Precise Measurement of Differential Cross Sections of the Σ

The differential cross sections of the Σ^{-}p→Λn reaction were measured accurately for the Σ^{-} momentum (p_{Σ}) ranging from 470 to 650 MeV/c at the J-PARC Hadron Experimental Facility. Precise angular information about the Σ^{-}p→Λn reaction was obtained for the first time by detecting approximately 100 reaction events at each angular step of Δcosθ=0.1. The obtained differential cross sections show a slightly forward-peaking structure in the measured momentum regions. The cross sections integrated for -0.7≤cosθ≤1.0 were obtained as 22.5±0.68 [statistical error(stat.)] ±0.65 [systematic error(syst.)] mb and 15.8±0.83(stat)±0.52(syst) mb for 470

Clinical relevance of nitrated beta 2-glycoprotein I in antiphospholipid syndrome: Implications for thrombosis risk.

Β2-Glycoprotein I (ß2GPI) is an important anti-thrombotic protein and is the major auto-antigen in the antiphospholipid syndrome (APS). The clinical relevance of nitrosative stress in post translational modification of ß2GPI was examined.The effects of nitrated (n)ß2GPI on its anti-thrombotic properties and its plasma levels in primary and secondary APS were determined with appropriate clinical control groups. ß2-glycoprotein I was nitrated at tyrosines 218, 275 and 309. ß2-glycoprotein I binds to lipid peroxidation modified products through Domains IV and V. Nitrated ß2GPI loses this binding (p < 0.05) and had diminished activity in inhibiting platelet adhesion to vWF under high shear flow (p < 0.01). Levels of nß2GPI were increased in patients with primary APS compared to patients with either secondary APS (p < 0.05), autoimmune disease without APS (p < 0.05) or non-autoimmune patients with arterial thrombosis (p < 0.01) and healthy individuals (p < 0.05).In conclusion tyrosine nitration of plasma ß2GPI is demonstrated and has important implications with regards to the pathophysiology of platelet mediated thrombosis in APS. Elevated plasma levels of nß2GPI in primary APS may be a risk factor for thrombosis warranting further investigation.

Observation of Coulomb-Assisted Nuclear Bound State of Ξ

In an emulsion-counter hybrid experiment performed at J-PARC, a Ξ^{-} absorption event was observed which decayed into twin single-Λ hypernuclei. Kinematic calculations enabled a unique identification of the reaction process as Ξ^{-}+^{14}N→_{Λ}^{10}Be+_{Λ}^{5}He. For the binding energy of the Ξ^{-} hyperon in the Ξ^{-}-^{14}N system a value of 1.27±0.21 MeV was deduced. The energy level of Ξ^{-} is likely a nuclear 1p state which indicates a weak ΞN-ΛΛ coupling.

Association of residual gastric acid secretion with persistent symptoms in gastroesophageal reflux disease patients receiving standard-dose proton pump inhibitor therapy.

BACKGROUND: Although a third of gastroesophageal reflux disease (GERD) patients are refractory to proton pump inhibitor (PPI) therapy, the underlying mechanism of the refractoriness remains unclear. We compared the level of gastric acid suppression during PPI treatment between responders and non-responders by directly measuring gastric acid secretion in GERD patients taking PPIs. METHODS: Seventy-five consecutive patients receiving standard-dose PPI therapy for GERD were prospectively recruited, irrespective of persistent GERD symptoms. They were asked about their GERD symptoms using a validated questionnaire, and simultaneously underwent both a routine endoscopic examination and a gastric acid secretory testing using an endoscopic gastrin test. Associations between residual gastric acid secretion during PPI treatment and persistent GERD symptoms were analyzed by a logistic regression analysis. RESULTS: Overall, 26 of 75 (34.7%) patients were judged to be positive for persistent GERD symptoms. The patients with and without persistent symptoms showed similar gastric acid secretion levels (1.3 [1.3] mEq/10 min vs. 1.4 [2.0] mEq/10 min). Sufficient gastric acid suppression, defined as < 0.6, was not significantly associated with persistent GERD symptoms (odds ratio 1.1, 95% confidence interval 0.40-3.5). CONCLUSIONS: This study provided solid evidence to support that the gastric acid suppression level during PPI treatment does not differ between patients with and without persistent GERD symptoms. The insignificant role of residual gastric acid in the persistent GERD symptoms suggests that the use of medications other than those that enhance gastric acid inhibitory effects would be an essential approach for the management of PPI-refractory GERD.

Experimental Evidence for Transverse Wobbling in

New rotational bands built on the ν(h_{11/2}) configuration have been identified in ^{105}Pd. Two bands built on this configuration show the characteristics of transverse wobbling: the ΔI=1 transitions between them have a predominant E2 component and the wobbling energy decreases with increasing spin. The properties of the observed wobbling bands are in good agreement with theoretical results obtained using constrained triaxial covariant density functional theory and quantum particle rotor model calculations. This provides the first experimental evidence for transverse wobbling bands based on a one-neutron configuration, and also represents the first observation of wobbling motion in the A∼100 mass region.

First Determination of the Level Structure of an sd-Shell Hypernucleus, _{Λ}

We report on the first observation of γ rays emitted from an sd-shell hypernucleus, _{Λ}^{19}F. The energy spacing between the ground state doublet, 1/2^{+} and 3/2^{+} states, of _{Λ}^{19}F is determined to be 315.5±0.4(stat)_{-0.5}^{+0.6}(syst) keV by measuring the γ-ray energy of the M1(3/2^{+}→1/2^{+}) transition. In addition, three γ-ray peaks are observed and assigned as E2(5/2^{+}→1/2^{+}), E1(1/2^{-}→1/2^{+}), and E1(1/2^{-}→3/2^{+}) transitions. The excitation energies of the 5/2^{+} and 1/2^{-} states are determined to be 895.2±0.3(stat)±0.5(syst) and 1265.6±1.2(stat)_{-0.5}^{+0.7}(syst) keV, respectively. It is found that the ground state doublet spacing is well described by theoretical models based on existing s- and p-shell hypernuclear data.

Risk of metachronous recurrence after endoscopic submucosal dissection of esophageal squamous cell carcinoma.

Development of endoscopic submucosal dissection (ESD) improves the en bloc resection rate of superficial esophageal squamous cell carcinoma (SESCC). Although the background mucosa after ESD remains malignant potential, esophageal (sub)circumferential ESD, in cases where the mucosal defect is greater than three-fourths of the circumference, might induce refractory stricture, and it may disturb early detection of the recurrence. Therefore, we aimed to elucidate whether the patients treated by (sub)circumferential ESD for SESCC may remain at risk of metachronous recurrence. In a single-center retrospective study, we collected data from 154 consecutive patients who were treated with curative ESD for SESCC from 2002 to 2013 and followed by surveillance for longer than 12 months. Metachronous recurrence was defined as histologically proven SESCC at other site of the ESD scar or abnormal nodal swelling was detected later than 12 months after ESD. The primary endpoint was to identify the risk of metachronous recurrence using multivariate analyses. The secondary endpoint was to investigate difference in clinical pathological features between patients with and without the recurrence. The overall rate of metachronous recurrence was 14.9% during 40.5 median months after the initial ESD. 24.1% and 9.0% of overall metachronous recurrence were observed in patients treated with (sub)circumferential ESD and non-subcircumferential ESD, respectively, despite no significant difference in their observation duration. After the application of a stepwise regression model that included all variants, a Cox proportional hazards regression model identified (sub)circumferential ESD as the only risk for the recurrence (hazard ratio (HR): 1.48, 95% confidence intervals (CI): 1.04-2.08, P = 0.028). The cumulative recurrence rate revealed a significant difference between patients treated by (sub)circumferential ESD and those by nonsubcircumferential ESD (HR: 3.094, 95% CI: 1.33-7.52, P = 0.009), despite no significant difference in their cause-specific survival. Additionally, the session numbers of the follow-up endoscopy until the detection of metachronous recurrence after the non-subcircumferential ESD were significantly less than those after the (sub)circumferential ESD (7.8 ± 1.8 vs. 15.2 ± 1.5 P = 0. 005), despite no significant difference in their cancer-free duration. In conclusion, we demonstrated that patients treated by curative (sub)circumferential ESD for SESCC might be high risk for metachronous recurrence. Therefore, we should establish a risk-stratified surveillance program after (sub)circumferential ESD and preventive strategies for post-ESD stricture.

Reducing glucocorticoid dosage improves serum osteocalcin in patients with rheumatoid arthritis-results from the TOMORROW study.

UNLABELLED: Decreasing the daily dose of glucocorticoids improved bone metabolic marker levels in patients with rheumatoid arthritis. However, changes in disease activity did not influence bone metabolism. Bone metabolism might thus remain uncontrolled even if disease activity is under good control. Decreasing glucocorticoid dosage appears important for improving bone metabolism. INTRODUCTION: Patients with rheumatoid arthritis (RA) develop osteoporosis more frequently than healthy individuals. Bone resorption is increased and bone formation is inhibited in patients with RA, and glucocorticoid negatively affects bone metabolism. We aimed to investigate factors influencing bone metabolic markers in patients with RA. METHODS: We started the 10-year prospective cohort Total Management of Risk Factors in Rheumatoid Arthritis Patients to Lower Morbidity and Mortality (TOMORROW) study in 2010. We compared changes in urinary cross-linked N-telopeptide of type I collagen (uNTx) and serum osteocalcin (OC), as markers of bone resorption and formation, respectively, in 202 RA patients and age- and sex-matched volunteers between 2010 and 2011. We also investigated factors influencing ΔuNTx and ΔOC in the RA group using multivariate analysis. RESULTS: Values of ΔuNTx were significantly lower in patients with RA than in healthy controls (-0.51 vs. 7.41 nmol bone collagen equivalents (BCE)/mmol creatinine (Cr); p = 0.0013), whereas ΔOC values were significantly higher in RA patients (0.94 vs. 0.37 ng/ml; p = 0.0065). Changes in prednisolone dosage correlated negatively with ΔOC (ß = -0.229, p = 0.001), whereas changes in disease activity score, bisphosphonate therapy, and period of biologics therapy did not correlate significantly with ΔOC. No significant correlation was seen between ΔuNTx and change in prednisolone dosage. CONCLUSIONS: Decreased glucocorticoid dosage improved bone metabolic markers in RA, but disease activity, bisphosphonate therapy, and period of biologics therapy did not influence levels of bone metabolic markers. Decreasing glucocorticoid dosage appears important for improving bone metabolic marker profiles in patients with RA.

Role of apolipoprotein B100 and oxidized low-density lipoprotein in the monocyte tissue factor induction mediated by anti-ß2 glycoprotein I antibodies.

OBJECTIVE: The objective of this paper is to elucidate the not yet known plasma molecule candidates involved in the induction of tissue factor (TF) expression mediated by ß2GPI-dependent anticardiolipin antibody (aCL/ß2GPI) on monocytes. METHODS: Human serum incubated with FLAG-ß2GPI was applied for affinity chromatography with anti- FLAG antibody. Immunopurified proteins were analyzed by a liquid chromatography coupled with mass spectrometry (LC-MS). TF mRNA induced by the identified molecules on monocytes was also analyzed. RESULTS: Apolipoprotein B100 (APOB) was the only identified serum molecule in the MS search. Oxidized LDL, containing APOB as well as ox-Lig1 (a known ligand of ß2GPI), was revealed as a ß2GPI-binding molecule in the immunoprecipitation assay. TF mRNA was markedly induced by oxidized LDL/ß2GPI complexes with either WBCAL-1 (monoclonal aCL/ß2GPI) or purified IgG from APS patients. The activities of lipoprotein-associated phospholipase A2, one of the component molecules of oxidized LDL, were significantly higher in serum from APS patients than in those from controls. CONCLUSION: APOB (or oxidized LDL) was detected as a major ß2GPI binding serum molecule by LC-MS search. Oxidized LDL/aCL/ß2GPI complexes significantly induced TF expressions on monocytes. These data suggest that complexes of oxidized LDL and aCL/ß2GPI may have a crucial role in the pathophysiology of APS.

Observation of Spin-Dependent Charge Symmetry Breaking in ΛN Interaction: Gamma-Ray Spectroscopy of _{Λ}

The energy spacing between the spin-doublet bound state of _{Λ}^{4}He(1^{+},0^{+}) was determined to be 1406±2±2 keV, by measuring γ rays for the 1^{+}→0^{+} transition with a high efficiency germanium detector array in coincidence with the ^{4}He(K^{-},π^{-})_{Λ}^{4}He reaction at J-PARC. In comparison to the corresponding energy spacing in the mirror hypernucleus _{Λ}^{4}H, the present result clearly indicates the existence of charge symmetry breaking (CSB) in ΛN interaction. By combining the energy spacings with the known ground-state binding energies, it is also found that the CSB effect is large in the 0^{+} ground state but is vanishingly small in the 1^{+} excited state, demonstrating that the ΛN CSB interaction has spin dependence.

Multiple chiral doublet bands of identical configuration in 103Rh.

Three sets of chiral doublet band structures have been identified in the ^{103}Rh nucleus. The properties of the observed chiral doublet bands are in good agreement with theoretical results obtained using constrained covariant density functional theory and particle rotor model calculations. Two of them belong to an identical configuration and provide the first experimental evidence for a novel type of multiple chiral doublets, where an "excited" chiral doublet of a configuration is seen together with the "yrast" one. This observation shows that the chiral geometry in nuclei can be robust against the increase of the intrinsic excitation energy.

My contribution, my dream - a look at the future of APS.

We found, in 1994, that the epitope for anticardiolipin antibodies (aCL) developed when ß2-glycoprotein I (ß2GPI) was adsorbed on polyoxygenated polystyrene plates. We also found, in 2009, that the cleaved form of ß2GPI (nicked ß2GPI) was bound to angiostatin 4.5 and attenuated its antiangiogenic property. We described in 2000 that antiprothrombin antibodies were bound to prothrombin exposed to immobilized phosphatidylserine (aPS/PT) and more than 95% of antiphospholipid syndrome patients who were positive for aPS/PT had lupus anticoagulant. We demonstrated that in the cells stimulated by human monoclonal anti-ß2GPI antibodies, p38 mitogen-activated protein kinase phosphorylation was observed in the presence of ß2GPI. Furthermore, we found that complement activation was essential for thrombus formation in patients with the antiphospholipid syndrome in vivo.

Comprehensive data on ionising radiation from Fukushima Daiichi nuclear power plant in the town of Miharu, Fukushima Prefecture: The Misho Project.

Data related to radioactivity released from the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident on 15 March 2011 gathered by residents of Miharu, Fukushima Prefecture, and by Tohoku University are presented. These data sets consist of (1) the earliest radiation monitoring by a Geiger counter in the town, (2) ratios of radioactivity between (132)Te and (137)Cs for a wide area between Fukushima and Tokyo, (3) radiation measurement of soil samples collected from 18 school grounds, and (4) external radiation exposure of 1400 students using OSL badges. By combining and analysing these various data sets, a curve for the cumulative total external exposure as a function of time, with 16 : 00 h on 15 March 2011 being time zero, is obtained. The average cumulative external dosage is estimated to be 10 mSv (σ = 4.2 mSv) over 10 years. In addition, the initiative that the residents of Miharu took in response to the FDNPP accident, which became known as The Misho Project (MP), is documented; in particular, the time at which the municipality instructed the immediate ingestion of iodine tablets by those under the age of 40, 13 : 00 h on 15 March 2011, is assessed.

Serious laryngeal edema during endoscopic resection for squamous cell carcinoma of the esophagus.

The detection of early esophageal squamous cell carcinoma (ESCC) in patients following radiotherapy for squamous cell carcinoma of the head and neck (HNSCC) has increased with the development of endoscopic technologies. The aim of the current case - control study was to elucidate the risk factors of serious laryngeal edema, a lethal complication that occurs during endoscopic resection for ESCC. Among 184 consecutive patients who were treated by endoscopic resection for ESCC between January 2009 and May 2012, five of 22 patients with a history of radiotherapy for HNSCC suffered from serious laryngeal edema, which was not observed in patients who had not undergone radiotherapy. The susceptibility to serious laryngeal edema in patients with a history of radiotherapy followed by neck dissection for HNSCC was significantly greater than those without such histories. Despite the limited number of cases, we suggest that previous radiotherapy followed by neck dissection for HNSCC might be a predictive factor for serious laryngeal edema during endoscopic resection.

The involvement of CD36 in monocyte activation by antiphospholipid antibodies.

BACKGROUND: CD36, known as a scavenger receptor, is a transmembrane glycoprotein expressed on monocytes, platelets and endothelial cells, recognizes multiple ligands, including phosphatidylserine, and regulates atherogenesis and thrombosis. The objective of this study is to investigate the possible involvement of CD36 in the pathophysiology of thrombosis in patients with antiphospholipid syndrome (APS). METHODS: First, rs3765187, a missense mutation linked to CD36 deficiency, was investigated by TaqMan polymerase chain reaction (PCR) genotyping method in 819 Japanese, including 132 patients with APS, 265 with systemic lupus erythematosus (SLE) in the absence of APS, and 422 healthy subjects. Then, the involvement of CD36 in antiphospholipid antibody (aPL)-induced tissue factor (TF) expression was examined using CD36-null mice or anti-CD36. Purified IgG from patients with APS and a monoclonal phosphatidylserine-dependent antiprothrombin antibody were used in these experiments. TF expression was tested by real-time PCR and flow cytometry. RESULTS: Minor allele carrier of rs3765187 was less frequent in patients with APS (3.8% p=0.032), but not in patients with SLE in the absence of APS (7.9% p=0.32), compared with healthy subjects (10.2%). The aPL-induced TF expression was significantly suppressed on peritoneal macrophages from CD36-null mice compared to wild type and significantly inhibited by anti-CD36 on human monocytes. CONCLUSIONS: The gene mutation linked to CD36 deficiency was less frequent in patients with APS. The deficient or suppressed CD36 function significantly reduced aPL-induced TF expression in vitro. Taken together, in a susceptible background CD36 scavenger receptor function may be involved in the thrombotic pathophysiology in patients with APS.

Reactive increase in gastric mucus secretion is an adaptive defense mechanism against low-dose aspirin-induced gastropathy.

BACKGROUND: Gastric mucus is considered to play an essential role in gastric mucosal defense mechanisms, especially when irritants are present in the stomach. AIM: To investigate the relationship between low-dose aspirin-induced gastropathy and gastric secretory function, especially gastric mucus secretion, in healthy volunteers. METHODS: Thirty male, asymptomatic, Helicobacter pylori pylori-negative healthy volunteers were asked to take 100 mg of enteric-coated aspirin (Bayaspirin) once a day for 10 days. Endoscopic examination was performed before and 3 and 10 days after drug administration. The extent of endoscopically assessed gastric mucosal injury was semi-quantitatively evaluated according to the modified Lanza score. The pentagastrin-stimulated gastric juice was collected for 10 min during the endoscopic examination and subjected to analysis for gastric acid (mEq/10 min) or mucus (mg hexose/10 min) output. RESULTS: Overall, the 10-day aspirin treatment significantly increased gastric mucus secretion from 0.8 (interquartile range 1.7) to 1.6 (1.6) mg hexose/10 min (P < 0.05), with a concomitant and significant decrease in the gastric acid/mucus ratio from 4.3 (5.2) to 2.9 (4.7) (P < 0.01). Subsequent analysis of two subgroups of volunteers categorized according to their endoscopic status ("severe gastropathy" vs. "modest gastropathy") revealed that changes in gastric secretory parameters occurred exclusively in those subjects without severe gastric injury; there was no alteration in these parameters in subjects with severe gastric injury. CONCLUSIONS: The results of this study suggest that the reactive increase in gastric mucus secretion is an adaptive defense mechanism against low-dose aspirin-induced gastropathy. In some individuals, such a response may be insufficient to prevent the development of severe mucosal injury and even ulcers and their complications.

Search for the Θ+ pentaquark via the π(-)p→K(-)X reaction at 1.92 GeV/c.

The Θ(+) pentaquark baryon was searched for via the π(-)p→K(-)X reaction with a missing mass resolution of 1.4 MeV/c(2) (FWHM) at the Japan Proton Accelerator Research Complex (J-PARC). π(-) meson beams were incident on the liquid hydrogen target with a beam momentum of 1.92 GeV/c. No peak structure corresponding to the Θ(+) mass was observed. The upper limit of the production cross section averaged over the scattering angle of 2° to 15° in the laboratory frame is obtained to be 0.26 µb/sr in the mass region of 1.51-1.55 GeV/c(2). The upper limit of the Θ(+) decay width is obtained to be 0.72 and 3.1 MeV for J(Θ)(P)=1/2(+) and J(Θ)(P)=1/2(-), respectively, using the effective Lagrangian approach.

Acute treatment with candesartan cilexetil, an angiotensin II type 1 receptor blocker, improves insulin sensitivity in high-fructose-diet-fed rats.

We aimed to determine whether acute treatment with candesartan cilexetil (CV-11974), an angiotensin II type 1 receptor blocker (ARB) can improve insulin sensitivity in high-fructose-diet (HFD)-fed rats. In vivo glucose utilization was measured by applying the euglycemic clamp technique and the expression levels of insulin-signaling molecules in skeletal muscles were examined by western blotting. A bolus injection of CV-11974 improved the glucose infusion rate (GIR) of HFD-fed rats to the level of the control rats. Furthermore, restoration of impaired tyrosine phosphorylation of insulin receptor (IR) ß, Akt phosphorylation at Ser47³ and Thr³°8, and phosphorylation of the 160-kDa Akt substrate (AS160) in the skeletal muscles of HFD-fed rats were achieved by this treatment. These results suggest that acute administration of candesartan cilexetil can increase insulin sensitivity of HFD-fed rats, which is associated with improved insulin signaling in skeletal muscles.

Predominant prevalence of arterial thrombosis in Japanese patients with antiphospholipid syndrome.

OBJECTIVE: To study the clinical and immunological manifestations of antiphospholipid syndrome (APS) in the Japanese population by a single-centre registration. METHODS: In this retrospective cohort study, 141 consecutive patients with APS, fulfilling the Sydney revised Sapporo criteria for definite APS, who visited our autoimmune clinic from 1988 to 2010, were recruited and followed up. All the patients were interviewed and underwent a general physical examination by qualified rheumatologists on the day of blood sampling. RESULTS: The population comprised 119 woman and 22 men with a mean age at diagnosis of 44 years (range 9-79 years). Seventy patients (49.6%) had primary APS, and 71 (50.4%) had systemic lupus erythematosus. The prevalence of thrombosis was 85.8 per cent, arterial thrombosis was found in 93 patients (66.0%) and venous thrombosis was found in 46 patients (32.6%). The most common thrombosis was cerebral infarction [86/141 (61.0%)] followed by deep vein thrombosis [33/141 (23.4%)]. Among 70 pregnant women, 45 (64.3%) had obstetric complications. Lupus anticoagulant was detected in 116 patients (82.3%), anticardiolipin antibodies in 83 (58.9%), anti-ß2 glycoprotein I antibodies in 73 (51.8%) and phosphatidylserine-dependent antiprothrombin antibodies in 98 (69.5%). CONCLUSION: High prevalence of arterial thrombosis was noted in Japanese patients with APS. The profile of heterogeneous and complex clinical manifestations was substantiated in Japanese patients with APS.

Visualization of lower extremity lymphedema in the same cohort using 99mTc-human serum albumin and 99mTc-phytate lymphoscintigraphy with SPECT-CT.

Lymphoscintigraphy with single-photon emission computed tomography (SPECT-CT) is useful in diagnosing lymphedema. However, there are multiple timings, techniques, and tracers utilized worldwide without any comparison. We examined and compared the image clarity with two different radiotracers, 99mTc human serum albumin (HSA) and 99mTc phytate (phytate), in the same patients. The study retrospectivity examined 46 limbs of 36 patients who underwent lymphoscintigraphy using HSA and phytate from January 2013 to September 2018. Tracer accumulation in the lymph nodes, linear pattern (LP), and dermal backflow (DBF) were qualitatively analyzed; contrast-to-noise ratios (CNR) of DBF and standardized uptake value ratio (SUVR) of LP were also quantitatively analyzed. Neither lymph node accumulation nor DBF identification showed significant difference. However, a significant difference was observed between the LP identification of the unaffected (p<0.001) and affected sides (p<0.001). On quantitative evaluation, CNR and SUVR of LP was significantly higher with HSA than with phytate (p<0.001). SUVR of LP was also significantly higher with HSA than with phytate in both unaffected (p=0.002) and affected (p=0.005) sides. Overall, images acquired with HSA were clearer than that with phytate, and the identification of LP was particularly better with HSA than with phytate. Thus, lymphoscintigraphy using HSA is preferred over phytate for both diagnosis and evaluation of disease severity and surgical site selection.