Nishimoto K.,University of Michigan |
Nishimoto K.,Tachikawa Hospital |
Harris R.B.S.,Georgia Regents University |
Rainey W.E.,University of Michigan |
Seki T.,Georgia Regents University
Endocrinology | Year: 2014
Aldosterone is the primary adrenocortical hormone regulating sodium retention, and its production is under the control of the renin-angiotensin- aldosterone system (RAAS). In vitro, angiotensin II can induce aldosterone production in adrenocortical cells without causing cell proliferation. In vivo, a low-sodium diet activates the RAAS and aldosterone production, at least in part, through an expansion of the adrenal zona glomerulosa (zG) layer. Although these mechanisms have been investigated, RAAS effects on zG gene expression have not been fully elucidated. In this study, we took an unbiased approach to define the complete list of zG transcripts involved in RAAS activation. Adrenal glands were collected from 11-week old Sprague-Dawley rats fed either sodium-deficient (SDef), normal sodium (NS), or high-sodium (HS) diet for 72 hours, and laser-captured zG RNA was analyzed on microarrays containing 27 342 probe sets. When the SDef transcriptome was compared with NS transcriptome (SDef/NS comparison), only 79 and 10 probe sets were found to be up- and down-regulated more than two-fold in SDef, respectively. In SDef/HS comparison, 201 and 68 probe sets were up- and down-regulated in SDef, respectively. Upon gene ontology (GO) analysis of these gene sets, we identified three groups of functionally related GO terms: cell proliferation-associated (group 1), response to stimulus-associated (group 2), and cholesterol/steroid metabolism-associated (group 3) GO terms. Although genes in group 1 may play a critical role in zG layer expansion, those in groups 2 and 3 may have important functions in aldosterone production, and further investigations on these genes are warranted. Copyright © 2014 by the Endocrine Society.
Nishimoto K.,Georgia Regents University |
Nishimoto K.,Tachikawa Hospital |
Nishimoto K.,University of Michigan |
Rainey W.E.,Georgia Regents University |
And 4 more authors.
Molecular and Cellular Endocrinology | Year: 2013
We recently identified hundreds of transcripts with differential expression in rat zona glomerulosa (zG) and zona fasciculata. Although the genes up-regulated in the zG may be playing important roles in aldosterone production, the relationship between most of these genes and aldosterone production has not been uncovered. Because aldosterone, in the presence of a high sodium diet, is now considered a significant cardiovascular risk factor, in this review we performed gene ontology and pathway analyses on the same microarray data to better define the genes that may influence zG function. Overall, we identified a number of genes that may be involved in aldosterone production through transforming growth factor β (TGF-β), WNT, calcium, potassium, and ACTH signaling pathways. The list of genes we present in the current report may become an important tool for researchers working on primary aldosteronism and aldosterone-related cardiovascular diseases. © 2012 Elsevier Ireland Ltd.
Aizawa Y.,Keio University |
Takatsuki S.,Keio University |
Sano M.,Keio University |
Kimura T.,Keio University |
And 12 more authors.
Circulation | Year: 2013
BACKGROUND-: The characteristic ECG of Brugada syndrome (BS) can be masked by complete right bundle-branch block (CRBBB) and exposed by resolution of the block or pharmacological or pacing maneuvers. METHODS AND RESULTS-: The study consisted of 11 patients who had BS and CRBBB. BS was diagnosed before the development of CRBBB, on the resolution of CRBBB, or from new characteristic ST-segment changes that could be attributable to BS. Structural heart diseases were excluded, and coronary spasm was excluded on the basis of a provocation test at catheterization. In 7 patients, BS was diagnosed before the development of CRBBB. BS was diagnosed when CRBBB resolved spontaneously (n=1) or by right ventricular pacing (n=3). The precipitating cause for the spontaneous resolution of CRBBB, however, was not apparent. On repeated ECGs, new additional upward-convex ST-segment elevation was found in V2 or V3 in 3 patients. In 2 patients, new ST-segment elevation was induced by class IC drugs. The QRS duration was more prolonged in patients with BS and CRBBB compared with age-and sex-matched controls: 170±13 versus 145±15 milliseconds in V1 and 144±19 versus 128±7 milliseconds in V5 (both P<0.0001). The amplitude of R in V1 was larger in the BS patients than in the control subjects (P=0.0323), but that of R′ was similar (P=0.0560). CONCLUSIONS-: BS can coexist behind CRBBB, and CRBBB can completely mask BS. BS might be demonstrated by relief of CRBBB or by spontaneous or drug-induced ST-segment elevation. The prevalence, mechanism, and clinical significance of a combination of CRBBB and BS are yet to be determined. © 2013 American Heart Association, Inc.
Lancaster E.,University of Pennsylvania |
Lai M.,University of Pennsylvania |
Peng X.,University of Pennsylvania |
Hughes E.,University of Pennsylvania |
And 12 more authors.
The Lancet Neurology | Year: 2010
Background: Some encephalitides or seizure disorders once thought idiopathic now seem to be immune mediated. We aimed to describe the clinical features of one such disorder and to identify the autoantigen involved. Methods: 15 patients who were suspected to have paraneoplastic or immune-mediated limbic encephalitis were clinically assessed. Confocal microscopy, immunoprecipitation, and mass spectrometry were used to characterise the autoantigen. An assay of HEK293 cells transfected with rodent GABAB1 or GABAB2 receptor subunits was used as a serological test. 91 patients with encephalitis suspected to be paraneoplastic or immune mediated and 13 individuals with syndromes associated with antibodies to glutamic acid decarboxylase 65 were used as controls. Findings: All patients presented with early or prominent seizures; other symptoms, MRI, and electroencephalography findings were consistent with predominant limbic dysfunction. All patients had antibodies (mainly IgG1) against a neuronal cell-surface antigen; in three patients antibodies were detected only in CSF. Immunoprecipitation and mass spectrometry showed that the antibodies recognise the B1 subunit of the GABAB receptor, an inhibitory receptor that has been associated with seizures and memory dysfunction when disrupted. Confocal microscopy showed colocalisation of the antibody with GABAB receptors. Seven of 15 patients had tumours, five of which were small-cell lung cancer, and seven patients had non-neuronal autoantibodies. Although nine of ten patients who received immunotherapy and cancer treatment (when a tumour was found) showed neurological improvement, none of the four patients who were not similarly treated improved (p=0·005). Low levels of GABAB1 receptor antibodies were identified in two of 104 controls (p<0·0001). Interpretation: GABAB receptor autoimmune encephalitis is a potentially treatable disorder characterised by seizures and, in some patients, associated with small-cell lung cancer and with other autoantibodies. Funding: National Institutes of Health. © 2010 Elsevier Ltd. All rights reserved.
Hirota S.,Ueki Hospital |
Sadanaga T.,Ueki Hospital |
Sadanaga T.,Keio University |
Mitamura H.,Tachikawa Hospital |
Fukuda K.,Keio University
Hypertension Research | Year: 2013
The purpose of this study was to evaluate long-term compliance with salt restriction in Japanese cardiology outpatients assessed by spot urine measurements. A total of 466 patients (72±10 years old, 216 females) who visited a cardiology outpatient clinic and were followed for at least 1 year were included in this study. Daily dietary salt intake was estimated based on the sodium and creatinine concentrations determined by spot urine at the time of enrollment, during an 8-26 week follow-up and at a long-term follow-up (>1 year). The average follow-up duration was 2.2±0.6 (1.0-3.4) years after enrollment, and spot urines were collected 5.2±2.8 times after 1 year. The baseline estimated salt excretion was 9.6±2.7 g per day, which was reduced to 8.7±2.3 g per day (P<0.01) at 8-26 weeks and remained unchanged at the long-term follow-up (8.9±2.0 g per day, P=0.36 vs. 8-26 weeks, P<0.01 vs. baseline). The percent of patients who achieved an average salt excretion<6.0 g per day was unchanged from baseline (6.9% vs. 7.7%, P=0.61). Among several variables (gender, age, body weight, salt excretion at enrollment) that might affect the incidence of salt excretion <6.0 g per day, salt excretion at baseline was the only determinant of successful salt restriction (P<0.01). In conclusion, compliance with salt restriction, assessed using a spot urine method, was maintained over the long term; however, achieving salt reduction to the level recommended by the guidelines remains a challenge. © 2013 The Japanese Society of Hypertension All rights reserved.
Koyama T.,Tachikawa Hospital |
Niikura H.,Ota Memorial Hospital |
Shibata M.,Tachikawa Hospital |
Moritani K.,Tachikawa Hospital |
And 4 more authors.
IJC Metabolic and Endocrine | Year: 2014
Background: Excessive early inflammation after myocardial infarction (MI) is associated with poor outcomes. However, an approach for suppressing this early inflammation has not been reported. We previously reported that postconditioning with lactate-enriched blood (PCLeB) induced excellent microcirculation recovery in patients with acute MI. We therefore tested the hypothesis that early inflammation after MI could be suppressed by PCLeB. Methods and results: We treated 17 consecutive patients with ST-elevation MI using primary percutaneous intervention with our modified postconditioning protocol within 12. h of onset. In this protocol, the duration of each brief reperfusion was prolonged from 10 to 60. s in a stepwise manner. Lactated Ringer's solution (20-30. mL) was injected directly into the culprit coronary artery at the end of each brief reperfusion, and the balloon was quickly inflated at the site of the lesion to trap lactate within the ischemic myocardium. Each brief ischemic period lasted 60. s. After 7. cycles of balloon inflation and deflation, full reperfusion was performed; subsequently, stenting was performed. C-reactive protein (CRP) levels were measured daily and the peak values within the first 7. days post-admission were recorded. Peak CRP values were compared with those in matched control patients with acute MI treated without postconditioning. In both groups, only patients with CRP values <. 0.3. mg/dL on admission were included. Peak CRP values were significantly lower in the postconditioned group (control group vs. postconditioned group, 5.05. ±. 4.85 vs. 1.66. ±. 1.57. mg/dL; p. <. 0.01). Conclusion: PCLeB may suppress early inflammation after MI. © 2014 The Authors.
Ohta K.,Tachikawa Hospital |
Osada T.,Tachikawa Hospital
Clinical Neuropharmacology | Year: 2015
Objectives: To assess quantitatively the influence of rotigotine transdermal patch on daytime sleepiness, the most common adverse event by nonergot dopamine agonists (DAs), in Parkinson disease (PD) patients. Methods: An open-label study enrolled PD patients with unsatisfactory control of motor symptoms. Treatment with rotigotine transdermal patch was titrated to optimal dose (4-8 mg/24 hours) over 2 to 4 weeks. Primary outcome was Epworth Sleepiness Scale (ESS) for daytime sleepiness. Secondary outcomes included Hoehn&Yahr stage, time spent with dyskinesia, Clinical Global Impression of Improvement (CGI-I) of motor symptoms, adverse events, and compliance. Results: The subjects were 31 PD patients (age 72 ± 8, Hoehn &Yahr stage 2.7 ± 0.9,mean ± SD). The ESS did not increase after rotigotine treatment (7.2 ± 4.9 before treatment, 6.2 ± 4.0with 4mg/24 hour, and 8.1 ± 6.4 with 8 mg/24 hour). The CGI-I score improved after treatment; responder rate reached 88.9% with 8 mg/24 hours. No patients showed worsening in other secondary outcomes. In 13 patients treated with equivalent doses of rotigotine switched from other DAs (pramipexole, ropinirole, and cabergoline), ESS did not increase after treatment (10.0 ± 4.6 before and 8.6 ± 4.5 after treatment) and decreased without worsening of CGI-I in 54% patients. Other secondary outcomes did not worsen after treatment. Conclusions: Twenty four-hour transdermal delivery of rotigotine at doses up to 8 mg/24 hours does not worsen the daytime sleepiness in PD patients and often improves it when switched from other non-ergot DAs. This is achieved together with satisfactory improvement in motor symptoms, demonstrating that this new modality of non-ergot DA is well tolerated and beneficial in PD patients. © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Nishimoto K.,University of Georgia |
Nishimoto K.,Tachikawa Hospital |
Rigsby C.S.,University of Georgia |
Rigsby C.S.,Macon State College |
And 5 more authors.
Endocrinology | Year: 2012
In mammals, aldosterone is produced in the zona glomerulosa (zG), the outermost layer of the adrenal cortex, whereas glucocorticoids are produced in adjacent zona fasciculata (zF). However, the cellular mechanisms controlling the zonal development and the differential hormone production (i.e. functional zonation) are poorly understood. To explore the mechanisms, we defined zone-specific transcripts in this study. Eleven-week-old male rats were used and adrenal tissues were collected from zG and zF using laser-capture microdissection. RNA was isolated, biotin labeled, amplified, and hybridized to Illumina microarray chips. The microarray data were compared by fold change calculations. In zG, 235 transcripts showed more than a 2-fold up-regulation compared to zF with statistical significance. Similarly, 231 transcripts showed up-regulation in zF. The microarray findings were validated using quantitative RT-PCR and immunohistochemical staining on selected transcripts, including Cyp11b2 (zG/zF: 214.2x), Rgs4 (68.4x), Smoc2 (49.3x), and Mia1 (43.1x) in zG as well as Ddah1 (zF/zG 16.2x), Cidea (15.5x), Frzb (9.5x), and Hsd11b2 (8.3x) in zF. The lists of transcripts obtained in the current study will be an invaluable tool for the elucidation of cellular mechanisms leading to zG and zF functional zonation. Copyright © 2012 by The Endocrine Society.
Mitamura H.,Tachikawa Hospital
Clinical Neurology | Year: 2013
Mural thrombus due to blood stasis develops in the left atrium as atrial fibrillation (AF) persists longer. Characteristically, its development depends on the endothelial function of the atrium, and the prevention and control of each component of CHADS2 score are thus important. Treatment of hypertension is essential in the primary prevention of AF, but once AF develops, its suppression will be the next step to address and catheter ablation is a useful intervention for this purpose. If these efforts fail, anticoagulation therapy for those with a substantial risk is mandatory. After the duration of AF and the bleeding risk are carefully taken into account, new oral anticoagulants with the risk of cerebral bleeding much less than warfarin are indicated.
PubMed | Tachikawa Hospital, Niigata University, St Mother Hospital and Joetsu General Hospital
Type: Journal Article | Journal: The journal of obstetrics and gynaecology research | Year: 2016
The molecular pathogenesis of non-obstructive azoospermia (NOA) is unclear. Our aim was to identify the genetic susceptibility for NOA in Japanese men by using a combination of transcriptome network analysis and SNP genotyping.We searched for candidate genes using RNA transcriptome network analysis of 2611 NOA-related genes that we had previously reported. We analyzed candidate genes for disease linkage with single nucleotide polymorphisms (SNP) in the genomes of 335 Japanese men with NOA and 410 healthy controls using SNP-specific real-time polymerase chain reaction TaqMan assays.Three candidate genes (NR3C1, YBX2, and BCL2) were identified by the transcriptome network analysis, each with three SNP. Allele frequency analysis of the nine SNP indicated a significantly higher frequency of the NR3C1 rs852977 G allele in NOA cases compared with controls (corrected P = 5.7e-15; odds ratio = 3.20; 95% confidence interval, 2.40-4.26). The other eight candidate polymorphisms showed no significant association.The NR3C1 rs852977 polymorphism is a potential marker for genetic susceptibility to NOA in Japanese men. Further studies are necessary to clarify the association between the NR3C1 polymorphism and alterations of glucocorticoid signaling pathway leading to male infertility.