Decreases in Brain Reward Function Reflect Nicotine- and Methamphetamine-Withdrawal Aversion in Rats

The purpose of the present study was to investigate whether brain reward function decreases during withdrawal from nicotine and methamphetamine, and whether decreased reward function is related to aversion during withdrawal from these drugs. For that purpose, male Sprague-Dawley rats were chronically infused subcutaneously with 9 mg/kg per day nicotine, or with 6 mg/kg per day methamphetamine using osmotic minipumps. In an intracranial self-stimulation (ICSS) paradigm, chronic infusion of nicotine and methamphetamine decreased the thresholds for lateral hypothalamic ICSS, whereas their antagonists, mecamylamine and haloperidol increased the ICSS thresholds in the rats treated with nicotine and methamphetamine, respectively. In a conditioned place aversion paradigm, mecamylamine and haloperidol produced place aversion in nicotine- and methamphetamine-infused rats, respectively. Interestingly, elevations in ICSS reward thresholds and place aversion during mecamylamine-precipitated nicotine withdrawal were almost the same in magnitude as those observed during haloperidol-precipitated methamphetamine withdrawal. The present study indicates that 1) brain reward function decreased during nicotine and methamphetamine withdrawal, and 2) a decrease in reward function may reflect the negative affective state (aversion) during withdrawal from nicotine and methamphetamine

Effects of a novel elastase inhibitor, ONO-5046, on nephrotoxic serum nephritis in rats

Effects of a novel elastase inhibitor, ONO-5046, on nephrotoxic serum nephritis in rats. ONO-5046 is a potent, specific and intravenously active inhibitor of neutrophil elastase. To examine the role of elastase in glomerulonephritis, we tested the effects of ONO-5046 on nephrotoxic serum (NTS) nephritis in a rat model of the disease in humans. Rats were administered ONO-5046 or phosphate-buffered saline (PBS) intraperitoneally 24hours prior to injection of NTS, and they were then given equal doses of ONO-5046 or PBS three hours and 1, 2, 3, 4, 5 and 6days later. Compared with the control groups, ONO-5046 significantly reduced proteinuria and hematuria, and suppressed the formation of crescentic glomeruli in a dose-dependent manner. Our results suggest that neutrophil elastase participates in NTS nephritis by degrading glomerular basement membrane proteins, and that the elastase inhibitor, ONO-5046, suppresses crescentic formation and glomerular injury caused by elastase

Identification of the Occipito-Pontine Tract Using Diffusion-Tensor Fiber Tracking in Adult-Onset Adrenoleukodystrophy with Topographic Disorientation

X-linked adrenoleukodystrophy is a severe and progressive neurodegenerative disease caused by the peroxisomal transporter ATP-binding cassette, subfamily D, member 1 gene mutations. The defect of this gene product results in accumulation of very-long-chain fatty acids in organs and serum, central demyelination, and peripheral axonopathy. Although there are different magnetic resonance (MR) findings which reflect various phenotypes in adrenoleukodystrophy, some cases present with specific symmetrical occipital white-matter lesions. We describe a patient with adult-onset X-linked adrenoleukodystrophy with topographic disorientation, whose brain MR images revealed T2-signal hyperintensity along the occipito-pontine tract and lateral lemnisci, but not in the cortico-spinal tract in the brainstem. The occipito-pontine tract and lateral lemnisci were clearly detected using diffusion-tensor fiber tracking, suggesting that the topographic disorientation of this patient might be related to the occipito-pontine tract. MR tractography can effectively identify the occipito-pontine tract and may help to localize the fibers associated with clinical symptoms

Explosive nucleosynthesis in the neutrino-driven aspherical supernova explosion of a non-rotating 15M⊙M_{\odot} star with solar metallicity

We investigate explosive nucleosynthesis in a non-rotating 15$M_\odot$ star with solar metallicity that explodes by a neutrino-heating supernova (SN) mechanism aided by both standing accretion shock instability (SASI) and convection. To trigger explosions in our two-dimensional hydrodynamic simulations, we approximate the neutrino transport with a simple light-bulb scheme and systematically change the neutrino fluxes emitted from the protoneutron star. By a post-processing calculation, we evaluate abundances and masses of the SN ejecta for nuclei with the mass number $\le 70$ employing a large nuclear reaction network. Aspherical abundance distributions, which are observed in nearby core-collapse SN remnants, are obtained for the non-rotating spherically-symmetric progenitor, due to the growth of low-mode SASI. Abundance pattern of the supernova ejecta is similar to that of the solar system for models whose masses ranges (0.4-0.5) \Ms of the ejecta from the inner region (\le 10,000\km) of the precollapse core. For the models, the explosion energies and the \nuc{Ni}{56} masses are $\simeq 10^{51} \rm erg$ and (0.05-0.06) \Ms, respectively; their estimated baryonic masses of the neutron star are comparable to the ones observed in neutron-star binaries. These findings may have little uncertainty because most of the ejecta is composed by matter that is heated via the shock wave and has relatively definite abundances. The abundance ratios for Ne, Mg, Si and Fe observed in Cygnus loop are well reproduced with the SN ejecta from an inner region of the 15\Ms progenitor.Comment: 15 pages, 1 table, 17 figures, accepted for publication in Astrophyscal Journa

Preliminary investigation of the clinical usefulness of super-high-resolution LCDs with 9 and 15 mega-sub-pixels: Observation studies with phantoms

金沢大学附属病院放射線部Our purpose in this study was to evaluate the preliminary clinical efficacy of soft-copy reading of digital mammography, for a 15-mega-sub-pixel (MsP) and a 9-MsP super-high-resolution liquid-crystal display (SHR-LCD) by use of an independent sub-pixel driving technology. We performed three kinds of phantom observation studies by six radiological technologists. Detectability of a contrast-detail phantom and simulated small objects (SSOs) resembling microcalcifications (MCLs), and shape discrimination ability of SSOs with round and square shapes, were examined and compared with a 5-MP conventional LCD (5-MP LCD). In each study, four types of display magnification ratio were used. The detectability and the shape discrimination ability of the 15-MsP SHR-LCD were highest among the three LCDs of most of the display magnification ratios. The 9-MsP SHR-LCD indicated a higher or equal performance as compared with the 5-MP LCD in the SSO detection and shape studies. The results of our study demonstrated that the SHR-LCDs had good potential to detect MCLs and to evaluate the shape in high-resolution digital mammography. © 2009 Japanese Society of Radiological Technology and Japan Society of Medical Physics

The Subaru-XMM-Newton Deep Survey (SXDS) VIII.: Multi-wavelength Identification, Optical/NIR Spectroscopic Properties, and Photometric Redshifts of X-ray Sources

We report the multi-wavelength identification of the X-ray sources found in the Subaru-XMM-Newton Deep Survey (SXDS) using deep imaging data covering the wavelength range between the far-UV to the mid-IR. We select a primary counterpart of each X-ray source by applying the likelihood ratio method to R-band, 3.6micron, near-UV, and 24micron source catalogs as well as matching catalogs of AGN candidates selected in 1.4GHz radio and i'-band variability surveys. Once candidates of Galactic stars, ultra-luminous X-ray sources in a nearby galaxy, and clusters of galaxies are removed there are 896 AGN candidates in the sample. We conduct spectroscopic observations of the primary counterparts with multi-object spectrographs in the optical and NIR; 65\% of the X-ray AGN candidates are spectroscopically-identified. For the remaining X-ray AGN candidates, we evaluate their photometric redshift with photometric data in 15 bands. Utilising the multi-wavelength photometric data of the large sample of X-ray selected AGNs, we evaluate the stellar masses, M*, of the host galaxies of the narrow-line AGNs. The distribution of the stellar mass is remarkably constant from z=0.1 to 4.0. The relation between M* and 2--10 keV luminosity can be explained with strong cosmological evolution of the relationship between the black hole mass and M*. We also evaluate the scatter of the UV-MIR spectral energy distribution (SED) of the X-ray AGNs as a function of X-ray luminosity and absorption to the nucleus. The scatter is compared with galaxies which have redshift and stellar mass distribution matched with the X-ray AGN. The UV-NIR SEDs of obscured X-ray AGNs are similar to those of the galaxies in the matched sample. In the NIR-MIR range, the median SEDs of X-ray AGNs are redder, but the scatter of the SEDs of the X-ray AGN broadly overlaps that of the galaxies in the matched sample.Comment: Accepted for publication in PASJ Subaru special issue. 42 pages, 22 figures. Entire contents of Tables 3, 8, 9, 10, and 11, and ASCII format tables are available from http://www.astr.tohoku.ac.jp/~akiyama/SXDS/index.htm

心不全を合併した心房細動患者のカテーテルアブレーション後の長期予後 : 左室駆出率に基づいた心不全のサブタイプ間における比較

Aims: Heart failure (HF) prognosis has been reported similar in patients with preserved vs. reduced left ventricular ejection fraction (LVEF). This study compared the long-term prognosis of HF patients undergoing radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). Methods and results: Among 5010 patients undergoing RFCA in Kansai Plus AF registry, 656 patients (13.1%) with a documented history of HF were enrolled in the study before RFCA. The primary endpoint was a composite of all-cause death, HF hospitalization, and stroke or systemic embolism. Patients with reduced (<40%), mid-range (40-49%), and preserved (≥50%) LVEF were 98 (14.9%), 107 (16.3%), and 451 (68.8%) patients, respectively. The prevalence of ischaemic heart disease and cardiomyopathies was higher among patients with reduced as compared with preserved LVEF (27.6% vs. 10.0%, P < 0.05 and 36.7% vs. 15.3%, P < 0.05, respectively). The median follow-up period was 2.9 years. The 3-year cumulative risk for the primary endpoint was higher in patients with reduced LVEF (32.7%) compared to those with mid-range (11.7%) or preserved (11.6%) LVEF (P < 0.001). Reduced LVEF was the most significant independent risk factor for primary endpoint (hazard ratio, 2.83; 95% confidence interval 1.74-4.61, P < 0.001). The 3-year arrhythmia recurrence rate was similar among the groups (48.2%, 42.8%, and 47.3%, respectively, P = 0.75). Conclusion : This study raises hypothesis that patients with HFrEF and AF had approximately three times higher risk for a composite of all-cause death, HF hospitalization, and stroke or systemic embolism after AF ablation compared with patients with HFmrEF or HFpEF.博士（医学）・甲第802号・令和3年12月21日Copyright: © Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021.This is a pre-copyedited, author-produced version of an article accepted for publication in Europace following peer review. The version of record "Europace Online ahead of print (2021 Aug 31;euab201) is available online at: https://doi.org/10.1093/europace/euab201.発行元が定める登録猶予期間終了の後、本文を登録予定（2022.08

Cleavage of a model DNA replication fork by a methyl-specific endonuclease

Epigenetic DNA methylation is involved in many biological processes. An epigenetic status can be altered by gain or loss of a DNA methyltransferase gene or its activity. Repair of DNA damage can also remove DNA methylation. In response to such alterations, DNA endonucleases that sense DNA methylation can act and may cause cell death. Here, we explored the possibility that McrBC, a methylation-dependent DNase of Escherichia coli, cleaves DNA at a replication fork. First, we found that in vivo restriction by McrBC of bacteriophage carrying a foreign DNA methyltransferase gene is increased in the absence of homologous recombination. This suggests that some cleavage events are repaired by recombination and must take place during or after replication. Next, we demonstrated that the enzyme can cleave a model DNA replication fork in vitro. Cleavage of a fork required methylation on both arms and removed one, the other or both of the arms. Most cleavage events removed the methylated sites from the fork. This result suggests that acquisition of even rarely occurring modification patterns will be recognized and rejected efficiently by modification-dependent restriction systems that recognize two sites. This process might serve to maintain an epigenetic status along the genome through programmed cell death