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1.
Eur Phys J A Hadron Nucl ; 59(3): 42, 2023.
Article in English | MEDLINE | ID: mdl-36915898

ABSTRACT

Neutron-capture cross sections of neutron-rich nuclei are calculated using a Hauser-Feshbach model when direct experimental cross sections cannot be obtained. A number of codes to perform these calculations exist, and each makes different assumptions about the underlying nuclear physics. We investigated the systematic uncertainty associated with the choice of Hauser-Feshbach code used to calculate the neutron-capture cross section of a short-lived nucleus. The neutron-capture cross section for 73 Zn (n, γ ) 74 Zn was calculated using three Hauser-Feshbach statistical model codes: TALYS, CoH, and EMPIRE. The calculation was first performed without any changes to the default settings in each code. Then an experimentally obtained nuclear level density (NLD) and γ -ray strength function ( γ SF ) were included. Finally, the nuclear structure information was made consistent across the codes. The neutron-capture cross sections obtained from the three codes are in good agreement after including the experimentally obtained NLD and γ SF , accounting for differences in the underlying nuclear reaction models, and enforcing consistent approximations for unknown nuclear data. It is possible to use consistent inputs and nuclear physics to reduce the differences in the calculated neutron-capture cross section from different Hauser-Feshbach codes. However, ensuring the treatment of the input of experimental data and other nuclear physics are similar across multiple codes requires a careful investigation. For this reason, more complete documentation of the inputs and physics chosen is important. Supplementary Information: The online version contains supplementary material available at 10.1140/epja/s10050-023-00920-0.

2.
Phys Rev Lett ; 129(17): 172701, 2022 Oct 21.
Article in English | MEDLINE | ID: mdl-36332266

ABSTRACT

The ß-delayed one- and two-neutron emission probabilities (P_{1n} and P_{2n}) of 20 neutron-rich nuclei with N≥82 have been measured at the RIBF facility of the RIKEN Nishina Center. P_{1n} of ^{130,131}Ag, ^{133,134}Cd, ^{135,136}In, and ^{138,139}Sn were determined for the first time, and stringent upper limits were placed on P_{2n} for nearly all cases. ß-delayed two-neutron emission (ß2n) was unambiguously identified in ^{133}Cd and ^{135,136}In, and their P_{2n} were measured. Weak ß2n was also detected from ^{137,138}Sn. Our results highlight the effect of the N=82 and Z=50 shell closures on ß-delayed neutron emission probability and provide stringent benchmarks for newly developed macroscopic-microscopic and self-consistent global models with the inclusion of a statistical treatment of neutron and γ emission. The impact of our measurements on r-process nucleosynthesis was studied in a neutron star merger scenario. Our P_{1n} and P_{2n} have a direct impact on the odd-even staggering of the final abundance, improving the agreement between calculated and observed Solar System abundances. The odd isotope fraction of Ba in r-process-enhanced (r-II) stars is also better reproduced using our new data.

3.
Phys Rev Lett ; 127(22): 222502, 2021 Nov 24.
Article in English | MEDLINE | ID: mdl-34889623

ABSTRACT

We investigate the angular momentum removal from fission fragments (FFs) through neutron and γ-ray emission, finding that about half the neutrons are emitted with angular momenta ≥1.5ℏ and that the change in angular momentum after the emission of neutrons and statistical γ rays is significant, contradicting usual assumptions. Per fission event, in our simulations, the neutron and statistical γ-ray emissions change the spin of the fragment by 3.5-5ℏ, with a large standard deviation comparable to the average value. Such wide angular momentum removal distributions can hide any underlying correlations in the fission fragment initial spin values. Within our model, we reproduce data on spin measurements from discrete transitions after neutron emissions, especially in the case of light FFs. The agreement further improves for the heavy fragments if one removes from the analysis the events that would produce isomeric states. Finally, we show that while in our model the initial FF spins do not follow a sawtoothlike behavior observed in recent measurements, the average FF spin computed after neutron and statistical γ emissions exhibits a shape that resembles a sawtooth. This suggests that the average FF spin measured after statistical emissions is not necessarily connected with the scission mechanism as previously implied.

4.
Toxicol Rep ; 6: 904-913, 2019.
Article in English | MEDLINE | ID: mdl-31508319

ABSTRACT

Focusing on licorice, a highly used raw material in health foods, quantitative analysis of functional/medicinal components and a safety and functional evaluation was carried out for herbal medicines, health food ingredients, and so-called health foods. A functional component, glabridin, was detected in herbal medicines from Glycyrrhiza glabra and G. inflata, health food ingredients, and in commercially available health foods that contain licorice. Likewise, glycyrrhizin, a medicinal component, was detected in these sources, except in licorice oil extract. Estrogen activity in vitro was detected in some of the herbal medicines, health food ingredients, and in health foods containing licorice. In the in vivo study, liver weight in ovariectomized (OVX) mice treated with licorice oil extract was significantly higher than that in OVX and sham mice in a dose dependent manner. These results suggest that excessive intake of licorice oil extract from health foods should be avoided, even though these ingredients might be beneficial for medical use in order to maintain bone health in postmenopausal women. Measurement of hepatic cytochrome P-450 (CYP) activity, reproductive organ weight, and fat and bone mass in OVX mice was considered useful for evaluating the safety and efficacy of estrogenic health food ingredients derived from herbal medicines.

5.
Phys Rev Lett ; 122(7): 072503, 2019 Feb 22.
Article in English | MEDLINE | ID: mdl-30848631

ABSTRACT

The physical properties of neutrons emitted from neutron-induced fission are fundamental to our understanding of nuclear fission. However, while state-of-the-art fission models still incorporate isotropic fission neutron spectra, it is believed that the preequilibrium prefission component of these spectra is strongly anisotropic. The lack of experimental guidance on this feature has not motivated incorporation of anisotropic neutron spectra in fission models, though any significant anisotropy would impact descriptions of a fissioning system. In the present work, an excess of counts at high energies in the fission neutron spectrum of ^{239}Pu is clearly observed and identified as an excess of the preequilibrium prefission distribution above the postfission neutron spectrum. This excess is separated from the underlying postfission neutron spectrum, and its angular distribution is determined as a function in incident neutron energy and outgoing neutron detection angle. Comparison with neutron scattering models provides the first experimental evidence that the preequilibrium angular distribution is uncorrelated with the fission axis. The results presented here also impact the interpretation of several influential prompt fission neutron spectrum measurements.

6.
Dis Esophagus ; 32(8)2019 Aug 01.
Article in English | MEDLINE | ID: mdl-30561581

ABSTRACT

Understanding the surgical anatomy is the key to reducing surgical invasiveness especially in the upper mediastinal dissection for esophageal cancer, which is supposed to have a significant impact on curability and morbidity. However, there is no theoretical recognition regarding the surgical anatomy required for esophagectomy, although the surgical anatomy in abdominal digestive surgery has been developed on the basis of embryological findings of intestinal rotation and fusion fascia. Therefore, we developed a hypothesis of a 'concentric-structured model' of the surgical anatomy in the upper mediastinum based on human embryonic development. This model was characterized by three factors: (1) a concentric and symmetric three-layer structure, (2) bilateral vascular distribution, and (3) an 'inter-layer potential space' composed of loose connective tissue. The concentric three-layer structure consists of the 'visceral layer', the 'vascular layer', and the 'parietal layer': the visceral layer containing the esophagus, trachea, and recurrent laryngeal nerves as the central core, the vascular layer of major blood vessels surrounding the visceral core to maintain the circulation, and the parietal layer as the outer frame of the body. The bilateral vascular distribution consists of the inferior thyroid arteries and bronchial arteries originating from the bilateral dorsal aortae in an embryo. This bilateral vascular distribution may be related to the formation of the proper mesentery of the esophagus and frequent lymph node metastasis observed in the visceral layer around recurrent laryngeal nerves. The three concentric layers are bordered by loose connective tissue called the 'inter-layer potential space'. This inter-layer potential space is the fundamental factor of our concentric-structured model as the appropriate surgical plane of dissection. The peripheral blood vessels, nerves, and lymphatics transition between each layer, thereby penetrating this loose connective tissue forming the inter-layer potential space. Recurrent laryngeal nerves also transition from the vascular layer after branching off from the vagal nerves and then ascend consistently in the visceral layer. We investigated the validity of this concentric-structured model, confirming the intraoperative images and the surgical outcomes of thoracoscopic esophagectomy in a prone position (TSEP) before and after the introduction of this hypothetical anatomy model. A total of 226 patients with esophageal cancer underwent TSEP from January 2015 to December 2016. After the introduction of this model, the surgical outcomes in 105 patients clearly improved for the operation time of the thoracoscopic procedure (160 min vs. 182 min, P = 0.01) and the incidence of recurrent laryngeal nerve palsy (19.0% vs. 36.4%, P = 0.004). Moreover, we were able to identify the concentric and symmetric layer structure through surgical dissection along the inter-layer potential space between the visceral and vascular layers ('viscero-vascular space') in all 105 cases after introduction of the hypothetical model. The concentric-structured model based on embryonic development is clinically beneficial for achieving less-invasive esophagectomy by ensuring a theoretical understanding of the surgical anatomy in the upper mediastinum.


Subject(s)
Esophageal Neoplasms/surgery , Esophagectomy/methods , Lymph Node Excision/methods , Mediastinum/anatomy & histology , Models, Theoretical , Thoracoscopy/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Mediastinum/surgery , Middle Aged
7.
Plant Signal Behav ; 13(8): e1494467, 2018.
Article in English | MEDLINE | ID: mdl-30067454

ABSTRACT

Changes in Ca2+ concentrations in cytosol ([Ca2+]C) or nucleus ([Ca2+]N) may play some vital roles in plants under hypoosmotic shock (Hypo-OS). Here, we observed that Hypo-OS induces biphasic increases in [Ca2+]C and [Ca2+]N in two tobacco cell lines (BY-2) expressing apoaequorin either in the cytosol or in the nucleus. Both [Ca2+]C and [Ca2+]N were sensitively modulated by the inhibitors of calmodulin and protein kinases, supporting the view that calmodulin suppresses the 1st peaks and and protein kinases enhance 2nd peaks in [Ca2+]C and [Ca2+]N. Data also suggested that the 1st and 2nd events depend on the internal and extracellular Ca2+ sources, respectively.


Subject(s)
Calmodulin/metabolism , Cytosol/metabolism , Nicotiana/metabolism , Protein Kinases/metabolism , Calcium Signaling/physiology , Cell Nucleus/metabolism
8.
Sci Rep ; 8(1): 7975, 2018 May 17.
Article in English | MEDLINE | ID: mdl-29773826

ABSTRACT

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

9.
Clin Exp Allergy ; 48(4): 379-393, 2018 04.
Article in English | MEDLINE | ID: mdl-29288569

ABSTRACT

BACKGROUND: Gender disparities in adult patients with asthma regarding its prevalence and severity are mainly due to enhanced type 2 T-helper (Th2) cytokine production in female patients compared to that in male patients. However, the pathways mediating this effect remain unclear. OBJECTIVE: We aimed to determine the roles of two major subsets of dendritic cells (DCs) in females, specifically those displaying CD11b or CD103, during enhanced Th2 priming after allergen exposure, using an ovalbumin-induced asthma mouse model. METHODS: Sex-based differences in the number of DCs at inflamed sites, costimulatory molecule expression on DCs, and the ability of DCs to differentiate naïve CD4+ T cells into Th2 population were evaluated after allergen exposure in asthmatic mice. In addition, we assessed the role of 17ß-oestradiol in CD103+ DC function during Th2 priming in vitro. RESULTS: The number of CD11bhigh DCs and CD103+ DCs in the lung and bronchial lymph node (BLN) was increased to a greater extent in female mice than in male mice at 16 to 20 hours after ovalbumin (OVA) inhalation. In BLNs, CD86 and I-A/I-E expression levels and antigen uptake ability in CD103+ DCs, but not in CD11bhigh DCs, were greater in female mice than in male mice. Furthermore, CD4+ T cells cultured with CD103+ DCs from female mice produced higher levels of interleukin (IL)-4, IL-5, and IL-13, compared with CD4+ T cells cultured with CD103+ DCs from male mice. The 17ß-oestradiol-oriented enhancement of CD86 expression on CD103+ DCs after allergen exposure induced the enhanced IL-5 production from CD4+ T cells. CONCLUSIONS AND CLINICAL RELEVANCE: These findings suggest that with regard to asthma, enhanced Th2 cytokine production in females might be attributed to 17ß-oestradiol-mediated Th2-oriented CD103+ DCs in the BLN.


Subject(s)
Asthma/immunology , Dendritic Cells/immunology , Hypersensitivity/immunology , Sex Characteristics , Animals , Antigens, CD/immunology , Cytokines/biosynthesis , Estradiol/immunology , Female , Integrin alpha Chains/immunology , Lymphocyte Activation/immunology , Male , Mice , Mice, Inbred C57BL , Th2 Cells/immunology
10.
Phys Rev Lett ; 119(22): 222504, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-29286762

ABSTRACT

Statistical reaction theories such as the Hauser-Feshbach theory assume that branching ratios follow Bohr's compound nucleus hypothesis by factorizing into independent probabilities for different channels. Corrections to the factorization hypothesis are known in both nuclear theory and quantum transport theory, particularly an enhanced memory of the entrance channel. We apply the Gaussian orthogonal ensemble to study a complementary suppression of exit channel branching ratios. The combined effect of the width fluctuation and the limitation on the transmission coefficient can provide a lower bound on the number of exit channels. The bound is demonstrated for the branching ratio in neutron-induced reactions on a ^{235}U target.

11.
Sci Rep ; 7(1): 7816, 2017 08 10.
Article in English | MEDLINE | ID: mdl-28798398

ABSTRACT

Strong magnetic fields, synchrotron emission, and Compton scattering are omnipresent in compact celestial X-ray sources. Emissions in the X-ray energy band are consequently expected to be linearly polarized. X-ray polarimetry provides a unique diagnostic to study the location and fundamental mechanisms behind emission processes. The polarization of emissions from a bright celestial X-ray source, the Crab, is reported here for the first time in the hard X-ray band (~20-160 keV). The Crab is a complex system consisting of a central pulsar, a diffuse pulsar wind nebula, as well as structures in the inner nebula including a jet and torus. Measurements are made by a purpose-built and calibrated polarimeter, PoGO+. The polarization vector is found to be aligned with the spin axis of the pulsar for a polarization fraction, PF = (20.9 ± 5.0)%. This is higher than that of the optical diffuse nebula, implying a more compact emission site, though not as compact as, e.g., the synchrotron knot. Contrary to measurements at higher energies, no significant temporal evolution of phase-integrated polarisation parameters is observed. The polarization parameters for the pulsar itself are measured for the first time in the X-ray energy band and are consistent with observations at optical wavelengths.

12.
Eur J Neurol ; 24(3): 503-508, 2017 03.
Article in English | MEDLINE | ID: mdl-28026909

ABSTRACT

BACKGROUND AND PURPOSE: Cancer patients with cryptogenic stroke often have high plasma D-dimer levels and lesions in multiple vascular regions. Hence, if patients with cryptogenic stroke display such characteristics, occult cancer could be predicted. This study aimed to investigate the clinical characteristics of cryptogenic stroke as the first manifestation of occult cancer and to determine whether plasma D-dimer levels and lesions in multiple vascular regions can predict occult cancer in patients with cryptogenic stroke. METHODS: Between January 2006 and October 2015, data on 1225 patients with acute ischaemic stroke were extracted from the stroke database of Osaka University Hospital. Among them, 184 patients were classified as having cryptogenic stroke, and 120 patients without a diagnosis of cancer at stroke onset were identified. Clinical variables were analyzed between cryptogenic stroke patients with and without occult cancer. RESULTS: Among 120 cryptogenic stroke patients without a diagnosis of cancer, 12 patients had occult cancer. The body mass index, hemoglobin levels and albumin levels were lower; plasma D-dimer and high-sensitivity C-reactive protein levels were higher; and lesions in multiple vascular regions were more common in patients with than in those without occult cancer. Multiple logistic regression analysis revealed that plasma D-dimer levels (odds ratio, 3.48; 95% confidence interval, 1.68-8.33; P = 0.002) and lesions in multiple vascular regions (odds ratio, 7.40; 95% confidence interval, 1.70-39.45; P = 0.01) independently predicted occult cancer. CONCLUSIONS: High plasma D-dimer levels and lesions in multiple vascular regions can be used to predict occult cancer in patients with cryptogenic stroke.


Subject(s)
Biomarkers, Tumor/blood , Fibrin Fibrinogen Degradation Products/analysis , Ischemia/blood , Neoplasms, Unknown Primary/blood , Neoplasms, Unknown Primary/diagnosis , Stroke/blood , Aged , Female , Humans , Ischemia/complications , Ischemia/physiopathology , Magnetic Resonance Imaging , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Stroke/complications , Stroke/physiopathology
13.
Sci Rep ; 6: 35806, 2016 10 25.
Article in English | MEDLINE | ID: mdl-27779197

ABSTRACT

Investigations into mechanisms in various cortical areas can be greatly improved and supported by stable recording of single neuronal activity. In this study, fine silicon wire electrodes (diameter 3 µm, length 160 µm) are fabricated by vapor-liquid-solid (VLS) growth with the aim of stabilizing recording and reducing the invasiveness on the measurement procedure. The electrode is fabricated on a modular 1 × 1 mm2 conductive silicon block that can be assembled into a number of different device packages, for example on rigid or flexible printed circuit boards (PCB). After plating with a 5 µm diameter platinum black, the needle exhibits an electrical impedance of ~100 kΩ at 1 kHz in saline. The in vivo recording capability of the device is demonstrated using mice, and spike signals with peak-to-peak amplitudes of 200-300 µV in the range 0.5-3 kHz are stably detected, including single-unit activities in cortical layer 2/3. In addition, the device packaged with a flexible PCB shows stable unit recordings for 98.5 min (n = 4). Consequently, our modular, low-invasive needle electrode block devices present an effective route for single-unit recordings in vivo, as well as demonstrating adaptability in device design for a diverse range of experiments.


Subject(s)
Electrodes, Implanted , Microelectrodes , Single-Cell Analysis/instrumentation , Somatosensory Cortex/physiology , Visual Cortex/physiology , Animals , Electric Impedance , Equipment Design , Male , Mice , Neurons/physiology , Photic Stimulation , Single-Cell Analysis/methods , Visual Cortex/cytology
14.
Oncogene ; 35(40): 5304-5316, 2016 10 06.
Article in English | MEDLINE | ID: mdl-27041563

ABSTRACT

Metastasis is a critical factor contributing to poor prognosis in cancer, but the underlying mechanisms of metastasis are still poorly understood. We established a highly metastatic cell subline (HOC313-LM) derived from an oral squamous cell carcinoma cell line (HOC313) for uncovering the mechanisms of metastasis, and identified deoxyhypusine synthase (DHPS) as a metastasis-associated gene within the specific amplification at 19p13.2-p13.13 in HOC313-LM. DHPS-mediated hypusine-modification of eukaryotic translation factor 5A facilitated the translation of RhoA, resulting in the activation of the RhoA signaling pathway and leading to not only increased cell motility, invasion and metastasis of cancer cells in vitro, but also increased tumor growth in vivo. Moreover, the use of N1-Guanyl-1,7-diaminoheptane, a DHPS inhibitor, resulted in a significant decrease in tumor formation in vivo. In patients with esophageal squamous cell carcinoma (ESCC), overexpression of DHPS in ESCC tumors was significantly associated with worse recurrence-free survival, and correlated with distant metastasis. The elucidation of these molecular mechanisms within the hypusine cascade suggests opportunities for novel therapeutic targets in SCC.


Subject(s)
Carcinoma, Squamous Cell/drug therapy , Esophageal Neoplasms/drug therapy , Lysine/analogs & derivatives , Oxidoreductases Acting on CH-NH Group Donors/genetics , rhoA GTP-Binding Protein/genetics , Adult , Aged , Animals , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/drug effects , Diamines/administration & dosage , Disease Progression , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Lysine/biosynthesis , Lysine/genetics , Male , Mice , Middle Aged , Neoplasm Metastasis , Oxidoreductases Acting on CH-NH Group Donors/antagonists & inhibitors , Signal Transduction/drug effects
15.
Epidemiol Infect ; 144(4): 787-95, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26243450

ABSTRACT

Although outbreaks of acute respiratory infection (ARI) at shelters are hypothesized to be associated with shelter crowding, no studies have examined this relationship. We conducted a retrospective study by reviewing medical records of evacuees presenting to one of the 37 clinics at the shelters in Ishinomaki city, Japan, during the 3-week period after the Great Eastern Japan Earthquake and tsunami in 2011. On the basis of a locally weighted scatter-plot smoothing technique, we categorized 37 shelters into crowded (mean space <5·5 m2/per person) and non-crowded (⩾5·5 m2) shelters. Outcomes of interest were the cumulative and daily incidence rate of ARI/10 000 evacuees at each shelter. We found that the crowded shelters had a higher median cumulative incidence rate of ARI [5·4/10 000 person-days, interquartile range (IQR) 0-24·6, P = 0·04] compared to the non-crowded shelters (3·5/10 000 person-days, IQR 0-8·7) using Mann-Whitney U test. Similarly, the crowded shelters had an increased daily incidence rate of ARI of 19·1/10 000 person-days (95% confidence interval 5·9-32·4, P < 0·01) compared to the non-crowded shelters using quasi-least squares method. In sum, shelter crowding was associated with an increased incidence rate of ARI after the natural disaster.


Subject(s)
Crowding , Disease Outbreaks , Personal Space , Respiratory Tract Infections/epidemiology , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Disasters , Earthquakes , Female , Humans , Incidence , Infant , Infant, Newborn , Japan/epidemiology , Male , Middle Aged , Respiratory Tract Infections/etiology , Retrospective Studies , Tsunamis , Young Adult
16.
Radiat Prot Dosimetry ; 167(1-3): 210-4, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25948831

ABSTRACT

Free water tritium (FWT) and organically bound tritium (OBT) concentrations in pine needles have been investigated to understand the regional background tritium concentration in Toki City. Samples were regularly collected from pine trees on the National Institute for Fusion Science campus (1998-2012) and the nearby Shiomi Park (SP; 2002-12). FWT and OBT concentrations of the former samples ranged from 0.33 to 0.92 and 0.41 to 1.10 Bq l(-1), respectively, while those of the latter samples ranged from 0.32 to 0.86 and 0.33 to 0.79 Bq l(-1), respectively. Results of both sampling sites were almost the same, and they have been gradually decreased year by year. Concentration level of tritium for Toki City was close to the average background level in Japan. The OBT/FWT ratios were almost 1.0. The apparent half-life of FWT in this period was estimated as almost 10 y, and that of OBT was estimated as almost 12 y; these values were almost the same as the physical half-life.


Subject(s)
Background Radiation , Pinus/chemistry , Plant Leaves/chemistry , Radiation Monitoring/methods , Tritium/analysis , Water/chemistry , Biological Assay/methods , Japan , Organic Chemicals/chemistry , Radiation Dosage , Reproducibility of Results , Sensitivity and Specificity
17.
Eur J Pain ; 19(5): 629-38, 2015 May.
Article in English | MEDLINE | ID: mdl-25158678

ABSTRACT

BACKGROUND: Synovial fluid in inflamed joint shows a drop in pH, which activates proton-gated ion channels in nociceptors. No studies have ever tried to develop and characterize acid-induced joint pain. METHODS: Rats were injected intra-articularly with pH 4.0 acidic saline twice, 5 days apart. Pain-related behaviour tests including weight-bearing asymmetry, paw withdrawal threshold and knee compression threshold were conducted. To clarify the roles of proton-gated ion channels, rats were injected intra-articularly with selective antagonists for ASIC1a, ASIC3 and TRPV1 on day 5 (before the second injection) or on day 14. Underlying peripheral and central pain mechanisms were evaluated using joint histology, interleukin-1ß concentrations in the synovium, single-fibre recording of the knee afferent and expression of phosphorylated cyclic adenosine monophosphate-responsive element-binding protein (p-CREB) in the spinal dorsal horn. RESULTS: Repeated injections of acidic saline induced weight-bearing asymmetry, decrease in paw withdrawal threshold and knee compression threshold bilaterally, which lasted until day 28. Early administration of ASIC3 antagonist reduced the bilateral and long-lasting hyperalgesia. Neither articular degeneration nor synovial inflammation was observed. C-fibre of the knee afferent was activated by acidic saline, which was attenuated by pre-injection of ASIC3 antagonist. p-CREB expression was transiently up-regulated bilaterally on day 6, but not on day 14. CONCLUSION: We developed and characterized a model of acid-induced long-lasting bilateral joint pain. Peripheral ASIC3 and spinal p-CREB played important roles for the development of hyperalgesia. This animal model gives insights into the mechanisms of joint pain, which is helpful in developing better pain treatments.


Subject(s)
Acids , Arthralgia/chemically induced , Hyperalgesia/chemically induced , Sodium Chloride , Acid Sensing Ion Channels/metabolism , Animals , Arthralgia/pathology , Behavior, Animal/drug effects , Cyclic AMP Response Element-Binding Protein/metabolism , Injections, Intra-Articular , Interleukin-1beta/metabolism , Ion Channels/antagonists & inhibitors , Joints/drug effects , Joints/pathology , Male , Neurons, Afferent/pathology , Pain Measurement/drug effects , Posterior Horn Cells/metabolism , Rats , Rats, Sprague-Dawley , Synovial Membrane/metabolism , TRPV Cation Channels/antagonists & inhibitors , TRPV Cation Channels/metabolism , Weight-Bearing
18.
Dis Esophagus ; 28(5): 460-7, 2015 Jul.
Article in English | MEDLINE | ID: mdl-24720357

ABSTRACT

'Salvage chemoradiotherapy (CRT)' was introduced in 2005 to treat thoracic esophageal carcinomas deemed unresectable based on the intraoperative findings. The therapeutic concept is as follows: the surgical plan is changed to an operation that aims to achieve curability by the subsequent definitive CRT. For this purpose, the invading tumor is resected as much as possible, and systematic lymph node dissection is performed except for in the area around the bilateral recurrent nerves. The definitive CRT should be started as soon as possible and should be performed as planned. We hypothesized that this treatment would be feasible and provide good clinical effects. We herein verified this hypothesis. Twenty-seven patients who received salvage CRT were enrolled in the study, and their clinical course, therapeutic response, and prognosis were evaluated. The patients who had poor oral intake because of esophageal stenosis were able to eat solid food soon after the operation. The radiation field could be narrowed after surgery, and this might have contributed to the high rate of finishing the definitive CRT as planned. As a result, the overall response rate was 74.1%, and 48.1% of the patients had a complete response. No patient experienced fistula formation. The 1-, 3-, and 5-year overall survival rates were 66.5%, 35.2%, and 35.2%, respectively. Salvage CRT had clinical benefits, such as the fact that patients became able to have oral intake, that fistula formation could be prevented, that the adverse events associated with the definitive CRT could be reduced, and that prognosis of the patients was satisfactory. Although the rate of recurrent nerve paralysis was relatively high even after the suspension of aggressive bilateral recurrent nerve lymph node dissection, and the rate of the progressive disease after the definitive CRT was high, salvage CRT appears to provide some advantages for the patients who would otherwise not have other treatment options following a non-curative and residual operation.


Subject(s)
Carcinoma, Squamous Cell/therapy , Chemoradiotherapy/methods , Esophageal Neoplasms/therapy , Salvage Therapy/methods , Adult , Aged , Carcinoma, Squamous Cell/pathology , Disease-Free Survival , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma , Female , Humans , Lymph Node Excision , Lymphatic Metastasis , Male , Middle Aged , Treatment Outcome
19.
Dis Esophagus ; 28(3): 269-75, 2015 Apr.
Article in English | MEDLINE | ID: mdl-24467464

ABSTRACT

Endocytoscopy (ECS) is a novel endoscopic technique that allows detailed diagnostic examination of the gastrointestinal tract at the cellular level. We previously reported that use of ECS at ×380 magnification (GIF-Y0002) allowed a pathologist to diagnose esophageal squamous cell carcinoma (ESCC) with high sensitivity (94.9%) but considerably low specificity (46.7%) because this low magnification did not reveal information about nuclear abnormality. In the present study, we used the same magnifying endoscope to observe various esophageal lesions, but employed digital 1.6-fold magnification to achieve an effective magnification of ×600, and evaluated whether this improved the diagnostic accuracy in distinguishing neoplastic from non-neoplastic lesions.We examined the morphology of surface cells using vital staining with toluidine blue and compared the histological features of 40 cases, including 19 case of ESCC and 21 non-neoplastic esophageal lesions (18 cases of esophagitis, 1 case of glycogenic acanthosis, 1 case of leiomyoma, and 1 case of normal squamous epithelium). One endoscopist classified the lesions using the type classification, and we consulted one pathologist for judgment of the ECS images as 'neoplastic', 'borderline', or 'non-neoplastic'. At ×600 magnification, the pathologist confirmed that nuclear abnormality became evident, in addition to the information about nuclear density provided by observation at ×380. The overall sensitivity and specificity with which the endoscopist was able to predict neoplastic lesions using the type classification was 100% (19/19) and 90.5% (19/21), respectively, in comparison with values of 94.7% (18/19 cases) and 76.2% (16/21), respectively, for the pathologist using a magnification of ×600. The pathologist diagnosed two non-neoplastic lesions and one case of ESCC showing an apparent increase of nuclear density with weak nuclear abnormality as 'borderline'. Among the 21 non-cancerous lesions, two cases of esophagitis that were misdiagnosed by the endoscopist were also misinterpreted as 'neoplastic' by the pathologist. We have shown, by consultation with a pathologist, that an ECS magnification of ×600 (on a 19-inch monitor) is adequate for recognition of nuclear abnormality. We consider that it is feasible to diagnose esophageal neoplasms on the basis of ECS images, and that biopsy histology can be omitted if a combination of increased nuclear density and nuclear abnormality is observed.


Subject(s)
Carcinoma, Squamous Cell/ultrastructure , Endoscopy/methods , Esophageal Neoplasms/ultrastructure , Nuclear Microscopy/methods , Radiographic Magnification/methods , Diagnostic Errors , Esophageal Neoplasms/classification , Esophageal Squamous Cell Carcinoma , Esophagitis/pathology , Esophagoscopy/methods , Esophagus/ultrastructure , Humans , Sensitivity and Specificity , Staining and Labeling , Tolonium Chloride
20.
Eur J Surg Oncol ; 40(10): 1376-82, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24915857

ABSTRACT

BACKGROUND: To clarify the patterns, timing and risk factors of recurrence of gastric cancer after laparoscopic gastrectomy. METHODS: From January 1999 to March 2012, 577 patients underwent laparoscopic or laparoscopy-assisted gastrectomy for curative resection of gastric cancer. Recurrence patterns were classified as locoregional, hematogenous, peritoneal, distant lymph node and mixed. Recurrence patterns and time to recurrence were retrospectively examined and risk factors for recurrence were analyzed. RESULTS: Recurrence occurred in 28 (4.9%) cases with patterns as follows: locoregional in 2 patients (7.1%), hematogenous in seven (25.0%), peritoneal in nine (32.1%), distant lymph node in four (14.3%), and mixed in 6 (21.4%). There was no recurrence pattern peculiar to laparoscopic surgery. Recurrence occurred at one site in 21 patients (78.6%), two in 4 patients (14.3%), and three in 2 patients (7.1%). The median time to recurrence was 384 days (range 83-1497 days). Recurrence was detected within a year in 13 cases (46.4%), within two years in 21 (75%), and within three years in 25 (89.3%). Univariate analysis revealed tumor location, tumor size, type of operation, tumor depth, and lymph node classification as risk factors for recurrence. Multivariate analysis indicated tumor depth and lymph node classification as risk factors of recurrence. CONCLUSIONS: Patterns, timing and risk factors of recurrence of gastric cancer after laparoscopic gastrectomy are similar to those after open gastrectomy, with no peculiarities specific to laparoscopic gastrectomy. Thus, as long as laparoscopic gastrectomy is performed according to the present inclusion criteria, follow-up can be similarly performed as for open gastrectomy.


Subject(s)
Adenocarcinoma/surgery , Lymph Nodes/pathology , Neoplasm Recurrence, Local/epidemiology , Stomach Neoplasms/surgery , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Cohort Studies , Follow-Up Studies , Gastrectomy/methods , Humans , Laparoscopy , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness , Neoplasm Staging , Risk Factors , Stomach Neoplasms/pathology , Time Factors , Tumor Burden
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