Exposure-response relationship of wind turbine noise with self-reported symptoms of sleep and health problems: A nationwide socioacoustic survey in Japan.

The association of wind turbine noise (WTN) with sleep and physical/mental health has not been fully investigated. To investigate the relationship of WTN with the prevalence of self-reported symptoms of sleep and health problems, a socioacoustic survey of 1079 adult residents was conducted throughout Japan (2010-2012): 747 in 34 areas surrounding wind turbine plants and 332 in 16 control areas. During face-to-face interviews, the respondents were not informed of the purpose of the survey.

Basic Equations in Statics and Kinetics of Protein Polymerization and the Mechanism of the Formation and Dissociation of Amyloid Fibrils Revealed by Pressure Perturbation.

Studies of the pressure-dissociation of several amyloid or amyloid-like fibrils have shown that the fibril state is considerably voluminous. Quantitative characterization of the protein fibrillation reaction with respect to volumetric parameters is necessary to elucidate mechanisms of amyloid fibrillation in molecular terms such as protein cavity and hydration. Here we discuss, firstly, basic equations in statics and kinetics of protein polymerization as employed to obtain thermodynamic, volumetric, and kinetic parameters.

Negative thermal expansibility change for dissociation of lysozyme variant amyloid protofibril.

A disulfide-deficient variant of hen lysozyme, 0SS, is known to form an amyloid protofibril spontaneously, and to dissociate into monomers at high hydrostatic pressure. We carried out native PAGE at various temperatures (20-35°C) and pressures (0.1-200 MPa), to characterize the dissociation equilibrium of disulfide-deficient variant of hen lysozyme amyloid protofibril.

Pressure-assisted dissociation and degradation of "proteinase K-resistant" fibrils prepared by seeding with scrapie-infected hamster prion protein.

The crucial step for the fatal neurodegenerative prion diseases involves the conversion of a normal cellular protein, PrP(C), into a fibrous pathogenic form, PrP(Sc), which has an unusual stability against heat and resistance against proteinase K digestion. A successful challenge to reverse the reaction from PrP(Sc) into PrP(C) is considered valuable, as it would give a key to dissolving the complex molecular events into thermodynamic and kinetic analyses and may also provide a means to prevent the formation of PrP(Sc) from PrP(C) eventually in vivo. Here we show that, by applying pressures at kbar range, the "proteinase K-resistant" fibrils (rHaPrP(res)) prepared from hamster prion protein (rHaPrP [23-231]) by seeding with brain homogenate of scrapie-infected hamster, becomes easily digestible.

Modulation of structure and dynamics by disulfide bond formation in unfolded states.

During oxidative folding, the formation of disulfide bonds has profound effects on guiding the protein folding pathway. Until now, comparatively little is known about the changes in the conformational dynamics in folding intermediates of proteins that contain only a subset of their native disulfide bonds. In this comprehensive study, we probe the conformational landscape of non-native states of lysozyme containing a single native disulfide bond utilizing nuclear magnetic resonance (NMR) spectroscopy, small-angle X-ray scattering (SAXS), circular dichroism (CD) data, and modeling approaches.

Glycerol-enhanced detection of a preferential structure latent in unstructured 1SS-variants of lysozyme.

Four species of 1SS-varinats of lysozyme were almost unstructured in water, judged from their near-UV CD and (1) H-(15) N-HSQC spectra. Some preferential structure might exist in such a disordered state, but the population of molecules in such a conformation must have been too small to be detected by spectroscopic methods. Indeed, our previous study showed that the addition of 30% glycerol induced the unstructured 2SS-variant of lysozyme to form a native-like structure.

Pressure-accelerated dissociation of amyloid fibrils in wild-type hen lysozyme.

The dynamics of amyloid fibrils, including their formation and dissociation, could be of vital importance in life. We studied the kinetics of dissociation of the amyloid fibrils from wild-type hen lysozyme at 25°C in vitro as a function of pressure using Trp fluorescence as a probe. Upon 100-fold dilution of 8 mg ml(-1) fibril solution in 80 mM NaCl, pH 2.

Comprehensive secondary-structure analysis of disulfide variants of lysozyme by synchrotron-radiation vacuum-ultraviolet circular dichroism.

To elucidate the effects of specific disulfide bridges (Cys6-Cys127, Cys30-Cys115, Cys64-Cys80, and Cys76-Cys94) on the secondary structure of hen lysozyme, the vacuum-ultraviolet circular dichroism (VUVCD) spectra of 13 species of disulfide-deficient variants in which Cys residues were replaced with Ala or Ser residues were measured down to 170 nm at pH 2.9 and 25 degrees C using a synchrotron-radiation VUVCD spectrophotometer. Each variant exhibited a VUVCD spectrum characteristic of a considerable amount of residual secondary structures depending on the positions and numbers of deleted disulfide bridges.

Glycerol-induced folding of unstructured disulfide-deficient lysozyme into a native-like conformation.

2SS[6-127,64-80] variant of lysozyme which has two disulfide bridges, Cys6-Cys127 and Cys64-Cys80, and lacks the other two disulfide bridges, Cys30-Cys115 and Cys76-Cys94, was quite unstructured in water, but a part of the polypeptide chain was gradually frozen into a native-like conformation with increasing glycerol concentration. It was monitored from the protection factors of amide hydrogens against H/D exchange. In solution containing various concentrations of glycerol, H/D exchange reactions were carried out at pH* 3.

Amyloid protofibril is highly voluminous and compressible.

We report here results of the first direct measurement of partial volume and compressibility changes of a protein as it forms an amyloid protofibril. We use a high precision density meter and an ultrasonic velocity meter on a solution of intrinsically denatured, disulfide-deficient variant of hen lysozyme, and follow the time-dependent changes in volume and compressibility, as the protein spontaneously forms a protofibril. We have found a large increase in partial specific volume with time from 0.

A phase II study of combination chemotherapy with docetaxel and carboplatin for patients with advanced or metastatic non-small cell lung cancer.

Background: The aim of this phase II study was to evaluate the efficacy of combination chemotherapy consisting of docetaxel and carboplatin in patients with inoperable non-small cell lung cancer (NSCLC).

Patients And Methods: For this multicenter phase II study, the eligibility criteria included histologically or cytologically proven inoperable NSCLC, measurable lesions, Eastern Cooperative Oncology Group performance status (PS) 0-2, adequate organ and bone marrow functions, and written informed consent. Patients received 60 mg/m2 of docetaxel and carboplatin (target AUC 5.

Kinetic analysis of amyloid protofibril dissociation and volumetric properties of the transition state.

We present here the first detailed kinetic analysis of the dissociation reaction of amyloid protofibrils by utilizing pressure as an accelerator of the reaction. The experiment is carried out on an excessively diluted typical protofibril solution formed from an intrinsically denatured disulfide-deficient variant of hen lysozyme with Trp fluorescence as the reporter in the pressure range 3-400 MPa. From the analysis of the time-dependent fluorescence decay and the length distribution of the protofibrils measured on atomic force microscopy, we conclude that the protofibril grows or decays by attachment or detachment of a monomer at one end of the protofibril with a monomer dissociation rate independent of the length of the fibril.

A case of acute hypersensitivity pneumonitis associated with an oil fan heater.

We report here a case of acute hypersensitivity pneumonitis induced by an oil fan heater. A 57-year-old man was admitted to our hospital because of fever, nonproductive cough, and dyspnea. Paeccilomyces variotii and Paeccilomyces nivea were identified from an oil fan heater in his house.

Characterisation of disulfide-bond dynamics in non-native states of lysozyme and its disulfide deletion mutants by NMR.

This report describes NMR-spectroscopic investigations of the conformational dynamics of disulfide bonds in hen-egg-white lysozyme substitution mutants. The following four systems have been investigated: 2SS(alpha), a lysozyme variant that contains C64A, C76A, C80A and C94A substitutions, was studied in water at pH 2 and 3.8 and in urea (8 M, pH 2); 2SS(beta) lysozyme, which has C6S, C30A, C115A and C127A substitutions, was studied in water (pH 2) and urea (8 M, pH 2).

Pressure-jump NMR study of dissociation and association of amyloid protofibrils.

The dissociation and reassociation processes of amyloid protofibrils initiated by pressure-jump have been monitored with real-time (1)H NMR spectroscopy using an intrinsically denatured disulfide-deficient variant of hen lysozyme. Upon pressure-jump up to 2 kbar, the matured protofibrils grown over several months become fully dissociated into monomers within a few days. Upon pressure-jump down to 30 bar, the dissociated monomers immediately start reassociating.

Importance of the angiotensin type 1 receptor in angiotensin II-induced bronchoconstriction and bronchial hyperresponsiveness in the guinea pig.

Although angiotensin II (Ang II) causes bronchoconstriction and bronchial hyperresponsiveness to methacholine in mildly asthmatic patients, the responsible mechanisms for these reactions are unclear. The authors examined the effect of intravenous infusion of Ang II on airway constriction in guinea pigs. Furthermore, the effects of subthreshold concentrations of Ang II on bronchial responsiveness to methacholine were investigated.

NMR characterization of three-disulfide variants of lysozyme, C64A/C80A, C76A/C94A, and C30A/C115A--a marginally stable state in folded proteins.

Our earlier NMR study showed that a two-disulfide variant of hen lysozyme containing intra-alpha-domain disulfide bridges, C6-C127 and C30-C115, is partially folded, with the alpha domain tightly folded to the nativelike conformation and the beta domain flexible or unfolded. With a view that the formation of a third disulfide bridge is a key for the accomplishment of the overall chain fold, three-dimensional structures of three-disulfide variants of hen lysozyme lacking one disulfide bridge (C64A/C80A, C76A/C94A, and C30A/C115A) were studied in detail using NMR spectroscopy. Amide hydrogen exchange rates were measured to estimate the degree of conformational fluctuation in a residue-specific manner.

Pressure-dissociable reversible assembly of intrinsically denatured lysozyme is a precursor for amyloid fibrils.

Although a diversity of proteins is known to form amyloid fibers, their common mechanisms are not clear. Here, we show that an intrinsically unfolded protein (U), represented by a disulfide-deficient variant of hen lysozyme with no tertiary structure, forms an amyloid-like fibril after prolonged incubation. Using variable pressure NMR along with sedimentation velocity, circular dichroism, and fluorescence measurements, we show that, before the fibril formation, the protein forms a pressure-dissociable, soluble assemblage (U'(n)) with a sedimentation coefficient of 17 S and a rich intermolecular beta-sheet structure.

Bronchodilator effects of intravenous olprinone, a phosphodiesterase 3 inhibitor, with and without aminophylline in asthmatic patients.

Aims: There is no evidence demonstrating the clinical usefulness of phosphodiesterase (PDE) inhibitors in the treatment of asthma, although PDE3 and 4 inhibitors have received much attention for the treatment of bronchial asthma. We compared the bronchodilator effects of intravenously administered olprinone, a selective PDE3 inhibitor, and aminophylline, a nonselective PDE inhibitor, both alone and concomitantly.

Methods: In 12 patients with mild stable asthma, we compared the acute bronchodilator effects of the following two drugs, alone and together using a double-blind crossover design: intravenous administration of olprinone, 30 micro g min-1; aminophylline, 2.

Immunochemical pulsed-labeling characterization of intermediates during hen lysozyme oxidative folding.

Previous studies have shown that reduced hen egg white lysozyme refolds and oxidizes according to a linear model, in which the number of disulfide bonds increases sequentially. In this study, we describe the kinetics of native tertiary structure formation during the oxidative-renaturation of reduced hen egg white lysozyme, as monitored using an immunochemical pulsed-labeling method based on enzyme-linked immunosorbent assay (ELISA) in conjunction with two monoclonal antibodies (mAb). Each of these antibodies recognizes a separate face of the native lysozyme surface and, more importantly, each epitope is composed of discontinuous regions of the polypeptide chain.

Effect of intranasal administration of CV-11974, a type 1 angiotensin II receptor antagonist, on airway hyperresponsiveness and airway inflammation induced by antigen inhalation in guinea pigs.

Background: Angiotensin II is a putative mediator in asthma, but the effect of topical administration of type 1 angiotensin II (AT1) receptor antagonists on allergic airway reactions is not known.

Objective: To investigate the effect of intranasal administration of CV-11974, an AT1 receptor antagonist, and of PD123319, a type 2 angiotensin II (AT2) receptor antagonist, on antigen-induced airway reactions in guinea pigs.

Methods: Thirty minutes after intranasal topical administration of CV-11974 (0.

Effect of ozagrel hydrochloride, a thromboxane synthetase inhibitor, on alcoholic beverage-induced bronchoconstriction in asthmatic patients.

Acetaldehyde is thought to be a main factor of alcohol-induced asthma. The thromboxane (TX) synthetase inhibitor, ozagrel hydrochloride, inhibits acetaldehyde-induced bronchoconstriction in asthmatic patients. The present study evaluated the involvement of TXA(2) on alcoholic beverage-induced bronchoconstriction.

NMR structural study of two-disulfide variant of hen lysozyme: 2SS[6-127, 30-115]--a disulfide intermediate with a partly unfolded structure.

The 15N-labeled recombinant hen lysozyme and two species of two-disulfide variants, denoted as 2SS[6-127, 30-115] and 2SS[64-80, 76-94], were studied by means of NMR spectroscopy. The former variant contains two disulfide bridges in the alpha-domain, while the latter has one disulfide bridge in the beta-domain and the other one at the interface between two domains. Resonance assignments were performed using 3D TOCSY-HSQC and NOESY-HSQC spectra.