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Find video protocols related to scientific articles indexed in Pubmed.
A strategy to improve the energy conversion efficiency and stability of quantum dot-sensitized solar cells using manganese-doped cadmium sulfide quantum dots.
Dalton Trans
PUBLISHED: 11-11-2014
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This article describes the effect of manganese (Mn) doping in CdS to improve the photovoltaic performance of quantum dot sensitized solar cells (QDSSCs). The performances of the QDSSCs are examined in detail using a polysulfide electrolyte with a copper sulfide (CuS) counter electrode. Under the illumination of one sun (AM 1.5 G, 100 mW cm(-2)), 10 molar% Mn-doped CdS QDSSCs exhibit a power conversion efficiency (?) of 2.85%, which is higher than the value of 2.11% obtained with bare CdS. The improved photovoltaic performance is due to the impurities from Mn(2+) doping of CdS, which have an impact on the structure of the host material and decrease the surface roughness. The surface roughness and morphology of Mn-doped CdS nanoparticles can be characterised from atomic force microscopy images. Furthermore, the cell device based on the Mn-CdS electrode shows superior stability in the sulfide/polysulfide electrolyte in a working state for over 10 h, resulting in a highly reproducible performance, which is a serious challenge for the Mn-doped solar cell. Our finding provides an effective method for the fabrication of Mn-doped CdS QDs, which can pave the way to further improve the efficiency of future QDSSCs.
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Mammographic density and risk of breast cancer in Korean women.
Eur. J. Cancer Prev.
PUBLISHED: 11-06-2014
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We carried out this study to evaluate the association between mammographic density adjusted for age and BMI and early-onset breast cancer in Asian women. We recruited 213 Korean patients with breast cancer (45% diagnosed before the age of 50 years) and 630 controls matched for age, menopausal status, and examination date. The percentage and absolute size of dense areas on digital mammograms were measured using a computer-assisted thresholding technique (Cumulus). We carried out an analysis using the conditional logistic regression model with adjustment for covariates. An increase by 1?SD in age and BMI-adjusted absolute dense area and percentage dense area was associated with a 1.15-fold (95% confidence interval: 1.03, 1.29) and 1.20-fold (95% confidence interval: 1.06, 1.37) increased risk of breast cancer, respectively. These associations were stronger for premenopausal disease (P=0.07 and 0.01, respectively) and for disease diagnosed before age 50 (P=0.07 and 0.02, respectively) than for postmenopausal disease (P=0.16 and 0.23, respectively) or later onset disease (P=0.10 and 0.10, respectively). There was no difference in the associations with premenopausal versus postmenopausal and early-onset versus late-onset disease. After adjusting for age and BMI, both a greater absolute dense area and a greater percentage dense area were associated with an increased risk of breast cancer, particularly at a young age.
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Trabecular bone score as an indicator for skeletal deterioration in diabetes.
J. Clin. Endocrinol. Metab.
PUBLISHED: 11-05-2014
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Context: Trabecular bone score (TBS) is a novel texture index that evaluates pixel gray-level variations in lumbar spine dual energy X-ray absorptiometry (DXA) images, and is related to bone microarchitecture independent of bone mineral density (BMD). Objective: We investigated lumbar spine TBS as an indicator for skeletal deterioration in diabetes. Design and Setting: Cross-sectional data were collected from subjects participating in an ongoing prospective community-based cohort study from 2009 to 2010. Participants: We included 1,229 men and 1,529 postmenopausal women over 50 years old in the Ansung cohort. Outcome: measures: Biochemical parameters, lumbar spine TBS and BMD from DXA image were measured. Results: Lumbar spine TBS was lower in men with diabetes than in non-diabetic men (1.287 ± 0.005 vs. 1.316 ± 0.003, p<0.001), whereas lumbar spine BMD was higher in men with diabetes (1.135 ± 0.010 vs.1.088 ± 0.006 g/cm(2)). Lumbar spine TBS was lower in women with diabetes than in non-diabetic women only in an unadjusted model (1.333 ± 0.004 vs. 1.353 ± 0.003). However, women <65 years (n=707) with diabetes had lower TBS than those without diabetes even after adjusted for covariates (p<0.001). Diabetes was not associated with BMD at femur sites in both genders. TBS was negatively correlated with HbA1c, fasting plasma glucose, fasting insulin, and homeostasis model assessment -insulin resistance (HOMA-IR), but not with HOMA-? cell function in both genders. Conclusions: The inverse association between lumbar spine TBS and insulin resistance may make it an indicator for determining skeletal deterioration in diabetic patients who have high BMD.
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Embedded biofilm: a new biofilm model based on the embedded growth of bacteria.
Appl. Environ. Microbiol.
PUBLISHED: 10-19-2014
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A variety of systems have been developed to study biofilm formation. However, most of the systems are based on the surface-attached growth of microbes under shear stress. In this study, we designed a microfluidic channel device, called an MAC (microfluidic agarose channel), and found that microbial cells in the MAC system formed an embedded cell aggregative structure (ECAS). The ECASs were generated from the embedded growth of bacterial cells in agarose matrix and better mimicked the clinical environment of biofilms formed within mucus or host tissue under shear-free conditions. ECASs were developed with the production of extracellular polymeric substances (EPS), the most important feature of biofilms, and eventually burst to release planktonic cells, which resembles the full developmental cycle of biofilms. Chemical and genetic effects have also confirmed that ECASs are a type of biofilm. Unlike the conventional biofilms formed in the flow cell model system, this embedded-type biofilm completes the developmental cycle in only 9?12 h and can easily be observed with ordinary microscopes. We suggest that ECASs are a type of biofilm and that the MAC is a system for observing biofilm formation.
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Protease IV, a quorum sensing-dependent protease of Pseudomonas aeruginosa modulates insect innate immunity.
Mol. Microbiol.
PUBLISHED: 10-11-2014
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In Pseudomonas aeruginosa, quorum sensing (QS) plays an essential role in pathogenesis and the QS response controls many virulence factors. Using a mealworm, Tenebrio molitor as a host model, we found that Protease IV, a QS-regulated exoprotease of P. aeruginosa functions as a key virulence effector causing the melanization and death of T. molitor larvae. Protease IV was able to degrade zymogens of spätzle processing enzyme (SPE) and SPE-activating enzyme (SAE) without the activation of the antimicrobial peptide (AMP) production. Since SPE and SAE function to activate spätzle, a ligand of Toll receptor in the innate immune system of T. molitor, we suggest that Protease IV may interfere with the activation of the Toll signaling. Independently of the Toll pathway, the melanization response, another innate immunity was still generated, since Protease IV directly converted Tenebrio prophenoloxidase into active phenoloxidase. Protease IV also worked as an important factor in the virulence to brine shrimp and nematode. These results suggest that Protease IV provides P. aeruginosa with a sophisticated way to escape the immune attack of host by interfering with the production of AMPs.
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GAGE12 mediates human gastric carcinoma growth and metastasis.
Int. J. Cancer
PUBLISHED: 10-06-2014
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The spontaneous metastasis from human gastric carcinoma (GC) remains poorly reproduced in animal models. Here, we established an experimental mouse model in which GC progressively developed in the orthotopic stomach wall and metastasized to multiple organs; the tumors colonized in the ovary exhibited typical characteristics of Krukenberg tumor. The expression of mesenchymal markers was low in primary tumors and high in those in intravasating and extravasating veins. However, the expression of epithelial markers did not differ, indicating that the acquisition of mesenchymal markers without a concordant loss of typical epithelial markers was associated with metastasis. We identified 35 differentially expressed genes (DEGs) in GC cells metastasized to ovary, among which overexpression of GAGE12 family genes, the top-ranked DEGs, were validated. In addition, knockdown of the GAGE12 gene family affected transcription of many of the aforementioned 35 DEGs and inhibited trans-well migration, tumor sphere formation in vitro and tumor growth in vivo. In accordance, GAGE12 overexpression augmented migration, tumor sphere formation and sustained in vivo tumor growth. Taken together, the GAGE12 gene family promotes GC growth and metastasis by modulating the expression of GC metastasis-related genes.
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Location of Irritative Zone in Epileptic Brains of Schizencephalic Patients.
Clin EEG Neurosci
PUBLISHED: 09-26-2014
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Although many schizencephaly patients suffer from epilepsy, the relationship between schizencephalic lesions and epileptic foci remains unclear. Previous studies have shown that schizencephalic lesions may be associated with, rather than contain, epileptogenic zones. Thus, the purpose of this study was to investigate the current source distribution (CSD) of epileptiform discharges in schizencephalic patients and to correlate this activity with existing structural lesions. A consecutive series of 30 schizencephalic patients who were diagnosed using brain magnetic resonance imaging (MRI) were selected retrospectively and prospectively. Of the original 30 subjects selected, 13 had epilepsy, and 6 of these patients exhibited schizencephaly, epilepsy, and interictal spikes on electroencephalograms (EEG) and were enrolled in the present study investigating the current source analysis of interictal spikes. The CSDs of the initial rising phases and the peak points of the interictal spikes were obtained using standardized low-resolution brain electromagnetic tomography (LORETA). Five patients exhibited a single focus of interictal spikes, while 1 patient showed 2 foci. Relative to the structural brain lesions, 5 patients displayed extrinsically localized CSDs, while 1 patient showed a partially intrinsically localized CSD. The present findings demonstrate that the CSDs of interictal spikes in schizencephalic patients are in general anatomically distinct from the cerebral schizencephalic lesions and that these lesions may display an extrinsic epileptogenicity.
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Pazopanib, a Novel Multitargeted Kinase Inhibitor, Shows Potent In Vitro Antitumor Activity in Gastric Cancer Cell Lines with FGFR2 Amplification.
Mol. Cancer Ther.
PUBLISHED: 09-23-2014
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Pazopanib is an orally bioavailable, ATP-competitive, multitargeted tyrosine kinase inhibitor mainly targeting VEGFR2 and PDGFR tyrosine kinases, but the biologic sequences of pazopanib activities beyond antiangiogenesis are poorly defined. We used a panel of 38 gastric cancer cell lines to test the efficacy of pazopanib. In a growth inhibition assay, genomic changes indicated that pazopanib had differential effects on cell growth. Treatment of the KATO-III, OCUM-2M, SNU-16, and HSC-39 gastric cancer cell lines harboring FGFR2 amplification with pazopanib resulted in marked decreases of cell survival with IC50 in ranges of 0.1 to 2.0 ?mol/L, whereas the same treatment of those cell lines without FGFR2 amplification had no growth-inhibitory effects. In the ectopic FGFR2-expressing model, treatment with the indicated concentrations of pazopanib significantly inhibited cell growth and colony formation by FGFR2-expressing NIH 3T3 cells with wild-type (WT) FGFR2 and mutant FGFR2 (S252W). Pazopanib also selectively suppressed constitutive FGFR2 signaling and phosphorylation of downstream effectors. In cell-cycle analysis, FGFR2-amplified cells underwent cell-cycle arrest at the G1-S phase after pazopanib treatment, whereas there were no significant effects on cell-cycle progression in cells without FGFR2 amplification treated with pazopanib. In addition, pazopanib increased a substantial fraction of sub-G1 only in FGFR2-amplified cells. These findings show that the activation of FGFR2 signaling by amplification may be a critical mediator of cell proliferation in a small subset of gastric cancer patients and that pazopanib may provide genotype-correlated clinical benefits beyond the setting of highly vascular tumors. Mol Cancer Ther; 13(11); 2527-36. ©2014 AACR.
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Production of a low calorie mandarin juice by enzymatic conversion of constituent sugars to oligosaccharides and prevention of insoluble glucan formation.
Biotechnol. Lett.
PUBLISHED: 09-18-2014
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Over 99 % of sucrose in mandarin juice (57.1 g/l in original juice to 428.4 g/l in concentrated juice) was enzymatically converted to glucooligosaccharides using 3 U dextransucrase/ml prepared from Leuconostoc mesenteroides at 28 °C. The oligosaccharide synthesis yields were 51 and 47 % for the original and the concentrated mandarin juice, respectively. The degree of polymerization of oligosaccharides in the enzyme-modified juice was 2-7. Calories in the original and modified mandarin juice were 433 and 301 kcal/l (30.5 % reduction). Compared with the original juice, the enzyme-modified juice showed 82 % decrease of insoluble glucan formation by mutansucrase from Streptococcus mutans. A sensory evaluation of the juices revealed that the original and modified mandarin juices had sweetness values of 4.5 and 4.9 and the same values for overall acceptability.
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Inhibition of adenylyl cyclase type 5 prevents L-DOPA-induced dyskinesia in an animal model of Parkinson's disease.
J. Neurosci.
PUBLISHED: 08-29-2014
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The dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) is widely used as a therapeutic choice for the treatment of patients with Parkinson's disease. However, the long-term use of L-DOPA leads to the development of debilitating involuntary movements, called L-DOPA-induced dyskinesia (LID). The cAMP/protein kinase A (PKA) signaling in the striatum is known to play a role in LID. However, from among the nine known adenylyl cyclases (ACs) present in the striatum, the AC that mediates LID remains unknown. To address this issue, we prepared an animal model with unilateral 6-hydroxydopamine lesions in the substantia nigra in wild-type and AC5-knock-out (KO) mice, and examined behavioral responses to short-term or long-term treatment with L-DOPA. Compared with the behavioral responses of wild-type mice, LID was profoundly reduced in AC5-KO mice. The behavioral protection of long-term treatment with L-DOPA in AC5-KO mice was preceded by a decrease in the phosphorylation levels of PKA substrates ERK (extracellular signal-regulated kinase) 1/2, MSK1 (mitogen- and stress-activated protein kinase 1), and histone H3, levels of which were all increased in the lesioned striatum of wild-type mice. Consistently, FosB/?FosB expression, which was induced by long-term L-DOPA treatment in the lesioned striatum, was also decreased in AC5-KO mice. Moreover, suppression of AC5 in the dorsal striatum with lentivirus-shRNA-AC5 was sufficient to attenuate LID, suggesting that the AC5-regulated signaling cascade in the striatum mediates LID. These results identify the AC5/cAMP system in the dorsal striatum as a therapeutic target for the treatment of LID in patients with Parkinson's disease.
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HER2-positive gastric cancer with concomitant MET and/or EGFR overexpression: A distinct subset of patients for dual inhibition therapy.
Int. J. Cancer
PUBLISHED: 08-26-2014
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Growth factor receptors, often carrying tyrosine kinase activities in their cytoplasmic domains, are overexpressed in many cancers. Coactivation of receptor tyrosine kinases (RTKs) plays a critical role in tumor response to targeted therapeutics. We examined concomitant overexpression of EGFR and MET in patients with HER2(+) and HER2(-) gastric cancers (GCs). Tissue microarray samples obtained from 1,589 GC patients who received R0 gastrectomy with extensive node dissection and adjuvant chemoradiationtherapy were analyzed by immunohistochemistry and fluorescence in situ hybridization. HER2(+) was observed in 169 patients (11%). Out of 169 HER2(+) patients, 15 (9%) were EGFR(+) and MET(+) , 29 (17%) were EGFR(+) , 37 (22%) were MET(+) and the remaining 88 patients (52%) were HER2(+) only, without concomitant EGFR or MET overexpression. Greater number of overexpressed RTKs correlated with younger age (p?
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Adenylyl cyclase-5 in the dorsal striatum function as a molecular switch for the generation of behavioral preferences for cue-directed food choices.
Mol Brain
PUBLISHED: 08-19-2014
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BackgroundBehavioral choices in habits and innate behaviors occur automatically in the absence of conscious selection. These behaviors are not easily modified by learning. Similar types of behaviors also occur in various mental illnesses including drug addiction, obsessive-compulsive disorder, schizophrenia, and autism. However, underlying mechanisms are not clearly understood. In the present study, we investigated the molecular mechanisms regulating unconditioned preferred behaviors in food-choices.ResultsMice lacking adenylyl cyclase-5 (AC5 KO mice), which is preferentially expressed in the dorsal striatum, consumed food pellets nearly one after another in cages. AC5 KO mice showed aversive behaviors to bitter tasting quinine, but they compulsively chose quinine-containing AC5 KO-pellets over fresh pellets. The unusual food-choice behaviors in AC5 KO mice were due to the gain of behavioral preferences for food pellets containing an olfactory cue, which wild-type mice normally ignored. Such food-choice behaviors in AC5 KO mice disappeared when whiskers were trimmed. Conversely, whisker trimming in wildtype mice induced behavioral preferences for AC5 KO food pellets, indicating that preferred food-choices were not learned through prior experience. Both AC5 KO mice and wildtype mice with trimmed whiskers had increased glutamatergic input from the barrel cortex into the dorsal striatum, resulting in an increase in the mGluR1-dependent signaling cascade. The siRNA-mediated inhibition of mGluR1 in the dorsal striatum in AC5 KO mice and wildtype mice with trimmed whiskers abolished preferred choices for AC5 KO food pellets, whereas siRNA-mediated inhibition of mGluR3 glutamate receptors in the dorsal striatum in wildtype mice induced behavioral preferences for AC5 KO food pellets, thus mimicking AC5 KO phenotypes.ConclusionsOur results show that the gain and loss of behavioral preferences for a specific cue-directed option were regulated by specific cellular factors in the dorsal striatum, such that the preferred food choices were switched on when either the mGluR3-AC5 pathway was inactive or the mGluR1 pathway was active, whereas the preferred food-choices were switched off when mGluR1 or its downstream pathway was suppressed. These results identify the AC5 and mGluR system in the dorsal striatum as molecular on/off switches to direct decisions on behavioral preferences for cue-oriented options.
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Lynch-like syndrome: Characterization and comparison with EPCAM deletion carriers.
Int. J. Cancer
PUBLISHED: 08-11-2014
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Colorectal cancers (CRCs) with microsatellite instability-high (MSI+) but without detectable germline mutation or hypermethylation in DNA mismatch repair (MMR) genes can be classified as Lynch-like syndrome (LLS). The underlying mechanism and clinical significances of LLS are largely unknown. We measured MSI and MMR protein expression in 4,765 consecutive CRC cases. Among these, MSI+ cases were further classified based on clinical parameters, germline sequencing of MMR genes or polymerase ? (POLE) and ? (POLD1) and promoter methylation analysis of MLH1 and MSH2. We found that MSI+ and MMR protein-deficient CRCs comprised 6.3% (N?=?302) of this cohort. On the basis of germline sequencing of 124 cases, we identified 54 LS with MMR germline mutation (LS-MMR), 15 LS with EPCAM deletions (LS-EPCAM) and 55 LLS patients. Of the 55 LLS patients, six (10.9%) had variants of unknown significance in the genes tested, and one patient had a novel somatic mutation (p.S459P) in POLE. In patients with biallelic deletions of EPCAM, all tumors and their matched normal mucosa showed promoter hypermethylation of MSH2. Finally, we found that patients with LLS and LS-EPCAM shared clinical features that differed from LS-MMR patients, including lower frequency of fulfillment of the revised Bethesda guidelines (83.6 and 86.7% vs. 98.1% for LS-MMR) and older mean age at CRC diagnosis (52.6 and 52.7 years vs. 43.9 years for LS-MMR). We identified somatic mutation in POLE as a rare underlying cause for MMR deficiency in LLS. The similarity between LLS and LS-EPCAM suggests LLS as a subset of familial MSI+ CRC.
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Endoscopic resection for undifferentiated early gastric cancer: focusing on histologic discrepancies between forceps biopsy-based and endoscopic resection specimen-based diagnosis.
Dig. Dis. Sci.
PUBLISHED: 08-09-2014
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Before endoscopic resection (ER), a considerable number of undifferentiated early gastric cancer (UD-EGC) cases were initially diagnosed as atypical glands, dysplasia, or differentiated EGC (D-EGC) based on forceps biopsy specimens. As UD-EGC carries a high risk of resection margin involvement, identifying the predictive factors for UD-EGC cases with histologic discrepancy (HD) is of clinical importance.
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Acute pancreatitis induced by methimazole treatment in a 51-year-old korean man: a case report.
J. Korean Med. Sci.
PUBLISHED: 07-30-2014
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Methimazole (MMI)-induced acute pancreatitis is very rare but severe adverse reaction. A 51-yr-old male developed a high fever, chills, and abdominal pain, two weeks after commencement on MMI for the treatment of Graves' disease. There was no evidence of agranulocytosis, and fever subsided soon after stopping MMI treatment. However, 5 hr after taking an additional dose of MMI, abdominal pain and fever developed again. His symptoms, biochemical, and imaging studies were compatible with acute pancreatitis. After withdrawal of MMI, he showed clinical improvement. This is the first case of MMI-induced acute pancreatitis in Korea. Clinicians should be aware of the rare but possible MMI-induced pancreatitis in patients complaining of fever and abdominal pain.
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Is endoscopic resection an alternative to surgery for early low-risk submucosal gastric cancers: analysis of a large surgical database.
Surg Endosc
PUBLISHED: 07-28-2014
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Although endoscopic resection (ER) for early gastric cancers (EGCs) has become popular with the development of endoscopic instruments and skillful endoscopists, the risk of lymph node metastasis (LNM) is still an obstacle in performing ER. In this study, we aimed to identify the risk factors of LNM and validated the expanded criteria, with the goal of suggesting modified criteria for ER in submucosal EGCs.
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Thyroid hormones and coronary artery calcification in euthyroid men and women.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 07-24-2014
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Overt and subclinical hypothyroidism are risk factors for atherosclerosis. It is unclear whether thyroid hormone levels within the normal range are also associated with atherosclerosis measured by coronary artery calcium (CAC).
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The protective role of NAD(P)H:quinone oxidoreductase 1 on acetaminophen-induced liver injury is associated with prevention of adenosine triphosphate depletion and improvement of mitochondrial dysfunction.
Arch. Toxicol.
PUBLISHED: 07-17-2014
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An overdose of acetaminophen (APAP) causes hepatotoxicity due to its metabolite, N-acetyl-p-benzoquinone imine. NAD(P)H:quinone oxidoreductase 1 (NQO1) is an important enzyme for detoxification, because it catabolizes endogenous/exogenous quinone to hydroquinone. Although various studies have suggested the possible involvement of NQO1 in APAP-induced hepatotoxicity, its precise role in this remains unclear. We investigated the role of NQO1 against APAP-induced hepatotoxicity using a genetically modified rodent model. NQO1 wild-type (WT) and knockout (KO) mice were treated with different doses of APAP, and we evaluated the mortality and toxicity markers for cell death caused by APAP. NQO1 KO mice showed high sensitivity to APAP-mediated hepatotoxicity (as indicated by a large necrotic region) as well as increased levels of nitrotyrosine adducts and reactive oxygen species. APAP-induced cell death in the livers and primary hepatocytes of NQO1 KO mice, which was accompanied by an extensive reduction in adenosine triphosphate (ATP) levels. In accordance with this ATP depletion, cytosolic increases in mitochondrial proteins such as apoptosis-inducing factor, second mitochondria-derived activator of caspases/DIABLO, endonuclease G, and cytochrome c, which indicate severe mitochondrial dysfunction, were observed in NQO1 KO mice but not in WT mice after APAP exposure. Severe mitochondrial depolarization was also greater in hepatocytes isolated from NQO1 KO mice. Collectively, our data suggest that NQO1 plays a critical role in protection against energy depletion caused by APAP, and NQO1 may be useful in the development of therapeutic approaches to effectively diminish the hepatotoxicity caused by an APAP overdose.
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The effect of long-term thyroid-stimulating hormone suppressive therapy on the cognitive function of elderly patients with differentiated thyroid carcinoma.
J. Clin. Endocrinol. Metab.
PUBLISHED: 07-16-2014
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Several studies have evidenced the association between subclinical hyperthyroidism and cognitive impairment in the elderly. However, the effect of long-term TSH suppressive therapy on the cognitive function in elderly patients with differentiated thyroid carcinoma (DTC) is still unclear.
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Human epidermal growth factor receptor 2 testing in gastric cancer: Recommendations of an Asia-Pacific Task Force.
Asia Pac J Clin Oncol
PUBLISHED: 06-30-2014
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Human epidermal growth factor receptor 2 (HER2) testing in gastric and gastroesophageal junction cancer is an evolving area in clinical practice that has particular relevance to Asia-Pacific countries, which face a high incidence of these diseases. A growing body of evidence demonstrates that HER2-targeted therapy improves survival for patients with HER2-positive advanced disease, and drives the need for high-quality testing procedures to identify patients who will respond to treatment. However, various factors challenge day-to-day testing of gastric specimens in these countries, to a degree greater than that observed for breast specimens. Recommendations for HER2 testing of gastric cancer specimens were published as a result of the Trastuzumab for Gastric Cancer (ToGA) trial. The guidelines proposed in this manuscript build on these recommendations and emphasize local testing environments, particularly in Asia-Pacific countries. A multidisciplinary task force comprising experts from Asia-Pacific who actively work and provide education in the area was convened to assess the applicability of existing recommendations in the Asia-Pacific region. The resulting recommendations reported here highlight and clarify aspects of testing that are of particular relevance to the region, and notably emphasize multidisciplinary collaborations to optimize HER2 testing quality.
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Therapeutic approach of wrist ganglion using electroacupuncture: two case reports.
Ann Rehabil Med
PUBLISHED: 06-26-2014
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A ganglion cyst is a relatively common benign tumor on the wrist. Conservative and surgical approaches have been used for its treatment. Various conservative treatment methods have been suggested such as reassurance, aspiration, sclerosant injection, and direct compression. But, there is no acceptable treatment of choice yet because each suggested method has a relatively high recurrence rate. We want to report two cases in which the size of the wrist ganglion was decreased by using electroacupuncture. One patient presented with a chronic ganglion for six years and the other patient presented with a recently occurred acute ganglion. We applied electroacupuncture for 20 minutes once a week for eight weeks to both of them. Afterwards, the size of the wrist ganglion diminished in the follow-up sonography and the accompanying pain was also relieved. Herein we report both cases along with a review of the relevant literature.
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Charcot-Marie-Tooth disease masquerading as acute demyelinating encephalomyelitis-like illness.
Pediatrics
PUBLISHED: 06-25-2014
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X-linked Charcot-Marie-Tooth disease (CMTX1) is a clinically heterogeneous hereditary motor and sensory neuropathy with X-linked transmission. Common clinical manifestations of CMTX1 disease, as in other forms of Charcot-Marie-Tooth (CMT) disease, are distal muscle wasting and weakness, hyporeflexia, distal sensory disturbance, and foot deformities. Mutations in the connexin-32 gene (gap junction protein ?1 [GJB1]) are responsible for CMTX1 disease. In this report, we describe a patient with CMTX1 disease presenting with recurrent attacks of transient and episodic acute demyelinating encephalomyelitis (ADEM)-like symptoms without previous signs of lower extremity weakness or foot deformities; the patient, as well as his asymptomatic mother, exhibited a novel GJB1 mutation (p.Met1Ile). Differential diagnosis of recurrent and transient ADEM-like illness, if unexplained, should include the possibility of CMTX1 disease.
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NAD(P)H:Quinone Oxidoreductase 1 Activation Reduces Blood Pressure Through Regulation of Endothelial Nitric Oxide Synthase Acetylation in Spontaneously Hypertensive Rats.
Am. J. Hypertens.
PUBLISHED: 06-22-2014
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Endothelial nitric oxide synthase (eNOS) is involved in blood pressure (BP) regulation through the production of nitric oxide. Sirtuin I (SIRT1), an NAD-dependent protein deacetylase, promotes vascular relaxation through deacetylation and activation of eNOS. ?-Lapachone (?L) increases the cellular NAD(+)/NADH ratio by activating NAD(P)H:quinone oxidoreductase 1 (NQO1). In this study, we verified whether activation of NQO1 by ?L modulates BP through regulation of eNOS acetylation in a hypertensive animal model.
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CK2? phosphorylates DBC1 and is involved in the progression of gastric carcinoma and predicts poor survival of gastric carcinoma patients.
Int. J. Cancer
PUBLISHED: 06-13-2014
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CK2? has diverse effects on the tumorigenesis owing to its kinase activity, which phosphorylates various proteins involved in tumorigenesis. We, therefore, investigated the expression and role of CK2? in the phosphorylation of deleted in breast cancer 1 (DBC1) in gastric carcinomas. We used 187 gastric carcinomas and human gastric cancer cells to investigate the roles and relationship between CK2? and DBC1 in gastric carcinomas. Positive expression of CK2? and phospho-DBC1 predicted shorter overall survival and relapse-free survival by univariate analysis. Especially, CK2? expression was an independent prognostic indicator for gastric carcinoma patients. In gastric carcinoma cells, CK2? was bound to DBC1 and phosphorylated DBC1. The phosphorylation of DBC1 by CK2? was evidenced by co-immunoprecipitation of CK2? and DBC1 in a GST pull-down assay, an in vitro kinase assay, and immunofluorescence staining. Inhibition of both CK2? and DBC1 decreased proliferation and invasive activity of cancer cells. Decreased migration and invasive activity was associated with a downregulation of MMP2, MMP9 and the epithelial-mesenchymal transition. A mutation at the phosphorylation site of DBC1 also downregulated the signals related with the epithelial-mesenchymal transition. Our study demonstrated that CK2? is an independent prognostic indicator for gastric carcinoma patients and is involved in tumorigenesis by regulating the phosphorylation of DBC1. In addition, the blocking of CK2? and DBC1 inhibited the proliferation and invasive potential of gastric cancer cells. Therefore, our study suggests that CK2?-DBC1 pathway might be a new therapeutic target for the treatment of gastric carcinoma.
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Role of various indices derived from an oral glucose tolerance test in the prediction of conversion from prediabetes to type 2 diabetes.
Diabetes Res. Clin. Pract.
PUBLISHED: 05-22-2014
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The clinical implications of prediabetes for development of type 2 diabetes may differ for Asian ethnicity. We investigated various indices derived from a 2-h oral glucose tolerance test (OGTT) in people with prediabetes to predict their future risk of diabetes.
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Predictive factors of durability to sitagliptin: Slower reduction of glycated hemoglobin, older age and higher baseline glycated hemoglobin.
J Diabetes Investig
PUBLISHED: 05-21-2014
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The goal of the present study was to evaluate predictive factors for good efficacy and durability to sitagliptin with ongoing metformin or metformin plus glimepiride therapy in a real practice situation. The present observational study was carried out over a 60-week period and involved Korean patients with type 2 diabetes mellitus.
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Purine biosynthesis, biofilm formation, and persistence of an insect-microbe gut symbiosis.
Appl. Environ. Microbiol.
PUBLISHED: 05-09-2014
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The Riptortus-Burkholderia symbiotic system is an experimental model system for studying the molecular mechanisms of an insect-microbe gut symbiosis. When the symbiotic midgut of Riptortus pedestris was investigated by light and transmission electron microscopy, the lumens of the midgut crypts that harbor colonizing Burkholderia symbionts were occupied by an extracellular matrix consisting of polysaccharides. This observation prompted us to search for symbiont genes involved in the induction of biofilm formation and to examine whether the biofilms are necessary for the symbiont to establish a successful symbiotic association with the host. To answer these questions, we focused on purN and purT, which independently catalyze the same step of bacterial purine biosynthesis. When we disrupted purN and purT in the Burkholderia symbiont, the ?purN and ?purT mutants grew normally, and only the ?purT mutant failed to form biofilms. Notably, the ?purT mutant exhibited a significantly lower level of cyclic-di-GMP (c-di-GMP) than the wild type and the ?purN mutant, suggesting involvement of the secondary messenger c-di-GMP in the defect of biofilm formation in the ?purT mutant, which might operate via impaired purine biosynthesis. The host insects infected with the ?purT mutant exhibited a lower infection density, slower growth, and lighter body weight than the host insects infected with the wild type and the ?purN mutant. These results show that the function of purT of the gut symbiont is important for the persistence of the insect gut symbiont, suggesting the intricate biological relevance of purine biosynthesis, biofilm formation, and symbiosis.
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Genomic landscape and genetic heterogeneity in gastric adenocarcinoma revealed by whole-genome sequencing.
Nat Commun
PUBLISHED: 05-01-2014
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Gastric cancer (GC) is the second most common cause of cancer-related deaths. It is known to be a heterogeneous disease with several molecular and histological subtypes. Here we perform whole-genome sequencing of 49 GCs with diffuse (N=31) and intestinal (N=18) histological subtypes and identify three mutational signatures, impacting TpT, CpG and TpCp[A/T] nucleotides. The diffuse-type GCs show significantly lower clonality and smaller numbers of somatic and structural variants compared with intestinal subtype. We further divide the diffuse subtype into one with infrequent genetic changes/low clonality and another with relatively higher clonality and mutations impacting TpT dinucleotide. Notably, we discover frequent and exclusive mutations in Ephrins and SLIT/ROBO signalling pathway genes. Overall, this study delivers new insights into the mutational heterogeneity underlying distinct histologic subtypes of GC that could have important implications for future research in the diagnosis and treatment of GC.
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Activation of multiple transcriptional regulators by growth restriction in Pseudomonas aeruginosa.
Mol. Cells
PUBLISHED: 04-28-2014
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Growth restriction by antibiotics is a common feature that pathogenic bacteria must overcome for survival. The struggle of bacteria to escape from growth restriction eventually results in development of antibiotic-resistance through the expression of a set of genes. Here we found that some physiologically important transcriptional regulators of Pseudomonas aeruginosa including QscR, a quorum sensing (QS) receptor, SoxR, a superoxide sensor-regulator, and AntR, a regulator of anthranilate-related secondary metabolism, are activated by various growth-restricted conditions. We generated the growth-restricted conditions by various methods, such as overexpression of PA2537 and treatment with antibiotics or disinfectants. The overexpression of PA2537, encoding an acyltransferase homologue, tightly restricted the growth of P. aeruginosa and significantly activated QscR during the growth restriction. Similarly, treatments with gentamycin, tetracycline, and ethanol also activated QscR near their minimal inhibitory concentrations (MICs). Some non-QS regulators, such as AntR and SoxR, were also activated near the MICs in the same conditions. However, LasR and PqsR, other QS receptors of P. aeruginosa, were not activated, suggesting that only a specific set of transcriptional regulators is activated by growth restriction. Since paraquat, a super-oxide generator, significantly activated QscR and AntR, we suggest that the oxidative stress generated by growth restriction may be partly involved in this phenomenon.
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Deregulation of Immune Response Genes in Patients with Epstein-Barr Virus-Associated Gastric Cancer and Outcomes.
Gastroenterology
PUBLISHED: 04-19-2014
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& Aims: Patients with Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) have a better prognosis than those with gastric cancer not associated with EBV infection (EBVnGC). This is partly because EBV infection recruits lymphocytes, which infiltrate the tumor. A high degree of tumor heterogeneity is likely to be associated with poor response. We investigated differences in gene expression patterns between EBVaGC and EBVnGC.
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Attenuation by a Vigna nakashimae extract of nonalcoholic fatty liver disease in high-fat diet-fed mice.
Biosci. Biotechnol. Biochem.
PUBLISHED: 04-14-2014
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A Vigna nakashimae (VN) extract has been shown to have antidiabetic and anti-obesity effects. However, the mechanism underlying the effect of a VN extract on hepatic inflammation and endoplasmic reticulum (ER) stress remains unclear. In the present study, we investigated how a VN extract protects against the development of non-alcoholic fatty liver disease (NAFLD). A VN extract for 12 weeks reduced the body weight, serum metabolic parameters, cytokines, and hepatic steatosis in high-fat diet (HFD)-fed mice. A VN extract decreased HFD-induced hepatic acetyl CoA carboxylase and glucose transporter 4 expressions. In addition to the levels of high-mobility group box 1 and receptor for advanced glycation, the hepatic expression of ATF4 and caspase-3 was also reduced by a VN extract. Thus, these data indicate that a chronic VN extract prevented NAFLD through multiple mechanisms, including inflammation, ER stress, and apoptosis in the liver.
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Counterintuitive relationship between visceral fat and all-cause mortality in an elderly Asian population.
Obesity (Silver Spring)
PUBLISHED: 04-04-2014
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Abdominal obesity is considered to be a risk factor for mortality. However, recent studies indicate that overweight may be negatively associated with mortality ("obesity paradox"). The relationships between mortality and various obesity markers in an elderly Asian cohort were evaluated.
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Alveolar bone resorption induced by CD4+CD45RB high-density T-cell transfer in immunocompromised mice.
J. Periodontol.
PUBLISHED: 03-30-2014
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The aims of this study are to determine whether the antigen-inexperienced (naive, CD45RB high-density) T-cell (CD4(+)CD45RB(High) T-cell) transfer model is associated with alveolar bone resorption, to elucidate the local osteogenic/adipogenic potential of alveolar bone marrow stromal cells (ABCs) from T-cell-transferred animals, and to investigate the systemic osteogenic potential by transplanting human periodontal ligament stem cells (hPDLSCs) into these animals.
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Emergency carotid artery stenting in patients with acute ischemic stroke due to occlusion or stenosis of the proximal internal carotid artery: a single-center experience.
J Neurointerv Surg
PUBLISHED: 03-18-2014
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The feasibility, safety and effectiveness of emergency carotid artery stenting (eCAS) in patients with acute ischemic stroke (AIS) due to proximal internal carotid artery (ICA) stenosis or occlusion are still controversial. In this study we analyzed our experience with eCAS in patients with AIS.
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Melanotic neuroectodermal tumor of infancy disseminated by a ventriculoperitoneal shunt and diagnosed from the inguinal sac.
J. Pediatr. Hematol. Oncol.
PUBLISHED: 03-01-2014
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Melanotic neuroectodermal tumor of infancy (MNTI) is a rare congenital neoplasm that originates from the neural crest cells, which give rise to the melanocytes of the skin and leptomeninges. We report a case of MNTI with neurocutaneous melanosis of a 28-month-old girl. She was born with hydrocephalus and several large congenital giant nevi. There were no findings except for hydrocephalus, after a ventriculoperitoneal (VP) shunt operation performed when she was 6 months old. She was operated on for a growing inguinal mass at 8 months. The specimen from the inguinal sac was positive for HMB45, vimentin, chromogranin, and neuron-specific enolase. Brain magnetic resonance imaging showed an extensive enhancing extra-axial mass with high signal intensity, along the cerebral spinal fluid space. We report a rare case of MNTI, diagnosed from an inguinal hernia sac, with a disseminated clinical manifestation.
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Epstein-Barr virus-associated lymphoepithelioma-like early gastric carcinomas and endoscopic submucosal dissection: case series.
World J. Gastroenterol.
PUBLISHED: 02-28-2014
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Epstein-Barr virus (EBV)-associated lymphoepithelioma-like gastric carcinoma (LELC) is characterized by a lower lymph node (LN) metastasis rate and a higher survival rate than other forms of gastric cancer. Although current prognosis for LELC is favorable, the most common approach is radical gastrectomy involving an extensive D2 lymph node dissection. Here, we report four cases of EBV-associated early LELC that were treated by an alternative approach, endoscopic submucosal dissection (ESD). The long-term outcome of this procedure is discussed. All patients were treated by ESD en bloc, and all ESD specimens showed tumor-free lateral resection margins. None of the lesions showed lymphovascular invasion. A pathological examination of ESD specimens revealed submucosal invasion of more than 500 ?m in all four cases. One patient underwent additional radical surgery post-ESD; no residual tumor or LN metastasis was noted in the surgical specimen. The other three patients did not undergo additional surgery, either because of severe comorbidity or their refusal to undergo operation, but were subjected to medical follow-up. None of the ESD-treated patients reported local recurrence or distant metastases during the 27-32 mo of follow-up after ESD.
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Impact of clinical performance examination on incoming interns' clinical competency in differential diagnosis of headache.
Korean J Fam Med
PUBLISHED: 02-21-2014
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In Korea, clinical performance examination (CPX) has been included in license examination for medical doctors since 2009 in order to improve clinical performance of medical students. This study aimed to evaluate the contribution of CPX to medical education.
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Poorly differentiated component in gastric pinch biopsies predicts submucosal invasion.
Diagn Pathol
PUBLISHED: 02-20-2014
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Endoscopic resection has become standard therapy for selected patients with early gastric carcinoma (EGC). However, the preoperative diagnostic accuracy for excluding submucosal (SM) invasion is not precise. Moreover, histologic features predicting SM invasion in gastric carcinomas (SMiGC) have not been studied extensively.
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Metabolically-healthy obesity and coronary artery calcification.
J. Am. Coll. Cardiol.
PUBLISHED: 02-10-2014
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The purpose of this study was to compare the coronary artery calcium (CAC) scores of metabolically-healthy obese (MHO) and metabolically healthy normal-weight individuals in a large sample of apparently healthy men and women.
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Thoracic coupled motions of korean men in good health in their 20s.
J Phys Ther Sci
PUBLISHED: 02-06-2014
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[Purpose] The purpose of this study was to investigate thoracic coupled motions of 20 Korean young individuals. [Methods] Thoracic motion of twenty healthy male college students aged 23.2±3.1 was examined. The coupled motions of the thoracic regions T1-4, T4-8, T8-12 were measured using a three dimensional motion capture system. [Results] Coupled axial rotation in the same direction as lateral bending was observed in T1-T4 and T4-T8 in the neutral, flexed, and extended postures of the thoracic spine. In T8-T12, coupled axial rotation in the same direction as lateral bending were observed in the neutral and flexed postures, while coupled axial rotation in the opposite direction was observed in an extended posture. [Conclusion] The patterns of coupled motions in the thoracic spine demonstrated some variability between postures and regions in vivo. However, coupled motions in the same direction were predominantly lateral flexion or axial rotation in the three postures.
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Pitx3 deficient mice as a genetic animal model of co-morbid depressive disorder and parkinsonism.
Brain Res.
PUBLISHED: 01-15-2014
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Approximately 40-50% of all patients with Parkinson?s disease (PD) show symptoms and signs of depressive disorders, for which neither pathogenic understanding nor rational treatment are available. Using Pit3x-deficient mice, a model for selective nigrostriatal dopaminergic neurodegeneration, we tested depression-related behaviors and acute stress responses to better understand how a nigrostriatal dopaminergic deficit increases the prevalence of depressive disorders in PD patients. Pitx3-deficient mice showed decreased sucrose consumption and preference in the two-bottle free-choice test of anhedonia. Acute restraint stress increased c-Fos (known as a neuronal activity marker) expression levels in various brain regions, including the prefrontal cortex, striatum, nucleus accumbens, and paraventricular nucleus of the hypothalamus (PVN), in both Pitx3+/+ and -/- mice. However, the stress-induced increases in c-Fos levels in the cortex, dorsal striatum, and PVN were significantly greater in Pitx3-/- than +/+ mice, suggesting that signs of depressive disorders in parkinsonism are related to altered stress vulnerability. Based on these results, we propose that Pitx3-/- mice may serve as a useful genetic animal model for co-morbid depressive disorder and parkinsonism.
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Preexisting oncogenic events impact trastuzumab sensitivity in ERBB2-amplified gastroesophageal adenocarcinoma.
J. Clin. Invest.
PUBLISHED: 01-14-2014
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Patients with gastric and esophageal (GE) adenocarcinoma tumors in which the oncogene ERBB2 has been amplified are routinely treated with a combination of cytotoxic chemotherapy and the ERBB2-directed antibody trastuzumab; however, the addition of trastuzumab, even when tested in a selected biomarker-positive patient population, provides only modest survival gains. To investigate the potential reasons for the modest impact of ERBB2-directed therapies, we explored the hypothesis that secondary molecular features of ERBB2-amplified GE adenocarcinomas attenuate the impact of ERBB2 blockade. We analyzed genomic profiles of ERBB2-amplified GE adenocarcinomas and determined that the majority of ERBB2-amplified tumors harbor secondary oncogenic alterations that have the potential to be therapeutically targeted. These secondary events spanned genes involved in cell-cycle regulation as well as phosphatidylinositol-3 kinase and receptor tyrosine kinase signaling. Using ERBB2-amplified cell lines, we demonstrated that secondary oncogenic events could confer resistance to ERBB2-directed therapies. Moreover, this resistance could be overcome by targeting the secondary oncogene in conjunction with ERBB2-directed therapy. EGFR is commonly coamplified with ERBB2, and in the setting of ERBB2 amplification, higher EGFR expression appears to mark tumors with greater sensitivity to dual EGFR/ERBB2 kinase inhibitors. These data suggest that combination inhibitor strategies, guided by secondary events in ERBB2-amplified GE adenocarcinomas, should be evaluated in clinical trials.
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Aberrant CDK4 amplification in refractory rhabdomyosarcoma as identified by genomic profiling.
Sci Rep
PUBLISHED: 01-11-2014
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Rhabdomyosarcoma (RMS) is the most commonly occurring type of soft tissue tumor in children. However, it is rare in adults, and therefore, very little is known about the most appropriate treatment strategy for adult RMS patients. We performed genomic analysis of RMS cells derived from a 27-year-old male patient whose disease was refractory to treatment. A peritoneal seeding nodule from the primary tumor, pleural metastases, malignant pleural effusion, and ascites obtained during disease progression, were analyzed. Whole exome sequencing revealed 23 candidate variants, and 10 of 23 mutations were validated by Sanger sequencing. Three of 10 mutations were present in both primary and metastatic tumors, and 3 mutations were detected only in metastatic specimens. Comparative genomic hybridization array analysis revealed prominent amplification in the 12q13-14 region, and more specifically, the CDK4 proto-oncogene was highly amplified. ALK overexpression was observed at both protein and RNA levels. However, an ALK fusion assay using NanoString technology failed to show any ALK rearrangements. Little genetic heterogeneity was observed between primary and metastatic RMS cells. We propose that CDK4, located at 12q14, is a potential target for drug development for RMS treatment.
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Outcomes of endoscopic submucosal dissection for differentiated-type early gastric cancer with histological heterogeneity.
Gastric Cancer
PUBLISHED: 01-10-2014
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Long-term clinical outcomes after endoscopic submucosal dissection (ESD) is unclear for differentiated-type-predominant early gastric cancer (EGC) mixed with undifferentiated component (MUC-EGC). Therefore, the role and appropriate indication of ESD for MUC-EGC remain to be evaluated.
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Effect of simvastatin plus cetuximab/irinotecan for KRAS mutant colorectal cancer and predictive value of the RAS signature for treatment response to cetuximab.
Invest New Drugs
PUBLISHED: 01-10-2014
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Preclinical data has demonstrated the potential of simvastatin to overcome cetuximab resistance in KRAS mutant CRC patients. Therefore, we designed a study using simvastatin/cetuximab/irinotecan for KRAS mutant CRC patients who are refractory to irinotecan and oxaliplatin-based chemotherapy.
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Quorum sensing-dependent metalloprotease VvpE is important in the virulence of Vibrio vulnificus to invertebrates.
Microb. Pathog.
PUBLISHED: 01-02-2014
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Vibrio vulnificus, a Gram-negative bacterium, is an opportunistic human pathogen responsible for fatal septicemia caused by contaminated sea foods in eastern Asia. Quorum sensing (QS) is a cell-density dependent gene regulation mechanism that controls the expression of many virulence genes in various bacteria and V. vulnificus has been also suggested to express their virulence genes through the QS system. In this study, we investigated the role of QS system and QS-regulated exoproteases in the virulence of V. vulnificus using several invertebrate host models, Tenebrio molitor, an insect, Caenorhabditis elegans, a nematode, and brine shrimp (Artemia), an aquatic crustacean. When the culture supernatant of smcR (major QS regulator of V. vulnificus) mutant was injected to T. molitor larvae, it failed to induce the melanization of T. molitor larvae, while the culture supernatant of luxO (upstream negative regulator of smcR) mutant more strongly induced the melanization than wild type. These results demonstrated that QS system of V. vulnificus is crucial for virulence to T. molitor larvae. Among several QS-dependently expressed exoproteases of V. vulnificus, vvpE encoding a metalloprotease was mainly responsible for the melanization of T. molitor larvae, in that the culture supernatant of vvpE mutant failed to induce the melanization. This result was confirmed using the C. elegans and Artemia salina model systems, in which the vvpE mutant strains were attenuated in killing C. elegans and A. salina, compared with wild type, indicating that VvpE is important in the infection of V. vulnificus. In conclusion, we suggest that QS system and a QS-dependent exoprotease, VvpE are crucial for the V. vulnificus virulence to invertebrates.
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Alpha lipoic Acid attenuates radiation-induced thyroid injury in rats.
PLoS ONE
PUBLISHED: 01-01-2014
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Exposure of the thyroid to radiation during radiotherapy of the head and neck is often unavoidable. The present study aimed to investigate the protective effect of ?-lipoic acid (ALA) on radiation-induced thyroid injury in rats. Rats were randomly assigned to four groups: healthy controls (CTL), irradiated (RT), received ALA before irradiation (ALA + RT), and received ALA only (ALA, 100 mg/kg, i.p.). ALA was treated at 24 h and 30 minutes prior to irradiation. The neck area including the thyroid gland was evenly irradiated with 2 Gy per minute (total dose of 18 Gy) using a photon 6-MV linear accelerator. Greater numbers of abnormal and unusually small follicles in the irradiated thyroid tissues were observed compared to the controls and the ALA group on days 4 and 7 after irradiation. However, all pathologies were decreased by ALA pretreatment. The quantity of small follicles in the irradiated rats was greater on day 7 than day 4 after irradiation. However, in the ALA-treated irradiated rats, the numbers of small and medium follicles were significantly decreased to a similar degree as in the control and ALA-only groups. The PAS-positive density of the colloid in RT group was decreased significantly compared with all other groups and reversed by ALA pretreatment. The high activity index in the irradiated rats was lowered by ALA treatment. TGF-ß1 immunoreactivity was enhanced in irradiated rats and was more severe on the day 7 after radiation exposure than on day 4. Expression of TGF-ß1 was reduced in the thyroid that had undergone ALA pretreatment. Levels of serum pro-inflammatory cytokines (TNF-?, IL-1ß and IL-6) did not differ significantly between the all groups. This study provides that pretreatment with ALA decreased the severity of radiation-induced thyroid injury by reducing inflammation and fibrotic infiltration and lowering the activity index. Thus, ALA could be used to ameliorate radiation-induced thyroid injury.
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Room temperature, ppb-level NO2 gas sensing of multiple-networked ZnSe nanowire sensors under UV illumination.
Beilstein J Nanotechnol
PUBLISHED: 01-01-2014
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Reports of the gas sensing properties of ZnSe are few, presumably because of the decomposition and oxidation of ZnSe at high temperatures. In this study, ZnSe nanowires were synthesized by the thermal evaporation of ZnSe powders and the sensing performance of multiple-networked ZnSe nanowire sensors toward NO2 gas was examined. The results showed that ZnSe might be a promising gas sensor material if it is used at room temperature. The response of the ZnSe nanowires to 50 ppb-5 ppm NO2 at room temperature under dark and UV illumination conditions were 101-102% and 113-234%, respectively. The responses of the ZnSe nanowires to 5 ppm NO2 increased from 102 to 234% with increasing UV illumination intensity from 0 to 1.2 mW/cm(2). The response of the ZnSe nanowires was stronger than or comparable to that of typical metal oxide semiconductors reported in the literature, which require higher NO2 concentrations and operate at higher temperatures. The origin of the enhanced response of the ZnSe nanowires towards NO2 under UV illumination is also discussed.
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High-throughput sequencing and copy number variation detection using formalin fixed embedded tissue in metastatic gastric cancer.
PLoS ONE
PUBLISHED: 01-01-2014
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In the era of targeted therapy, mutation profiling of cancer is a crucial aspect of making therapeutic decisions. To characterize cancer at a molecular level, the use of formalin-fixed paraffin-embedded tissue is important. We tested the Ion AmpliSeq Cancer Hotspot Panel v2 and nCounter Copy Number Variation Assay in 89 formalin-fixed paraffin-embedded gastric cancer samples to determine whether they are applicable in archival clinical samples for personalized targeted therapies. We validated the results with Sanger sequencing, real-time quantitative PCR, fluorescence in situ hybridization and immunohistochemistry. Frequently detected somatic mutations included TP53 (28.17%), APC (10.1%), PIK3CA (5.6%), KRAS (4.5%), SMO (3.4%), STK11 (3.4%), CDKN2A (3.4%) and SMAD4 (3.4%). Amplifications of HER2, CCNE1, MYC, KRAS and EGFR genes were observed in 8 (8.9%), 4 (4.5%), 2 (2.2%), 1 (1.1%) and 1 (1.1%) cases, respectively. In the cases with amplification, fluorescence in situ hybridization for HER2 verified gene amplification and immunohistochemistry for HER2, EGFR and CCNE1 verified the overexpression of proteins in tumor cells. In conclusion, we successfully performed semiconductor-based sequencing and nCounter copy number variation analyses in formalin-fixed paraffin-embedded gastric cancer samples. High-throughput screening in archival clinical samples enables faster, more accurate and cost-effective detection of hotspot mutations or amplification in genes.
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Nanostring-based multigene assay to predict recurrence for gastric cancer patients after surgery.
PLoS ONE
PUBLISHED: 01-01-2014
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Despite the benefits from adjuvant chemotherapy or chemoradiotherapy, approximately one-third of stage II gastric cancer (GC) patients developed recurrences. The aim of this study was to develop and validate a prognostic algorithm for gastric cancer (GCPS) that can robustly identify high-risk group for recurrence among stage II patients. A multi-step gene expression profiling study was conducted. First, a microarray gene expression profiling of archived paraffin-embedded tumor blocks was used to identify candidate prognostic genes (N=432). Second, a focused gene expression assay including prognostic genes was used to develop a robust clinical assay (GCPS) in stage II patients from the same cohort (N=186). Third, a predefined cut off for the GCPS was validated using an independent stage II cohort (N=216). The GCPS was validated in another set with stage II GC who underwent surgery without adjuvant treatment (N=300). GCPS was developed by summing the product of Cox regression coefficients and normalized expression levels of 8 genes (LAMP5, CDC25B, CDK1, CLIP4, LTB4R2, MATN3, NOX4, TFDP1). A prospectively defined cut-point for GCPS classified 22.7% of validation cohort treated with chemoradiotherapy (N=216) as high-risk group with 5-year recurrence rate of 58.6% compared to 85.4% in the low risk group (hazard ratio for recurrence=3.16, p=0.00004). GCPS also identified high-risk group among stage II patients treated with surgery only (hazard ratio=1.77, p=0.0053).
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A comparative study of telomerase activity and cytologic diagnosis in malignant ascites.
Anal. Quant. Cytol. Histol.
PUBLISHED: 12-19-2013
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To evaluate telomerase activity as an adjunct in the cytologic diagnosis of malignant ascites.
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Protection of NAD(P)H:quinone oxidoreductase 1 against renal ischemia/reperfusion injury in mice.
Free Radic. Biol. Med.
PUBLISHED: 08-28-2013
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Ischemia/reperfusion (I/R) is the most common cause of acute renal injury. I/R-induced reactive oxygen species (ROS) are thought to be a major factor in the development of acute renal injury by promoting the initial tubular damage. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a well-known antioxidant protein that regulates ROS generation. The purpose of this study was to investigate whether NQO1 modulates the renal I/R injury (IRI) associated with NADPH oxidase (NOX)-derived ROS production in an animal model. We analyzed renal function, oxidative stress, and tubular apoptosis after IRI. NQO1(-/-) mice showed increased blood urea nitrogen and creatinine levels, tubular damage, oxidative stress, and apoptosis. In the kidneys of NQO1(-/-) mice, the cellular NADPH/NADP(+) ratio was significantly higher and NOX activity was markedly higher than in those of NQO1(+/+) mice. The activation of NQO1 by ?-lapachone (?L) significantly improved renal dysfunction and reduced tubular cell damage, oxidative stress, and apoptosis by renal I/R. Moreover, the ?L treatment significantly lowered the cellular NADPH/NADP(+) ratio and dramatically reduced NOX activity in the kidneys after IRI. From these results, it was concluded that NQO1 has a protective role against renal injury induced by I/R and that this effect appears to be mediated by decreased NOX activity via cellular NADPH/NADP(+) modulation. These results provide convincing evidence that NQO1 activation might be beneficial for ameliorating renal injury induced by I/R.
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Spurious elevation of glucose concentration during administration of high dose of ascorbic acid in a patient with type 2 diabetes on hemodialysis.
Yonsei Med. J.
PUBLISHED: 08-07-2013
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We describe herein a case of life-threatening hypoglycemia due to spurious elevation of glucose concentration during the administration of ascorbic acid in a type 2 diabetic patient. A 31-year-old female was admitted for proliferative diabetic retinopathy treatment and prescribed high dose ascorbic acid. During hospitalization, she suddenly lost her consciousness and her glucose concentration was 291 mg/dL, measured using self-monitoring blood glucose (SMBG) device, while venous blood glucose concentration was 12 mg/dL. After intravenous injection of 50% glucose solution, the patient became alert. We reasoned that glucose measurement by SMBG device was interfered by ascorbic acid. Physicians should be aware of this interference; high dose ascorbic acid may cause spurious elevation of glucose concentration when measuring with SMBG devices.
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Serum response factor induces epithelial to mesenchymal transition with resistance to sorafenib in hepatocellular carcinoma.
Int. J. Oncol.
PUBLISHED: 08-06-2013
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The epithelial to mesenchymal transition (EMT) is a crucial process in tumor progression. EMT of tumor cells not only causes increased metastasis, but also contributes to drug resistance. Serum response factor (SRF) is a transcription factor that plays a central role in carcinogenesis and tumor progression in several types of cancers. We investigated the effect of EMT-related SRF, focusing on its promotion of chemoresistance against sorafenib in hepatocellular carcinoma (HCC). We examined SRF and Snail expression in 146 cases of HCCs by immunohistochemistry. We also examined the chemoresistance effect of SRF in HCC cells by transfecting HLE cells with SRF cDNA and SH-J1 cells with SRF antisense cDNA. Expression of SRF and Snail were detected in 37.6% (55 of 146 cases) and in 12.3% (18 of 146 cases) of the HCCs, respectively. None of the tumor-free liver tissues showed SRF or Snail expression. SRF expression was closely correlated with the expression of Snail (p<0.001) and expression of both SRF and Snail showed significant correlation with the high histological grade (p=0.015 and 0.003, respectively). Overexpression of SRF in HLE cells led to increased expression of mesenchymal markers, as well as increased cell growth and colony formation. Overexpression of SRF also led to a significant reduction in the cytotoxic effect of sorafenib in HLE cells. Conversely, inhibition of SRF expression in the SH-J1 cells significantly enhanced the apoptotic effects of sorafenib, along with the reduced expression of mesenchymal markers and restored the expression of E-cadherin. These results suggest that SRF is critical for HCC to acquire a mesenchymal phenotype, which leads to resistance against a sorafenib-mediated apoptotic effect.
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Enhancement of light extraction efficiency of GaN-based light-emitting diodes by ZnO nanorods with different sizes.
J Nanosci Nanotechnol
PUBLISHED: 07-18-2013
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The improvement of the optical output power of GaN-based light emitting diodes (LEDs) was achieved by employing nano-sized flat-top hexagonal ZnO rods. ZnO nanorods (NRs) with the average diameters of 250, 350, and 580 nm were grown on p-GaN top surfaces by a simple wet-chemical method at relatively low temperature (90 degrees C) to investigate the effect of the diameter of ZnO NRs on the light extraction efficiency. Consequently, the enhancement by the factor of as high as 2.63 in the light output intensity at 20 mA for the LED with 350 nm ZnO NRs was demonstrated without the increase in the operation voltage compared to the reference LED.
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Phase II trial of capecitabine and everolimus (RAD001) combination in refractory gastric cancer patients.
Invest New Drugs
PUBLISHED: 07-15-2013
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The aim of this study was to assess the efficacy and safety of combination regimen of capecitabine plus everolimus in patients with refractory gastric cancer who have failed to at least two cytotoxic regimens.
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Development of osteoporosis animal model using micropigs.
Lab Anim Res
PUBLISHED: 07-14-2013
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Osteoporosis is a known major health problem and a serious disease of the bone, there has been a great need to develop more and newer animal models for this disease. Among animal models used for testing drug efficacy, the minipig model has become useful and effective due to its close similarity with humans (validity), particularly with the pharmacokinetics of compounds via subcutaneous administration, the structure and function of the organs, the morphology of bone and the overall metabolic nature. Based on these advantages, we sought to develop a new animal model of osteoporosis using micropig, which differs from other miniature pigs in the genetic background. Female micropigs were used for the induction of a moderate osteoporosis model by bilateral ovariectomy (OVX) and compared with shamoperated animals. For osteoporosis evaluation, clinical biomarkers such as blood osteocalcin (OSC) and parathyroid hormone (PTH) levels were measured, as well as bone mineral density (BMD) using micro-computed tomography (micro-CT). Compared to sham, OVX animals have decreased blood OSC level, while the blood PTH level increased in blood sera. In addition, we observed the significantly decreased BMDs of tibia region in OVX animals. Based on these results, we report that the micropig model developed in this study can be used to develop a new and effective medical method for diagnosis and treatment of osteoporosis.
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Gastrointestinal stromal tumors in children and young adults: a clinicopathologic and molecular genetic study of 22 Korean cases.
APMIS
PUBLISHED: 06-12-2013
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Studies on gastrointestinal stromal tumors (GISTs) in young patients are limited due to their rarity, and none have been conducted in Asian populations. GISTs from patients under the age of 30 were retrospectively reviewed and were analyzed for clinicopathologic features, immunohistochemistry for SDHB (succinate dehydrogenase subunit B), and mutations for exon 9, 11, 13, and 17 of KIT gene and exon 12, 14, and 18 of PDGFRA gene. We found two pediatric (<18 years old) and 20 young adult (18-30 years old) GIST cases. Pediatric GISTs occurred in two girls, both as solitary masses with epithelioid histology in the stomach. Both GISTs were wild type for KIT and PDGFRA genes, were negative for SDHB, and there was no recurrence during follow-up. Of the 20 GISTs in young adults, 12 (60%) were from extra-gastric locations (six duodenum, five jejunum, and one esophagus), and 16 (80%) showed a spindle cell morphology. Mutations of KIT or PDGFRA genes were identified in 14 (78%) of the 18 cases. One patient with multiple gastric GISTs with perigastric lymph node metastases at presentation developed multiple distant metastases and died of the disease 7.3 years after diagnosis. Of the 19 R0-resected young adult patients, one patient with small intestinal GIST harboring KIT exon 11 deletion mutation developed recurrence and showed partial responses for imatinib. In summary, compared with pediatric GIST cases, young adult GISTs are heterogeneous and share the characteristics of both pediatric and adult GISTs. When a mesenchymal tumor is clinically suspected in the small intestine of young adults, a GIST should be included in the differential diagnoses. Further mutation studies and extensive treatments are recommended for these cases.
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Trends in Cervical Cancer Mortality by Socioeconomic Status in Korean Women between 1998 and 2009.
Korean J Fam Med
PUBLISHED: 06-05-2013
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Death from uterine cervical cancer could be preventable by an active participation of women at risk in a screening program such as the Papanicolaou test. In order to examine the presence of socioeconomic disparity in preventable deaths, we evaluated the time trends of cervical cancer mortality by socioeconomic status in Korean women.
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Factors associated with persistent smoking after the diagnosis of cardiovascular disease.
Korean J Fam Med
PUBLISHED: 05-07-2013
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Although cigarette smoking is a major modifiable risk factor for the occurrence of primary and secondary cardiovascular disease (CVD), not all survivors from CVD attacks can successfully stop smoking. However, little is known about the factors associated with the change in smoking behavior after CVD attack.
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Protective role of NAD(P)H:quinone oxidoreductase 1 (NQO1) in cisplatin-induced nephrotoxicity.
Toxicol. Lett.
PUBLISHED: 04-26-2013
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Although cisplatin is widely used as an anti-cancer agent, its use is significantly limited because of its tendency to induce nephrotoxicity through poorly understood mechanisms. NAD(P)H:quinone oxidoreductase 1 (NQO1) is well known to regulate ROS generation. The purpose of this study was to investigate whether NQO1 modulates cisplatin-induced renal failure associated with NADPH oxidase (NOX)-derived ROS production in an animal model. NQO1-/- mice were treated with cisplatin (18 mg/kg) and renal function, oxidative stress, and tubular apoptosis were assessed. NQO1-/- mice showed increased blood urea nitrogen and creatinine levels, tubular damage, oxidative stress, and apoptosis. In accordance with these results, the cellular NADPH/NADP ratio and NOX activity were markedly increased in the kidneys of NQO1-/- mice compared to NQO1+/+ mice. In addition, activation of NQO1 by ?L treatment significantly improved renal dysfunction and reduced tubular cell damage, oxidative stress, and apoptosis. This study demonstrates that NQO1 protects cells against renal failure induced by cisplatin, and that this effect is mediated by decreased NOX activity via cellular NADPH/NADP modulation. These results provide convincing evidence that NQO1 might be beneficial for ameliorating renal failure induced by cisplatin.
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Silent Colonic Malakoplakia in a Living-Donor Kidney Transplant Recipient Diagnosed during Annual Medical Examination.
Korean J Pathol
PUBLISHED: 04-24-2013
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Malakoplakia is a characteristic inflammatory condition, which is usually seen in the urogenital tract, and less frequently in the gastrointestinal tract. We present a case of colonic malakoplakia in an immunocompromised patient. A 55-year-old female visited the outpatient clinic for routine cancer surveillance. Her past medical history was significant for kidney transplantation 11 years ago, and she had been taking immunosuppressants. A colonoscopy revealed several depressed flat lesions and elevated polyps, which were 0.3 to 0.4 cm in size and accompanied by whitish exudates. A biopsy revealed an infiltration of histiocytes with ample granular eosinophilic cytoplasm, with some lymphocytes and plasma cells. Many histiocytes had the characteristic morphology, described as Michaelis-Gutmann bodies: one or several round basophilic structures of approximately 1 to 10 µm in size with some being laminated, some appearing homogeneous, and others having a dense central core with a targetoid appearance. These Michaelis-Gutmann bodies were positively stained on von Kossa stain, and were diagnostic for malakoplakia.
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CD151 Overexpression is Associated with Poor Prognosis in Patients with pT3 Gastric Cancer.
Ann. Surg. Oncol.
PUBLISHED: 04-21-2013
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CD151, a transmembrane protein of the tetraspanin family, is implicated in the regulation of cell-substrate adhesion and cell migration. Overexpression of CD151 has been reported in several cancers and controls MET-dependent neoplastic growth by enhancing receptor signaling. However, association of CD151 overexpression with MET or tumor progression has not been reported in gastric cancer.
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Comparison of Three BRAF Mutation Tests in Formalin-Fixed Paraffin Embedded Clinical Samples.
Korean J Pathol
PUBLISHED: 04-14-2013
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Recently, BRAF inhibitors showed dramatic treatment outcomes in BRAF V600 mutant melanoma. Therefore, the accuracy of BRAF mutation test is critical.
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Improved survival of gastric cancer with tumour Epstein-Barr virus positivity: an international pooled analysis.
Gut
PUBLISHED: 04-12-2013
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About 9% of gastric carcinomas have Epstein-Barr virus (EBV) in the tumour cells, but it is unclear whether viral presence influences clinical progression. We therefore examined a large multicentre case series for the association of tumour EBV status with survival after gastric cancer diagnosis, accounting for surgical stage and other prognostic factors.
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Scoparone inhibits adipocyte differentiation through down-regulation of peroxisome proliferators-activated receptor ? in 3T3-L1 preadipocytes.
Food Chem
PUBLISHED: 04-07-2013
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This study was performed to investigate the effect of scoparone on the differentiation of 3T3-L1 preadipocytes. Scoparone inhibited triglyceride (TG) accumulation in the mature adipocytes, evidenced by Oil-red O staining and intracellular quantification. Real time-PCR analysis showed that scoparone significantly down-regulated the mRNA expression of key adipogenic transcription factors, PPAR?, C/EBP?, compared with mature adipocytes. Scoparone appeared to reduce mRNA expression of SREBP1c and FAS being related to the late stage of adipogenesis. Furthermore, aP2 and CD36/FAT, as adipocyte-specific genes, were decreased in mature adipocytes by scoparone treatment. Moreover, scoparone inhibited the up-regulated expression of PPAR? target genes by rosiglitazone to near that observed in cells treated with GW9662. The luciferase assay revealed that scoparone negatively regulates the transcriptional activity of PPAR?. Chromatin immunoprecipitation assay also showed that participation of scoparone in the regulation of PPAR?. Collectively, scoparone has a PPAR? antagonic effect and suppresses differentiation through down-regulation of adipogenic genes by PPAR? inhibition in 3T3-L1 preadipocytes.
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Diabetes-free survival in patients who underwent islet autotransplantation after 50% to 60% distal partial pancreatectomy for benign pancreatic tumors.
Transplantation
PUBLISHED: 04-06-2013
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Several retrospective studies with short-term follow-up have demonstrated a low rate of new-onset diabetes after distal pancreatectomy for benign pancreatic tumors. We sought to determine the long-term diabetes-free survival of patients who underwent islet autotransplantation (IAT) after distal pancreatectomy and to identify any associations between the isolation parameters of autologous islets and diabetes-free survival.
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The orphan nuclear receptor small heterodimer partner negatively regulates pancreatic beta cell survival and hyperglycemia in multiple low-dose streptozotocin-induced type 1 diabetic mice.
Int. J. Biochem. Cell Biol.
PUBLISHED: 03-27-2013
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The small heterodimer partner (SHP; NR0B2) regulates the transcription of a variety of target genes and controls a variety of physiological functions in various tissues. However, the role of SHP in beta cell has not been fully determined yet. We used SHP knockout (SHP KO) mice to investigate the role of SHP in multiple low-dose streptozotocin (MLDS)-induced diabetes. Blood glucose and insulin levels were measured until 20 days, and intraperitoneal glucose tolerance and glucose-stimulated insulin secretion tests were performed. The expression of apoptotic genes and beta cell markers were detected by quantitative realtime-polymerase chain reaction, immunostaining and western blot analysis. SHP KO mice showed significantly lower blood glucose, higher insulin levels, and enhanced glucose tolerance compared with wild type (WT) mice after MLDS treatment. Moreover, beta cell mass and pancreatic insulin content were remarkably increased in SHP KO mice. In the response to glucose stimulation, islets of SHP KO showed increased insulin secretion via up-regulation of beta cell enriched transcription factors compared to WT mice after streptozotocin (STZ) treatment. In quantification for beta cell apoptosis at day 1 post STZ treatment, the SHP KO mice showed significantly increased anti-apoptotic gene expression and decreased release of apoptotic markers cytochrome c, smac/diablo, and only a few apoptotic beta cells were found in SHP KO pancreas through inactivation of caspase-3, compared to those of WT. These data demonstrate that SHP deficiency ameliorates hyperglycemia and preserves islet function by inhibiting apoptosis of pancreatic beta cells and up-regulating of their enriched transcriptional factors.
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In vivo imaging of islet transplantation using PLGA nanoparticles containing iron oxide and indocyanine green.
Magn Reson Med
PUBLISHED: 03-22-2013
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PURPOSE: We determined whether poly(lactic-co-glycolic acid) nanoparticles would be a useful reagent for the successful monitoring of isolated islets by magnetic resonance imaging and optical imaging systems, without clinically relevant toxicity in vitro or in vivo. METHODS: We used iron oxide for MR imaging and a cyanide dye approved by the Food and Drug Administration (indocyanine green) for optical imaging and estimated the in vivo detection of transplanted pancreatic islets. RESULTS: The poly(lactic-co-glycolic acid) nanoparticles were associated with the islets in vitro and were successfully detected by 4.7 T (MR) and optical imaging, without other toxic effects. When labeled islets were transplanted under the mouse kidney capsule, in vivo T2 / T2*-weighted scans with 4.7 T MR detected as few as 300 labeled islets by 4 weeks. Optical in vivo imaging revealed indocyanine green fluorescence by 2 and 4 days after transplantation of islets containing 250 and 500 µg/mL poly(lactic-co-glycolic acid) nanoparticles, respectively. These results were further supported by the immunohistochemical results for insulin and iron in the recipient mouse kidney and pancreas. CONCLUSIONS: Taken together, these data indicate that poly(lactic-co-glycolic acid) nanoparticles may be used to label transplanted islets and may be imaged with in vivo MR and optical imaging systems. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.
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