Determination of ADAMTS13 and Its Clinical Significance for ADAMTS13 Supplementation Therapy to Improve the Survival of Patients with Decompensated Liver Cirrhosis

The liver plays a central role in hemostasis by synthesizing clotting factors, coagulation inhibitors, and fibrinolytic proteins. Liver cirrhosis (LC), therefore, impacts on both primary and secondary hemostatic mechanisms. ADAMTS13 is a metalloproteinase, produced exclusively in hepatic stellate cells, and specifically cleaves unusually large von Willebrand factor multimers (UL-VWFM). Deficiency of ADAMTS13 results in accumulation of UL-VWFM, which induces platelet clumping or thrombi under high shear stress, followed by sinusoidal microcirculatory disturbances and subsequent progression of liver injuries, eventually leading to multiorgan failure. The marked imbalance between decreased ADAMTS13 activity (ADAMTS13 : AC) and increased production of UL-VWFM indicating a high-risk state of platelet microthrombi formation was closely related to functional liver capacity, hepatic encephalopathy, hepatorenal syndrome, and intractable ascites in advanced LC. Some end-stage LC patients with extremely low ADAMTS13 : AC and its IgG inhibitor may reflect conditions similar to thrombotic thrombocytopenic purpura (TTP) or may reflect “subclinical TTP.” Hence, cirrhotic patients with severe to moderate deficiency of ADAMTS13 : AC may be candidates for FFP infusion as a source of ADAMTS13 or for recombinant ADAMTS13 supplementation. Such treatments may improve the survival of patients with decompensated LC

Paeoniflorin ameliorates acquisition impairment of a simple operant discrimination performance caused by unilateral nucleus basalis magnocellularis lesion in rats

The effect of paeoniflorin on learning impairment of operant brightness discrimination performance　was investigated in rats with unilateral nucleus basalis magnocellularis（NBM）lesion. The animals　with unilateral NBM lesion exhibited a significant acquisition impairment of brightness discrimination task during the early phase of a training period（1-5days after starting the training session). When　administered daily during a training period，paeoniflorin significantly improved the learning impairment　of unilateral NBM-lesioned rats at 0.01 but not 0.1mg／kg／day（p.o.）. Tacrine （0.3mg／kg／day，p.o.）， a　cholinesterase inhibitor，also significantly ameliorated the learning deficit. These results suggest that　paeoniflorin improves the impairment of non-spatial learning performance caused by cholinergic　dysfunction in rats and that it may have a beneficial effect on senile dementia

Studies on children’s lifestyle circumstances and health (First report)

In this first report we aimed to clarify the factors of life environments which affect children’s health. Our subjects were the guardians of 93 elder (6 years-old) male and female preschoolers of K nursery school in Tokyo met. (abbreviated as KNS) and Y nursery school in Yamaguchi pref. (abbreviated as YNS). Questionnaires regarding the life environments of the preschoolers covered 29 items concerning fundamental life habits including their wake-up time, bedtime, and sleeping period, dietary habits, activity habits, and circumstances of playing. In both preschools more than 80％ of preschoolers live with parents, and the number of preschoolers living with only their mothers was less than 15％, therefore no significant difference of family constitution was observed between YNS and KNS. The average wake-up time of preschoolers attending YNS was significantly earlier (p＜0.01) than that of KNS. The average bedtime of KNS was significantly later (p＜0.001) than that of YNS. The average sleeping period of YNS was significantly longer (p＜0.001) than that of KNS. The means of going to school showed much difference between the two schools. The percentage taken by car was greater in YNS than KNS, while the percentages of being taken by bicycle or walking were greater in KNS than YNS. All means of transportation to school had significant difference of rates (p＜0.05) between YNS and KNS. Results of this study clarified that the preschool located in the city area is characterized by life habits such as short sleeping period, late wake-up time and bedtime, and the preschool located in the mountain area is characterized by longer sleeping period, early wake-up time and bedtime. However, the location of playing spaces did not show significant difference, probably because of the social backgrounds including TV games rather than environmental factors. Considering the health of preschoolers, emphasis on physical activities by playing outside and ensuring sufficient sleep are important factorsdepartmental bulletin pape

Theoretical treatments of fusion processes in collisions of weakly bound nuclei

We review the theoretical methods to evaluate fusion cross sections in collisions of weakly bound nuclei. We piont out that in such collisions the coupling to the breakup channel leads to the appearance of different fusion processes. The extentsion of the coupled-channel method to coupling with the continuum is the most successful treatment for these collisions. However, evaluating separate cross section for each fusion process remains a very hard task.Comment: 8 pages, 3 figures. Invited talk (LFC) at the IX International Conference on Nucleus-Nucleus Collisions, Rio de Janeiro, August 28- September 1, 2006. Nuclear Physics A, in pres

Long-range interactions in the effective low energy Hamiltonian of Sr2IrO4: a core level resonant inelastic x-ray scattering study

We have investigated the electronic structure of Sr2IrO4 using core level resonant inelastic x-ray scattering. The experimental spectra can be well reproduced using ab initio density functional theory based multiplet ligand field theory calculations, thereby validating these calculations. We found that the low-energy, effective Ir t2g orbitals are practically degenerate in energy. We uncovered that covalency in Sr2IrO4, and generally in iridates, is very large with substantial oxygen ligand hole character in the Ir t2g Wannier orbitals. This has far reaching consequences, as not only the onsite crystal-field energies are determined by the long range crystal-structure, but, more significantly, magnetic exchange interactions will have long range distance dependent anisotropies in the spin direction. These findings set constraints and show pathways for the design of d^5 materials that can host compass-like magnetic interactions

Building primary care in Japan: Literature review.

Japan's health system is well known for achieving one of the world's highest life expectancy with universal health coverage. However, the country now faces challenges of a rapidly aging population and changes in patterns and burden of disease. Primary care is an important component of a well-functioning health system. In Japan, primary care services are provided in both the community and hospital settings. The distinction between primary and secondary care may not always be clear. This review is based on the framework from the 2015 WHO publication on primary care systems in Europe. Our aim is to describe the journey of primary care in Japan, with its past, present, and future as a valuable addition to the academic English literature. We also hope that this article would inspire readers outside of Japan who might face similar issues in their respective countries

Oxaliplatinによる肝類洞障害は肝臓内にvon Willebrand因子が血小板血栓を形成することにより発症する

Oxaliplatin-based chemotherapy is widely used to treat advanced colorectal cancer (CRC). Sinusoidal obstruction syndrome (SOS) due to oxaliplatin is a serious type of chemotherapy-associated liver injury (CALI) in CRC patients. SOS is thought to be caused by the sinusoidal endothelial cell damage, which results in the release of unusually-large von Willebrand factor multimers (UL-VWFMs) from endothelial cells. To investigate the pathophysiology of CALI after oxaliplatin-based chemotherapy, we analyzed plasma concentration of von Willebrand factor (VWF) and the distribution of VWFMs in CRC patients. Twenty-three patients with advanced CRC who received oxaliplatin-based chemotherapy with (n = 6) and without (n = 17) bevacizumab were analyzed. CALI (n = 6) and splenomegaly (n = 9) were found only in patients who did not treated with bevacizumab. Plasma VWF antigen (VWF:Ag) and serum aspartate aminotransferase (AST) levels increased after chemotherapy only in patients without bevacizumab. VWFM analysis in patients who did not receive bevacizumab showed the presence of UL-VWFMs and absence of high molecular weight VWFMs during chemotherapy, especially in those with CALI. In addition, plasma VWF:Ag and AST levels increased after chemotherapy in patients with splenomegaly (n = 9), but not in patients without splenomegaly (n = 14). Histological findings in the liver tissue of patients who did not receive bevacizumab included sinusoidal dilatation and microthrombi in the sinusoids. Many microthrombi were positive for both anti-IIb/IIIa and anti-VWF antibodies. Plasma UL-VWFM levels might be increased by damage to endothelial cells as a result of oxaliplatin-based chemotherapy. Bevacizumab could prevent CALI and splenomegaly through inhibition of VWF-rich platelet thrombus formation.博士（医学）・乙第1373号・平成28年3月15日Copyright: © 2015 Nishigori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Nonlinear Parker Instability with the Effect of Cosmic-Ray Diffusion

We present the results of linear analysis and two-dimensional local magnetohydrodynamic (MHD) simulations of the Parker instability, including the effects of cosmic rays (CRs), in magnetized gas disks (galactic disks). As an unperturbed state for both the linear analysis and the MHD simulations, we adopted an equilibrium model of a magnetized two-temperature layered disk with constant gravitational acceleration parallel to the normal of the disk. The disk comprises a thermal gas, cosmic rays and a magnetic field perpendicular to the gravitational accelerartion. Cosmic ray diffusion along the magnetic field is considered; cross field-line diffusion is supposed to be small and is ignored. We investigated two cases in our simulations. In the mechanical perturbation case we add a velocity perturbation parallel to the magnetic field lines, while in the explosional perturbation case we add cosmic ray energy into a sphere where the cosmic rays are injected. Linear analysis shows that the growth rate of the Parker instability becomes smaller if the coupling between the CR and the gas is stronger (i.e., the CR diffusion coefficient is smaller). Our MHD simulations of the mechanical perturbation confirm this result. We show that the falling matter is impeded by the CR pressure gradient, this causes a decrease in the growth rate. In the explosional perturbation case, the growth of the magnetic loop is faster when the coupling is stronger in the early stage. However, in the later stage the behavior of the growth rate becomes similar to the mechanical perturbation case.Comment: 18 pages, 11 figures, accepted in Ap