Objectives: Even in a lupus low disease activity state (LLDAS), many patients with SLE continue to face residual symptoms and disease burden. We aimed to evaluate the quality of life, activity impairment and overall work productivity impairment among patients in LLDAS. Residual disease burden was also evaluated for patients in LLDAS.
View Article and Find Full Text PDFObjectives: We aimed to evaluate the performance of the optic disc-macula distance to disc-diameter ratio (DM/DD) in qualitative and quantitative assessment of optic disc size.
Methods: In 300 apparently normal eyes, we determined the correlation between DM/DD and the planimetric disc area (DA) and evaluated the performance of DM/DD in discriminating between small and large discs. The ability of DM/DD to predict the actual DA was validated in a separate cohort of 200 eyes.
Objectives: Some patients with sarcoidosis achieve spontaneous remission, whereas others repeatedly experience relapse. We examined differences in the clinical course of active sarcoidosis according to peripheral blood immunophenotypes before treatment.
Methods: This retrospective study compared peripheral blood immunophenotypes between patients with active sarcoidosis (n=28) and healthy control subjects (n=10).
Respir Investig
November 2024
In 2022, the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) proposed new diagnostic criteria for pulmonary hypertension (PH). These criteria include significant changes to the definitions of pulmonary hemodynamic indices. Specifically, the threshold for mean pulmonary artery pressure (mPAP) has been lowered from ≥25 mmHg to >20 mmHg, and the threshold for pulmonary vascular resistance (PVR) has been adjusted from ≥3 Wood units (WU) to >2 WU.
View Article and Find Full Text PDFImmunoglobulin G4-related disease (IgG4-RD) is mainly treated with glucocorticoids. In many cases, this disease is resistant to glucocorticoids, and their toxicity can be a problem. We encountered a patient with IgG4-RD affecting multiple organs (such as the skin, lung, and lacrimal gland), who had comorbidities, including atopic dermatitis and diabetes.
View Article and Find Full Text PDFTo search for low-energy resonant structures in isospin T=3/2 three-body systems, we have performed the experiments ^{3}H(t,^{3}He)3n and ^{3}He(^{3}He,t)3p at intermediate energies. For the 3n experiment, we have newly developed a thick Ti-^{3}H target that has the largest tritium thickness among targets of this type ever made. The 3n experiment for the first time covered the momentum-transfer region as low as 15 MeV/c, which provides ideal conditions for producing fragile systems.
View Article and Find Full Text PDFSIRT5, one of the mammalian sirtuins, specifically recognizes succinyl-lysine residues on proteins and catalyzes the desuccinylation reaction. In this study, we characterized SIRT5 mutants with hydrophobic amino acid substitutions at Q140 and N141, in addition to the catalytic residue H158, known as an active site residue, by the Michaelis-Menten analysis and X-ray crystallography. Kinetic analysis showed that the catalytic efficiency (k/K) of the Q140L and N141V mutants decreased to 0.
View Article and Find Full Text PDFGum arabic (GA) is widely used as an emulsion stabilizer and edible coating and consists of a complex carbohydrate moiety with a rhamnosyl-glucuronate group capping the non-reducing ends. Enzymes that can specifically cleave the glycosidic chains of GA and modify their properties are valuable for structural analysis and industrial application. Cryogenic X-ray crystal structure of GA-specific L-rhamnose-α-1,4-D-glucuronate lyase from Fusarium oxysporum (FoRham1), belonging to the polysaccharide lyase (PL) family 42, has been previously reported.
View Article and Find Full Text PDFObjective: While opioids are a key part of palliative care, few studies have evaluated opioid demand in the home care context. This study aims to compare opioid usage in home care and hospital care settings.
Methods: This cross-sectional study retrospectively recruited patients receiving palliative care in home care and hospital settings, between November 2018 and October 2020.
Hereditary ATTR amyloidosis is a disease caused by the deposition of amyloid fibrils formed by mutated transthyretin (TTR), a protein that binds to thyroid hormone in the serum, in the organs. The development of a small molecule that binds to and stabilizes TTR is a promising strategy for the treatment of ATTR amyloidosis. In the present study, we demonstrated that the resveratrol derivatives including pterostilbene available as a dietary supplement inhibit the fibrillization of V30M-TTR to the same extent as the approved drug tafamidis.
View Article and Find Full Text PDF[NiFe]-hydrogenase from Miyazaki F is an O-sensitive enzyme that is inactivated in the presence of O but the oxidized enzyme can recover its catalytic activity by reacting with H under anaerobic conditions. Here, we report the first neutron structure of [NiFe]-hydrogenase in its oxidized state, determined at a resolution of 2.20 Å.
View Article and Find Full Text PDFTransthyretin (TTR) is a carrier protein for thyroid hormone thyroxine (T ) in plasma, placental cytosol, and cerebrospinal fluid. While the potential toxicity of small molecules that compete with T for binding to TTR should be carefully studied, these small molecules can also serve as anti-ATTR amyloidosis drugs by stabilizing the TTR structure. Here, we demonstrated that rafoxanide, an EU-approved anthelmintic drug for domesticated animals, binds to the T -binding site of TTR.
View Article and Find Full Text PDFA 65-year-old man experienced a cough and mild hemoptysis suddenly one morning. He was prescribed tranexamic acid and carbazochrome salicylate by the local clinic at the first visit, and his hemoptysis stopped. However, 2 days later, he experienced recurrent hemoptysis that was prolonged intermittently.
View Article and Find Full Text PDFDeath-associated protein kinase 1 (DAPK1), a Ca2+/calmodulin-regulated serine/threonine kinase, regulates cell apoptosis and autophagy and has been implicated in the pathogenesis of Alzheimer's disease (AD). Targeting DAPK1 may be a promising approach for treating AD. In our previous study, we found that a natural polyphenol, resveratrol (1), is a moderate DAPK1 inhibitor.
View Article and Find Full Text PDFThe development in the crystal structure analysis of synthetic polymers using the hybridized combination of wide-angle X-ray and neutron diffraction (WAXD and WAND, respectively) techniques has been reviewed with many case studies performed by the authors. At first, the technical development was reviewed, in which the usage of high-energy synchrotron X-ray source was emphasized for increasing the total number of the observable diffraction peaks, and several examples were introduced. Secondly, the usage of the WAND method was introduced, in which the successful extraction of hydrogen atomic positions was described.
View Article and Find Full Text PDFBackground: The standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC) is chemoradiotherapy (CRT) followed by durvalumab, based on the PACIFIC study. Although multiple Japanese phase II studies have shown high efficacy and tolerability of CRT with cisplatin plus S-1 (SP), no prospective study using durvalumab after SP-based CRT has been reported.
Objectives: We conducted a multicenter phase II study of this approach, the interim analysis of which showed a high transition rate to durvalumab consolidation therapy.
PcyA, a ferredoxin-dependent bilin pigment reductase, catalyzes the site-specific reduction of the two vinyl groups of biliverdin (BV), producing phycocyanobilin. Previous neutron crystallography detected both the neutral BV and its protonated form (BVH) in the wildtype (WT) PcyA-BV complex, and a nearby catalytic residue Asp105 was found to have two conformations (protonated and deprotonated). Semiempirical calculations have suggested that the protonation states of BV are reflected in the absorption spectrum of the WT PcyA-BV complex.
View Article and Find Full Text PDFThe new isotope ^{39}Na, the most neutron-rich sodium nucleus observed so far, was discovered at the RIKEN Nishina Center Radioactive Isotope Beam Factory using the projectile fragmentation of an intense ^{48}Ca beam at 345 MeV/nucleon on a beryllium target. Projectile fragments were separated and identified in flight with the large-acceptance two-stage separator BigRIPS. Nine ^{39}Na events have been unambiguously observed in this work and clearly establish the particle stability of ^{39}Na.
View Article and Find Full Text PDFAdult Still's disease (ASD) is rarely complicated by pulmonary hypertension (PH). A 76-year-old woman experienced ASD relapse with repeated exacerbation of PH and interstitial lung disease. Although she had been treated with immunosuppressive agents and pulmonary vasodilators, the ASD relapsed with fever, rash, increased inflammatory responses and exacerbated interstitial lung disease, and PH.
View Article and Find Full Text PDFActa Crystallogr D Struct Biol
June 2022
Hen egg-white lysozyme (HEWL) is an enzymatic protein with two acidic amino acids, Glu35 and Asp52, in its active site. Glu35 acts as a proton donor to the substrate and Asp52 interacts with the positively charged substrate, suggesting different protonation states of these residues. However, neutron crystallographic studies thus far have not provided a consistent picture of the protonation states of these residues.
View Article and Find Full Text PDFThe planarity of the peptide bond is important for the stability and structure formation of proteins. However, substantial distortion of peptide bonds has been reported in several high-resolution structures and computational analyses. To investigate the peptide bond planarity, including hydrogen atoms, we report a 1.
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