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Islam Z.,Tokyo Institute of Technology | Kato A.,Tokyo Institute of Technology | Romero M.F.,Physiology and Biomedical Engineering | Romero M.F.,Rochester College | Hirose S.,Tokyo Institute of Technology
American Journal of Physiology - Regulatory Integrative and Comparative Physiology | Year: 2011

Seawater (SW) contains ~10 mM Ca 2+, yet marine fish must drink seawater as their major water source. Thus marine teleosts fish need to excrete Ca 2+ to maintain whole body Ca 2+ homeostasis. In the intestine, seawater Ca 2+ interreacts with epithelial-secreted HCO 3 - by the intestinal epithelium, and the resulting CaCO 3 precipitates, which is rectally excreted. Recently the transporters involved in intestinal HCO 3 - secretion were identified. Ca 2+ is also excreted by the kidney, but the protein(s) involved in renal Ca 2+ excretion have not been identified. Here we identified a candidate transporter by using SW pufferfish torafugu (Takifugu rubripes) and its closely related euryhaline species mefugu (Takifugu obscurus), which are becoming useful animal models for studying molecular mechanisms of seawater adaptation. RT-PCR analyses of Na +/Ca 2+ exchanger (NCX) family members in various torafugu tissues demonstrated that only NCX2a is highly expressed in the kidney. Renal expression of NCX2a was markedly elevated when mefugu were transferred from freshwater to seawater. In situ hybridization and immunohistochemical analyses indicated that NCX2a is expressed in the proximal tubule at the apical membrane. NCX2a, expressed in Xenopus oocytes, conferred [Ca 2+] out- and Na +-dependent currents. These results suggest that NCX2a mediates renal Ca 2+ secretion at the apical membrane of renal proximal tubules and has an important role in whole body Ca 2+ homeostasis of marine teleosts. © 2011 the American Physiological Society. Source


Sandberg K.,Center for the Study of Sex Differences in Health | Sandberg K.,Georgetown Howard Universities | Umans J.G.,Center for the Study of Sex Differences in Health | Umans J.G.,Georgetown University | And 23 more authors.
FASEB Journal | Year: 2015

The U.S. National Institutes of Health (NIH) announced last May that steps will be taken to address the over-reliance on male cells and animals in preclinical research. To further address this announcement, in September 2014, scientists with varying perspectives came together at Georgetown University to discuss the following questions. (1) What metrics should the NIH use to assess tangible progress on policy changes designed to address the over-reliance on male cells and animals in preclinical research? (2) How effective can education be in reducing the over-reliance on male cells and animals in preclinical research and what educational initiatives sponsored by the NIH would most likely effect change? (3) What criteria should the NIH use to determine rigorously defined exceptions to the future proposal requirement of a balance of male and female cells and animals in preclinical studies? (4) What additional strategies in addition to proposal requirements should NIH use to reduce the overreliance of male cells and animals in preclinical research? The resulting consensus presented herein includes input from researchers not only from diverse disciplines of basic and translational science including biology, cell and molecular biology, biochemistry, physiology, pharmacology, neuroscience, cardiology, endocrinology, nephrology, psychiatry, and obstetrics and gynecology, but also from recognized experts in publishing, industry, advocacy, science policy, clinical medicine, and population health. We offer our recommendations to aid the NIH as it selects, implements, monitors, and optimizes strategies to correct the over-reliance on male cells and animals in preclinical research. © FASEB. Source


Shepherd A.,Creighton University | Miller V.M.,Physiology and Biomedical Engineering | Hunter L.W.,Physiology and Biomedical Engineering | Jayachandran M.,Physiology and Biomedical Engineering | And 2 more authors.
New Mathematics and Natural Computation | Year: 2014

Carotid intima-medial thickness (CIMT) allows for early detection of carotid atherosclerotic vascular disease. Using fuzzy logic techniques, we propose a model for calculating the risk for predicting CIMT using expert opinion and various factors associated with CIMT in recently menopausal women. Study participants were enrolled in the Kronos Early Estrogen Prevention Study (KEEPS), a four year study where participants were assigned to either oral or transdermal hormone therapy or to the placebo group. The fuzzy mathematical model uses five fuzzy logic methods to calculate this risk factor for CIMT, including the analytic hierarchy process (AHP) method, Guiasu method, Yen method, Dempster-Shafer (DS) method, and the set valued statistical method (SVSM). The four methods, AHP, Guiasu, Yen, DS, and SVSM, were correlated to each other according to the Pearson ranking method. In addition, results showed that the estrogen treatment groups showed a statically significant decrease in calculated CIMT risk compared to placebo when all the methods were combined together (p = 0.0017). Our fuzzy mathematical model provides the first fuzzy mathematical model to predict the risk of CIMT in recently menopausal women and menopausal hormone therapy may be beneficial in reducing this risk. © 2014 World Scientific Publishing Company. Source


Song P.,Mayo Medical School | Mellema D.C.,Physiology and Biomedical Engineering | Sheedy S.P.,Mayo Medical School | Meixner D.D.,Mayo Medical School | And 7 more authors.
Journal of Ultrasound in Medicine | Year: 2016

Objectives-To investigate the correlation between 2-dimensional (2D) ultrasound shear wave elastography (SWE) and magnetic resonance elastography (MRE) in liver stiffness measurement and the diagnostic performance of 2D SWE for liver fibrosis when imaging from different intercostal spaces and using MRE as the reference standard. Methods-Two-dimensional SWE was performed on 47 patients. One patient was excluded from the study. Each of the remaining 46 patients underwent same-day MRE for clinical purposes. The study was compliant with the Health Insurance Portability and Accountability Act and approved by the Institutional Review Board. Informed consent was obtained from each patient. Two-dimensional SWE measurements were acquired from the ninth, eighth, and seventh intercostal spaces. The correlation with MRE was calculated at each intercostal space and multiple intercostal spaces combined. The performance of 2D SWE in diagnosing liver fibrosis was evaluated by receiver operating characteristic curve analysis using MRE as the standard. Results-The 47 patients who initially underwent 2D SWE included 22 female and 25 male patients (age range, 19-77 years). The highest correlation between 2D SWE and MRE was from the eighth and seventh intercostal spaces (r = 0.68-0.76). The ranges of the areas under the receiver operating characteristic curves for separating normal or inflamed livers from fibrotic livers using MRE as the clinical reference were 0.84 to 0.92 when using the eighth and seventh intercostal spaces individually and 0.89 to 0.90 when combined. Conclusions-The results suggest that 2D SWE and MRE are well correlated when SWE is performed at the eighth and seventh intercostal spaces. The ninth intercostal space is less reliable for diagnosing fibrosis with 2D SWE. Combining measurements from multiple intercostal spaces does not significantly improve the performance of 2D SWE for detection of fibrosis. © 2016 by the American Institute of Ultrasound in Medicine. Source


Wang X.,Mayo Clinic 200 1st Street SW | Lieske J.C.,Mayo Clinic 200 1st Street SW | Jayachandran M.,Physiology and Biomedical Engineering | Denic A.,Mayo Clinic 200 1st Street SW | And 6 more authors.
American Journal of Nephrology | Year: 2016

Background: Non-invasive biomarkers that detect occult pathology in patients with normal glomerular filtration rate (GFR) and normal urine albumin excretion may help identify patients at risk for chronic kidney diseases. Methods: Two promising biomarkers of interstitial fibrosis, urinary monocyte chemoattractant protein 1 (MCP-1) and collagen IV, were assayed among 634 living kidney donors from 2005 to 2011, who had both a frozen pre-donation spot urine sample and a core needle biopsy of their donated kidney at transplantation (time zero biopsy'). The association of urine MCP- 1 and collagen IV with kidney function (GFR and urine albumin excretion), kidney volume on computed tomographic imaging and histological findings was assessed. Results: The mean SD age was 45 12 years, 24-hour urine albumin was 4 ± 7 mg and measured GFR (mGFR) was 102 ± 18 ml/ min/1.73 m 2 . The median (25th-75th percentile) urine level of MCP-1 was 146 (54-258) pg/ml and of collagen IV was 2.0 (1.0-3.5) ?g/l. Higher urine MCP-1 associated with higher 24- hour urine albumin excretion; higher urine collagen IV asso- ciated with male gender. On kidney biopsy, any interstitial fibrosis was present in 22% and fibrosis >5% in 4% of donors. The mean MCP-1/Cr ratio was 1.49 pg/mg for 0% fibrosis, 1.80 pg/mg for 1-5% fibrosis, 2.33 pg/mg for 6-10% fibrosis and 4.33 pg/mg for >10% fibrosis. After adjustment for age, sex, mGFR and 24-hour urine albumin, higher urine MCP-1 but not collagen IV associated with interstitial fibrosis and tubular atrophy. Conclusion: Urine MCP-1 may detect early tubulointerstitial fibrosis in adults with normal kidney function. © 2016 S. Karger AG, Basel. Source

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