD8⁺ T cells and perforin-producing effector CD8⁺ T cells were efficiently produced from the naive T cell population by BCG-DHTM stimulation. Single primary infection with BCG-DHTM in C57BL/6 mice efficiently produced T cells responsive to in vitro secondary stimulation with HSP70, MMP-II, and M. tuberculosis-derived cytosolic protein and inhibited the multiplication of subsequently aerosol-challenged M. tuberculosis more efficiently than did vector control BCG. These results indicate that the introduction of MMP-II and HSP70 into urease-deficient BCG may be useful for improving BCG for control of tuberculosis.     

A method for partitioning dissolved polycyclic aromatic hydrocarbons associated with humic substances using polyethylenimine-coated glass fiber filters

The use of a glass fiber filter coated with polyethyleneimine (PcGF) for partitioning dissolved polycyclic aromatic hydrocarbons (PAHs) that are associated with humic substances (HSs) is reported. The PAHs pass through the PcGF, while HS-associated PAHs are trapped by electrostatic interaction between the HSs and the PcGF. Based on this strategy, free- and associated-PAHs can be separated by simple filtration. Approximately 60–90% of the deuterated benzo[a]pyrene (BaP-d12) that was added to the sample solutions was in the associated form with soil type HAs, while the percentages were lower in the case of aquatic HA (ca. 25%) and FAs (ca. 10–15%). Strong correlations (R² = 0.84–0.90) were observed between the %-association for deuterated pyrene (Pyr-d10) or BaP and the degree of HS''s aromaticity (log E₂₈₀), regardless of the HS fractions or their origins. The separation technique was used to evaluate the association coefficient (log K_assoc) and the capacity (C_assoc) for soil type HAs based on a Langmuir adsorption model. The log K_assoc values were not highly dependent on the origin of the HA (ca. 3.5–4.5). The BaP-d12 and Pyr-d10-C_assoc values for the HA derived from compost were more than one order larger than the corresponding values for peat. The findings indicate that C_assoc values vary with the origin of the HA and affect the environmental behavior of PAHs. The present study reports on the development of a simple partitioning technique that does not require any special training and equipment.

The use of a glass fiber filter coated with polyethyleneimine (PcGF) for partitioning dissolved polycyclic aromatic hydrocarbons (PAHs) that are associated with humic substances (HSs) is reported.     

Experimental and theoretical study on converting myoglobin into a stable domain-swapped dimer by utilizing a tight hydrogen bond network at the hinge region

Various factors, such as helical propensity and hydrogen bonds, control protein structures. A frequently used model protein, myoglobin (Mb), can perform 3D domain swapping, in which the loop at the hinge region is converted to a helical structure in the dimer. We have previously succeeded in obtaining monomer–dimer equilibrium in the native state by introducing a high α-helical propensity residue, Ala, to the hinge region. In this study, we focused on another factor that governs the protein structure, hydrogen bonding. X-ray crystal structures and thermodynamic studies showed that the myoglobin dimer was stabilized over the monomer when keeping His82 to interact with Lys79 and Asp141 through water moleclues and mutating Leu137, which was located close to the H-bond network at the dimer hinge region, to a hydrophilic amino acid (Glu or Asp). Molecular dynamics simulation studies confirmed that the number of H-bonds increased and the α-helices at the hinge region became more rigid for mutants with a tighter H-bond network, supporting the hypothesis that the myoglobin dimer is stabilized when the H-bond network at the hinge region is enhanced. This demonstrates the importance and utility of hydrogen bonds for designing a protein dimer from its monomer with 3D domain swapping.

The tight H-bond network enhanced the helices at the hinge region and stabilized the myoglobin dimer, providing a unique example of using H-bonds in the design of a dimeric protein through 3D domain swapping.     

N–C bond formation between two anilines coordinated to a ruthenium center in cis-form affording a 3,5-cyclohexadiene-1,2-diimine moiety

Ruthenium complexes containing two anilines or its derivatives, cis-[Ru^II(NH₂C₆H₅)₂(bpy)₂]²⁺ ([1]²⁺) and cis-[Ru^II(NH₂C₆H₄(4-CH₃))₂(bpy)₂]²⁺ ([2]²⁺), were oxidized by four molar equivalents of (NH₄)₄[Ce^IV(SO₄)₄]·2H₂O to give N¹-phenylcyclohexa-3,5-diene-1,2-diimineruthenium(ii) complexes, cis-[Ru^II(NHC₆H₄NC₆H₅)(bpy)₂]²⁺ ([4]²⁺) and cis-[Ru^II(NHC₆H₃(4-CH₃)NC₆H₄(4-CH₃))(bpy)₂]²⁺ ([5]²⁺), respectively, through an N–C bond formation between two aniline ligands cis-coordinated to the ruthenium center.

Four-electron oxidation of two anilines coordinated to a ruthenium(ii) center in a cis-form affords N¹-phenylcyclohexa-3,5-diene-1,2-diimine through an N–C bond formation with N–H and C–H bond activation.     

Accelerated Tau Aggregation,Apoptosis and Neurological Dysfunction Caused by Chronic Oral Administration of Aluminum in a Mouse Model of Tauopathies

To clarify whether long‐term oral ingestion of aluminum (Al) can increase tau aggregation in mammals, we examined the effects of oral Al administration on tau accumulation, apoptosis in the central nervous system (CNS) and motor function using tau transgenic (Tg) mice that show very slowly progressive tau accumulation. Al‐treated tau Tg mice had almost twice as many tau‐positive inclusions in the spinal cord as tau Tg mice without Al treatment at 12 months of age, a difference that reached statistical significance, and the development of pretangle‐like tau aggregates in the brain was also significantly advanced from 9 months. Al exposure did not induce any tau pathology in wild‐type (WT) mice. Apoptosis was observed in the hippocampus in Al‐treated tau Tg mice, but was virtually absent in the other experimental groups. Motor function as assessed by the tail suspension test was most severely impaired in Al‐treated tau Tg mice. Given our results, chronic oral ingestion of Al may more strongly promote tau aggregation, apoptosis and neurological dysfunction if individuals already had a pathological process causing tau aggregation. These findings may also implicate chronic Al neurotoxicity in humans, who frequently have had mild tau pathology from a young age.