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Hasegawa J.,Soma General Hospital | Hasegawa J.,Tohoku University | Hidaka H.,Tohoku University | Kuriyama S.,Tohoku University | And 6 more authors.

On March 11, 2011, Japan's northeast Pacific coast was hit by a gigantic earthquake and subsequent tsunami. Soma City in Fukushima Prefecture is situated approximately 44 km north of Fukushima Daiichi Nuclear Power Plant. Soma General Hospital is the only hospital in Soma City that provides full-time otolaryngological medical care. We investigated the changes in new patients from one year before to three years after the disaster. We investigated 18,167 new patients treated at our department during the four years from April 1, 2010 to March 31, 2014. Of the new patients, we categorized the diagnoses into Meniere's disease, acute low-tone sensorineural hearing loss, vertigo, sudden deafness, tinnitus, and facial palsy as neuro-otologic symptoms. We also investigated the changes in the numbers of patients whom we examined at that time concerning other otolaryngological disorders, including epistaxis, infectious diseases of the laryngopharynx, and allergic rhinitis. The total number of new patients did not change remarkably on a year-to-year basis. Conversely, cases of vertigo, Meniere's disease, and acute low-tone sensorineural hearing loss increased in number immediately after the disaster, reaching a plateau in the second year and slightly decreasing in the third year. Specifically, 4.8% of patients suffering from these neuro-otologic diseases had complications from depression and other mental diseases. With regard to new patients in our department, there was no apparent increase in the number of patients suffering from diseases other than neuro-otologic diseases, including epistaxis, and allergic rhinitis. Patients suffering from vertigo and/or dizziness increased during the first few years after the disaster. These results are attributed to the continuing stress and tension of the inhabitants. This investigation of those living in the disaster area highlights the need for long-term support. © 2015 Hasegawa et al. Source

Hirayama A.,Yamagata University | Konta T.,Yamagata University | Hozawa A.,Tohoku Medical Megabank Organization | Kawasaki R.,Yamagata University | And 5 more authors.
Hypertension Research

Recent studies have suggested that urine albumin excretion in the high normal range predicts hypertension. However, the relationship between urinary albumin excretion in spot urine and incident hypertension remains unclear in the general Japanese population. To clarify this relationship, we conducted a cohort study in a community-based population of 412 normotensive individuals without diabetes and renal insufficiency and examined the incidence of hypertension using the urinary albumin-to-creatinine ratio (UACR) at baseline. Incident hypertension was defined as new-onset systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg and/or the use of anti-hypertensive drugs. During the follow-up period (median, 6.7 years), 133 subjects (32.3%) newly developed hypertension. The incidence of hypertension increased with an increase in baseline UACR (20.4% for UACR <5 mg g -1, 34.0% for 5-9.9 mg g -1 UACR and 40.4% for 10-29.9 mg g -1, P=0.002). Multivariate logistic regression analysis, after adjustment for possible confounders, showed that UACR 5-9.9 mg g -1 and 10-29.9 mg g -1 were independent risks for incident hypertension compared with UACR <5 mg g -1 (odds ratio (OR) 2.15, 95% confidence interval (CI) 1.16-4.10 and OR 2.67, 95% CI 1.36-5.38, respectively). Subgroup analysis revealed that subjects with increased UACR (≥5 mg g -1) had a higher risk of incident hypertension than did those with low UACR (<5 mg g -1), irrespective of their backgrounds (age, sex, smoking, alcohol consumption, obesity and urinary sodium excretion). In conclusion, this study showed that a slight increase in urinary albumin excretion might predict incident hypertension in a community-based Japanese population. © 2015 The Japanese Society of Hypertension. Source

Nakano T.,Jikei University School of Medicine | Mizoue S.,Ehime University | Fuse N.,Tohoku Medical Megabank Organization | Iwase A.,Tajimi Iwase Eye Clinic | And 2 more authors.
Advances in Therapy

Introduction: The efficacy of lowering intraocular pressure (IOP) and safety of switching to travoprost/timolol fixed combination ophthalmic solution (Duotrav®, Alcon Laboratories, Inc., Fort Worth, TX, USA) in patients with primary open-angle glaucoma, normal tension glaucoma or ocular hypertension undergoing prostaglandin analog (PGA) monotherapy was investigated. Methods: Patients treated with travoprost, latanoprost, tafluprost, or bimatoprost for ≥3 months and requiring additional medication were switched to Duotrav without washout. Baseline IOP was calculated from measurements at two visits during PGA monotherapy. IOP reductions at 4, 8, and 12 weeks after switching to Duotrav and adverse events were assessed. Results: Of 162 patients enrolled, 157 patients (96.9%) with ≥4 weeks of follow-up after switching to Duotrav were analyzed. The mean IOP decreased significantly (baseline = 16.3 ± 3.1 mmHg; 4 weeks = 14.6 ± 3.1 mmHg, 8 weeks = 14.7 ± 3.3 mmHg, 12 weeks = 14.6 ± 3.2 mmHg; all P < 0.0001). When study eyes were divided into three groups according to baseline IOP (≥19 mmHg: 33 eyes, 21.0%; ≥15 to <19 mmHg: 78 eyes, 49.7%; <15 mmHg: 46 eyes, 29.3%), all groups showed significant IOP reductions (P = 0.0324 ~ P < 0.0001) after switching to Duotrav. Twenty-seven of 166 patients (16.3%) in the safety analysis experienced adverse events and 26/166 patients (15.7%) experienced adverse events, for which a relationship to Duotrav could not be ruled out. Adverse events in five patients led to treatment discontinuation (eye pruritus; eye irritation; increased blood pressure and rash; increased blurred vision; deepening of the eyelid sulcus and blepharoptosis). Twelve weeks after treatment switching, eyelash changes, blepharal pigmentation and deepening of the eyelid sulcus occurred in 42 (26.8%), 29 (18.5%), and 13 (8.3%) cases, respectively, among 157 patients with follow-up. There was no significant worsening from baseline for superficial punctate keratopathy (SPK) or conjunctival hyperemia after switching (SPK score: baseline = 0.58 ± 1.31; 12 weeks = 0.92 ± 1.76, P = 0.1819; conjunctival hyperemia score: baseline = 0.41 ± 0.64; 12 weeks = 0.49 ± 0.63, P = 0.3774). Conclusion: Our findings confirm that switching to Duotrav® in PGA monotherapy patients shows IOP-lowering effect with minimal safety concerns. Funding: Japan Association of Health Service and Alcon Japan. Ltd. Trial registration: UMIN Clinical Trials Registry identifier, UMIN000007028. © 2015, The Author(s). Source

Takehana Y.,Japan National Institute for Basic Biology | Takehana Y.,Graduate University for Advanced Studies | Matsuda M.,Utsunomiya University | Myosho T.,Niigata University | And 16 more authors.
Nature Communications

Sex chromosomes harbour a primary sex-determining signal that triggers sexual development of the organism. However, diverse sex chromosome systems have been evolved in vertebrates. Here we use positional cloning to identify the sex-determining locus of a medaka-related fish, Oryzias dancena, and find that the locus on the Y chromosome contains a cis-regulatory element that upregulates neighbouring Sox3 expression in developing gonad. Sex-reversed phenotypes in Sox3 Y transgenic fish, and Sox3 Y loss-of-function mutants all point to its critical role in sex determination. Furthermore, we demonstrate that Sox3 initiates testicular differentiation by upregulating expression of downstream Gsdf, which is highly conserved in fish sex differentiation pathways. Our results not only provide strong evidence for the independent recruitment of Sox3 to male determination in distantly related vertebrates, but also provide direct evidence that a novel sex determination pathway has evolved through co-option of a transcriptional regulator potentially interacted with a conserved downstream component. © 2014 Macmillan Publishers Limited. All rights reserved. Source

Takahashi M.,Tokyo Medical and Dental University | Kamei Y.,Tokyo Medical and Dental University | Ehara T.,Tokyo Medical and Dental University | Ehara T.,Morinaga Milk Industry Co | And 5 more authors.
Biochemical and Biophysical Research Communications

DNA methylation is a key epigenetic contributor to gene regulation in mammals. We have recently found that in the mouse liver, the promoter region of glycerol-3-phosphate acyltransferase 1, a rate-limiting enzyme of de novo lipogenesis, is regulated by DNA methylation, which is mediated by Dnmt3b, an enzyme required for the initiation of de novo methylation. In this study, using primary cultures of mouse hepatocytes with adenoviral overexpression of Dnmt3b, we characterized Dnmt3b-dependent DNA methylation on a genome-wide basis. A genome-wide DNA methylation analysis, called microarray-based integrated analysis of methylation by isoschizomers, identified 108 genes with Dnmt3b dependent DNA methylation. In DNA expression array analysis, expression of some genes with Dnmt3b-dependent DNA methylation was suppressed. Studies with primary mouse hepatocytes overexpressing Dnmt3b or Dnmt3a revealed that many genes with Dnmt3b-dependent methylation are not methylated by Dnmt3a, whereas those methylated by Dnmt3a are mostly methylated by Dnmt3b. Bioinformatic analysis showed that the CANAGCTG and CCGGWNCSC (N denotes A, T, G, or C; W denotes A or T; and S denotes C or G) sequences are enriched in genes methylated by overexpression of Dnmt3b and Dnmt3a, respectively. We also observed a large number of genes with Dnmt3b-dependent DNA methylation in primary cultures of mouse hepatocytes with adenoviral overexpression of Dnmt3, suggesting that Dnmt3b is an important DNA methyltransferase in primary mouse hepatocytes, targets specific genes, and potentially plays a role in vivo. © 2013 Elsevier Inc. Source

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