Publications by authors named "Rie Saito"

56 Publications

Long Spinal Cord Lesions Caused by Venous Congestive Myelopathy Associated with Intravascular Large B-cell Lymphoma.

Intern Med 2021 Jun 19. Epub 2021 Jun 19.

Department of Neurology, Tsubame Rosai Hospital, Japan.

Intravascular large B-cell lymphoma (IVLBCL) is a subtype of B-cell lymphoma, characterized by lymphoma cell proliferation within small blood vessels. We herein describe a rare case with long spinal cord lesions caused by venous congestive myelopathy associated with IVLBCL. An 81-year-old man presented with paraplegia of the lower limbs and sensory disturbances. Magnetic resonance imaging revealed intramedullary longitudinal T2-hyperintensity lesions in the thoracic cords. The patient died three months after disease onset, and a neuropathological analysis revealed predominantly atypical B-lymphocytes located sparsely in the veins of the spinal cord. IVLBCL should be considered in the differential diagnoses of long spinal cord lesions.
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http://dx.doi.org/10.2169/internalmedicine.6717-20DOI Listing
June 2021

Effects of Cs contamination after the TEPCO Fukushima Dai-ichi Nuclear Power Station accident on food and habitat of wild boar in Fukushima Prefecture.

J Environ Radioact 2020 Dec 16;225:106342. Epub 2020 Sep 16.

The Life Museum of Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara, Kanagawa, 252-5201, Japan.

After the Tokyo Electric Power Company Fukushima Dai-ichi Nuclear Power Station accident, wild boar was found to have greater radiocesium (Cs) activity concentrations in their bodies than other wild animals in Japan; however, the reason for this remains unknown. To understand the mechanism of Cs transfer from the environment to wild boar, and the factors that affect variation in Cs contamination in wild boar, we sampled muscle and stomach contents from wild boar captured in Fukushima Prefecture and analyzed the relationships among Cs concentrations in muscle tissue and in the stomach contents, Cs ground deposition at capture sites, and wild boar food habits. Significant positive relationships were observed among Cs activity concentrations in muscle and stomach contents, as well as Cs deposition density at capture sites. These results suggest that Cs is transferred from the environment to plant and animal materials consumed by wild boar, and then from these foods to the bodies of wild boar through digestion. However, no correlation was observed between Cs concentrations in stomach contents and the presence of any particular food item in stomachs of wild boar, including mushrooms. These findings suggest mushrooms and underground food items, which were found to affect Cs concentrations in wild animals in Europe, were not important contributors to high levels of Cs contamination in Japanese wild animals.
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http://dx.doi.org/10.1016/j.jenvrad.2020.106342DOI Listing
December 2020

Novel CHP1 mutation in autosomal-recessive cerebellar ataxia: autopsy features of two siblings.

Acta Neuropathol Commun 2020 08 12;8(1):134. Epub 2020 Aug 12.

Department of Pathology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-ku, Niigata, 951-8585, Japan.

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http://dx.doi.org/10.1186/s40478-020-01008-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425070PMC
August 2020

Relationship between radiocaesium in muscle and physicochemical fractions of radiocaesium in the stomach of wild boar.

Sci Rep 2020 04 22;10(1):6796. Epub 2020 Apr 22.

Institute of Environmental Radioactivity, Fukushima University, 1 Kanayagawa, Fukushima-shi, Fukushima, 960-1296, Japan.

After the accident at the TEPCO Fukushima Daiichi Nuclear Power Plant in 2011, it became important to study radiation dynamics, assess internal radiation exposure and specify factors affecting radionuclide variation in wildlife. Therefore, it is necessary to investigate which physicochemical fractions of radiocaesium (Cs) are absorbed from ingested material in species with high activity concentrations of Cs, such as wild boar. This study analysed the physicochemical fractions of Cs in the stomach contents of wild boar to evaluate the transfer from ingested food to muscle. The Cs activity concentration in muscle showed a significantly positive relationship with the Cs activity concentration in the exchangeable fraction, and the sum of the Cs activity concentrations in the exchangeable and bound to organic matter fractions. Seasonal variations were also found in the Cs activity concentration in the exchangeable fraction, and the sum of the Cs activity concentrations in the exchangeable and bound to organic matter fractions. These findings suggest that the proportions of the physicochemical fractions of Cs in the exchangeable and bound to organic matter fractions in the stomach contents are important factors affecting the increases and seasonal dynamics of the activity concentrations of Cs in wild boar muscle.
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http://dx.doi.org/10.1038/s41598-020-63507-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176735PMC
April 2020

Dramatic response of BRAF V600E-mutant epithelioid glioblastoma to combination therapy with BRAF and MEK inhibitor: establishment and xenograft of a cell line to predict clinical efficacy.

Acta Neuropathol Commun 2019 07 25;7(1):119. Epub 2019 Jul 25.

From the Departments of Neurosurgery, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, Japan.

Epithelioid glioblastoma is a rare aggressive variant of glioblastoma (GBM) characterized by a dismal prognosis of about 6 months and frequent leptomeningeal dissemination. A recent study has revealed that 50% of epithelioid GBMs harbor three genetic alterations - BRAF V600E mutation, TERT promoter mutations, and homozygous deletions of CDKN2A/2B. Emerging evidence support the effectiveness of targeted therapies for brain tumors with BRAF V600E mutation. Here we describe a dramatic radiographical response to combined therapy with BRAF and MEK inhibitors in a patient with epithelioid GBM harboring BRAF V600E mutation, characterized by thick spinal dissemination. From relapsed tumor procured at autopsy, we established a cell line retaining the BRAF V600E mutation, TERT promoter mutation and CDKN2A/2B loss. Intracranial implantation of these cells into mice resulted in tumors closely resembling the original, characterized by epithelioid tumor cells and dissemination, and invasion into the perivascular spaces. We then confirmed the efficacy of treatment with BRAF and MEK inhibitor both in vitro and in vivo. Epithelioid GBM with BRAF V600E mutation can be considered a good treatment indication for precision medicine, and this patient-derived cell line should be useful for prediction of the tumor response and clarification of its biological characteristics.
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http://dx.doi.org/10.1186/s40478-019-0774-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659204PMC
July 2019

Rapid chemical clearing of white matter in the post-mortem human brain by 1,2-hexanediol delipidation.

Bioorg Med Chem Lett 2019 08 28;29(15):1886-1890. Epub 2019 May 28.

Department of System Pathology for Neurological Disorders, Center for Bioresources, Brain Research Institute, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata 951-8585, Japan. Electronic address:

Three-dimensional (3D) imaging based on chemical tissue clearing in the post-mortem human brain is a promising approach for stereoscopic understanding of central nervous system diseases. Especially, delipidation of lipid-rich white matter (WM) is a rate-determining step in human brain clearing by hydrophilic reagents. In this study, we described the rapid delipidation of WM by a 1,2-hexanediol (HxD)-based aqueous solution. HxD delipidation enabled rapid clearing of a formalin-fixed human brain specimen including the WM. Although harsh HxD delipidation was applied to the brain tissue, conventional pathological staining patterns and various types of antigenicity were sufficiently preserved. Furthermore, HxD delipidation was compatible with 3D imaging of fluorescently-labeled tissue samples. HxD delipidation could be useful in future 3D neuropathological diagnosis.
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http://dx.doi.org/10.1016/j.bmcl.2019.05.049DOI Listing
August 2019

Retinal Vasculopathy With Cerebral Leukodystrophy: Clinicopathologic Features of an Autopsied Patient With a Heterozygous TREX 1 Mutation.

J Neuropathol Exp Neurol 2019 02;78(2):181-186

Departments of Pathology.

Retinal vasculopathy with cerebral leukodystrophy (RVCL) is an autosomal-dominant disorder involving the cerebral, retinal, renal, and other systemic microvessels due to frameshift mutations in the TREX1 gene. Under physiological conditions, the TREX1 protein is localized in the cellular cytoplasm and perinuclear area, but translocates into the nucleus in response to oxidative DNA damage. It has been speculated that aberrant localization of the protein may be associated with systemic microangiopathy in patients with RVCL. However, cellular expression of TREX1 in the brain and visceral organs of patients with RVCL has been unclear. Here, we report the clinicopathologic features of an autopsied patient with a heterozygous T249fs mutation in TREX1. The patient showed the clinical phenotype of vasculopathy with retinopathy, nephropathy, and stroke. CT with contrast enhancement demonstrated a tumorous lesion in the subcortical white matter. Histologically, the lesion consisted of confluent foci of necrosis with calcification and fibrous thickening of small vessel walls. TREX1 immunohistochemistry demonstrated positivity in the nuclei of cells in the CNS and visceral organs, indicating aberrant localization of the truncated protein, and the expression was remarkable in oligodendrocytes within the lesion, suggesting possible involvement of the protein in the pathomechanism of vasculopathy leading to white matter degeneration.
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http://dx.doi.org/10.1093/jnen/nly115DOI Listing
February 2019

Monitoring Cs concentrations in bird species occupying different ecological niches; game birds and raptors in Fukushima Prefecture.

J Environ Radioact 2019 Feb 10;197:67-73. Epub 2018 Dec 10.

Fukushima Prefectural Centre for Environmental Creation, 10-2 Fukasaku, Miharu, Fukushima, 963-7700, Japan.

This study was conducted to assess radiocesium accumulation in birds after the accident at Tokyo Electric Power Company's Fukushima Daiichi Nuclear Power Station in 2011, with a particular focus on Cs, which has a long physical half-life. Results of Cs monitoring in four game bird species including two pheasant species and two duck species (copper pheasant, green pheasant, spot-billed duck and mallard) were assessed in Fukushima Prefecture. We also obtained samples from rescued raptors that died during treatment or rehabilitation at the Wildlife Symbiosis Centre in Fukushima Prefecture because of severe injury. We measured the muscle concentrations of Cs in four of these raptor species (black kite, northern goshawk, peregrine falcon and ural owl). Comparison of the two pheasant species showed that the copper pheasants inhabiting forested areas had higher Cs concentrations in muscle (Bq/kg, fresh mass) than the green pheasants inhabiting mountainous areas near human habitation (i.e., Satoyama). No clear tendencies were observed in Cs concentration in muscle of copper pheasants over time, but a tendency to decrease was observed in green pheasants over time. The difference in tendencies between species may be attributable to differences in their food habits and its Cs concentration, and also differences in the situation of Cs accumulation in their habitat. No significant differences were observed in Cs concentration in muscle between the resident spot-billed duck and migratory mallard because of the comparatively short biological of effective half-life of radiocesium. Analysis of Cs concentration in muscle of raptor revealed that the concentration was similar to, or lower than, those of pheasants and ducks.
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http://dx.doi.org/10.1016/j.jenvrad.2018.10.016DOI Listing
February 2019

Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents.

Cell Rep 2018 08;24(8):2196-2210.e9

Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, 1-3 Yamadaoka, Suita, Osaka 565-5241, Japan; International Research Center for Neurointelligence (WPI-IRCN), UTIAS, The University of Tokyo, Tokyo, Japan. Electronic address:

We describe a strategy for developing hydrophilic chemical cocktails for tissue delipidation, decoloring, refractive index (RI) matching, and decalcification, based on comprehensive chemical profiling. More than 1,600 chemicals were screened by a high-throughput evaluation system for each chemical process. The chemical profiling revealed important chemical factors: salt-free amine with high octanol/water partition-coefficient (logP) for delipidation, N-alkylimidazole for decoloring, aromatic amide for RI matching, and protonation of phosphate ion for decalcification. The strategic integration of optimal chemical cocktails provided a series of CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis) protocols, which efficiently clear mouse organs, mouse body including bone, and even large primate and human tissues. The updated CUBIC protocols are scalable and reproducible, and they enable three-dimensional imaging of the mammalian body and large primate and human tissues. This strategy represents a future paradigm for the rational design of hydrophilic clearing cocktails that can be used for large tissues.
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http://dx.doi.org/10.1016/j.celrep.2018.07.056DOI Listing
August 2018

Seasonal variation of Cesium-137 concentration in Asian black bear (Ursus thibetanus) and wild boar (Sus scrofa) in Fukushima Prefecture, Japan.

PLoS One 2018 18;13(7):e0200797. Epub 2018 Jul 18.

Research Department, Fukushima Prefectural Centre for Environmental Creation, Miharu Town, Fukushima, Japan.

To elucidate and reduce the risk of radionuclide contamination in wildlife caused by the Tokyo Electric Power Company Fukushima Dai-ichi Nuclear Power Station accident, it is important to understand radionuclide variations in the wild animal population. Here, we used environmental monitoring data and muscle samples collected from Asian black bear (Ursus thibetanus) and wild boar (Sus scrofa) from May 2011 to March 2016 to examine seasonal variation in radiocesium (137Cs) concentrations in muscle tissues (hereafter, muscle 137Cs) of these important game species in Fukushima Prefecture. We measured muscle 137Cs of bears and wild boars killed by hunters or in animal control culls. First, using a linear mixed model (LMM), we tested for a positive relationship between muscle 137Cs and 137Cs in the soil at the site of capture (hereafter, soil 137Cs) estimated from a soil 137Cs deposition map produced by the Japan Atomic Energy Agency. In the LMM, muscle 137Cs was positively related to estimated soil 137Cs, which corroborates the results of previous studies. The LMM regression coefficients differed between the two species, with wild boar muscle 137Cs being higher than that of bears sampled at the same locations. We then employed a generalized additive mixed model (GAMM) to estimate seasonal variation in the muscle 137Cs of the target species. GAMM showed that muscle 137Cs varied seasonally and that this seasonal variation also differed between the two species. In bears, muscle 137Cs decreased from spring to early autumn, before increasing in winter. Wild boar muscle 137Cs remained low during spring and summer and was high during autumn and early spring. These patterns are likely influenced by differences in diet, habitat use, and physiology between these two species.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0200797PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051634PMC
January 2019

Rapid diagnosis of mixed phenotype acute leukemia after identifying a blood histogram abnormality.

Pract Lab Med 2018 Nov 12;12:e00101. Epub 2018 May 12.

Department of Clinical Laboratory, Tohoku Medical and Pharmaceutical University Hospital, Japan.

A 38-year-old woman was suffering from back, right arm, and ankle joint pain, and visited our emergency department. Upon admission, the white blood cell (WBC) count was high (11,700/µL), and low numbers of red blood cells (2.21 × 10/µL) and platelets (PLTs) (42,000/µL) were observed. A PLT histogram showed an abnormally shaped peak at around 20-30 fL, suggesting the presence of giant PLTs or PLT aggregation. The WBC histogram showed abnormal elevation at 35 fL and around 100 fL, suggesting abnormal cells including nucleated red blood cells. A peripheral blood smear was prepared, and morphology was examined. As a result, blasts (4%) including many orthochromatic erythroblasts (48/100 WBCs) were observed. Acute leukemia was suspected, and the patient was transferred the next day to a hospital with a hematology department. Bone marrow aspiration revealed that 99% of cells were blasts positive for B lymphoid lineage markers and myeloperoxidase. The patient was diagnosed with mixed phenotype lineage acute leukemia, treated immediately, and achieved remission. Thus, careful observation of histogram abnormalities of an automatic blood cell analyzer is important for rapid diagnosis of acute leukemia.
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http://dx.doi.org/10.1016/j.plabm.2018.e00101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041423PMC
November 2018

Loss of Motor Neurons Innervating Cervical Muscles in Patients With Multiple System Atrophy and Dropped Head.

J Neuropathol Exp Neurol 2018 04;77(4):317-324

Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan.

We investigated whether loss of motor neurons innervating the neck muscles contributes to dropped head (DH) in multiple system atrophy (MSA). From 75 patients with autopsy-proven MSA, we retrieved 3 who had DH (MSA-DH), and examined the 4th cervical cord segments. Neurons of the medial and lateral nuclear groups (MNG and LNG) innervate the neck and shoulder muscles, respectively. We measured the area of individual neurons in the MNG and LNG, and created an area-frequency histogram. Neurons were classified as large or small based on their area, and their total numbers in the MNG and LNG were counted. In the MNG, the numbers of both total neurons and large neurons were significantly lower in MSA patients than in the controls (214.2 ± 91.4 vs 521.3 ± 74.8, p = 0.0030, and 26.2 ± 9.1 vs 88.0 ± 34.6, p = 0.020, respectively), and were significantly lower in MSA-DH than in MSA-nonDH (139.7 ± 7.6 vs 288.7 ± 74.6, p = 0.048, and 18.0 ± 4.1 vs 34.3 ± 4.1, p = 0.016, respectively). There were no differences in the LNG neuron counts between the MSA-DH and MSA-nonDH groups. Loss of cervical motor neurons may be responsible for DH in MSA.
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http://dx.doi.org/10.1093/jnen/nly007DOI Listing
April 2018

Renal histopathological findings of retinal vasculopathy with cerebral leukodystrophy.

CEN Case Rep 2018 May 10;7(1):83-89. Epub 2018 Jan 10.

Divisions of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Retinal vasculopathy with cerebral leukodystrophy (RVCL) is a rare autosomal dominant systemic microvascular disease. Neurological disorders and visual disturbance are highlighted as manifestations of RVCL; however, there are few reports focused on nephropathy. Herein, we describe detailed renal histopathological findings in a daughter and father with RVCL, proven by TREX1 genetic analysis. A kidney biopsy of the daughter, 35-year-old with asymptomatic proteinuria, revealed unique and various glomerular changes. Atypical double contour (not tram track-like) of the capillary wall was widely found, an apparent characteristic finding. Glomerular findings were varied due to a combination of new and old segmental mesangial proliferative changes, mesangiolysis, and segmental glomerulosclerosis-like lesions; these changes may be related to endothelial cell damage. Collapsed tufts were also found and thought to be the result of ischemia due to arterial changes. Glomerular findings in a kidney biopsy of the father revealed similarity to the daughter's glomerulus at a relatively advanced stage, but the degree of variety in the glomerular findings was much less. Kidney biopsy findings suggesting endothelial cell damage of unknown etiology need to be considered for possible RVCL.
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http://dx.doi.org/10.1007/s13730-017-0300-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886931PMC
May 2018

Palonosetron, aprepitant, and dexamethasone for prevention of nausea and vomiting after high-dose melphalan in autologous transplantation for multiple myeloma: A phase II study.

Int J Hematol 2017 Apr 21;105(4):478-484. Epub 2016 Nov 21.

Department of Pharmacy, National Hospital Organization Shibukawa Medical Center, Shibukawa, Gunma, Japan.

Chemotherapy-induced nausea and vomiting (CINV) is a significant side effect in multiple myeloma (MM) patients receiving high-dose melphalan treatment followed by autologous stem cell transplantation (ASCT). We evaluated the efficacy and safety of a triple antiemetic combination of palonosetron, aprepitant, and low-dose dexamethasone in 24 MM patients who received melphalan conditioning (100 mg/m on days 1-2) before ASCT (on day 4). Intravenous palonosetron (0.75 mg on day 1), oral aprepitant (125 mg on day 1; 80 mg on days 2-4), and intravenous dexamethasone (6.6 mg on days 1-4) were administered for prevention of CINV. Complete response (no emesis and no rescue antiemetic) and complete control (no emesis, no rescue antiemetic, and no more than mild nausea) rates were 75 and 68% during the overall phase (0-120 h), while they were 88 and 86% in the acute phase (0-48 h), 75 and 68% in the delayed phase (48-120 h), and 67 and 59% in the extended phase (120-168 h), respectively. There were no serious adverse events related to the antiemetic therapy. In conclusion, the three-antiemetic regimen consisting of palonosetron, aprepitant, and dexamethasone was safe and effective for controlling CINV due to high-dose melphalan treatment, especially during the delayed phase.
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http://dx.doi.org/10.1007/s12185-016-2152-6DOI Listing
April 2017

[With the Characteristics of Chronic Pain Patients, Can the Therapeutic Effect of Antidepressant Duloxetine be Predicted?].

Masui 2016 10;65(10):1005-1008

Background: Duloxetine, an antidepressant, is used for treatment of pain, but the factors related to its effectiveness are not well known, and therefore we have performed a retrospective study.

Methods: Over a 22-month period from June 2012 patients with pain lasting for 3 months or more, with an NRS of 4 or higher, and given duloxetine within 3 months from their first diagnosis, were extracted from the medical records. These patients were compared and studied regarding their scores of the HADS (hos- pital anxiety and depression scale) at the time of first visit, duration of the disease, type of patient, and treat- ment effect after 1 month.

Results: The subjects were 61 patients, and they were categorized based on the presence of anxiety, the presence of dysphoria whether from organic or inor- ganic condition, and the duration of the disease, and no significant difference in the effectiveness of duloxetine was found.

Conclusions: Duloxetine had an overall effectiveness of 50.8%, regardless of the presence of anxiety or depression, the duration of the disease and the type of diseases.
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October 2016

First record of Plethus Hagen (Trichoptera, Hydroptilidae) from Japan, with description of a species.

Zootaxa 2016 Aug 23;4154(4):466-76. Epub 2016 Aug 23.

Division of Mountain and Environmental Science, Interdisciplinary Graduate School of Science and Technology, Shinshu University, Asahi 3-1-1, Matsumoto, Nagano 390-8621 Japan; Email: unknown.

The tropical and subtropical caddisfly genus Plethus Hagen (Hydroptilidae) is recorded from Japan for the first time. The species, Plethus ukalegon Malicky and Chantaramongkol 2007, originally described from Taiwan, is redescribed based on material from Iriomote-jima and Ishigaki-jima, southern Ryukyu Islands, the southernmost region of Japan. Female and immature stages are newly described and compared with Indonesian congeners. The early instar larva was associated with the adult through mitochondrial DNA sequence comparisons, and is described in the genus Plethus for the first time. Larvae live in fast-flowing waters such as hygropetric zones, rapid streams, and waterfalls. Final instar larvae make flattened cases of silk that they attach tightly on smooth rock surfaces.
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http://dx.doi.org/10.11646/zootaxa.4154.4.6DOI Listing
August 2016

Larvae and females of two Stenopsyche species in Taiwan with redescription of the male of S. formosana (Insecta: Trichoptera).

Zootaxa 2016 Jun 10;4121(4):485-94. Epub 2016 Jun 10.

Department of Biology, Faculty of Science, Shinshu University, Matsumoto, Nagano, Japan; Email: unknown.

Larvae and females of two Stenopsyche species, S. formosana Kobayashi and S. drakon Weaver, are described for the first time. They were associated with the adult male through mitochondrial DNA sequence comparisons. The male of S. formosana, which has been recorded as Stenopsyche banksi Mosely from Taiwan, is redescribed. The males of S. formosana and S. banksi can be distinguished from each other by the shape of segments IX and X, and endothecal spines. In larvae, S. formosana and S. drakon are distinguishable from each other and from other known species by the combination of different dark marking patterns and shapes of no. 18 setae of the head, and by the shapes of forecoxae. The larval morphology of S. formosana and S. drakon suggests that the phylogenetic relationships based mainly on male genitalia in the genus Stenopsyche should be reconsidered.
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http://dx.doi.org/10.11646/zootaxa.4121.4.8DOI Listing
June 2016

[A Clinical Comparison of Continuous Sciatic Nerve Block and Epidural Anesthesia for Postoperative Pain Control in Patients with Fracture of the Foot].

Masui 2015 Apr;64(4):388-91

Background: Epidural analgesia provides good pain relief for patients with fracture of the foot Ultrasound-guided peripheral nerve block offers safety and efficacy without affecting the leg.

Methods: We compared the continuous sciatic nerve block with the continuous epidural anesthesia regarding postoperative pain after the open reduction and internal fixation (ORIF) of the ankle fracture or calcaneal bone fracture.

Results: Fifteen patients were included in the epidural group (group E), and 17 patients in the sciatic nerve block group (group S). The postoperative pain scores were significantly lower in group S 3 hours and 12 hours after the procedure, and tended to be lower in other periods. Perioperative periods were uneventful in both groups.

Conclusions: Continuous sciatic nerve block developed good postoperative analgesia in ORIF of ankle fracture or calcaneal bone fracture compared with continuous epidural anesthesia.
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April 2015

Discovery of Overcoating Metal Oxides on Photoelectrode for Water Splitting by Automated Screening.

ACS Comb Sci 2015 Oct 14;17(10):592-9. Epub 2015 Sep 14.

National Institute of Advanced Industrial Science and Technology (AIST) , Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8565 Japan.

We applied an automated semiconductor synthesis and screen system to discover overcoating film materials and optimize coating conditions on the BiVO4/WO3 composite photoelectrode to enhance stability and photocurrent. Thirteen metallic elements for overcoating oxides were examined with various coating amounts. The stability of the BiVO4/WO3 photoelectrode in a highly concentrated carbonate electrolyte aqueous solution was significantly improved by overcoating with Ta2O5 film, which was amorphous and porous when calcined at 550 °C. The photocurrent for the water oxidation reaction was only minimally inhibited by the presence of the Ta2O5 film on the BiVO4/WO3 photoelectrode.
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http://dx.doi.org/10.1021/acscombsci.5b00022DOI Listing
October 2015

Nonfunctional intra- and suprasellar tumor in a patient with visual disturbance and panhypopituitarism.

Neuropathology 2016 Feb 17;36(1):107-12. Epub 2015 Aug 17.

Departments of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.

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http://dx.doi.org/10.1111/neup.12236DOI Listing
February 2016

[A case of 77-year-old male with spinocerebellar ataxia type 31 with left dominant dystonia].

Rinsho Shinkeigaku 2015 ;55(6):434

Department of Neurology, Toranomon Hospital.

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http://dx.doi.org/10.5692/clinicalneurol.cn-000677DOI Listing
March 2016

[Succesful management of esophageal banding and gastrostomy for esophageal atresia in a trisomy 18 child with complex cardiac malformation].

Masui 2014 Nov;63(11):1266-8

Trisomy 18 is one of the congenital disorders caused by a chromosomal abnormality. Ninety percent of fetuses with trisomy 18 have various other malformations. The present patient had heart failure due to a complex cardiac malformation and a Gross C type esophageal atresia. Before the esophageal banding, ventilation of the lungs was impossible and respiratory condition was unstable. Considering that direction of the shunt can easily change by hyperventilation and high oxygen concentration, we employed the lowest oxygen concentration and ventilation as possible. In the present case, it was necessary to provide respiratory care for both esophageal atresia and complex cardiac malformation.
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November 2014

Qing Dai attenuates nonsteroidal anti-inflammatory drug-induced mitochondrial reactive oxygen species in gastrointestinal epithelial cells.

J Clin Biochem Nutr 2015 Jan 1;56(1):8-14. Epub 2014 Nov 1.

Faculty of Medicine, University of Tsukuba, 1-1-1 Ten-nohdai, Tsukuba, Ibaraki 305-8577, Japan.

Treatments with nonsteroidal anti-inflammatory drugs (NSAIDs) have increased the number of patients with gastrointestinal complications. Qing Dai has been traditionally used in Chinese herbal medicine for various inflammatory diseases such as ulcerative colitis. We previously reported that Qing Dai suppressed inflammations by scavenging reactive oxygen species (ROS) in ulcerative colitis patients. Thus, Qing Dai can attenuate the production of ROS, which play an important role in NSAID-induced gastrointestinal injuries. In this study, we aimed to elucidate whether Qing Dai decreased mitochondrial ROS production in NSAID-treated gastrointestinal cells by examining cellular injury, mitochondrial membrane potentials, and ROS production with specific fluorescent indicators. We also performed electron paramagnetic resonance measurement in isolated mitochondria with a spin-trapping reagent (CYPMPO or DMPO). Treatments with indomethacin and aspirin induced cellular injury and mitochondrial impairment in the gastrointestinal cells. Under these conditions, mitochondrial alterations were observed on electron microscopy. Qing Dai prevented these complications by suppressing ROS production in gastrointestinal cells. These results indicate that Qing Dai attenuated the ROS production from the NSAID-induced mitochondrial alteration in the gastrointestinal epithelial cells. Qing Dai treatment may be considered effective for the prevention NSAID-induced gastrointestinal injury.
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http://dx.doi.org/10.3164/jcbn.14-59DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306662PMC
January 2015

MDM4 expression as an indicator of TP53 reactivation by combined targeting of MDM2 and MDM4 in cancer cells without TP53 mutation.

Oncoscience 2014 25;1(12):830-43. Epub 2014 Nov 25.

Department of Gastroenterology and Hepatology, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.

MDM2 and MDM4, a structurally related MDM2 homolog, negatively regulates expression and functions of TP53 tumor suppressor gene. To explore the precise expression patterns and function of MDM2 and MDM4 in wild-type (wt) TP53 cancer cells, we analyzed 11 various cancer cell lines with wt TP53. All cell lines exhibited deregulated expression of MDM2 and MDM4, and were divided into two distinct types; the one expressing high levels of MDM4 and another expressing low levels of MDM4. The low MDM4 type expressed higher MDM2 levels than the high MDM4 type. In cells with high MDM4 expression, knockdown of MDM4 or MDM2 reactivated TP53, and simultaneous knockdown of MDM2 and MDM4 synergistically reactivated TP53. In contrast, in cells with low MDM4 expression, knockdown of only MDM2 reactivated TP53. These results suggest that both MDM2 and MDM4 are closely involved in TP53 inactivation in cancer cells with high MDM4 expression, whereas only MDM2, and not MDM4, is a regulator of TP53 in cells with low MDM4 expression. MDM4 expression in wt TP53-tumors is a potential indicator for TP53 reactivation cancer therapy by simultaneous targeting of MDM4 and MDM2. Specific knockdown of MDM2 and MDM4 might be applicable for TP53 restoration therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303891PMC
http://dx.doi.org/10.18632/oncoscience.103DOI Listing
January 2015

[A case of 77-year-old male with spinocerebellar ataxia type 31 with left dominant dystonia].

Rinsho Shinkeigaku 2014 ;54(8):643-7

Department of Neurology, Toranomon Hospital.

We report on the case of a 77-year-old male with genetically proven spinocerebellar ataxia type 31 (SCA31) who had dystonia. He was referred to our hospital for evaluation following a 6-year history of slowly progressive unsteadiness of his left leg during walking and dysarthria at the age of 62 years old. On the basis of his symptoms, we diagnosed him as spinocerebellar degeneration (SCD), and prescribed taltirelin hydrate. However, his symptoms continued to worsen. He required a cane for walking at the age of 63 years, and a wheelchair at the age of 66 years. He was admitted to our hospital following acute cerebral infarction at the age of 77 years. On examination at admission, right hemiparesis and cerebellar ataxia were detected. And left hallux moved involuntarily toward the top surface of the foot at rest, that is dystonia. The dystonia was not associated with cerebral infarction, because it had been several years with dystonia that he got cerebral infarction. Genetic analysis revealed that this patient harbored a heterozygous SCA31 mutation. Previously there have been no reports of SCA31 associated with dystonia. Our case report support clinical heterogeneity of SCA31, and highlight the importance of considering this type in patients with dystonia and ataxia. Patients with the combination of dystonia and ataxia and a family history of a neurodegenerative disorder should be tested for SCA31.
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http://dx.doi.org/10.5692/clinicalneurol.54.643DOI Listing
October 2015

Antitumor effects of a sirtuin inhibitor, tenovin-6, against gastric cancer cells via death receptor 5 up-regulation.

PLoS One 2014 17;9(7):e102831. Epub 2014 Jul 17.

Department of Gastroenterology, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Up-regulated sirtuin 1 (SIRT1), an NAD+-dependent class III histone deacetylase, deacetylates p53 and inhibits its transcriptional activity, leading to cell survival. SIRT1 overexpression has been reported to predict poor survival in some malignancies, including gastric cancer. However, the antitumor effect of SIRT1 inhibition remains elusive in gastric cancer. Here, we investigated the antitumor mechanisms of a sirtuin inhibitor, tenovin-6, in seven human gastric cancer cell lines (four cell lines with wild-type TP53, two with mutant-type TP53, and one with null TP53). Interestingly, tenovin-6 induced apoptosis in all cell lines, not only those with wild-type TP53, but also mutant-type and null versions, accompanied by up-regulation of death receptor 5 (DR5). In the KatoIII cell line (TP53-null), DR5 silencing markedly attenuated tenovin-6-induced apoptosis, suggesting that the pivotal mechanism behind its antitumor effects is based on activation of the death receptor signal pathway. Although endoplasmic reticulum stress caused by sirtuin inhibitors was reported to induce DR5 up-regulation in other cancer cell lines, we could not find marked activation of its related molecules, such as ATF6, PERK, and CHOP, in gastric cancer cells treated with tenovin-6. Tenovin-6 in combination with docetaxel or SN-38 exerted a slight to moderate synergistic cytotoxicity against gastric cancer cells. In conclusion, tenovin-6 has potent antitumor activity against human gastric cancer cells via DR5 up-regulation. Our results should be helpful for the future clinical development of sirtuin inhibitors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0102831PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102575PMC
November 2015

Effectiveness of an endoscopic biopsy procedure using EUS-FNA and EMR-C for diagnosing adenocarcinoma arising from ectopic pancreas: two case reports and a literature review.

Intern Med 2014 ;53(10):1055-62

Division of Gastroenterology, University of Tsukuba Hospital, Japan.

Adenocarcinomas arising from the ectopic pancreas in the gastrointestinal wall are rarely described in the literature. In addition, obtaining an accurate preoperative diagnosis is difficult in most cases because these adenocarcinomas occur primarily in the submucosal layer and form submucosal tumors. Endoscopic ultrasonography-guided fine-needle aspiration and endoscopic mucosal resection with a transparent plastic cap-fitted panendoscope followed by a biopsy are useful for histological typing and making the differential diagnosis of adenocarcinoma, gastrointestinal stromal tumor, malignant lymphoma or other. These procedures represent the first step toward diagnosing ectopic pancreatic adenocarcinoma. We herein report two such cases with a review of the pertinent literature.
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http://dx.doi.org/10.2169/internalmedicine.53.1420DOI Listing
April 2015

[A case of malignant peritoneal mesothelioma with the epithelioid histological type, successfully treated with pemetrexed plus cisplatin].

Gan To Kagaku Ryoho 2014 Mar;41(3):361-4

Division of Gastroenterology,University of Tsukuba Hospital.

A 45-year-old man presented with severe abdominal distention with massive ascites due to a diffusely disseminated peritoneal tumor. A core needle biopsy specimen was obtained from the peritoneal lesion. Histological diagnosis was epithelioid type mesothelioma. He did not choose to receive chemotherapy. For 2.5 years, he went without medical intervention, and his disease gradually progressed, leading to a worsening of his symptoms. The patient then chose to be treated with combination chemotherapy of cisplatin and pemetrexed, followed by pemetrexed alone. There was remarkable tumor shrinkage and his symptoms improved. These effects have been sustained for two years after the initial chemotherapy. Chemotherapy appears to have contributed to survival prolongation for this patient. This case exemplifies the fact that malignant peritoneal mesothelioma may progress slowly when fits with some good prognostic factors, and it is important to consider the prognostic factors.
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March 2014

The sirtuin inhibitor tenovin-6 upregulates death receptor 5 and enhances cytotoxic effects of 5-fluorouracil and oxaliplatin in colon cancer cells.

Oncol Res 2013 ;21(3):155-64

Department of Gastroenterology, University of Tsukuba Graduate School, Tsukuba, Ibaraki, Japan.

It has been reported that upregulated SIRT1 (NAD(+)-dependent class III histone deacetylase) deacetylates the p53 protein, represses its function, and allows for tumor cell growth in various cancers. Here we investigated antitumor effects of tenovin-6, a small-molecule inhibitor of SIRT1 and SIRT2, in various colon cancer cell lines. Tenovin-6 induced apoptosis in all five colon cancer cell lines investigated (two cell lines with wild-type p53 and three with mutant p53) regardless of the p53 mutation status. This effect was accompanied by accumulation of death receptor 5 (DR5) in most cell lines. DR5 silencing in HCT116 cells strongly attenuated tenovin-6-induced apoptosis. We investigated the effect of combining tenovin-6 with conventional anticancer agents 5-fluorouracil (5-FU), SN-38 (an active metabolite of irinotecan), and oxaliplatin. Synergistic antitumor effects of tenovin-6 were observed in combination with either 5-FU or oxaliplatin in vitro. The combination of tenovin-6 and oxaliplatin exhibited potent growth inhibition of HCT116 xenograft tumors in vivo. In conclusion, tenovin-6 induced apoptosis in human colon cancer cells through the activation of the DR5 signaling pathway and enhanced the antitumor properties of 5-FU and oxaliplatin. These results may help develop a novel treatment option for colorectal cancer using a SIRT inhibitor.
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http://dx.doi.org/10.3727/096504013X13854886566598DOI Listing
August 2014
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