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Find video protocols related to scientific articles indexed in Pubmed.
Production of Water-Soluble Few-Layer Graphene Mesosheets by Dry Milling with Hydrophobic Drug.
Langmuir
PUBLISHED: 11-20-2014
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A novel, fast and easy mechano-chemistry-based (dry milling) method has been developed to exfoliate graphene with hydrophobic drugs generating few layer graphene mesosheets (< 10 nm in thickness and ~ 1 µm in width). The electronic properties of the graphitic structure were partially preserved after the milling treatment compared to Graphene Oxide (GO) prepared by Hummers' method. Several characterization techniques such as thermogravimetric analysis (TGA), Raman spectroscopy, atomic force microscopy (AFM), Electron Microscopy (EM) and molecular dynamics simulation were used to characterize this material. The drug-exfoliated mesosheets were pharmacologically inactive offering a new approach for making water-soluble few-layer graphene mesosheets upon dry milling with hydrophobic drugs, mainly used as exfoliating agents.
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Urinary neutrophil gelatinase-associated lipocalin and clinical outcomes in chronic kidney disease patients.
Clin. Chem. Lab. Med.
PUBLISHED: 08-07-2014
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Abstract Background: Tubulointerstitial damage is a final common pathway of most renal diseases. Whether urinary neutrophil gelatinase-associated lipocalin (uNGAL), a biomarker for renal tubular damage, is of prognostic value for clinical outcomes in chronic kidney disease (CKD) patients has not been well investigated. Methods: The uNGAL and proteinuria levels were measured among a cohort of 473 advanced CKD patients of various etiologies recruited during 2002-2009. Results: The estimated glomerular filtration rate (eGFR) was 32.3±22.0 mL/min/1.73 m2 with a urine protein-to-creatinine ratio (UPCR) 680 (255-1248) mg/g and 132 (27.9%) participants had diabetes. The baseline uNGAL level was significantly associated with male gender, eGFR, UPCR, and hemoglobin. The hazard ratio (HR) of the highest uNGAL tertile for end-stage renal disease (ESRD) was 3.44 (95% CI 1.47-8.06, p=0.004). With the adjustment of urine creatinine and urine protein, HR of the highest urine NGAL-to-creatinine ratio (UNCR) tertile and the highest urine NGAL-to-protein ratio (UNPR) tertile was 3.06 (95% CI 1.19-7.90, p=0.02) and 2.10 (95% CI 1.13-3.89, p=0.02), respectively. UNPR increased the prediction of survival model for ESRD. HR of the highest UNCR tertile and UNPR tertile for cardiovascular (CV) events was 2.21 (95% CI 0.81-5.98, p=0.08) and 2.79 (95% CI 1.25-6.26, p=0.01), respectively. None of these were associated with all-cause mortality. Conclusions: Elevated uNGAL in CKD patients is associated with risks for ESRD and probably CV events. UNPR could improve the prediction for ESRD.
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Tumor suppressor FOXO3 regulates ribonucleotide reductase subunit RRM2B and impacts on survival of cancer patients.
Oncotarget
PUBLISHED: 06-21-2014
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The role of Ribonucleotide reductase (RR) subunits in different cancers has been intensively studied in our laboratory. RRM2B was identified as a p53-inducible RR subunit that involves in various critical cellular mechanisms such as cell cycle regulation, DNA repair and replication, and mitochondrial homeostasis, etc. However, little is known about the p53-independent regulation of RRM2B in cancer pathology. In this study, we discovered tumor suppressor FOXO3 as the novel regulator of RRM2B. FOXO3 directly bound to and transcriptionally activated the promoter of RRM2B, and induced the expression of RRM2B at RNA and protein levels. Moreover, Overexpression of RRM2B and/or FOXO3 inhibited the proliferation of cancer cells. The cancer tissue microarray data also demonstrated a strong correlation between the co-expression of FOXO3 plus RRM2B and increased disease survival and reduced recurrence or metastasis in lung cancer patients. Our results suggest a novel regulatory control of RRM2B function, and imply the importance of FOXO signaling pathway in DNA replication modulation. This study provides the first time evidence that RRM2B is transcriptionally and functionally regulated independent of p53 pathway by FOXO3, and it establishes that FOXO3 and RRM2B could be used as predictive biomarkers for cancer progression.
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Reciprocal regulation of autophagy and dNTP pools in human cancer cells.
Autophagy
PUBLISHED: 05-16-2014
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Ribonucleotide reductase (RNR) plays a critical role in catalyzing the biosynthesis and maintaining the intracellular concentration of 4 deoxyribonucleoside triphosphates (dNTPs). Unbalanced or deficient dNTP pools cause serious genotoxic consequences. Autophagy is the process by which cytoplasmic constituents are degraded in lysosomes to maintain cellular homeostasis and bioenergetics. However, the role of autophagy in regulating dNTP pools is not well understood. Herein, we reported that starvation- or rapamycin-induced autophagy was accompanied by a decrease in RNR activity and dNTP pools in human cancer cells. Furthermore, downregulation of the small subunit of RNR (RRM2) by siRNA or treatment with the RNR inhibitor hydroxyurea substantially induced autophagy. Conversely, cancer cells with abundant endogenous intracellular dNTPs or treated with dNTP precursors were less responsive to autophagy induction by rapamycin, suggesting that autophagy and dNTP pool levels are regulated through a negative feedback loop. Lastly, treatment with si-RRM2 caused an increase in MAP1LC3B, ATG5, BECN1, and ATG12 transcript abundance in xenografted Tu212 tumors in vivo. Together, our results revealed a previously unrecognized reciprocal regulation between dNTP pools and autophagy in cancer cells.
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Phyllanthus urinaria induces mitochondrial dysfunction in human osteosarcoma 143B cells associated with modulation of mitochondrial fission/fusion proteins.
Mitochondrion
PUBLISHED: 04-14-2014
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Phyllanthus urinaria (P. urinaria), a widely used herbal medicine, has been reported to possess various biological characteristics including anti-inflammation, anti-virus, anti-bacteria, anti-hepatotoxicity and anti-cancer. This study provides molecular evidence associated with the dynamics and organization of mitochondria in osteosarcoma 143B cells resulted from P urinaria. Herein, P. urinaria-induced cytotoxicity and ROS associated with the inhibition of mitochondrial membrane potential were reversed by N-acetylcysteine (NAC). The endogenous antioxidant enzymes such as manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX1) were activated by P. urinaria, but not correlated to catalase. P. urinaria decreased mitochondrial respiration activity as well as respiratory chain enzymes and HIF-1? in osteosarcoma 143B cells. Additionally, both adenosine triphosphate (ATP) synthase activation and ATP production were suppressed by P. urinaria. We further investigated changes of mitochondrial dynamic in osteosarcoma 143B cells. P. urinaria indeed fragmented the mitochondrial network of osteosarcoma 143B cells. We found a significant decrease in optic atrophy type 1 (Opa1) and mitofusin 1 (Mfn1) related to fusion proteins as well as increase mitochondrial fission 1 protein (Fis1) related to fission protein. It indicated that P. urinaria modulated the mitochondrial dynamics via fusion and fission machinery. Altogether, this study offers the evidence that mitochondrial dysfunction with dynamic change is essential components for the anti-cancer mechanism elicited by P. urinaria.
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Celecoxib suppresses hepatoma stemness and progression by up-regulating PTEN.
Oncotarget
PUBLISHED: 04-12-2014
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Celecoxib, a COX-2 inhibitor and non-steroidal anti-inflammatory drug, can prevent several types of cancer, including hepatocellular carcinoma (HCC). Here we show that celecoxib suppressed the self-renewal and drug-pumping functions in HCC cells. Besides, celecoxib depleted CD44+/CD133+ hepatic cancer stem cells (hCSC). Prostaglandin E2 (PGE2) and CD133 overexpression did not reverse the celecoxib-induced depletion of hCSC. Also, celecoxib inhibited progression of rat Novikoff hepatoma. Moreover, a 60-day celecoxib program increased the survival rate of rats with hepatoma. Histological analysis revealed that celecoxib therapy reduced the abundance of CD44+/CD133+ hCSCs in hepatoma tissues. Besides, the hCSCs depletion was associated with elevated apoptosis and blunted proliferation and angiogenesis in hepatoma. Celecoxib therapy activated peroxisome proliferator-activated receptor ? (PPAR?) and up-regulated PTEN, thereby inhibiting Akt and disrupting hCSC expansion. PTEN gene delivery by adenovirus reduced CD44/CD133 expression in vitro and hepatoma formation in vivo. This study suggests that celecoxib suppresses cancer stemness and progression of HCC via activation of PPAR?/PTEN signaling.
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Functional connectivity between parietal cortex and the cardiac autonomic system in uremics.
Kaohsiung J. Med. Sci.
PUBLISHED: 03-04-2014
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Although the central autonomic network (CAN) has been well researched in animal models, the CAN in humans is still unclear, especially for cardiovascular control. This study aimed to investigate which areas of the cerebral cortices are associated with the peripheral cardiac autonomic control involved in the CAN in uremic patients with autonomic dysfunction and normal controls. The central and peripheral autonomic network in 19 uremic patients with significant autonomic dysfunction and 24 age- and sex-matched controls [mean age ± standard deviation (SD), 55.16 ± 10.45 years and 55.42 ± 5.42 years, respectively] were evaluated by simultaneous spectral analysis of electroencephalography (EEG) and electrocardiography recording (ECG), along with serial autonomic tests [autonomic questionnaire and orthostatic blood pressure (BP) change]. Only frequency-domain heart rate variability (f-HRV) during the deep-breathing stage could differentiate the two groups. Although there is no significant difference in f-HRV during the quiet-breathing stage, different patterns of central oscillation and their correlation with peripheral cardiac autonomic indices could be found for the two groups. Although the power of specific EEG bands under electrode T3 and T6 correlated significantly with the power of peripheral HRV indices in the control group, those under electrodes P3 and Pz had significant correlations in the uremic group suggesting a role of functional connectivity between them. In addition, sympathetic activity is correlated with slow wave EEG (theta/delta) power whereas parasympathetic activity is correlated with fast wave EEG (beta) power. In conclusion, there is functional connectivity between the parietal cortex and the peripheral cardiac autonomic system (PAN) in uremics and the pattern of central autonomic connectivity differs between uremic patients with autonomic dysfunction and normal controls.
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Fluid overload, pulse wave velocity, and ratio of brachial pre-ejection period to ejection time in diabetic and non-diabetic chronic kidney disease.
PLoS ONE
PUBLISHED: 01-01-2014
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Fluid overload is one of the characteristics in chronic kidney disease (CKD). Changes in extracellular fluid volume are associated with progression of diabetic nephropathy. Not only diabetes but also fluid overload is associated with cardiovascular risk factors The aim of the study was to assess the interaction between fluid overload, diabetes, and cardiovascular risk factors, including arterial stiffness and left ventricular function in 480 patients with stages 4-5 CKD. Fluid status was determined by bioimpedance spectroscopy method, Body Composition Monitor. Brachial-ankle pulse wave velocity (baPWV), as a good parameter of arterial stiffness, and brachial pre-ejection period (bPEP)/brachial ejection time (bET), correlated with impaired left ventricular function were measured by ankle-brachial index (ABI)-form device. Of all patients, 207 (43.9%) were diabetic and 240 (50%) had fluid overload. For non-diabetic CKD, fluid overload was associated with being female (??=?-2.87, P?=?0.003), heart disease (??=?2.69, P?=?0.04), high baPWV (??=?0.27, P?=?0.04), low hemoglobin (??=?-1.10, P<0.001), and low serum albumin (??=?-5.21, P<0.001) in multivariate analysis. For diabetic CKD, fluid overload was associated with diuretics use (??=?3.69, P?=?0.003), high mean arterial pressure (??=?0.14, P?=?0.01), low bPEP/ET (??=?-0.19, P?=?0.03), low hemoglobin (??=?-1.55, P?=?0.001), and low serum albumin (??=?-9.46, P<0.001). In conclusion, baPWV is associated with fluid overload in non-diabetic CKD and bPEP/bET is associated with fluid overload in diabetic CKD. Early and accurate assessment of these associated cardiovascular risk factors may improve the effects of entire care in late CKD.
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Association of angiopoietin-2 with renal outcome in chronic kidney disease.
PLoS ONE
PUBLISHED: 01-01-2014
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The pathophysiological mechanisms of renal function progression in chronic kidney disease (CKD) have still not been completely explored. In addition to well-known traditional risk factors, non-traditional risk factors, such as endothelial dysfunction, have gradually attracted physicians' attention. Angiopoietin-2 (Ang-2) impairs endothelial function through preventing angiopoietin-1 from binding to Tie2 receptor. Whether Ang-2 is associated with renal function progression in CKD is unknown.
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Modification of diet in renal disease (MDRD) study and CKD epidemiology collaboration (CKD-EPI) equations for Taiwanese adults.
PLoS ONE
PUBLISHED: 01-01-2014
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Estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) study or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations may not be accurate for Asians; thus, we developed modified eGFR equations for Taiwanese adults.
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Development of a human breast-cancer derived cell line stably expressing a bioluminescence resonance energy transfer (BRET)-based phosphatidyl inositol-3 phosphate (PIP3) biosensor.
PLoS ONE
PUBLISHED: 01-01-2014
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Stimulation of tyrosine kinase receptors initiates a signaling cascade that activates PI3K. Activated PI3K uses PIP2 to generate PIP3, which recruit Akt to the plasma membrane through its pleckstrin homology (PH) domain, permitting its activation by PDKs. Activated Akt controls important biological functions, including cell metabolism, proliferation and survival. The PI3K pathway is therefore an attractive target for drug discovery. However, current assays for measurement of PIP3 production are technically demanding and not amenable to high-throughput screening. We have established a MCF-7-derived breast cancer cell line, that stably co-expresses the PH domain of Akt fused to Renilla luciferase and YFP fused to a membrane localization signal. This BRET biosensor pair permits to monitor, in real time, in living cells, PIP3 production at the plasma membrane upon stimulation by different ligands, including insulin, the insulin analogue glargine, IGF1, IGF2 and EGF. Moreover, several known inhibitors that target different steps of the PI3K/Akt pathway caused inhibition of ligand-induced BRET. Cetuximab, a humanized anti-EGF receptor monoclonal antibody used for the treatment of cancer, completely inhibited EGF-induced BRET, and the tyrosine kinase inhibitor tyrphostine AG1024 inhibited insulin effect on PIP3 production. Moreover, the effects of insulin and IGF1 were inhibited by molecules that inhibit PI3K catalytic activity or the interaction between PIP3 and the PH domain of Akt. Finally, we showed that human serum induced a dose-dependent increase in BRET signal, suggesting that this stable clone may be used as a prognostic tool to evaluate the PI3K stimulatory activity present in serum of human patients. We have thus established a cell line, suitable for the screening and/or the study of molecules with stimulatory or inhibitory activities on the PI3K/Akt pathway that will constitute a new tool for translational research in diabetes and cancer.
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O-GlcNAcylation of FoxO1 in pancreatic ? cells promotes Akt inhibition through an IGFBP1-mediated autocrine mechanism.
FASEB J.
PUBLISHED: 10-30-2013
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O-GlcNAcylation on serine/threonine is a post-translational modification that controls the activity of nucleocytoplasmic proteins according to glucose availability. We previously showed that O-GlcNAcylation of FoxO1 in liver cells increases its transcriptional activity. In the present study, we evaluated the potential involvement of FoxO1 O-GlcNAcylation in the context of pancreatic ?-cell glucotoxicity. FoxO1 was O-GlcNAcylated in INS-1 832/13 ? cells and isolated rat pancreatic islets. O-GlcNAcylation of FoxO1 resulted in a 2-fold increase in its transcriptional activity toward a FoxO1 reporter gene and a 3-fold increase in the expression of the insulin-like growth factor-binding protein 1 (Igfbp1) gene at the mRNA level, resulting in IGFBP1 protein oversecretion by the cells. Of note, increased IGFBP1 in the culture medium inhibited the activity of the insulin-like growth factor 1 receptor (IGF1R)/phosphatidyl inositol 3 kinase (PI3K)/Akt pathway. We reveal in this report a novel mechanism by which O-GlcNAcylation inhibits Akt activity through an autocrine mechanism. However, although inhibition of IGFBP1 expression using siRNA restored the PI3 kinase/Akt pathway, it did not rescue INS-1 832/13 cells from high-glucose- or O-glcNAcylation-induced cell death. In contrast, FoxO1 down-regulation by siRNA led to 30 to 60% protection of INS-1 832/13 cells from death mediated by glucotoxic conditions. Therefore, whereas FoxO1 O-GlcNAcylation inhibits Akt through an IGFBP1-mediated autocrine pathway, the deleterious effects of FoxO1 O-GlcNAcylation on cell survival appeared to be independent of this pathway.-Fardini, Y., Masson, E., Boudah, O., Ben Jouira, R., Cosson, C., Pierre-Eugene, C., Kuo, M.-S., Issad, T. O-GlcNAcylation of FoxO1 in pancreatic ? cells promotes Akt inhibition through an IGFBP1-mediated autocrine mechanism.
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Effects of positioning on radiographic measurements of ankle morphology: a computerized tomography-based simulation study.
Biomed Eng Online
PUBLISHED: 09-13-2013
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Measurements of the morphology of the ankle joint, performed mostly for surgical planning of total ankle arthroplasty and for collecting data for total ankle prosthesis design, are often made on planar radiographs, and therefore can be very sensitive to the positioning of the joint during imaging. The current study aimed to compare ankle morphological measurements using CT-generated 2D images with gold standard values obtained from 3D CT data; to determine the sensitivity of the 2D measurements to mal-positioning of the ankle during imaging; and to quantify the repeatability of the 2D measurements under simulated positioning conditions involving random errors.
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Clinical Epidemiology of Reduced Kidney Function among Elderly Male Fishing and Agricultural Population in Taipei, Taiwan.
Biomed Res Int
PUBLISHED: 08-30-2013
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Purpose. To quantify the prevalence of and associated factors for chronic kidney disease (CKD) among male elderly fishing and agricultural population in Taipei, Taiwan. Methods. Subjects (n = 2,766) aged 65 years and over voluntarily admitted to a teaching hospital for a physical checkup were collected in 2010. CKD was defined as an estimated glomerular filtration rate <60?mL/min/1.73?m(2). Results. Among these subjects, the over prevalence of chronic kidney disease was 13.6% (95% CI: 12.3-14.9%). The age-specific prevalence of CKD in 65-74 years, 75-84 years, and ?85 years was 8.2%, 19.1%, and 27.0%, respectively. From the multiple logistic regression, age (OR = 1.05, 95% CI: 1.02-1.09), hyperuricemia (OR = 2.94, 95% CI: 1.90-3.78), central obesity (OR = 1.17, 95% CI: 1.02-1.56), hyperglycemia (OR = 1.23, 95% CI: 1.11-1.67), hypertriglyceridemia (OR = 1.25, 95% CI: 1.08-1.66), and lower HDL-C (OR = 1.61, 95% CI: 1.23-1.92) were statistically significantly related to CKD. The presence of metabolic components (one or two versus none, OR = 1.10, 95% CI: 1.04-1.25; three or more versus none, OR = 2.12, 95% CI: 1.86-2.78) also appeared to be statistically significantly related to CKD after adjustment for other independent factors. Conclusion. Several clinical factors independently affect the development of CKD in the elderly male fishing and agricultural population.
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Multiple hypovascular tumors in kidney: a rare case report and differential diagnosis.
Case Rep Med
PUBLISHED: 08-28-2013
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The most common malignant renal tumor is renal cell carcinoma and surgery is the standard treatment. The proportion of lymphoma with renal involvement is 2~15% and lymphoma could be cured by chemotherapy without nephrectomy. Sonography, computed tomography (CT), and magnetic resonance imaging (MRI) can detect and characterize a renal mass. We present a case of right renal hypovascular tumors and differential diagnosis of hypovascular tumors by image study. CT scan showed hypovascular tumors and MRI image revealed multifocal hypovascular solid tumors with significantly increased apparent diffusion coefficient (ADC) of diffusion weighted imaging (DWI). Based on image finding, renal lymphoma was highly suspected. Renal lymphoma was confirmed by renal biopsy and this patient received chemotherapy without surgery. The noninvasive CT scan and MRI image can help clinicians to diagnose the characteristics of renal mass and to avoid unnecessary nephrectomy.
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Impact of Navigation on Knowledge and Attitudes About Clinical Trials Among Chinese Patients Undergoing Treatment for Breast and Gynecologic Cancers.
J Immigr Minor Health
PUBLISHED: 08-22-2013
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Racial, ethnic and economic disparities in cancer rates, outcomes, and clinical trials participation persist despite significant research. We examined barriers to clinical trials enrollment among Chinese patients, and developed a navigation program for Chinese gynecologic and breast cancer patients. Six bilingual navigators were trained and a navigator assigned to each patient for at least 2 months. All patients received a clinical trials booklet in Chinese and English. Data collection included pre-and post-navigation surveys, intake forms, and documentation of navigation encounters. Between July 2010 and May 31, 2011, we recruited 28 breast and gynecologic cancer patients. Patients averaged 317 min of navigation (range 63-1,852) during 8 sessions (range 3-28). They improved in 4 of 10 true-false knowledge statements about clinical trials. A patient navigation program for Chinese-speaking cancer patients is feasible. It results in high patient satisfaction rates and modest improvements in clinical trials knowledge and participation.
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Association of cholesterol levels with mortality and cardiovascular events among patients with CKD and different amounts of proteinuria.
Clin J Am Soc Nephrol
PUBLISHED: 08-08-2013
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Malnutrition and/or inflammation may modify the risk relationship of total cholesterol with cardiovascular disease in CKD patients. However, it is unclear whether the relationship of total cholesterol with cardiovascular events and mortality varies by proteinuria.
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Profile of elderly with multiple physician visits: Advocacy for tailored comprehensive geriatric assessment use in clinics.
Geriatr Gerontol Int
PUBLISHED: 05-21-2013
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The rapid growth of the elderly population has given rise to the need for better geriatric care. The present study explored the common conditions of elderly outpatients with multiple physician visits in order to develop feasible clinical indicators that can be rapidly administered for the evaluation of geriatric syndromes in outpatient settings.
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Three-dimensional computer graphics-based ankle morphometry with computerized tomography for total ankle replacement design and positioning.
Clin Anat
PUBLISHED: 04-05-2013
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Morphometry of the bones of the ankle joint is important for the design of joint replacements and their surgical implantations. However, very little three-dimensional (3D) data are available and not a single study has addressed the Chinese population. Fifty-eight fresh frozen Chinese cadaveric ankle specimens, 26 females, and 32 males, were CT-scanned in the neutral position and their 3D computer graphics-based models were reconstructed. The 3D morphology of the distal tibia/fibula segment and the full talus was analyzed by measuring 31 parameters, defining the relevant dimensions, areas, and volumes from the models. The measurements were compared statistically between sexes and with previously reported data from Caucasian subjects. The results showed that, within a general similarity of ankle morphology between the current Chinese and previous Caucasian subjects groups, there were significant differences in 9 out of the 31 parameters analyzed. From a quantitative comparison with available prostheses designed for the Caucasian population, few of these designs have both tibial and talar components suitable in dimension for the Chinese population. The current data will be helpful for the sizing, design, and surgical positioning of ankle replacements and for surgical instruments, especially for the Chinese population. Clin. Anat., 2013. © 2013 Wiley Periodicals, Inc.
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Prevalence of and associated factors with chronic kidney disease in human immunodeficiency virus-infected patients in Taiwan.
J Microbiol Immunol Infect
PUBLISHED: 04-03-2013
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Chronic kidney disease (CKD) is an important issue for individuals who live with human immunodeficiency virus (HIV) following the use of highly active antiretroviral therapy; however, the prevalence rate of CKD varies between countries.
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A novel method for analyzing genetic association with longitudinal phenotypes.
Stat Appl Genet Mol Biol
PUBLISHED: 03-19-2013
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Knowledge of genes influencing longitudinal patterns may offer information about predicting disease progression. We developed a systematic procedure for testing association between SNP genotypes and longitudinal phenotypes. We evaluated false positive rates and statistical power to localize genes for disease progression. We used genome-wide SNP data from the Framingham Heart Study. With longitudinal data from two real studies unrelated to Framingham, we estimated three trajectory curves from each study. We performed simulations by randomly selecting 500 individuals. In each simulation replicate, we assigned each individual to one of the three trajectory groups based on the underlying hypothesis (null or alternative), and generated corresponding longitudinal data. Individual Bayesian posterior probabilities (BPPs) for belonging to a specific trajectory curve were estimated. These BPPs were treated as a quantitative trait and tested (using the Wald test) for genome-wide association. Empirical false positive rates and power were calculated. Our method maintained the expected false positive rate for all simulation models. Also, our method achieved high empirical power for most simulations. Our work presents a method for disease progression gene mapping. This method is potentially clinically significant as it may allow doctors to predict disease progression based on genotype and determine treatment accordingly.
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Association of Fluid Overload With Kidney Disease Progression in Advanced CKD: A Prospective Cohort Study.
Am. J. Kidney Dis.
PUBLISHED: 03-13-2013
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Fluid overload is a common phenomenon in patients in a late stage of chronic kidney disease (CKD). However, little is known about whether fluid overload is related to kidney disease progression in patients with CKD. Accordingly, the aim of the study was to assess the association of the severity of fluid status and kidney disease progression in an advanced CKD cohort.
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Terlipressin-induced hyponatremic encephalopathy in a noncirrhotic patient.
Kaohsiung J. Med. Sci.
PUBLISHED: 03-04-2013
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Terlipressin, an analogue of vasopressin, is frequently used for the management of esophageal varices bleeding and hepatorenal syndrome. Terlipressin therapy in portal hypertensive patients is frequently associated with hyponatremia, but is rarely accompanied with serious neurological manifestations. A 39-year-old female with pancreatic neuroendocrine tumor, liver metastasis, main portal vein thrombosis, and a history of esophageal varices presented to the emergency room because of hematemesis. Terlipressin was given with a loading dose of 2 mg followed by 1 mg every 6 hours. After a total of 6 mg terlipressin injection, she suffered from acute delirium. Pertinent examinations showed there was no gross brain lesion by computed tomography, whereas her serum sodium level dropped from baseline (136 mmol/L) to 116 mmol/L with a serum osmolality of 256 mOsm/kg. At that time, urine sodium and urine osmolality were 142 mmol/L and 488 mOsm/kg, respectively. Under the tentative diagnosis of terlipressin-induced hyponatremic encephalopathy, terlipressin was withheld and hypertonic saline infusion was given. Within 12 hours, her serum sodium level recovered to 130 mmol/L and she gradually regained her cognitive functions. Although symptomatic hyponatremic encephalopathy is a rare complication of terlipressin treatment, close monitoring of serum electrolyte level is warranted in patients receiving terlipressin.
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Effect of warming with temperature oscillations on a low-latitude aphid, Aphis craccivora.
Bull. Entomol. Res.
PUBLISHED: 03-01-2013
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To estimate the net effect of climate change on natural populations, we must take into account the positive and negative effects of temperature oscillations and climate variability. Warming because of climate change will likely exceed the physiological optima of tropical insects, which currently live very close to their thermal optima. Tropical insects will be negatively affected if their optima are exceeded otherwise warming may affect them positively. We evaluate the demographic responses of the cowpea aphid, Aphis craccivora, to summer warming in subtropical and tropical Taiwan, and examine the effects of diel temperature oscillation on these responses. Aphids were reared at four temperatures (current summer mean, +1.4, +3.9 and +6.4 °C), the latter three simulating different levels of warming. At each average temperature, aphids experienced constant or oscillating (from -2.9 to +3.6 °C of each mean temperature) regimes. As the simulated summer temperatures increased, so did the negative effects on life-history traits and demographic parameters. Compared with aphids reared in constant temperatures, aphids reared in oscillating temperatures developed more slowly and had a longer mean generation time, but their net reproductive rate was higher. These findings demonstrate that climate warming will affect demographic parameters and life-history traits differentially. Studies that use constant temperatures are unlikely to accurately predict biotic responses to climate change.
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Up-regulation of hepatoma-derived growth factor facilities tumor progression in malignant melanoma.
PLoS ONE
PUBLISHED: 02-12-2013
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Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF) is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200) showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn) expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16-F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma.
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Association of dyslipidemia with renal outcomes in chronic kidney disease.
PLoS ONE
PUBLISHED: 02-04-2013
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Dyslipidemia is highly prevalent in patients with chronic kidney disease (CKD) and the relationship between dyslipidemia with renal outcomes in patients with moderate to advanced CKD remains controversial. Hence, our objective is to determine whether dyslipidemia is independently associated with rapid renal progression and progression to renal replacement therapy (RRT) in CKD patients. The study analyzed the association between lipid profile, RRT, and rapid renal progression (estimated glomerular filtration rate [eGFR] slope <-6 ml/min/1.73 m(2)/yr) in 3303 patients with stages 3 to 5 CKD. During a median 2.8-year follow-up, 1080 (32.3%) participants commenced RRT and 841 (25.5%) had rapid renal progression. In the adjusted models, the lowest quintile (hazard ratios [HR], 1.23; 95% confidence interval [CI], 1.01 to 1.49) and the highest two quintiles of total cholesterol (HR, 1.25; 95% CI, 1.02 to 1.52 and HR, 1.35; 95% CI, 1.11 to 1.65 respectively) increased risks for RRT (vs. quintile 2). Besides, the highest quintile of total cholesterol was independently associated with rapid renal progression (odds ratio, 1.36; 95% CI, 1.01 to 1.83). Our study demonstrated that certain levels of dyslipidemia were independently associated with RRT and rapid renal progression in CKD stage 3-5. Assessment of lipid profile may help identify high risk groups with adverse renal outcomes.
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Cost-effectiveness analysis of carrier and prenatal genetic testing for X-linked hemophilia.
J. Formos. Med. Assoc.
PUBLISHED: 01-31-2013
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Hemophilia involves a lifelong burden from the perspective of the patient and the entire healthcare system. Advances in genetic testing provide valuable information to hemophilia-affected families for family planning. The aim of this study was to analyze the cost-effectiveness of carrier and prenatal genetic testing in the health-economic framework in Taiwan.
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Study of insulin resistance in cybrid cells harboring diabetes-susceptible and diabetes-protective mitochondrial haplogroups.
Mitochondrion
PUBLISHED: 01-27-2013
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This study aims to elucidate the independent role of mitochondria in the pathogenesis of insulin resistance (IR).
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Functional regulation of Alu element of human angiotensin-converting enzyme gene in neuron cells.
Neurobiol. Aging
PUBLISHED: 01-05-2013
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The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) genotype and its protein activity have been widely implicated to be associated with Alzheimers disease (AD). However, whether the insertion sequence, Alu element, in intron 16 of the human ACE gene plays a functional role remains uncertain. To investigate the influence of the I/D polymorphism on ACE promoter, we recombined the I and D form fragments with the human ACE promoter sequence before the reporter gene in pSEAP-Basic2 vector. The effect of the Alu element on regulating the transcriptional activity of ACE promoter was examined using transient transfection in SH-SY5Y cells. We found that the I form fragment upregulated the transcriptional activity of ACE promoter by approximately 70% but that the D form fragment did not. Our study first reveals that Alu sequence in human ACE gene possesses a regulatory function on the ACE promoter activity in neuron. This novel finding bridges the gap between the association of ACE I/D genotype with AD, and suggests that Alu sequence is not merely a "junk" DNA in human ACE gene.
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Is fluid overload more important than diabetes in renal progression in late chronic kidney disease?
PLoS ONE
PUBLISHED: 01-01-2013
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Fluid overload is one of the major presentations in patients with late stage chronic kidney disease (CKD). Diabetes is the leading cause of renal failure, and progression of diabetic nephropathy has been associated with changes in extracellular fluid volume. The aim of the study was to assess the association of fluid overload and diabetes in commencing dialysis and rapid renal function decline (the slope of estimated glomerular filtration rate (eGFR) less than -3 ml/min per 1.73 m(2)/y) in 472 patients with stages 4-5 CKD. Fluid status was determined by bioimpedance spectroscopy method, Body Composition Monitor. The study population was further classified into four groups according to the median of relative hydration status (?HS =fluid overload/extracellular water) and the presence or absence of diabetes. The median level of relative hydration status was 7%. Among all patients, 207(43.9 %) were diabetic. 71 (15.0%) subjects had commencing dialysis, and 187 (39.6%) subjects presented rapid renal function decline during a median 17.3-month follow-up. Patients with fluid overload had a significantly increased risk for commencing dialysis and renal function decline independent of the presence or absence of diabetes. No significantly increased risk for renal progression was found between diabetes and non-diabetes in late CKD without fluid overload. In conclusion, fluid overload has a higher predictive value of an elevated risk for renal progression than diabetes in late CKD.
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High cost and low survival rate in high comorbidity incident elderly hemodialysis patients.
PLoS ONE
PUBLISHED: 01-01-2013
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The comorbidity index is a predictor of mortality in dialysis patients but there are few reports for predicting elderly dialysis mortality and national population-based cost studies on elderly dialysis. The aim of this study was to evaluate the long-term mortality of incident elderly dialysis patients using the Deyo-Charlson comorbidity index (CCI) and to assess the inpatient and outpatient visits along with non-dialysis costs.
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Hypokalemia, its contributing factors and renal outcomes in patients with chronic kidney disease.
PLoS ONE
PUBLISHED: 01-01-2013
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In the chronic kidney disease (CKD) population, the impact of serum potassium (sK) on renal outcomes has been controversial. Moreover, the reasons for the potential prognostic value of hypokalemia have not been elucidated.
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Predicting mortality of incident dialysis patients in Taiwan--a longitudinal population-based study.
PLoS ONE
PUBLISHED: 01-01-2013
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Comorbid conditions are highly prevalent among patients with end-stage renal disease (ESRD) and index score is a predictor of mortality in dialysis patients. The aim of this study is to perform a population-based cohort study to investigate the survival rate by age and Charlson comorbidity index (CCI) in incident dialysis patients.
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Interaction between uric acid and HMGB1 translocation and release from endothelial cells.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 12-21-2011
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We aimed to investigate the potential relationship between alarmins [acting via Toll-like receptor-4 (TLR4)], uric acid (UA), and high-mobility group box-1 protein (HMGB1) during acute kidney injury. UA, which is significantly increased in the circulation following renal ischemia-reperfusion injury (IRI), was used both in vitro and in vivo as an early response-signaling molecule to determine its ability to induce the secretion of HMGB1 from endothelial cells. Treatment of human umbilical vein endothelial cells (HUVEC) with UA resulted in increased HMGB1 mRNA expression, acetylation of nuclear HMGB1, and its subsequent nuclear-cytoplasmic translocation and release into the circulation, as determined by Western blotting and immunofluorescence. Treatment of HUVEC with UA and a calcium mobilization inhibitor (TMB-8) or a MEK/Erk pathway inhibitor (U0126) prevented translocation of HMGB1 from the nucleus, resulting in reduced cytoplasmic and circulating levels of HMGB1. Once released, HMGB1 in autocrine fashion promoted further HMGB1 release while also stimulating NF-?B activity and increased angiopoietin-2 expression and protein release. Transfection of HUVEC with TLR4 small interfering (si) RNA reduced HMGB1 levels during UA and HMGB1 treatment. In summary, UA after IRI mediates the acetylation and release of HMGB1 from endothelial cells by mechanisms that involve calcium mobilization, the MEK/Erk pathway, and activation of TLR4. Once released, HMGB1 promotes its own further cellular release while acting as an autocrine and paracrine to activate both proinflammatory and proreparative mediators.
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Anuric acute renal failure after elective abortion.
Intern. Med.
PUBLISHED: 08-15-2011
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Elective abortion complicated by bilateral renal cortical necrosis (BRCN) is not common in a developed country. We reported a patient having anuric acute renal failure after elective abortion. Initial laboratory studies implied thrombotic thrombocytopenic purpura/Hemolytic uremic syndrome, but plasma exchange was not prescribed since magnetic resonance imaging study suggested BRCN soon after. The patient was treated as septic abortion and reached partial renal recovery after antibiotic treatment and short-term hemodialysis. Early diagnosis of BRCN is essential not only for prognosis prediction but also for treatment decision. We suggest that any anuric patient in suspicion of BRCN should receive MRI study as soon as possible.
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Pneumothorax in a female with renal angiomyolipoma.
Kaohsiung J. Med. Sci.
PUBLISHED: 07-23-2011
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Spontaneous pneumothorax occurs less in females than in males, in contrast to the relatively more commonly and incidentally found renal angiomyolipoma (AML). We report a renal AML in a 23-year-old female patient, which presented as right palpable abdominal mass. This renal tumor was removed owing to enlargement and internal hemorrhage and AML was proved by pathological examination. Three years later, she experienced a life-threatening spontaneous tension pneumothorax and pulmonary lymphangioleiomyomatosis (LAM), which was diagnosed by chest computed tomography. Clinically, she did not have tuberous sclerosis. Pulmonary LAM and renal AML are related lesions and both of these proliferative lesions occur in sporadic patients without family history and at much higher frequency in patients with tuberous sclerosis. Because of the nonspecific symptoms and high rate of complications, we should consider the possibility of LAM in patients diagnosed with AML. The association between renal AML and pulmonary LAM is reviewed.
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Glial cell line-derived neurotrophic factor gene transfer exerts protective effect on axons in sciatic nerve following constriction-induced peripheral nerve injury.
Hum. Gene Ther.
PUBLISHED: 05-23-2011
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Damage to peripheral nerves following trauma or neurodegenerative diseases often results in various sensory and motor abnormalities and chronic neuropathic pain. The loss of neurotrophic factor support has been proposed to contribute to the development of peripheral neuropathy. The main objective of this study was to investigate the protective effect of glial cell line-derived neurotrophic factor (GDNF) using peripheral gene delivery in a rat model of constriction-induced peripheral nerve injury. In this study, it was shown that mechanical and thermal hypersensitivity increased on the injured limb at day 7 after chronic constrictive injury (CCI) was induced. The neurological changes were correlated with the structural changes and loss of GDNF/Akt signaling, particularly in the distal stump of the injured sciatic nerve. Subsequently, recombinant adenovirus was employed to evaluate the potential of intramuscular GDNF gene delivery to alleviate the CCI-induced nerve degeneration ad neuropathic pain. After CCI for 3 days, intramuscular injection of adenovirus encoding GDNF (Ad-GDNF) restored the protein level and activity of GDNF/Akt signaling pathway in the sciatic nerve. This was associated with an improved myelination profile and behavioral outcomes in animals with CCI. In conclusion, the present study demonstrates the involvement of GDNF loss in the pathogenesis of CCI-induced neuropathic pain and the therapeutic potential of intramuscular GDNF gene delivery for the treatment of peripheral nerve degeneration.
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Ribonucleotide reductase subunit p53R2 regulates mitochondria homeostasis and function in KB and PC-3 cancer cells.
Biochem. Biophys. Res. Commun.
PUBLISHED: 05-18-2011
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Ribonucleotide reductase (RR) is a rate-limiting enzyme that catalyzes de novo conversion of ribonucleotide 5-diphosphates to the corresponding 2-deoxynucleotide, essential for DNA synthesis and replication. The mutations or knockout of RR small subunit, p53R2, results in the depletion of mitochondrial DNA (mtDNA) in human, implying that p53R2 might play a critical role for maintaining mitochondrial homeostasis. In this study, siRNA against p53R2 knockdown approach is utilized to examine the impact of p53R2 depletion on mitochondria and to derive underlying mechanism in KB and PC-3 cancer cells. Our results reveal that the p53R2 expression not only positively correlates with mtDNA content, but also partakes in the proper mitochondria function, such as ATP synthesis, cytochrome c oxidase activity and membrane potential maintenance. Furthermore, overexpression of p53R2 reduces intracellular ROS and protects the mitochondrial membrane potential against oxidative stress. Unexpectedly, knockdown of p53R2 has a modest, if any, effect on mitochondrial and total cellular dNTP pools. Taken together, our study provides functional evidence that mitochondria is one of p53R2-targeted organelles and suggests an unexpected function of p53R2, which is beyond known RR function on dNTP synthesis, in mitochondrial homeostatic control.
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Ellagic acid inhibits oxidized low-density lipoprotein (OxLDL)-induced metalloproteinase (MMP) expression by modulating the protein kinase C-?/extracellular signal-regulated kinase/peroxisome proliferator-activated receptor ?/nuclear factor-?B (PKC-?/ERK/
J. Agric. Food Chem.
PUBLISHED: 04-11-2011
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Previous studies have shown that vascular endothelium-derived matrix metalloproteinases (MMPs) contribute to the destabilization of atherosclerotic plaques, a key event triggering acute myocardial infarction. In addition, studies have reported that the PKC-MEK-PPAR? signaling pathway is involved in oxidized low-density lipoprotein (oxLDL)-induced expression of MMPs. Ellagic acid, a phenolic compound found in fruits and nuts, has potent antioxidant, anti-inflammatory, and anticancerous properties. However, the molecular mechanisms underlying its antiatherogenic effects remain to be clarified. This study aimed to assess whether the effects of ellagic acid on the fibrotic markers MMP-1 and MMP-3 are modulated by the PKC-ERK-PPAR-? signaling pathway in human umbilical vein endothelial cells (HUVECs) that have been exposed to oxLDL. It was found that ellagic acid significantly inhibited oxLDL-induced expressions of MMP-1 and MMP-3. Pretreatment with ellagic acid and DPI, a well-known ROS inhibitor, attenuated the oxLDL-induced expression and activity of PKC-?. In addition, ellagic acid as well as pharmacological inhibitors of ROS, calcium, and PKC strongly suppressed the oxLDL-induced phosphorylation of extracellular signal-regulated kinase (ERK) and NF-?B activation. Moreover, ellagic acid ameliorated the oxLDL-induced suppression of PPAR-? expression. In conclusion, the data suggest that ellagic acid elicits its protective effects by modulating the PKC-?/ERK/PPAR-?/NF-?B pathway, resulting in the suppression of ROS generation and, ultimately, inhibition of MMP-1 and MMP-3 expression in HUVECs exposed to oxLDL.
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Primary Sjögrens syndrome with minimal change disease--a case report.
Kaohsiung J. Med. Sci.
PUBLISHED: 04-02-2011
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Glomerular involvement in patients with primary Sjögrens syndrome (pSS) has rarely been reported. Among them, membranoproliferative glomerulonephritis and membranous nephropathy are the more common types. We report a middle-aged female presenting concurrently with nephrotic syndrome and microscopic hematuria, and her pSS was diagnosed by positive anti-Ro (SSA)/anti-La (SSB) autoantibodies, dry mouth, severely diffuse impaired function of both bilateral parotid and submandibular glands, and a positive Schirmer test. Renal pathology revealed minimal change disease and thin basement membrane nephropathy. The patients nephrotic syndrome resolved after treatment with corticosteroids. To our knowledge, this is the first report of minimal change disease in a patient with pSS.
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CYP17A1 intron mutation causing cryptic splicing in 17?-hydroxylase deficiency.
PLoS ONE
PUBLISHED: 03-22-2011
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17?-Hydroxylase/17, 20-lyase deficiency (17OHD) is an autosomal recessive disease causing congenital adrenal hyperplasia and a rare cause of hypertension with hypokalemia. The CYP17A1 gene mutation leads to 17OHD and its clinical features. We described an 18 y/o female with clinical features of 17?-hydroxylase/17, 20-lyase deficiency and characterized the functional consequences of an intronic CYP17A1 mutation. The coding regions and flanking intronic bases of the CYP17A1 gene were amplified by PCR and sequenced. The patient is a compound heterozygote for the previously described p.R358X and IVS1 +2T>C mutations. A first intron splice donor site mutation was re-created in minigene and full-length expression vectors. Pre-mRNA splicing of the variant CYP17A1 intron was studied in transfected cells and in a transformed lymphoblastoid cell line. When the full-length CYP17A1 gene and minigene containing the intronic mutation was expressed in transfected cells, the majority (>90%) of mRNA transcripts were incorrectly spliced. Only the p.R358X transcript was detected in the EBV-transformed lymphoblastoid cell line. The IVS1 +2T>C mutation abolished most 17?-hydroxylase/17, 20-lyase enzyme activity by aberrant mRNA splicing to an intronic pseudo-exon, causing a frame shift and early termination.
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Ribonucleotide reductase small subunit M2B prognoses better survival in colorectal cancer.
Cancer Res.
PUBLISHED: 03-17-2011
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Ribonucleotide reductase subunit RRM2B (p53R2) has been reported to suppress invasion and metastasis in colorectal cancer (CRC). Here, we report that high levels of RRM2B expression are correlated with markedly better survival in CRC patients. In a fluorescence-labeled orthotopic mouse xenograft model, we confirmed that overexpression of RRM2B in nonmetastatic CRC cells prevented lung and/or liver metastasis, relative to control cells that did metastasize. Clinical outcome studies were conducted on a training set with 103 CRCs and a validation set with 220 CRCs. All participants underwent surgery with periodic follow-up to determine survivability. A newly developed specific RRM2B antibody was employed to carry out immunohistochemistry for determining RRM2B expression levels on tissue arrays. In the training set, the Kaplan-Meier and multivariate Cox analysis revealed that RRM2B is associated with better survival of CRCs, especially in stage IV patients (HR = 0.40; 95% CI = 0.18-0.86, P = 0.016). In the validation set, RRM2B was negatively related to tumor invasion (OR = 0.45, 95% CI = 0.19-0.99, P = 0.040) and lymph node involvement (OR = 0.48, 95% CI = 0.25-0.92, P = 0.026). Furthermore, elevated expression of RRM2B was associated with better prognosis in this set as determined by multivariate analyses (HR = 0.48, 95% CI = 0.26-0.91, P = 0.030). Further investigations revealed that RRM2B was correlated with better survival of CRCs with advanced stage III and IV tumors rather than earlier stage I and II tumors. Taken together, our findings establish that RRM2B suppresses invasiveness of cancer cells and that its expression is associated with a better survival prognosis for CRC patients.
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Determination of differential cross sections and kinetic energy release of co-products from central sliced images in photo-initiated dynamic processes.
Phys Chem Chem Phys
PUBLISHED: 02-07-2011
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For photo-initiated inelastic and reactive collisions, dynamic information can be extracted from central sliced images of state-selected Newton spheres of product species. An analysis framework has been established to determine differential cross sections and the kinetic energy release of co-products from experimental images. When one of the reactants exhibits a high recoil speed in a photo-initiated dynamic process, the present theory can be employed to analyze central sliced images from ion imaging or three-dimensional sliced fluorescence imaging experiments. It is demonstrated that the differential cross section of a scattering process can be determined from the central sliced image by a double Legendre moment analysis, for either a fixed or continuously distributed recoil speeds in the center-of-mass reference frame. Simultaneous equations which lead to the determination of the kinetic energy release of co-products can be established from the second-order Legendre moment of the experimental image, as soon as the differential cross section is extracted. The intensity distribution of the central sliced image, along with its outer and inner ring sizes, provide all the clues to decipher the differential cross section and the kinetic energy release of co-products.
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Influence of soft tissue artifacts on the calculated kinematics and kinetics of total knee replacements during sit-to-stand.
Gait Posture
PUBLISHED: 01-11-2011
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The current study aimed to quantify the soft tissue artifacts of selected markers on the thigh and shank, and their effects on the calculated joint center translations, angles and moments of the knee during sit-to-stand. Ten patients with total knee replacements rose from a chair under simultaneous surveillance of a motion capture system, a force-plate and a fluoroscopy system. The "true" poses of the thigh and shank were defined by those of the femoral and tibial components obtained using a three-dimensional fluoroscopy method. The soft tissue artifacts of the skin markers were calculated as their movement relative to the underlying prosthesis components. The joint center translations, angles and moments at the knee were also calculated separately using skin markers and the registered prosthesis poses. Considerable soft tissue artifacts were found, leading to significantly underestimated flexion and internal rotation angles, and extensor moments, but overestimated joint center translations and adduction. The current study provides accurate data of the kinematics and kinetics of total knee replacements during sit-to-stand. The effects of soft tissue artifacts on the calculated joint center translations, angles and moments were also quantified for the first time in the literature. The results may help in developing guidelines for using skin markers and in establishing databases in the biomechanical assessment of sit-to-stand in patients with total knee replacements.
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Effects of soft tissue artifacts on the calculated kinematics and kinetics of the knee during stair-ascent.
J Biomech
PUBLISHED: 01-10-2011
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Biomechanics of the knee during stair-ascent has mostly been studied using skin-marker-based motion analysis techniques, but no study has reported a complete assessment of the soft tissue artifacts (STA) and their effects on the calculated joint center translation, angles and moments at the knee in normal subjects during this activity. This study aimed to bridge the gap. Twelve young adults walked up a three-step stair while data were acquired simultaneously from a three-dimensional motion capture system, a force plate and a dynamic fluoroscopy system. The "gold standards" of poses of the knee were obtained using a 3D fluoroscopy method. The STA of the markers on the thigh and shank were then calculated, together with their effects on the calculated joint center translations, angles and moments at the knee. The STA of the thigh markers were greater than those on the shank, leading to significantly underestimated flexion and extensor moments, but overestimated joint center translations during the first half of the stance phase. The results will be useful for a better understanding of the normal biomechanics of the knee during stair-ascent, as a baseline for future clinical applications and for developing a compensation method to correct for the effects of STA.
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p53R2 inhibits the proliferation of human cancer cells in association with cell-cycle arrest.
Mol. Cancer Ther.
PUBLISHED: 01-07-2011
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Deregulation of the expression of p53R2, a p53-inducible homologue of the R2 subunit of ribonucleotide reductase, has been found in various human cancer tissues; however, the roles p53R2 plays in cancer progression and malignancy remain controversial. In the present study, we examined changes in gene expression profiles associated with p53R2 in cancer cells, using the analysis of cDNA microarray. Gene set enrichment analysis identified that the gene set regulating cell-cycle progression was significantly enriched in p53R2-silencing human oropharyngeal carcinoma KB cells. Attenuation of p53R2 expression significantly reduced p21 expression and moderately increased cyclin D1 expression in both wild-type p53 cancer cells (KB and MCF-7) and mutant p53 cancer cells (PC3 and MDA-MB-231). Conversely, overexpression of p53R2-GFP resulted in an increase in the expression of p21 and decrease in the expression of cyclin D1, which correlated with reduced cell population in S-phase in vitro and suppressed growth in vivo. Furthermore, the MAP/ERK kinase inhibitor PD98059 partially abolished modulation of p21 and cyclin D1 expression by p53R2. Moreover, under the conditions of nonstress and adriamycin-induced genotoxic stress, attenuation of p53R2 in KB cells significantly increased phosphorylated H2AX, which indicates that attenuation of p53R2 may enhance DNA damage induced by adriamycin. Overall, our study shows that p53R2 may suppress cancer cell proliferation partially by upregulation of p21 and downregulation of cyclin D1; p53R2 plays critical roles not only in DNA damage repair but also in proliferation of cancer cells.
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Efficient and directed Nano-LED emission by a complete elimination of transverse-electric guided modes.
Nano Lett.
PUBLISHED: 12-20-2010
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A key to the success of solid-state lighting is an ultraefficient light extraction, ?90%. Recent advances in nanotechnology, particularly in creating nanorods, present an unprecedented opportunity to manipulate optical modes at nanometer scales. Here, we report an optically pumped nanorod light-emitting diode (LED) with an ultrahigh extraction efficiency of 79% at ? = 460 nm without the use of either a back reflector or thin film technology. We demonstrated experimentally three key mechanisms for achieving high efficiency: guided mode-reduction, embedded quantum wells, and ultraefficient light out-coupling by the fundamental HE(11) mode. Furthermore, we show that size reduction at nanoscale represents a new degree-of-freedom for alternating and achieving a more directed LED emission.
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Ridge alterations following immediate implant placement and the treatment of bone defects with Bio-Oss in an animal model.
Clin Implant Dent Relat Res
PUBLISHED: 10-26-2010
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Conflicting data exist on the outcome of placing Bio-Oss® (Geitslich Pharm AG, Wolhausen, Switzerland) into extraction sockets. It is therefore relevant to study whether the incorporation of Bio-Oss into extraction sockets would influence bone healing outcome at the extraction sites. PurpOSE: The aim of this study was to assess peri-implant bone changes when implants were placed in fresh extraction sockets and the remaining defects were filled with Bio-Oss particles in a canine mandible model.
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Three-dimensional inverted photonic grating with engineerable refractive indices for broadband antireflection of terahertz waves.
Opt Lett
PUBLISHED: 10-05-2010
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Reduction of reflection is of great importance in optical spectroscopy to reduce interference and increase throughput. Here we demonstrate a three-dimensional inverted photonic grating device design using only one material-silicon. Enhanced transmission compared to planar silicon wafers is observed from 0.2 THz to over 7.3 THz for a device with a 15 µm period, which covers most of the terahertz band, and its relative 3 dB bandwidth (?f/f(c)) is a noteworthy 116.3%. Moreover, the device is polarization independent and can perform up to a large incident angle.
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Three-dimensional sliced fluorescence imaging in bulbs.
J Chem Phys
PUBLISHED: 10-05-2010
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To study dynamic behaviors of molecular photodissociation processes and photoinitiated inelastic and reactive collisions in a bulb environment, a three-dimensional sliced fluorescence imaging method has been developed. This experimental method combines the sliced fluorescence imaging techniques and a double resonance spectroscopic detection scheme to acquire the central slice of state-selected Newton spheres of scattering products. To illustrate the essence and simplicity of the present method, experimental images of state-selected CN photofragments from the ICN photodissociation are presented. For other chemically significant product species with a single fluorescent excited state, an infrared-optical double resonance detection scheme warrants the present technique a general method in the study of dynamic processes in bulbs.
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Topical application of recombinant calreticulin peptide, vasostatin 48, alleviates laser-induced choroidal neovascularization in rats.
Mol. Vis.
PUBLISHED: 04-24-2010
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Vasostatin 48 (VS48) is a peptide of 48 amino acids derived from calreticulin. This study aimed to investigate the effects of topical application of VS48 eyedrops on experimental choroidal neovascularization (CNV).
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A volumetric model-based 2D to 3D registration method for measuring kinematics of natural knees with single-plane fluoroscopy.
Med Phys
PUBLISHED: 04-14-2010
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Accurate measurement of the three-dimensional (3D) rigid body and surface kinematics of the natural human knee is essential for many clinical applications. Existing techniques are limited either in their accuracy or lack more realistic experimental evaluation of the measurement errors. The purposes of the study were to develop a volumetric model-based 2D to 3D registration method, called the weighted edge-matching score (WEMS) method, for measuring natural knee kinematics with single-plane fluoroscopy to determine experimentally the measurement errors and to compare its performance with that of pattern intensity (PI) and gradient difference (GD) methods.
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Enhanced progenitor cell recruitment and endothelial repair after selective endothelial injury of the mouse kidney.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 03-17-2010
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Primary and/or secondary injury of the renal microvascular endothelium is a common finding in various renal diseases. Besides well-known endothelial repair mechanisms, including endothelial cell (EC) proliferation and migration, homing of extrinsic cells such as endothelial progenitor cells (EPC) and hematopoietic stem cells (HSC) has been shown in various organs and may contribute to microvascular repair. However, these mechanisms have so far not been studied after selective microvascular injury in the kidney. The present study investigated the time course of EPC and HSC stimulation and homing following induction of selective EC injury in the mouse kidney along with various angiogenic factors potentially involved in EC repair and progenitor cell stimulation. Erythropoietin was used to stimulate progenitor cells in a therapeutic approach. We found that selective EC injury leads to a marked stimulation of EPCs, HSCs, and various angiogenic factors to orchestrate microvascular repair. Angiogenic factors started to increase as early as 30 min after disease induction. Progenitor cells could be first detected in the circulation and the spleen before they selectively homed to the diseased kidney. Injection of a high dose of erythropoietin 2 h after disease induction markedly attenuated vascular injury through nonhemodynamic mechanisms, possibly involving vascular endothelial growth factor release.
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Rapid induction of orthotopic hepatocellular carcinoma in immune-competent rats by non-invasive ultrasound-guided cells implantation.
BMC Gastroenterol
PUBLISHED: 03-14-2010
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The fact that prognoses remain poor in patients with advanced hepatocellular carcinoma highlights the demand for suitable animal models to facilitate the development of anti-cancer medications. This study employed a relatively non-invasive approach to establish an orthotopic hepatocellular carcinoma model in immune-competent rats. This was done by ultrasound-guided implantation of cancer cells and the model was used to evaluate the therapeutic efficacy of short-term and low-dose epirubicin chemotherapy.
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Renal capsule as a stem cell niche.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 03-03-2010
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Renal resident stem cells were previously reported within the renal tubules and papillary area. The aim of the present study was to determine whether renal capsules harbor stem cells and whether this pool can be recruited to the renal parenchyma after ischemic injury. We demonstrated the presence of label-retaining cells throughout the renal capsule, at a density of ?10 cells/mm(2), and their close apposition to the blood vessels. By flow cytometry, in vitro cultured cells derived from the renal capsule were positive for mesenchymal stem cell (MSC) markers (CD29+, vimentin+, Sca-1+, nestin+) but did not express hematopoietic and endothelial stem cell markers. Moreover, renal capsule-derived cells also exhibited self-renewal, clonogenicity, and multipotency in differentiation conditions, all favoring stem cell characteristics and identifying them with MSC. In situ labeling of renal capsules with CM-DiI CellTracker demonstrated in vivo a directed migration of CM-DiI-labeled cells to the ischemic renal parenchyma, with the rate of migration averaging 30 ?m/h. Decapsulation of the kidneys during ischemia resulted in a modest, but statistically significant, deceleration of recovery of plasma creatinine compared with ischemic kidneys with intact renal capsule. Comparison of these conditions allows the conclusion that renal capsular cells may contribute ?25-30% of the recovery from ischemia. In conclusion, the data suggest that the renal capsule may function as a novel stem cell niche harboring MSC capable of participating in the repair of renal injury.
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False elevation of blood glucose levels measured by GDH-PQQ-based glucometers occurs during all daily dwells in peritoneal dialysis patients using icodextrin.
Perit Dial Int
PUBLISHED: 02-26-2010
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False elevation of blood glucose levels measured by glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ)-based glucose self-monitoring systems; glucometer) in peritoneal dialysis (PD) patients using icodextrin solution has been well documented. However, adverse hypoglycemic events caused by misreadings for blood glucose are still being reported. We aimed to study blood glucose levels measured simultaneously using different methods in PD patients with switching of icodextrin, and throughout daily exchanges either using icodextrin or not.
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PTEN overexpression attenuates angiogenic processes of endothelial cells by blockade of endothelin-1/endothelin B receptor signaling.
Atherosclerosis
PUBLISHED: 02-12-2010
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Arteriovenous (AV) graft is frequently used as vascular access in hemodialysis patients. However, clotting or thrombosis of AV grafts often occurs and requires surgical removal. At present, the molecular pathogenesis underlying thrombosis of AV graft is not clear. The PTEN/Akt signaling has been implicated in the pathogenesis of vascular diseases. In this study, elevated PTEN expression and concomitant Akt inactivation was observed in endothelium of atherosclerotic brachial arteries from hemodialysis patients. To investigate whether PTEN upregulation affects endothelial function, adenovirus-mediated PTEN (Ad-PTEN) overexpression was performed in aorta rings and cultured endothelial cells. It was found that PTEN overexpression potently inhibited the microvessel sprouting in aorta rings and the angiogenic activities of endothelial cells including migration and tube formation. On the contrary, PTEN knockdown by RNA interference promoted the endothelial migration and reversed the Ad-PTEN-induced inhibition of endothelial migration. Expression analysis showed that PTEN overexpression attenuated the expression of endothelin-1 (ET-1) and endothelin B receptor (ETBR) in endothelial cells at transcriptional levels. However, exogenous ET-1 supply only partially reversed the PTEN-induced inhibition of migration and tube formation. This was delineated due to that PTEN overexpression also perturbed endothelial nitric oxide synthase (eNOS) activation and vascular endothelial growth factor (VEGF) release. In summary, PTEN upregulation induces endothelial dysfunction by attenuating the availability and signaling of multiple angiogenic pathways in endothelial cells, thereby may contribute to thrombosis of AV graft.
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Kinematic analysis of a functional and sequential bimanual task in patients with left hemiparesis: intra-limb and interlimb coordination.
Disabil Rehabil
PUBLISHED: 09-26-2009
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To characterise upper limb performance of each hand (intra-limb coordination) and interlimb coordination on a functional, sequential bimanual task in patients with left hemiparesis and age-matched controls.
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[Living donor liver transplantation: the decision experience].
Hu Li Za Zhi
PUBLISHED: 07-28-2009
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Living donor liver transplantation is a treatment choice for end-stage liver disease patients who face a shortage of currently available donated livers. The decision process involved in living donor organ donation has been described as a complicate process within the family of the patient. Donors have expressed willingness to donate a part of their own living liver in order to ensure the health of a loved one or relative when such a proposition was raised by the attending physician. Such decisions were taken even in the face of certain struggle, fear and ambiguous feelings. Donation decisions may be reinforced through feelings of confidence and trust in the physician and positive evaluations of the risk to donor health of making a living donation. Necessary surgery will impact not only the recipient and donor but also family members. Staff on the transplantation team should make greater efforts to explore perceptions and concerns within families of living donors in order to deliver effective evidence-based care.
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Use of floating balls for reducing bacterial aerosol emissions from aeration in wastewater treatment processes.
J. Hazard. Mater.
PUBLISHED: 07-23-2009
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The microorganism emissions from aeration in the wastewater treatment process may adversely affect air quality and human health. To control the liquid-to-air transport of microorganisms, commercially available balls were used and their control efficiencies were evaluated by a lab-scale aeration system. Escherichia coli as the test agent were aerosolized by the aeration system and size-fractionated E. coli-containing aerosol samples were collected by using an Andersen six-stage impactor with eosin methylene blue agar for subsequent culturing and enumeration of colonies. Aerosol samples were obtained without any control measure and with balls of four diameters (1.9, 2.9, 3.4 and 4.8 cm) in one, three and five layers covering the bubbling liquid surface. Experimental results showed that the control efficiencies of balls on bacterial aerosols varied from over 50% to nearly 100% under various control settings and substantially increased as the ball size decreased and the number of applied layers increased.
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Large enhancement of light-extraction efficiency from optically pumped, nanorod light-emitting diodes.
Opt Lett
PUBLISHED: 07-03-2009
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We report a threefold enhancement of light-emission intensity at lambda=460 nm and a 16-fold extraction-efficiency enhancement measured from a 2D array of nanorod LEDs. The nano-LEDs are randomly arranged and have a typical rod diameter of 100-250 nm. From a combination of photoluminescence, reflectance, and excitation power-dependence measurements, we show that the enhanced emission is due mainly to modification of the extraction efficiency, and not to that of the internal efficiency. Furthermore, we show that the extraction enhancement originates from the randomness of the 2D array that scatters light efficiently into the air and the smallness of the nanorods that eliminates the guiding modes that trap light.
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Weibel-Palade bodies--sentinels of acute stress.
Nat Rev Nephrol
PUBLISHED: 06-27-2009
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Weibel-Palade bodies are uniquely present in endothelial cells and harbor a range of bioactive substances that participate in hemostasis, vasomotion, inflammation and fibrinolysis, in addition to modulating vascular permeability, angiogenic sprouting, and stem cell mobilization. This Perspectives article examines the latest insights into the biogenesis of these organelles and the cellular and molecular mechanisms of their exocytosis. In addition, we advance two hypotheses on the pathogenic role of these organelles: first, in the development of endothelial dysfunction associated with the reduction of nitric oxide bioavailability and accumulation of peroxynitrite and second, as a first-line response to acute stress that determines the balance between regenerative and proinflammatory signals.
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Sliced fluorescence imaging: a versatile method to study photo-induced dynamic processes.
Phys Chem Chem Phys
PUBLISHED: 06-16-2009
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To reduce the image blurring which originates from contributions of a cylindrical array of photolysis events in a photo-induced experiment, a variant of fluorescence imaging techniques has been developed to study photodissociation dynamics and collisional relaxation processes in the bulk. The experimental arrangement utilizes sliced imaging techniques of photofragments by the laser-induced fluorescence detection scheme. An unconventional procedure is employed to guide the photolysis laser in the viewing direction of the imaging detector with an appropriate obstruction. The sliced image in the direction perpendicular to the photolysis laser is equivalent to a two-dimensional projection of the fluorescence image of photoproducts from a single photolysis center. Experimental images of state-selected CN photofragments from the ICN photodissociation are presented to illustrate the versatility of the present method.
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Review article: endothelial progenitor cells in renal disease.
Nephrology (Carlton)
PUBLISHED: 05-16-2009
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This brief overview is intended to provide basic information about endothelial progenitors, their definition and consensus markers used for their detection, describe the pathways of their mobilization and homing and highlight the mechanisms and manifestations of their incompetence that occurs in some chronic kidney diseases. Discussion is geared towards the potential role of endothelial progenitor cells in organ regeneration, in particular, in kidney regeneration. The concept we attempted to promote attributes to the incompetence of endothelial progenitor cells in failed regeneration and ensuing progression of chronic kidney disease. This field of inquiry remains insufficiently explored, especially in renal diseases. Promising areas for future exploration are emphasized.
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Upregulation of hepatoma-derived growth factor is involved in murine hepatic fibrogenesis.
J. Hepatol.
PUBLISHED: 04-29-2009
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Hepatoma-derived growth factor (HDGF) expression is correlated with progression of hepatocellular carcinoma. Since liver fibrosis frequently occurs before hepatoma development, this study investigated the expression profile of HDGF and its relationship with transforming growth factor-beta (TGF-beta) signaling in experimental models of hepatofibrogenesis.
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The Krebs cycle and mitochondrial mass are early victims of endothelial dysfunction: proteomic approach.
Am. J. Pathol.
PUBLISHED: 02-04-2009
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Endothelial cell dysfunction is associated with bioavailable nitric oxide deficiency and an excessive generation of reactive oxygen species. We modeled this condition by chronically inhibiting nitric oxide generation with subpressor doses of N(G)-monomethyl-L-arginine (L-NMMA) in C57B6 and Tie-2/green fluorescent protein mouse strains. L-NMMA-treated mice exhibited a slight reduction in vasorelaxation ability, as well as detectable abnormalities in soluble adhesion molecules (soluble intercellular adhesion molecule-1 and vascular cellular adhesion molecule-1, and matrix metalloproteinase 9), which represent surrogate indicators of endothelial dysfunction. Proteomic analysis of the isolated microvasculature using 2-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy revealed abnormal expression of a cluster of mitochondrial enzymes, which was confirmed using immunodetection. Aconitase-2 and enoyl-CoA-hydratase-1 expression levels were decreased in L-NMMA-treated animals; this phenotype was absent in nitric oxide synthase-1 and -3 knockout mice. Depletion of aconitase-2 and enoyl-CoA-hydratase-1 resulted in the inhibition of the Krebs cycle and enhanced pyruvate shunting toward the glycolytic pathway. To assess mitochondrial mass in vivo, co-localization of green fluorescent protein and MitoTracker fluorescence was detected by intravital microscopy. Quantitative analysis of fluorescence intensity showed that L-NMMA-treated animals exhibited lower fluorescence of MitoTracker in microvascular endothelia as a result of reduced mitochondrial mass. These findings provide conclusive and unbiased evidence that mitochondriopathy represents an early manifestation of endothelial dysfunction, shifting cell metabolism toward "metabolic hypoxia" through the selective depletion of both aconitase-2 and enoyl-CoA-hydratase-1. These findings may contribute to an early preclinical diagnosis of endothelial dysfunction.
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Structural and mutational analyses of Deinococcus radiodurans UvrA2 provide insight into DNA binding and damage recognition by UvrAs.
Structure
PUBLISHED: 02-03-2009
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UvrA proteins are key actors in DNA damage repair and play an essential role in prokaryotic nucleotide excision repair (NER), a pathway that is unique in its ability to remove a broad spectrum of DNA lesions. Understanding the DNA binding and damage recognition activities of the UvrA family is a critical component for establishing the molecular basis of this process. Here we report the structure of the class II UvrA2 from Deinococcus radiodurans in two crystal forms. These structures, coupled with mutational analyses and comparison with the crystal structure of class I UvrA from Bacillus stearothermophilus, suggest a previously unsuspected role for the identified insertion domains of UvrAs in both DNA binding and damage recognition. Taken together, the available information suggests a model for how UvrA interacts with DNA and thus sheds new light on the molecular mechanisms underlying the role of UvrA in the early steps of NER.
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Copolymerization of divinylsilyl-11-silicotungstic acid with butyl acrylate and hexanediol diacrylate: synthesis of a highly proton-conductive membrane for fuel-cell applications.
ChemSusChem
PUBLISHED: 01-27-2009
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Highly conducive to high conductivity: Polyoxometalates were incorporated in the backbone of a hydrocarbon polymer to produce proton-conducting films. These first-generation materials contain large, dispersed clusters of polyoxometalates. Although the morphology of these films is not yet optimal, they already demonstrate practical proton conductivities and proton diffusion within the clusters appears to be very high.
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Acute renal failure and its risk factors in Stevens-Johnson syndrome and toxic epidermal necrolysis.
Am. J. Nephrol.
PUBLISHED: 01-21-2009
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Skin lesion is the most frequent manifestation of adverse drug reactions. Drug-induced cutaneous hypersensitivity and drug-induced acute interstitial nephritis might share a similar mechanism involving drug-specific T cells. We thus investigated the renal outcome of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), the most severe drug-induced cutaneous hypersensitivity, and hypothesize that skin detachment in SJS/TEN might be associated with acute renal failure (ARF).
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.