Development and application of 2.5 GPa-25 T high-pressure high-field electron spin resonance system using a cryogen-free superconducting magnet.

We have developed a high-pressure electron spin resonance probe and successfully installed into the world's highest-field cryogen-free superconducting magnet having a maximum central field of 24.6 T. The high pressure of 2.5 GPa is achieved by the specially designed piston-cylinder pressure cell using THz-wave-transparent components. In the first application of this high-pressure high-field ESR system, we observed that the orthogonal dimer spin system SrCu2(BO3)2 undergoes a quantum phase transition from the dimer singlet ground to the plaquette singlet ground states.

The relationship between stroke severity and prior direct oral anticoagulant therapy in patients with acute ischaemic stroke and non-valvular atrial fibrillation.

BACKGROUND AND PURPOSE: Anticoagulant treatment with a vitamin K antagonist (VKA) has been reported to reduce stroke severity when patients with atrial fibrillation (AF) suffer acute ischaemic stroke (AIS). Direct oral anticoagulant (DOAC) therapy also has the potential to reduce the initial severity of AIS. However, the effect of DOAC therapy on the severity of AIS is not well known. The aim of the present study was to investigate the effect of DOACs on initial stroke severity in patients with AIS and non-valvular AF. METHODS: From March 2011 to July 2016, consecutive patients with AIS having non-valvular AF were recruited. The effects of prior DOAC treatment on severity were assessed by multivariate logistic regression analyses. RESULTS: A total of 484 patients [208 women; median age 79 (interquartile range, 71-85) years; National Institutes of Health Stroke Scale (NIHSS) score 9 (interquartile range, 3-20)] were enrolled. Of these, 352 (73%) were on no anticoagulant medication, 54 (11%) were undertreated with a VKA, 35 (7%) were sufficiently treated (admission prothrombin time-international normalized ratio: ≥2.0 for patients <70 years old and ≥1.6 for ≥70 years old) with a VKA and 43 (9%) were on a DOAC. The initial NIHSS score (median 10 in patients with no anticoagulation, 13 in undertreated VKA, 7 in sufficient VKA and 6 in DOAC, P = 0.018) was different among the groups. Multivariate analysis showed that DOAC was independently and negatively associated with severe (initial NIHSS score ≥ 10) stroke (odds ratio, 0.39; P = 0.041), compared with no anticoagulant therapy. CONCLUSIONS: Direct oral anticoagulant treatment prior to the event should reduce initial stroke severity in patients with AIS and non-valvular AF.

Fast x-ray detector system with simultaneous measurement of timing and energy for a single photon.

We developed a fast X-ray detector system for nuclear resonant scattering (NRS) experiments. Our system employs silicon avalanche photo-diode (Si-APD) as a fast X-ray sensor. The system is able to acquire both timing and energy of a single X-ray photon simultaneously in a high rate condition, 106 counts per second for one Si-APD. The performance of the system was investigated in SPring-8, a synchrotron radiation facility in Japan. Good time resolution of 120 ps (FWHM) was achieved with a slight tail distribution in the time spectrum by a level of 10-9 at 1 ns apart from the peak. Using this system, we successfully observed the NRS from the 26.27-keV level of mercury-201, which has a half-life of 630(50) ps. We also demonstrated the reduction of background events caused by radioactive decays in a radioactive sample by discriminating photon energy.

High-field/high-pressure ESR.

We present a historical review of high-pressure ESR systems with emphasis on our recent development of a high-pressure, high-field, multi-frequency ESR system. Until 2000, the X-band system was almost established using a resonator filled with dielectric materials or a combination of the anvil cell and dielectric resonators. Recent developments have shifted from that in the low-frequency region, such as X-band, to that in multi-frequency region. High-pressure, high-field, multi-frequency ESR systems are classified into two types. First are the systems that use a vector network analyzer or a quasi-optical bridge, which have high sensitivity but a limited frequency region; the second are like our system, which has a very broad frequency region covering the THz region, but lower sensitivity. We will demonstrate the usefulness of our high-pressure ESR system, in addition to its experimental limitations. We also discuss the recent progress of our system and future plans.

Development of multi-frequency ESR system for high-pressure measurements up to 2.5 GPa.

A new piston-cylinder pressure cell for electron spin resonance (ESR) has been developed. The pressure cell consists of a double-layer hybrid-type cylinder with internal components made of the ZrO2-based ceramics. It can generate a pressure of 2 GPa repeatedly and reaches a maximum pressure of around 2.5 GPa. A high-pressure ESR system using a cryogen-free superconducting magnet up 10T has also been developed for this hybrid-type pressure cell. The frequency region is from 50 GHz to 400 GHz. This is the first time a pressure above 2 GPa has been achieved in multi-frequency ESR system using a piston-cylinder pressure cell. We demonstrate its potential by showing the results of the high-pressure ESR of the S=1 system with the single ion anisotropy NiSnCl6·6H2O and the S=1/2 quantum spin system CsCuCl3. We performed ESR measurements of these systems above 2 GPa successfully.

Disappearance of Ising nature in Ca3ZnMnO6 studied by high-field ESR.

High-field electron spin resonance measurements of an antiferromagnet Ca3ZnMnO6 isostructure, with the Ising-chain multiferroic Ca3CoMnO6, have been carried out. Two distinct resonance modes were observed below TN = 25 K, which is well explained by conventional antiferromagnetic resonance theory with easy-plane anisotropy. The zero-field spin gap is derived to be about 166 GHz, originating from the easy-plane anisotropy and exchange interaction. Our result suggests that the Dzyaloshinsky-Moriya interaction, which may induce spin canting, is absent. Disappearance of Ising anisotropy in Ca3ZnMnO6 suggests that the Co(4+) ion, as well as the Co-Mn superexchange, plays an important role for the Ising nature in Ca3CoMnO6.

Temperature distributions of electron beam-irradiated samples by scanning electron microscopy.

An electron beam (EB) generated by a scanning electron microscope (SEM) was used to irradiate two samples having different thermal conductivities, and the resulting temperatures of the EB-irradiated areas as well as the temperature distributions within the samples were then measured using a thermal camera. These measurements showed overall increases in sample temperatures, as well as revealed temperature rises at the EB-irradiated areas that had little difference with one of the theoretical predictions. Differences between the actual and the predicted temperature measurements were analysed in terms of the accuracy with which parameters could be estimated. The temperature distributions of the samples were measured and, On the basis of the results, it was hypothesized that the temperature differential over an irradiated sample will be inversely correlated with its thermal conductivity.

Development of high-pressure and high-field ESR system using SQUID magnetometer.

We have developed a high-pressure and high-field electron spin resonance (ESR) system using the combination of a commercially available superconducting quantum interference device (SQUID) magnetometer and a clamp-type piston cylinder pressure cell. The magnetic field range is up to 5 T, and the maximum pressure reaches 1.5 GPa. The most characteristic feature of this system is its easy handling as compared with other high-pressure ESR systems. Moreover, the macroscopic magnetization measurement can be performed simultaneously with the microscopic ESR measurement. In addition to these features, the well-established pressure calibration method utilizing the change of superconducting transition temperature of tin can be applied to this system. By using this system, we obtained pressure dependence of the single ion magnetic anisotropy parameter D of NiSnCl(6)·6H(2)O up to 1.5 GPa precisely, and the magnetization behavior of this material under pressure was explained well by its pressure dependence of the D value.

Development of high-pressure, high-field and multifrequency electron spin resonance system.

The electron spin resonance (ESR) system which covers the magnetic field region up to 16 T, the quasicontinuous frequency region from 60 to 700 GHz, the temperature region from 1.8 to 4.2 K, and the hydrostatic pressure region up to 1.1 GPa has been developed. This is the first pulsed high-field and multifrequency ESR system with the pressure region over 1 GPa as far as we know. Transmission ESR spectra under hydrostatic pressure can be obtained by combining a piston-cylinder-type pressure cell and the pulsed magnetic field ESR apparatus. The pressure cell consists of a NiCrAl cylinder and sapphire or zirconia inner parts. The use of sapphire or zirconia as inner parts enables us to observe ESR under pressure because these inner parts have high transmittance for the electromagnetic wave with millimeter and submillimeter wavelengths. We have successfully applied this system for the pressure dependence measurements of an isolated spin system NiSnCl(6)6H(2)O up to 1.1 GPa. It was found that the single ion anisotropy parameter D of this compound strongly depends on pressure. The parameter D is approximately proportional to the pressure up to 0.75 GPa, and the relation between D and the pressure can be used for the pressure calibration of this high-field and high-pressure ESR system.

Cardioprotective effect of edaravone against ischaemia-reperfusion injury in the rabbit heart before, during and after reperfusion treatment.

The free radical scavenger edaravone is able to stimulate prostacyclin release and inhibit the lipoxygenase pathway in the arachidonic acid cascade. The effect of edaravone administration on myocardial damage in rabbit hearts subjected to ischaemia-reperfusion was examined at different times relative to reperfusion. All rabbits underwent sustained coronary artery occlusion for 30 min followed by 3 h of reperfusion. Rabbits were divided into the following groups: control; early (3 mg/kg edaravone IV 10 min before reperfusion); immediate (3 mg/kg edaravone IV immediately after the start of reperfusion); and late (3, 6 or 10 mg/kg edaravone IV 5 min after the start of reperfusion). Single bolus administration of edaravone 10 min before reperfusion or immediately upon initiation of reperfusion appears to be associated with reductions in infarction size and the percentage of apoptotic cells, but treatment with edaravone 5 min after initiation of reperfusion does not appear to have this protective effect.

Effect of vitamin C on common cold: randomized controlled trial.

OBJECTIVE: To investigate the relationship between the common cold and vitamin C supplementation. DESIGN: A double-blind, 5-year randomized controlled trial. SETTING: A village in Akita prefecture, one of the regions in Japan with the highest mortality from gastric cancer. SUBJECTS: Participants in annual screening programs for circulatory diseases conducted under the National Health and Welfare Services Law for the Aged, and diagnosed as having atrophic gastritis. Of the 439 eligible subjects, 144 and 161 were assigned to receive 50 or 500 mg of vitamin C, respectively, after protocol amendment. During the supplementation phase, 61 dropped out, and 244 completed the trial. INTERVENTION: Daily vitamin C supplementation of 50 mg (low-dose group) or 500 mg (high-dose group). RESULTS: Total number of common colds (per 1000 person-months) was 21.3 and 17.1 for the low- and high-dose groups, respectively. After adjustment for several factors, the relative risks (95% confidence interval (CI)) of suffering from a common cold three or more times during the survey period was 0.34 (0.12-0.97) for the high-dose group. No apparent reduction was seen for the severity and duration of the common cold. CONCLUSION: A randomized, controlled 5-year trial suggests that vitamin C supplementation significantly reduces the frequency of the common cold but had no apparent effect on the duration or severity of the common cold. However, considering several limitations due to protocol amendment, the findings should be interpreted with caution.

Energy structure of a finite Haldane chain in Y2BaNi0.96Mg0.04O5 studied by high field electron spin resonance.

This Letter presents the fine structure of energy levels for the edge states of a Haldane chain. In order to investigate the edge states, we have performed high field and multifrequency electron spin resonance (ESR) measurements of finite length S=1 antiferromagnetic chains in Y2BaNi0.96Mg0.04O5. Owing to the high spectral resolution by high fields and high frequencies, observed ESR signals can be separated into the contributions of the finite chains with various chain lengths. Our results clearly show that the edge spins actually interact with each other through the quantum spin chain and the interaction depends on the chain length N. This N dependence has been obtained experimentally for the first time, and shows that the correlation length xi in the real system is somewhat larger than that calculated by a simple Heisenberg model.

Chronotropic effect of the antithrombotic agent cilostazol in a patient with sick sinus syndrome and syncope.

In this case report we describe an 80-year-old man with sick sinus syndrome (SSS) who developed syncope attacks. The diagnosis of SSS was based on electrocardiographic evidence of markedly prolonged sinus arrests associated with syncope attacks while in hospital. The patient was given cilostazol, an antithrombotic agent that selectively inhibits cyclic nucleotide phosphodiesterase type 3, at a dose of 100 mg twice daily. The syncope attacks ceased, and an electrocardiogram obtained 1 week after the start of cilostazol administration showed no evidence of sinus arrest. The outcome of this case suggests that cilostazol may be useful in patients with syncope attacks due to SSS, although the long-term chronotropic effects of cilostazol need to be evaluated.

Additive antitumour effect of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (Iressa, ZD1839) and the antioestrogen fulvestrant (Faslodex, ICI 182,780) in breast cancer cells.

A high expression level of epidermal growth factor receptor (EGFR)/HER1 has been suggested to lead to a shorter survival time and resistance to endocrine therapy in patients with breast cancer. To test the hypothesis that inhibition of the EGFR signalling pathway affects the antitumour effect of endocrine therapy, an EGFR tyrosine kinase inhibitor (EGFR-TKI), gefitinib, and an oestrogen receptor (ER) antagonist, fulvestrant, were administered to human breast cancer cells. A total of five human breast cancer cell lines were used. The effects of single or combined treatments with gefitinib and/or fulvestrant on cell growth, cell cycle progression and apoptosis were analysed. Changes in the expression levels of cyclin-dependent kinase inhibitors, p21 and p27, an antiapoptotic factor, Bcl-2, and a proapoptotic factor, Bax, were also investigated. All cell lines tested were sensitive to gefitinib (50% growth inhibitory concentration, 10-28.5 microM). Breast cancer cell lines with a high expression level of HER1 or HER2 were more sensitive to gefitinib than the others. Gefitinib induced a significant G1-S blockade in ER-positive KPL-3C cells. Gefitinib induced significant apoptosis in HER1-overexpressing MDA-MB-231 cells. Gefitinib additively increased the antitumour effect of fulvestrant in all three ER-positive cell lines in a medium supplemented with 17beta-oestradiol. The combined treatment promoted cell cycle retardation in KPL-3C cells, which is associated with an upregulation of p21 by fulvestrant and gefitinib, respectively. Apoptosis was associated with downregulation of Bcl-2 by gefitinib in MDA-MB-231 cells. These results suggest an additive interaction between the EGFR-TKI gefitinib and the antioestrogen fulvestrant in ER-positive breast cancer cells.

A case of micrographia after subcortical infarction: possible involvement of frontal lobe function.

Most reports of micrographia associated with focal brain lesions have related this finding to damage in the left basal ganglia. Here we describe the case of a 68-year-old man presenting with reversible micrographia accompanied by hypophonia in the absence of extrapyramidal signs after cerebral infarction in the left subcortical region. At the time of the patient's admission, diffusion-weighted magnetic resonance imaging sequence showed the lesion to principally involve the corona radiata, with some involvement of the putamen. Neurologically, mild right-sided brachiofacial hemiparesis and grasp reflexes - a frontal lobe sign - were observed. As his micrographia and hypophonia improved, the patient's grasp reflexes improved in parallel. In addition, recovery of regional cerebral blood flow in the left frontal lobe was confirmed by single photon emission computed tomography (technetium-99 m HMPAO). The present case suggests the possibility that the function of frontal-subcortical circuit might also be involved in the production and improvement of micrographia and that micrographia and hypophonia may share a common pathophysiology.

Squamous cell carcinoma developing in a 12-year-old boy with nonHallopeau-Siemens recessive dystrophic epidermolysis bullosa.

We report a 12-year-old boy with nonHallopeau-Siemens recessive dystrophic epidermolysis bullosa (nHS-RDEB) who developed two skin lesions of squamous cell carcinoma (SCC) on the left foot. The incidence of SCC in nHS-RDEB is much lower than in the HS-RDEB subtype. Furthermore, this boy is the youngest among 92 previously described patients with DEB to develop SCC. This study emphasizes the importance of vigilance in monitoring the possible development of SCC in DEB patients regardless of age or clinical severity.

Residuals of beta-hexachlorocyclohexane, dichlorodiphenyltrichloroethane, and hexachlorobenzene in serum, and relations with consumption of dietary components in rural residents in Japan.

To estimate levels of organochlorine residuals in the Japanese population and the contribution of dietary factors to these levels, we determined serum levels of beta-hexachlorocyclohexane (beta-HCH), hexachlorobenzene (HCB), p,p'-dichlorodiphenyldichloroethane (p,p'-DDD), 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE) and p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) in 41 volunteers (14 men and 27 women) in a rural area of Northern Japan. These organochlorine levels were measured using gas-chromatography mass-spectrometry. By a self-administered dietary history questionnaire, the usual dietary intake was estimated. Their median levels (range) were as follows: beta-HCH, 0.50 (0.05-1.50); HCB, 0.20 (0.02-0.70); and total DDT (p,p'-DDE + p,p'-DDT), 5.0 (0.9-31.0) ng/ml serum. Levels of p,p'-DDD were detected in only seven subjects (0.05-0.6 ng/ml serum). The beta-HCH levels were increased with rice and milk intakes, but the least squares means were not simply increased according to the quartile of the intakes. Concerning HCB, fish intake showed a borderline significant correlation (0.20, P = 0.052). In terms of total DDT, intakes of meat, fish, vegetable and milk showed a positive relationship, although none of them provided statistically significant results. No other statistically significant relation between any organochlorines and any food intakes examined was observed in this study. The present study suggests that organochlorine compounds are transported into the human body via foods in the Japanese population. Their effects on health should thus be investigated and monitored.

Gastrointestinal symptoms associated with enteric-coated sulfasalazine (Azulfidine EN tablets).

Abstract To investigate both the incidence and the dosage used to treat gastrointestinal (GI) symptoms associated with enteric-coated sulfasalazine (Azulfidine EN, AZL) in patients with rheumatoid arthritis (RA), we studied the clinical history of 153 RA patients, and any available data on GI symptoms that might have been associated with AZL. GI symptoms appeared in 64 (42.5%) of the 153 cases. There were 19 events of nausea, vomiting, or dyspepsia, 14 events each of epigastric discomfort and reduction or loss of appetite, 10 events of epigastric, stomach, or abdominal pain, 9 events of heartburn, 8 events of mouth ulcer, 3 events each of loss of taste and abdominal bloating or borborygmus, 2 events each of diarrhea or loose stools, hematemesis or melanemia, and gastric or esophageal ulcer, and 1 event of stomatitis. These results indicate that GI symptoms associated with AZL are usually mild and treatment can continue, with almost all cases responding to a reduction in dose or drug cessation. In some cases, a histamine receptor-2 blocker or proton pump inhibitor is also required.