Sanin Rosai Hospital

Tottori, Japan

Sanin Rosai Hospital

Tottori, Japan
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Yu Y.,Tottori University | Mena-Barragan T.,University of Seville | Higaki K.,Tottori University | Johnson J.L.,Georgia Institute of Technology | And 12 more authors.
ACS Chemical Biology | Year: 2014

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene often leading to missense α-galactosidase A (α-Gal A) variants that undergo premature endoplasmic reticulum-associated degradation due to folding defects. We have synthesized and characterized a new family of neutral amphiphilic pharmacological chaperones, namely 1-deoxygalactonojirimycin-arylthioureas (DGJ-ArTs), capable of stabilizing α-Gal A and restoring trafficking. Binding to the enzyme is reinforced by a strong hydrogen bond involving the aryl-N′H thiourea proton and the catalytic aspartic acid acid D231 of α-Gal A, as confirmed by a 2.55 Å resolution cocrystal structure. Selected candidates enhanced α-Gal A activity and ameliorate globotriaosylceramide (Gb3) accumulation and autophagy impairments in FD cell cultures. Moreover, they acted synergistically with the proteostasis regulator 4-phenylbutyric acid, appearing to be promising leads as pharmacological chaperones for FD. © 2014 American Chemical Society.

Nakamura T.,University of Occupational and Environmental Health Japan | Sugimoto T.,The University of Shimane | Nakano T.,Tamana Central Hospital | Kishimoto H.,Sanin Rosai Hospital | And 8 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: Weekly teriparatide injection at a dose of 56.5 μg has been shown to increase bone mineral density. Objective: A phase 3 study was conducted to determine the efficacy of once-weekly teriparatide injection for reducing the incidence of vertebral fractures in patients with osteoporosis. Design and Setting: In this randomized, multicenter, double-blind, placebo-controlled trial conducted in Japan, the incidence of morphological vertebral fractures by radiographs was assessed. Patients: Subjects were 578 Japanese patients between the ages of 65 and 95 yr who had prevalent vertebral fracture. Intervention: Subjects were randomly assigned to receive once-weekly sc injections of teriparatide (56.5 μg) or placebo for 72 wk. Main Outcome Measure: The primary endpoint was the incidence of new vertebral fracture. Results: Once-weekly injections of teriparatide reduced the risk of new vertebral fracture with a cumulative incidence of 3.1% in the teriparatide group, compared with 14.5% in the placebo group (P < 0.01), and a relative risk of 0.20 (95% confidence interval, 0.09 to 0.45). At 72 wk, teriparatide administration increased bone mineral density by 6.4, 3.0, and 2.3% at the lumbar spine, the total hip, and the femoral neck, respectively, compared with the placebo (P < 0.01). Adverse events (AE) and the dropout rates by AE were more frequently experienced in the teriparatide group, but AE were generally mild and tolerable. Conclusion: Weekly sc administration of teriparatide at a dose of 56.5 μg may provide another option of anabolic treatments in patients with osteoporosis at higher fracture risk. Copyright © 2012 by The Endocrine Society.

Mizuta E.,Sanin Rosai Hospital
Yakugaku Zasshi | Year: 2015

Individual taste sensitivity affiects one's eating habits, and could thus play a role in the development of lifestylerelated diseases, such as obesity, hypertension and dyslipidemia. However, only a handful of studies have been conducted to investigate these associations. Therefore, we performed taste sensitivity tests on approximately 250 patients with lifestyle-related diseases who were undergoing outpatient treatment at the Department of Internal Medicine, or received a health check-up in order to examine the associations of individual taste sensitivity with their eating habits and lifestylerelated diseases. Our findings showed that sensitivity to sweet or salt taste was significantly lower in patients with cardiovascular diseases, and sensitivity to umami taste was significantly lower in obese patients. These findings suggest that taste sensitivity disorders may be linked not only to eating habits and lifestyle-related diseases, but also to the onset of cardiovascular diseases. Many of the drugs used in the treatment of lifestyle-related diseases and cardiovascular diseases, including antihypertensive agents, statins, fibrates, and allopurinol, are known to form zinc chelates and thereby possibly cause drug-induced taste disorders. Focusing on individual taste sensitivity to improve or maintain intake levels may become a new target for drug development in the areas of lifestyle-related and cardiovascular diseases. © 2015 The Pharmaceutical Society of Japan.

PubMed | Sanin Rosai Hospital, Dokkyo Medical College, Tottori University, Fujii Masao Memorial Hospital and 2 more.
Type: Journal Article | Journal: Drug research | Year: 2016

Although urate impaired the endothelial function, its underlying mechanism remains unknown. We hypothesized that urate impaired nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) via activation of uric acid transporters (UATs).In the present study, we studied effects of urate on NO production and eNOS protein expression in HUVEC cells in the presence and absence of urate lowering agents using molecular biological and biochemical assays.HUVECs expressed the 4 kinds of UATs, URATv1, ABCG2, MRP4 and MCT9. Exposure to urate at 7mg/dl for 24h significantly reduced production of NO. Pretreatment with benzbromarone, losartan or irbesartan normalized NO production. The same exposure resulted in dephosphorylation of endothelial NO synthase (eNOS) in HUVECs. Again pretreatment with benzbromarone, losartan or irbesartan abolished this effect.Urate reduced NO production by impaired phosphorylation of eNOS in HUVEC via activation of UATs, which could be normalized by urate lowering agents.

PubMed | Sanin Rosai Hospital, Nishi Niigata Chuo National Hospital, Tottori University and Nagaoka Chuo General Hospital
Type: | Journal: Case reports in pediatrics | Year: 2016

Niemann-Pick disease type C (NPC) is a rare progressive neurodegenerative disorder, often with onset after normal early childhood development. Juvenile onset NPC patients slowly develop cerebellar symptoms and cognitive impairment and often experience difficulties at school. However, these problems may be overlooked due to the unpublicized nature of NPC, given that it is a rare metabolic disorder. In this report, we present an 11-year-old male NPC patient, who suffered from clumsiness and difficulties in attention and academic and social skills. His symptoms were initially considered to be due to developmental coordination disorder (DCD) coexisting with bullying by peers. DCD is a type of neurodevelopmental disorder defined according to DSM-IV and is characterized by clumsiness that interferes with academic achievement and social integration not due to other general medical conditions. However, a detailed investigation of the patient suggested that the problems could be attributed to the onset of NPC. Clinicians should keep neurodegenerative disorders as differential diagnosis of children with multiple school problems.

Suzuki Y.,Tokyo Metropolitan Institute of Medical Science | Ohno K.,Sanin Rosai Hospital | Narita A.,Tottori University
Current Bioinformatics | Year: 2016

Chaperone therapy was proposed as a new molecular therapeutic approach almost simultaneously to lysosomal diseases and cystic fibrosis, caused by gene mutations resulting in misfolding of expressed proteins. In our original papers, we reported that unstable mutant lysosomal enzymes causing lysosomal diseases resulted in rapid intracellular degradation and loss of catalytic function. However, in the presence of some low molecular competitive inhibitors (chemical chaperones), after binding to enzyme active sites, paradoxically stabilized and enhanced catalytic activities in somatic cells (proteostasis) by correcting the enzyme protein folding. After oral administration, they were transferred to the bloodstream, reached the brain tissue through the blood-brain barrier, and normalized pathophysiology of the disease. Our reports of these inhibitory chaperones were followed by reports of non-competitive (or allosteric) chaperones without inhibitory bioactivity. Furthermore heat shock proteins and other endogenous proteins were recognized as candidates for the third-type chaperone therapy. Theoretically they could be utilized for handling abnormally accumulated intracellular mutant proteins, if they are overexpressed by small molecules particularly in neurodegenerative diseases. These three types of chaperone therapies are expected as promising approaches to a variety of diseases, genetic or nongenetic, and neurological or non-neurological, in addition to lysosomal diseases. Finally, in this article, possible chaperones for Gaucher disease are discussed, and preliminary clinical results of ambroxol therapy are summarized. © 2016 Bentham Science Publishers.

PubMed | Kumamoto University, Sanin Rosai Hospital, Saga University and Tottori University
Type: Journal Article | Journal: Molecular genetics and metabolism | Year: 2016

This study was conducted to evaluate the attenuating potential of 2-hydroxypropyl--cyclodextrin (HPBCD) against Niemann-Pick Type C (NPC) disease, as well as the physical and chemical properties, particularly the cholesterol-solubilizing ability, in an NPC disease model in vitro. As parameters of NPC abnormalities, intracellular free and esterified cholesterol levels and lysosome volume were measured in Npc1 null Chinese hamster ovary cells. HPBCD showed dose-dependent effects against dysfunctional intracellular cholesterol trafficking, such as the accumulation and shortage of free and esterified cholesterols, respectively, in Npc1 null cells. However, the effectiveness was gradually offset by exposure to 8mM HPBCD. The same effect was also observed for increasing lysosome volume in Npc1 null cells. The degree of substitution of the hydroxypropyl group had little influence on the attenuating effects of HPBCD against the NPC abnormalities, at least in the range between 2.8 and 7.4. Next, we compared the effects of other hydroxyalkylated -cyclodextrin derivatives with different cholesterol-solubilizing abilities, such as 2-hydroxyethyl--cyclodextrin (HEBCD) and 2-hydroxybutyl--cyclodextrin (HBBCD). The cholesterol solubilizing potential, attenuating effects against NPC abnormalities and cytotoxicity induction were HBBCDHPBCD>HEBCD, HBBCD=HPBCD>HEBCD and HBBCDHPBCD=HEBCD, respectively. HPBCD may be superior in terms of safety and efficacy in Npc1 null cells compared with HEBCD and HBBCD. The results of this study will provide a rationale for the optimization of HPBCD therapy for NPC disease.

PubMed | Red Cross, Tottori Prefectural Central Hospital, Tottori University and Sanin Rosai Hospital
Type: | Journal: Geriatrics & gerontology international | Year: 2016

An association between body mass index (BMI) and stroke outcome have been reported, but the results are controversial. The aim of the present study was to evaluate whether BMI is associated with ischemic stroke outcome.Consecutive Japanese acute ischemic stroke patients were analyzed. BMI was categorized as underweight (BMI <18.5kg/mA total of 1206 acute ischemic stroke patients (760 men; mean age 72.5 years) were analyzed in the present study. There were 111 underweight cases (9.2%), 785 normal weight cases (65.1%) and 310 obese cases (25.7%). The underweight group had a significantly higher rate of poor short and long-term outcomes than the normal weight group. The outcomes of the obese group were not significantly different from those of the normal weight group. Recurrence was not significantly different among the groups.Lower BMI might be a predictor of poorer short-term and long-term stroke outcomes. Geriatr Gerontol Int 2016; : -.

Kuroda H.,Sanin Rosai Hospital
Kyobu geka. The Japanese journal of thoracic surgery | Year: 2013

We report a case of a 57-year-old woman who presented with cardiac tamponade 13 days after thoracoscopic excision of the diverticulum of the esophagus. Computed tomography and electrocardiogram revealed neither evidence of aortic dissection nor acute myocardial ischemia. Unstable hemodynamic condition continued even after 400 ml blood drainage through pericardiocentesis, and emergency open surgery was performed. Active arterial bleeding was seen at the marginal branch of the left circumflex coronary artery. The stump of the suture [4-0 polydioxanone (PDS) II], which had been used for closure of the overlying esophageal muscle layer, penetrated the pericardium and injured the coronary artery. Vessel injury caused by a stump of a suture seems to be extremely rare. Careful selection of the suture around the pericardium and management of its stump are necessary.

Kuroda H.,Sanin Rosai Hospital | Ono K.,Sanin Rosai Hospital
Kyobu geka. The Japanese journal of thoracic surgery | Year: 2016

A 61-year-old female on hemodialysis with chronic renal failure presented with hemoptysis 10 years after replacement of the distal arch and the descending aorta. Computed tomography showed hematoma around the prosthetic graft and intrapulmonary hemorrhage adjacent to the graft. At emergency open surgery, perforation was revealed in the distal portion of the graft. It was considered to be caused by the friction between the surrounding calcified aortic wall and the graft. The ruptured graft was successfully replaced.

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