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Find video protocols related to scientific articles indexed in Pubmed.
Potential ecological footprints of active pharmaceutical ingredients: an examination of risk factors in low-, middle- and high-income countries.
Philos. Trans. R. Soc. Lond., B, Biol. Sci.
PUBLISHED: 11-19-2014
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Active pharmaceutical ingredients (APIs) can enter the natural environment during manufacture, use and/or disposal, and consequently public concern about their potential adverse impacts in the environment is growing. Despite the bulk of the human population living in Asia and Africa (mostly in low- or middle-income countries), limited work relating to research, development and regulations on APIs in the environment have so far been conducted in these regions. Also, the API manufacturing sector is gradually shifting to countries with lower production costs. This paper focuses mainly on APIs for human consumption and highlights key differences between the low-, middle- and high-income countries, covering factors such as population and demographics, manufacture, prescriptions, treatment, disposal and reuse of waste and wastewater. The striking differences in populations (both human and animal), urbanization, sewer connectivity and other factors have revealed that the environmental compartments receiving the bulk of API residues differ markedly between low- and high-income countries. High sewer connectivity in developed countries allows capture and treatment of the waste stream (point-source). However, in many low- or middle-income countries, sewerage connectivity is generally low and in some areas waste is collected predominantly in septic systems. Consequently, the diffuse-source impact, such as on groundwater from leaking septic systems or on land due to disposal of raw sewage or septage, may be of greater concern. A screening level assessment of potential burdens of APIs in urban and rural environments of countries representing low- and middle-income as well as high-income has been made. Implications for ecological risks of APIs used by humans in lower income countries are discussed.
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Longistatin in tick saliva blocks advanced glycation end-product receptor activation.
J. Clin. Invest.
PUBLISHED: 11-18-2014
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Ticks are notorious hematophagous ectoparasites and vectors of many deadly pathogens. As an effective vector, ticks must break the strong barrier provided by the skin of their host during feeding, and their saliva contains a complex mixture of bioactive molecules that paralyze host defenses. The receptor for advanced glycation end products (RAGE) mediates immune cell activation at inflammatory sites and is constitutively and highly expressed in skin. Here, we demonstrate that longistatin secreted with saliva of the tick Haemaphysalis longicornis binds RAGE and modulates the host immune response. Similar to other RAGE ligands, longistatin specifically bound the RAGE V domain, and stimulated cultured HUVECs adhered to a longistatin-coated surface; this binding was dramatically inhibited by soluble RAGE or RAGE siRNA. Treatment of HUVECs with longistatin prior to stimulation substantially attenuated cellular oxidative stress and prevented NF-?B translocation, thereby reducing adhesion molecule and cytokine production. Recombinant longistatin inhibited RAGE-mediated migration of mouse peritoneal resident cells (mPRCs) and ameliorated inflammation in mouse footpad edema and pneumonia models. Importantly, tick bite upregulated RAGE ligands in skin, and endogenous longistatin attenuated RAGE-mediated inflammation during tick feeding. Our results suggest that longistatin is a RAGE antagonist that suppresses tick bite-associated inflammation, allowing successful blood-meal acquisition from hosts.
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RAGE Expression in Tumor-associated Macrophages Promotes Angiogenesis in Glioma.
Cancer Res.
PUBLISHED: 10-19-2014
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Interaction of RAGE with its ligands can promote tumor progression, invasion and angiogenesis. Although blocking RAGE signaling has been proposed as a potential anti-cancer strategy, functional contributions of RAGE expression in the tumor microenvironment (TME) has not been investigated in detail. Here, we evaluated the effect of genetic depletion of RAGE in TME on the growth of gliomas. In both invasive and non-invasive glioma models, animal survival was prolonged in RAGE knockout (Ager-/-) mice. However, the improvement in survival in Ager-/- mice was not due to changes in tumor growth rate but rather to a reduction in tumor-associated inflammation. Furthermore, RAGE ablation in the TME abrogated angiogenesis by downregulating the expression of pro-angiogenic factors which prevented normal vessel formation, thereby generating a leaky vasculature. These alterations were most prominent in non-invasive gliomas, where the expression of VEGF and pro-inflammatory cytokines were also lower in tumor-associated macrophages (TAM) in Ager-/- mice. Interestingly, reconstitution of Ager-/- TAM with wild-type microglia or macrophages normalized tumor vascularity. Our results establish that RAGE signaling in glioma-associated microglia and TAM drives angiogenesis, underscoring the complex role of RAGE and its ligands in gliomagenesis.
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A case report of endosonography used for the diagnosis of early gastric cancer and gastrointestinal stromal tumor.
Nihon Shokakibyo Gakkai Zasshi
PUBLISHED: 10-07-2014
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A 79-year-old man was referred to our hospital complaining of weight loss. Esophagogastroduodenoscopy revealed a flat, elevated lesion of 30-mm diameter located on the posterior wall of the upper gastric body. The lesion was histologically diagnosed as a well-differentiated adenocarcinoma. Endosonography showed a submucosal tumor under the carcinoma, which was highly suspicious of a gastrointestinal tumor derived from the muscle layer. Adenocarcinoma was diagnosed as an intramucosal lesion, but laparoscopic fundectomy was performed because of the submucosal tumor. Pathological diagnosis was U, less, pType 0-IIa, 18×30 mm, pT1b (SM1), tub2, int, INFa, ly0, v0, pN0, H0, P0, CYX, M0, pStage IA, gastrointestinal stromal tumors, prognostic group 1.
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Emphysema Requires the Receptor for Advanced Glycation End Products Triggering on Structural Cells.
Am. J. Respir. Cell Mol. Biol.
PUBLISHED: 09-04-2014
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Pulmonary emphysema is characterized by persistent inflammation and progressive alveolar destruction. The receptor for advanced glycation end products (RAGE) is a multi-ligand cell surface receptor reported to be involved in the process of acute alveolar epithelial cell injury. However, studies that address the role of RAGE in pulmonary emphysema are inconclusive. We investigated the role of RAGE in the development of elastase-induced pulmonary inflammation and emphysema in mice. RAGE sufficient (RAGE+/+) mice and RAGE deficient (RAGE-/-) mice were treated with intratracheal elastase on day 0. Airway inflammation, static compliance (Cst), lung histology and the levels of neutrophil-related chemokine and pro-inflammatory cytokines in bronchoalveolar lavage (BAL) fluid were determined on days 4 and 21. Neutrophilia in BAL fluid, seen in elastase-treated RAGE+/+ mice, was reduced in elastase-treated RAGE-/- mice on day 4, and was associated with decreased levels of KC, MIP-2 and IL-1?. Cst values and emphysematous changes in the lung tissue were decreased in RAGE-/- mice compared to RAGE+/+ mice on day 21 after elastase treatment. Experiments using irradiated, bone marrow chimeric mice showed that the mice expressing RAGE on radioresistant structural cells but not hematopoietic cells developed elastase-induced neutrophilia and emphysematous change in the lung. In contrast, mice expressing RAGE on hematopoietic cells but not radioresistant structural cells showed reduced neutrophilia and emphysematous change in the lung. These data identify the importance of RAGE expressed on lung structural cells in the development of elastase-induced pulmonary inflammation and emphysema. Thus, RAGE represents a novel therapeutic target for preventing pulmonary emphysema.
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Refractory Sacrococcygeal Germ Cell Tumor in Schinzel-Giedion Syndrome.
J. Pediatr. Hematol. Oncol.
PUBLISHED: 08-28-2014
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We describe a boy with Schinzel-Giedion syndrome who developed refractory sacrococcygeal germ cell tumor with elements of embryonal carcinoma and immature teratoma. He developed local recurrence soon after tumor resection. The tumor was highly resistant to platinum-based combination chemotherapy, local irradiation, and salvage chemotherapy. Frequent infections resulted in a delay in treatment, although apparent fragility had not been observed clinically. He died from tumor progression at 32 months of age. Intensification of chemotherapy does not seem to be feasible for tumors in patients with Schinzel-Giedion syndrome.
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Late-onset rejection of a unilateral donor lung with vascular C4d deposition in bilateral living-donor lobar lung transplantation: an autopsy case report.
Intern. Med.
PUBLISHED: 08-01-2014
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A 37-year-old woman had undergone bilateral living-donor lobar lung transplantation 11 years previously for idiopathic pulmonary arterial hypertension. Her father donated the right lobe and her brother donated the left lobe. She subsequently developed progressively worsening respiratory dysfunction due to pneumonia. CT showed left dominant pulmonary artery dilatation, bronchial wall thickening and airway stenosis, followed by sudden death. An autopsy showed marked pathologic left dominant rejection of the pulmonary artery, small airway and large airway. Notably, only the left lung showed C4d vascular deposition, thus suggesting that antibody-mediated lung rejection may have occurred.
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cAMP ameliorates inflammation by modulation of macrophage receptor for advanced glycation end-products.
Biochem. J.
PUBLISHED: 07-05-2014
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Clarification of the roles of PAMPs (pathogen-associated molecular patterns) and DAMPs (damage-associated molecular patterns) is indispensable for therapeutic strategies against various inflammatory diseases. RAGE (receptor for advanced glycation end-products) is one of the PRRs (pattern recognition receptors) and has been implicated in autoimmune and inflammatory diseases. Effective remedies targeting RAGE are required for the diseases. In the present study, we show that cAMP-induced modulation of the RAGE isoform in macrophages can control the inflammatory state in both in vitro and in vivo experimental conditions. The RAGE ligand S100B stimulated MCP-1 (monocyte chemoattractant protein-1) secretion from peritoneal macrophages, but cAMP elevation suppressed it by converting the RAGE isoform from a membrane-bound into a soluble form. This shedding is the result of ectodomain cleavage of mRAGE (membrane-bound RAGE) by MMP9 (matrix metalloproteinase 9). Furthermore, forskolin significantly inhibited peritoneal macrophage accumulation in a mouse S100B-induced peritonitis model. These results suggest that cAMP serves as a negative regulator of ligand-RAGE signalling and macrophage recruitment by mRAGE down-regulation and formation of decoys as soluble receptors. The present study should deepen our understanding of the pathogenesis of RAGE-mediated tissue derangement and provide new clues for overcoming RAGE-related inflammatory diseases.
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Ileal glucose infusion leads to increased insulin sensitivity and decreased blood glucose levels in wistar rats.
J Invest Surg
PUBLISHED: 06-24-2014
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ABSTRACT Purpose of the study: Rerouting of nutrients and/or increasing nutrient delivery to the small intestine after Roux-en-Y gastric bypass may have important potential as a diabetes treatment modality. However, it is still important question which part of the gastrointestinal tract is the most important for control of glycemia. The aim of this study was to investigate the role of different segments of the gastrointestinal tract on glucose metabolism in the physiological state.
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Structure of the mammalian 80S initiation complex with initiation factor 5B on HCV-IRES RNA.
Nat. Struct. Mol. Biol.
PUBLISHED: 06-20-2014
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The universally conserved eukaryotic initiation factor (eIF) 5B, a translational GTPase, is essential for canonical translation initiation. It is also required for initiation facilitated by the internal ribosomal entry site (IRES) of hepatitis C virus (HCV) RNA. eIF5B promotes joining of 60S ribosomal subunits to 40S ribosomal subunits bound by initiator tRNA (Met-tRNAi(Met)). However, the exact molecular mechanism by which eIF5B acts has not been established. Here we present cryo-EM reconstructions of the mammalian 80S-HCV-IRES-Met-tRNAi(Met)-eIF5B-GMPPNP complex. We obtained two substates distinguished by the rotational state of the ribosomal subunits and the configuration of initiator tRNA in the peptidyl (P) site. Accordingly, a combination of conformational changes in the 80S ribosome and in initiator tRNA facilitates binding of the Met-tRNAi(Met) to the 60S P site and redefines the role of eIF5B as a tRNA-reorientation factor.
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O2-dependent large electron flow functioned as an electron sink, replacing the steady-state electron flux in photosynthesis in the cyanobacterium Synechocystis sp. PCC 6803, but not in the cyanobacterium Synechococcus sp. PCC 7942.
Biosci. Biotechnol. Biochem.
PUBLISHED: 04-16-2014
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To determine whether alternative electron flow (AEF) can replace the photosynthetic electron flow in cyanobacteria, we used an open O2-electrode system to monitor O2-exchange over a long period. In air-grown Synechocystis sp. PCC 6803 (S. 6803(WT)), the quantum yield of PSII, Y(II), held even after photosynthesis was suppressed by CO2 shortage. The S. 6803 mutant, deficient in flavodiiron (FLV) proteins 1 and 3, showed the same phenotype as S. 6803(WT). In contrast, Y(II) decreased in Synechococcus sp. PCC 7942 (S. 7942). These results suggest that AEF functioned as the Y(II) in S. 6803 and replaced the photosynthetic electron flux. In contrast, the activity of AEF in S. 7942 was lower. The affinity of AEF for O2 in S. 6803 did not correspond to those of FLVs in bacteria or terminal oxidases in respiration. AEF might be driven by photorespiration.
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Glycyrrhizin inhibits traumatic brain injury by reducing HMGB1-RAGE interaction.
Neuropharmacology
PUBLISHED: 03-05-2014
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Glycyrrhizin (GL) is a major constituent of licorice root and has been suggested to inhibit the release of high mobility group box-1 (HMGB1), a protein considered representative of damage-associated molecular patterns. We found that GL bound HMGB1 but not RAGE with a moderate equilibrium dissociation constant value based on surface plasmon resonance analysis. This complex formation prevented HMGB1 from binding to RAGE in vitro. The effects of glycyrrhizin on traumatic brain injury (TBI) induced by fluid percussion were examined in rats or mice in the present study. GL was administered intravenously after TBI. Treatment of rats with GL dose-dependently suppressed the increase in BBB permeability and impairment of motor functions, in association with the inhibition of HMGB1 translocation in neurons in injured sites. The beneficial effects of GL on motor and cognitive functions persisted for 7 days after injury. The expression of TNF-?, IL-1? and IL-6 in injured sites was completely inhibited by GL treatment. In RAGE-/- mice, the effects of GL were not observed. These results suggested that GL may be a novel therapeutic agent for TBI through its interference with HMGB1 and RAGE interaction.
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Successful Management of Enzyme Replacement Therapy in Related Fabry Disease Patients with Severe Adverse Events by Switching from Agalsidase Beta (Fabrazyme(®)) to Agalsidase Alfa (Replagal (®)).
JIMD Rep
PUBLISHED: 02-19-2014
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Background: Enzyme replacement therapy (ERT) is the only approved therapy for Fabry disease. In June 2009, there was a worldwide shortage of agalsidase beta, necessitating dose reductions or switching to agalsidase alfa in some patients. Case presentation: We present two cases of Fabry disease (a parent and a child) who received agalsidase beta for 27 months at the licensed dose and 10 months at a reduced dose, followed by a switch to agalsidase alfa for 28 months. Case 1, a 26-year-old male had severe coughing and fatigue during ERT with agalsidase beta requiring antitussive and asthmatic drug therapy. After switching to agalsidase alfa, the coughing gradually resolved completely. Case 2, a 62-year-old female had advanced cardiac manifestations at the time of diagnosis. Despite receiving ERT with the approved dose of agalsidase beta, she experienced aggravation of congestive heart failure and was hospitalized. After switching to agalsidase alfa with standard care in heart disease, BNP level, echocardiographic parameters, eGFR rate and lyso-Gb3 levels were improved or stabilized. Conclusions: We report on two Fabry disease patients who experienced severe adverse events while on approved and/or reduced doses of agalsidase beta. Switching to agalsidase alfa associated with standard care in heart disease led to resolution or improvement in the cardiorespiratory status. And reduction in dose associated with standard care in respiratory disease was useful for decrease in cough and fatigue. Plasma BNP level was useful for monitoring heart failure and the effects of ERT.
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Clinical course of patients with Fabry disease who were switched from agalsidase-? to agalsidase-?.
Genet. Med.
PUBLISHED: 02-18-2014
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Between 2009 and 2012, there was a worldwide shortage of agalsidase-? for the treatment of Fabry disease. Therefore, alternative treatments were needed, including switching to a different enzyme-replacement therapy.
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Laparoscopy in the management of hilar cholangiocarcinoma.
World J. Gastroenterol.
PUBLISHED: 01-10-2014
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The use of minimally invasive surgery has become widely accepted in many gastrointestinal fields, even in patients with malignancy. However, performing laparoscopic resection for the treatment of hilar cholangiocarcinoma is still not universally accepted as an alternative approach to open surgery, and only a limited number of such procedures have been reported due to the difficulty of performing oncologic resection and the lack of consensus regarding the adequacy of this approach. Laparoscopy was initially limited to staging, biopsy and palliation. Recent technological developments and improvements in endoscopic procedures have greatly expanded the applications of laparoscopic liver resection and lymphadenectomy, and some reports have described the use of laparoscopic or robot-assisted laparoscopic resection for hilar cholangiocarcinoma as being feasible and safe in highly selected cases, with the ability to obtain an adequate surgical margin. However, the benefits of major laparoscopic surgery have yet to be conclusively proven, and carefully selecting patients is essential for successfully performing this procedure.
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Occurrence of preservatives and antimicrobials in Japanese rivers.
Chemosphere
PUBLISHED: 01-09-2014
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We established a method for the simultaneous analysis of seven preservatives and five antimicrobials in water. These chemicals are widely used in cosmetics, and their presence in river water is of concern. We used the method to test 13 sites in Japanese rivers and streams contaminated by domestic wastewater, effluent, or industrial wastewater. 2-Phenoxyethanol (2-PE), isopropylmethylphenol, resorcinol, and triclosan were detected at most sites; the maximum concentration of 2-PE detected was 14000 ng L(-1). The results suggest that the major sources of 2-PE were cosmetics and household detergents. The ratio of methylparaben to n-propylparaben in river waters with direct wastewater drainage was similar to that in common cosmetics. This is the first research on levels of 2-PE, isopropylmethylphenol, and chlorphenesin in river water.
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EF-G and EF4: translocation and back-translocation on the bacterial ribosome.
Nat. Rev. Microbiol.
PUBLISHED: 12-23-2013
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Ribosomes translate the codon sequence of an mRNA into the amino acid sequence of the corresponding protein. One of the most crucial events is the translocation reaction, which involves movement of both the mRNA and the attached tRNAs by one codon length and is catalysed by the GTPase elongation factor G (EF-G). Interestingly, recent studies have identified a structurally related GTPase, EF4, that catalyses movement of the tRNA2-mRNA complex in the opposite direction when the ribosome stalls, which is known as back-translocation. In this Review, we describe recent insights into the mechanistic basis of both translocation and back-translocation.
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Scavenging Systems for Reactive Carbonyls in the Cyanobacterium Synechocystis sp. PCC 6803.
Biosci. Biotechnol. Biochem.
PUBLISHED: 12-07-2013
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To elucidate the scavenging systems of sugar- and lipid-derived reactive carbonyls (RCs) in the cyanobacterium Synechocystis sp. PCC 6803 (S. 6803), we selected proteins from S. 6803 based on amino-acid (AA) sequence similarities with proteins from Arabidopsis thaliana, and characterized the properties of the GST-fusion proteins expressed. Slr0942 catalyzed the aldo-keto reductase (AKR) reaction scavenging mainly sugar-derived RCs, methylglyoxal (MG). Slr1192 is the medium-chain dehydrogenase/redutase (MDR). It catalyzed the AKR reaction scavenging several lipid-derived RCs, acrolein, propionaldehyde, and crotonaldehyde. Slr0315 is a short-chain dehydrogenase/redutase (SDR), and it catalyzed only the reduction of MG in the AKR reaction. Slr0381 catalyzed the conversion of hemithioacetal to S-lactoylglutahione (SLG) in the glyoxalase (GLX) 1 reaction. Sll1019 catalyzed the conversion of SLG to glutathione and lactate in the GLX2 reaction. GLX1 and GLX2 compose the glyoxalase system, which scavenges MG. These enzymes contribute to scavenging sugar- and lipid-derived RCs as scavenging systems.
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Tips of laparoscopic pancreaticoduodenectomy: superior mesenteric artery first approach (with video).
J Hepatobiliary Pancreat Sci
PUBLISHED: 12-05-2013
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In previous reports of laparoscopic pancreaticoduodenectomy, the Kocher maneuver with a wide mobilization of the right colonic flexure is carried out in the early phase, and dissection of the superior mesenteric artery is performed in the last phase of resection. This report describes laparoscopic superior mesenteric artery first approach, in which the superior mesenteric artery is dissected in the early phase of resection. Through the ligament of Treitz, the retroperitoneum is widely opened and the superior mesenteric artery is isolated just superior to the left renal vein. The periarterial connective tissue and nerve plexuses surrounding the superior mesenteric artery are dissected longitudinally to identify the inferior pancreaticoduodenal artery, which is then tied and divided. The superior mesenteric artery first approach and early ligation of the inferior pancreaticoduodenal artery is considered to be a feasible, safe, and effective method for performing pure laparoscopic pancreaticoduodenectomy.
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In Planta Mutagenesis of Src Homology 3 Domain-like Fold of NdhS, a Ferredoxin-binding Subunit of the Chloroplast NADH Dehydrogenase-like Complex in Arabidopsis: A CONSERVED ARG-193 PLAYS A CRITICAL ROLE IN FERREDOXIN BINDING.
J. Biol. Chem.
PUBLISHED: 11-13-2013
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Chloroplast NADH dehydrogenase-like (NDH) complex mediates cyclic electron transport around photosystem I and chlororespiration in angiosperms. The Src homology 3 domain (SH3)-like fold protein NdhS/CRR31 is an NDH subunit that is necessary for high affinity binding of ferredoxin, indicating that chloroplast NDH functions as a ferredoxin:plastoquinone oxidoreductase. However, the mechanism of the interaction between NdhS and ferredoxin is unclear. In this study, we analyzed their interaction in planta by using site-directed mutagenesis of NdhS. In general, binding of ferredoxin to its target proteins depends on electrostatic interaction. In silico analysis predicted the presence of a positively charged pocket in the SH3-like domain of NdhS, where nine charged residues are highly conserved among plants. Systematic alteration of these sites with neutral glutamine revealed that only arginine 193 was required for high NDH activity in vivo. Further replacement of arginine 193 with negatively charged aspartate or glutamate or hydrophobic alanine significantly decreased the efficiency of ferredoxin-dependent plastoquinone reduction by NDH in ruptured chloroplasts. Similar results were obtained in in vivo analyses of NDH activity and electron transport. From these results, we propose that the positive charge of arginine 193 in the SH3-like domain of NdhS is critical for electrostatic interaction with ferredoxin in vivo.
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Ecological risk assessment of urban creek sediments contaminated by untreated domestic wastewater: potential contribution of antimicrobials and a musk fragrance.
Environ Technol
PUBLISHED: 11-07-2013
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Despite the fact that some hydrophobic pharmaceuticals and personal care products (PPCPs) have been found to accumulate in river sediments, little is known about the contribution of these compounds to the toxicity of the whole sediment. We sampled river sediments from two urban creeks with an unsewered drainage area to investigate the toxicity for a benthic organism, Chironomus yoshimatsui. The concentrations of selected hydrophobic PPCPs, triclosan (TCS), triclocarban (TCC) and galaxolide (HHCB) were analysed using gas chromatographic mass spectroscopy or liquid chromatographic mass spectroscopy and were found to lie within the range 50 to 200 ng g(-1). The toxicity of the three individual contaminants for the chironomid was also determined. The toxicity of TCC was found to be the strongest, with an NOEC value of 2.5 microg g(-1). Combining the toxicity and measured environmental concentration, the ecological risk was assessed and the contribution of these contaminants to the whole sediment toxicity estimated, assuming additivity. The hazard quotient of all three compounds, determined without assessment factor, ranged between 0.01 and 0.1. The combined contribution of the three compounds to total sediment toxicity was as high as 8.2%, but other unknown factors may also make an important contribution.
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Low-molecular weight fractions of Japanese soy sauce act as a RAGE antagonist via inhibition of RAGE trafficking to lipid rafts.
Food Funct
PUBLISHED: 11-06-2013
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Advanced glycation end-products (AGE) have been implicated in aging and the pathogenesis of diabetic complications, inflammation, Alzheimers disease, and cancer. AGE engage the cell surface receptor for AGE (RAGE), which in turn elicits intracellular signaling, leading to activation of NF-?B to cause deterioration of tissue homeostasis. AGE are not only formed within our bodies but are also derived from foods, endowing them with flavor. In the present study, we assessed the agonistic/antagonistic effects of food-derived AGE on RAGE signaling in a reporter assay system and found that low-molecular weight AGE can antagonize the action of AGE-BSA. Foods tested were Japanese soy sauce, coffee, cola, and red wine, all of which showed fluorescence characteristics of AGE. Soy sauce and coffee contained N(?)-carboxymethyl-lysine (CML). Soy sauce, coffee, and red wine inhibited the RAGE ligand-induced activation of NF-?B, whereas cola had no effect on the ligand induction of NF-?B. The liquids were then fractionated into high-molecular weight (HMW) fractions and low-molecular weight (LMW) fractions. Soy sauce-, coffee-, and red wine-derived LMW fractions consistently inhibited the RAGE ligand induction of NF-?B, whereas the HMW fractions of these foods activated RAGE signaling. Using the LMW fraction of soy sauce as a model food-derived RAGE antagonist, we performed a plate-binding assay and found that the soy sauce LMW fractions competitively inhibited AGE-RAGE association. Further, this fraction significantly reduced AGE-dependent monocyte chemoattractant protein-1 (MCP-1) secretion from murine peritoneal macrophages. The LMF from soy sauce suppressed the AGE-induced RAGE trafficking to lipid rafts. These results indicate that small components in some, if not all, foods antagonize RAGE signaling and could exhibit beneficial effects on RAGE-related diseases.
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Comparison of Combined Transcatheter Arterial Chemoembolization and Radiofrequency Ablation with Surgical Resection by Using Propensity Score Matching in Patients with Hepatocellular Carcinoma within Milan Criteria.
Radiology
PUBLISHED: 10-28-2013
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Purpose To retrospectively compare the outcome of combined transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) (hereafter, TACE-RFA) with that of surgical resection (SR) in patients with hepatocellular carcinoma (HCC) within the Milan criteria. Materials and Methods Institutional review board approval and informed consent were obtained. From January 2000 to December 2010, 154 patients (mean age, 69.9 years; age range, 50-89 years; 107 men, 47 women) underwent TACE-RFA, and 176 patients (mean age, 66.9 years; age range, 29-83 years; 128 men, 48 women) underwent SR. Patients with HCC who underwent TACE-RFA or SR were enrolled if they met the following inclusion criteria: no previous HCC treatment, one HCC lesion no larger than 5 cm or up to three nodules smaller than 3 cm without vascular invasion or extrahepatic metastasis, and Child-Pugh class A or B disease. Cumulative overall survival (OS) and disease-free survival (DFS) rates were compared after adjustment with propensity score matching. Results After this adjustment, OS rates were comparable between the groups (P = .393), but DFS was superior in the SR group (P < .048). Among patients with very early stage HCC (lesions <2 cm in diameter), OS and DFS rates in the SR group were significantly higher than those in the TACE-RFA group (P < .001 and P = .008, respectively). However, adjustment with propensity score matching yielded comparable OS and DFS rates between the two groups (P = .348 and P = .614, respectively). Conclusion TACE-RFA may be a viable alternative treatment for early-stage HCC when SR is not feasible. © RSNA, 2013.
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Is presence or history of extracolonic primary malignancy a risk for colorectal neoplasia? An analysis of patients who underwent colonoscopy.
Acta Med. Okayama
PUBLISHED: 10-23-2013
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Whether presence or history of extracolonic primary malignancy is a risk for colorectal neoplasia is not fully known. In this study, 26,452 first-time colonoscopy cases were examined using a colonoscopy database. Among the analyzed subjects, 3,026 (11%) subjects had history or concomitance of extracolonic primary malignancy, while the remaining 23,426 subjects did not. Colorectal neoplasia was observed in 39% of all the subjects. A crude comparison showed that the prevalence of any type of colorectal neoplasia was higher in subjects with extracolonic malignancy than in those without (42% vs. 39%, p?0.0012). However, after adjusting for confounding factors, the odds ratios (ORs) of subjects with extracolonic malignancy for having colorectal neoplasia, advanced neoplasia, and cancer were all less than 1.0, and all significantly different from those of subjects without extracolonic malignancy. Analysis according to the type of extracolonic malignancy revealed that gastric cancer cases had a significantly lower risk for colorectal advanced neoplasia (OR:0.81;95% CI:0.67-0.99). Among major malignancies, only esophageal squamous cell cancer cases had increased risk for colorectal neoplasia (OR:1.66;95% CI:1.20-2.29). Patients with presence or history of extracolonic malignancy did not carry a higher risk of occurrence of colorectal neoplasia.
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Functional analysis of the AKR4C subfamily of Arabidopsis thaliana: model structures, substrate specificity, acrolein toxicity, and responses to light and [CO(2)].
Biosci. Biotechnol. Biochem.
PUBLISHED: 10-07-2013
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In Arabidopsis thaliana, the aldo-keto reductase (AKR) family includes four enzymes (The AKR4C subfamily: AKR4C8, AKR4C9, AKR4C10, and AKR4C11). AKR4C8 and AKR4C9 might detoxify sugar-derived reactive carbonyls (RCs). We analyzed AKR4C10 and AKR4C11, and compared the enzymatic functions of the four enzymes. Modeling of protein structures based on the known structure of AKR4C9 found an (?/?)8-barrel motif in all four enzymes. Loop structures (A, B, and C) which determine substrate specificity, differed among the four. Both AKR4C10 and AKR4C11 reduced methylglyoxal. AKR4C10 reduced triose phosphates, dihydroxyacetone phosphate (DHAP), and glyceraldehydes 3-phosphate (GAP), the most efficiently of all the AKR4Cs. Acrolein, a lipid-derived RC, inactivated the four enzymes to different degrees. Expression of the AKR4C genes was induced under high-[CO2] and high light, when photosynthesis was enhanced and photosynthates accumulated in the cells. These results suggest that the AKR4C subfamily contributes to the detoxification of sugar-derived RCs in plants.
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Diagnostic potential of endotoxin scattering photometry for sepsis and septic shock.
Shock
PUBLISHED: 10-04-2013
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Endotoxin scattering photometry (ESP) is a novel Limulus amebocyte lysate (LAL) assay that uses a laser light-scattering particle-counting method. In the present study, we compared ESP, standard turbidimetric LAL assay, and procalcitonin assay for the evaluation of sepsis after emergency gastrointestinal surgery. A total of 174 samples were collected from 40 adult patients undergoing emergency gastrointestinal surgery and 10 patients with colorectal cancer undergoing elective surgery as nonseptic controls. Plasma endotoxin levels were measured with ESP and turbidimetric LAL assay, and plasma procalcitonin levels were assessed with a standard procalcitonin assay. Plasma endotoxin and procalcitonin levels increased corresponding to the degree of sepsis. Endotoxin scattering photometry significantly discriminated between patients with or without septic shock: sensitivity, 81.1%; specificity, 76.6%; positive predictive value, 48.4%; negative predictive value, 93.8%; and accuracy, 77.6%. The area under the receiver operating characteristic curve for septic shock with the ESP assay (endotoxin cutoff value, 23.8 pg/mL) was 0.8532 ± 0.0301 (95% confidence interval, 0.7841-0.9030; P < 0.0001). The predictive power of ESP was superior to that of turbidimetric assay (difference, 0.1965 ± 0.0588; 95% confidence interval, 0.0812-0.3117; P = 0.0008). There was no significant difference in predictive power between ESP and procalcitonin assay. Endotoxin scattering photometry also discriminated between patients with and without sepsis. Area under the receiver operating characteristic curve analysis showed that ESP had the best predictive power for diagnosing sepsis. In conclusion, compared with turbidimetric LAL assay, ESP more sensitively detected plasma endotoxin and significantly discriminated between sepsis and septic shock in patients undergoing gastrointestinal emergency surgery.
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Intact neural system of the portal vein is important for maintaining normal glucose metabolism by regulating glucagon-like peptide-1 and insulin sensitivity.
Peptides
PUBLISHED: 09-07-2013
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The portal neural system may have an important role on the regulation of glucose homeostasis since activation of the gut-brain-liver neurocircuit by nutrient sensing in the proximal intestine reduces hepatic glucose production through enhanced liver insulin sensitivity. Although there have been many studies investigating the role of portal neural system, surgical denervation of the sole portal vein has not been reported to date. The aim of this study was to clarify the role of the portal neural system on the regulation of glucose homeostasis and food intake in the physiological condition. Surgical denervation of portal vein (DV) was performed in 10 male 12 week-old Wistar rats. The control was a sham operation (SO). One week after surgery, food intake and body weight were monitored; an oral glucose tolerance test (OGTT) was performed; and glucagon-like peptide-1 (GLP-1) and insulin levels during OGTT were assayed. In addition, insulinogenic index, homeostatic model assessment, and Matsuda index were calculated. All rats regained the preoperative body weight at one week after surgery. There was no significant difference in food intake between DV and SO rats. DV rats exhibited increased blood glucose levels associated with decreased insulin sensitivity but increased GLP-1 and insulin secretion during OGTT. In summary, in the physiological state, loss of the portal neural system leads to decreased insulin sensitivity and increased blood glucose levels but does not affect food intake. These data indicate that an intact portal neural system is important for maintaining normal glucose metabolism.
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ABC1K1/PGR6 kinase: a regulatory link between photosynthetic activity and chloroplast metabolism.
Plant J.
PUBLISHED: 08-14-2013
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Arabidopsis proton gradient regulation (pgr) mutants have high chlorophyll fluorescence and reduced non-photochemical quenching (NPQ) caused by defects in photosynthetic electron transport. Here, we identify PGR6 as the chloroplast lipid droplet (plastoglobule, PG) kinase ABC1K1 (activity of bc1 complex kinase 1). The members of the ABC1/ADCK/UbiB family of atypical kinases regulate ubiquinone synthesis in bacteria and mitochondria, and impact various metabolic pathways in plant chloroplasts. Here, we demonstrate that abc1k1 has a unique photosynthetic and metabolic phenotype that is distinct from that of the abc1k3 homolog. The abc1k1/pgr6 single mutant is specifically deficient in the electron carrier plastoquinone, as well as in ?-carotene and the xanthophyll lutein, and is defective in membrane antioxidant tocopherol metabolism. After 2 days of continuous high light stress, abc1k1/pgr6 plants suffer extensive photosynthetic and metabolic perturbations, strongly affecting carbohydrate metabolism. Remarkably, however, the mutant acclimates to high light after 7 days together with a recovery of carotenoid levels and a drastic alteration in the starch-to-sucrose ratio. Moreover, ABC1K1 behaves as an active kinase and phosphorylates VTE1, a key enzyme of tocopherol (vitamin E) metabolism in vitro. Our results indicate that the ABC1K1 kinase constitutes a new type of regulatory link between photosynthetic activity and chloroplast metabolism.
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Acrolein, an ?,?-unsaturated carbonyl, inhibits both growth and PSII activity in the cyanobacterium Synechocystis sp. PCC 6803.
Biosci. Biotechnol. Biochem.
PUBLISHED: 08-07-2013
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In this study, we sought to determine whether and how an ?,?-unsaturated carbonyl, acrolein, can inhibit the growth of the cyanobacterium Synechocystis sp. PCC6803 (S. 6803). Treatment of S. 6803 with 200 µM acrolein for 3 d significantly and irreversibly inhibited its growth. To elucidate the inhibitory mechanism, we examined the effects of acrolein on photosynthesis. In contrast to dark conditions, the addition of acrolein to S. 6803 under conditions of illumination lowered the CO?-dependent O? evolution rate (photosynthetic activity). Furthermore, treatment with acrolein lowered the activity reducing dimethyl benzoquinone in photosystem II (PSII). Acrolein also suppressed the reduction rate for the oxidized form of the reaction center chlorophyll of photosystem I (PSI), P700. These results indicate that acrolein inhibited PSII activity in thylakoid membranes. The addition of 200 µM acrolein to the illuminated S. 6803 cells gradually increased the steady-state level (Fs) of Chl fluorescence and decreased the quantum yield of PSII. These results suggested that acrolein damaged the acceptor side of PSII. On the other hand, acrolein did not inhibit respiration. From the above results, we gained insight into the metabolism of acrolein and its physiological effects in S. 6803.
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Validated Liquid Culture Monitoring System for Lifespan Extension of Caenorhabditis elegans through Genetic and Dietary Manipulations.
Aging Dis
PUBLISHED: 08-01-2013
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Nutritional and genetic factors influence aging and life expectancy. The reduction of food intake without malnutrition, referred to caloric restriction (CR), has been shown to increase lifespan in a wide variety of species. The nematode Caenorhabditis elegans (C. elegans) is one of the principle models with which to study the biology of aging and search for anti-aging compounds. In this study, we validated and optimized a high-throughput liquid culture system to monitor C. elegans lifespan with minimized mechanical stress. We used alive and ultraviolet (UV)-killed Escherichia coli (E. coli) OP50 at 10(8) or 10(9) colony-forming units (cfu)/ml to feed Bristol N2 wild-type (WT) and mutant worms of a well-characterized insulin/insulin-like growth factor signaling (ILS) pathway: the insulin receptor homolog daf-2 (e1370), phosphatidylinositol 3-kinase age-1 (hx546), and transcriptional factor FOXO homolog daf-16 (mu86 and mgDf50). Compared with alive E. coli at 10(9) cfu/ml, supplementations of alive E. coli at 10(8) cfu/ml or UV-killed E. coli at 10(9) cfu/ml dramatically prolonged lifespan in WT and age-1 mutants, and to a lesser extent, in daf-2 and daf-16 mutants, suggesting that signaling pathways in CR and ILS do not overlap fully. Feeding 10(8) cfu/ml UV-killed E. coli, which led to maximally saturated longevity in WT and daf-2 mutant, can prolonged lifespan in age-1, but not daf-16, mutants. This approach will be useful for investigating the biology of aging, physiological responses and gene functions under CR conditions and also for screening pharmacologic compounds to extend lifespan or affect other biologic processes.
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Myocardial protection in cardiac surgery: a historical review from the beginning to the current topics.
Gen Thorac Cardiovasc Surg
PUBLISHED: 07-23-2013
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Myocardial protection has become an essential adjunctive measure in cardiac surgery for a couple of decades, because since the 1950s, the methods of cardioprotection (cardioplegic solutions and related procedures) have been improved by the mechanism of myocardial ischemia/reperfusion-induced damage being unveiled through the untiring efforts of researchers and clinicians. The concept of myocardial protection in cardiac surgery was proposed along with introduction of hypothermic crystalloid potassium cardioplegia in the beginning and has been diversified by pharmacological additives, blood cardioplegia, temperature modulation (warm; tepid), retrograde cardioplegia, controlled reperfusion, integrated cardioplegia, and pre-and postconditioning. This historical review summarized experimental and clinical studies dealing with the methods and results of myocardial protection in cardiac surgery, introducing the newly developed concepts for the last decade and the current topics.
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Sivelestat prevents cytoskeletal rearrangements in neutrophils resulting from lung re-expansion following one-lung ventilation during thoracic surgery.
Inflammation
PUBLISHED: 07-23-2013
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Patients undergoing lobectomy are at risk of developing acute lung injury resulting from one-lung ventilation (OLV) during surgery. We investigated the morphological and functional behavior of neutrophils in patients who underwent lobectomy and assessed the ability of sivelestat to inhibit neutrophil activity. This was a blinded randomized study. Sixteen patients who underwent lobectomy were given intravenous sivelestat (n = 8) or intravenous saline (n = 8). We studied the cytoskeletal rearrangements of circulating neutrophils by determining the localization of filamentous actin (F-actin). Pulmonary oxygenation was evaluated by measuring the partial pressure of arterial oxygen. We found that the number of circulating, F-actin-rimmed neutrophils increased during OLV and after lung re-expansion. Our results suggest that, in addition to the surgical procedure and OLV, re-expansion of the remaining lung after lobectomy increases the neutrophil activation levels. Furthermore, administration of sivelestat limited neutrophil activation and improved pulmonary oxygenation in our patients.
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Protein-bound polysaccharide-K augments the anticancer effect of fluoropyrimidine derivatives possibly by lowering dihydropyrimidine dehydrogenase expression in gastrointestinal cancers.
Oncol. Rep.
PUBLISHED: 07-18-2013
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Protein-bound polysaccharide-K (PSK) enhances the antitumor effect of anticancer drug when used clinically in combination with such drugs. PSK is known to act by immune-mediated mechanisms; however, the relationship between PSK and metabolic enzymes of anticancer drugs is unknown. We used the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) clinically to evaluate the sensitivity of anticancer drugs. In the present study, we modified the CD-DST by adding peripheral blood mononuclear cells (PBMCs) (immuno-CD-DST) and examined the antitumor effect of PSK in combination with anticancer drugs. First, HCT116 human colon cancer cells were cultured with PSK and 5-fluorouracil (5-FU) or 5-deoxy-5-fluorouridine (5-DFUR) in the presence or absence of PBMCs, and the antiproliferative effects were compared. In the presence of PBMCs, PSK augmented the inhibitory effects of 5-FU and 5-DFUR on HCT116 cell proliferation. Next, using human gastric cancer and colon cancer cell lines, the effects of PSK on mRNA expression of various metabolic enzymes of fluoropyrimidines: dihydropyrimidine dehydrogenase (DPD), thymidylate synthase, thymidine phosphorylase and orotate phosphoribosyl transferase, were examined by real-time PCR. PSK significantly enhanced DPD mRNA expression in all of the cancer cell lines tested, but not those of the other enzymes. Addition of IFN-? and TRAIL, cytokines known to inhibit DPD expression, to the cultures reduced DPD mRNA expression in the cancer cells. When PBMC samples collected from healthy volunteers were cultured with PSK, IFN-? mRNA expression increased in 3 of the 5 PBMC samples, while TRAIL mRNA expression was unchanged. The present results propose the possibility that PSK induces PBMCs to express IFN-? which inhibits DPD expression, and consequently augments the antitumor effect of 5-FU or 5-DFUR. Immuno-CD-DST is useful for evaluating drugs with immunological mechanisms of action.
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Thrombomodulin Modulates Dendritic Cells via Both Antagonism of High Mobility Group Protein B1 and an Independent Mechanism.
Allergol Int
PUBLISHED: 06-17-2013
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Background: Thrombomodulin treatment modulates the properties of dendritic cells (DCs) converting them from immunogenic to tolerogenic and inducing its own expression on DCs. Thrombomodulin binds to the inflammatory mediator, high mobility group protein B1 (HMGB1), antagonizing signalling through its receptor, receptor for advanced glycation end products (RAGE). Methods: To test if soluble thrombomodulin could antagonize HMGB1 signaling via RAGE on DCs. DCs were prepared from mouse bone marrow cells or human monocytes. In some experiments dendritic cells were sorted into thrombomodulin+ and thrombomodulin- populations. Expression of surface maturation markers was determined by flow cytometry following treatment with thrombomodulin in the presence or absence of HMGB1. Results: Thrombomodulin+ dendritic cells secrete less HMGB1 into the medium. HMGB1 reduces the effects of thrombomodulin on expression of DC maturation markers. Treatment with thrombomodulin reduces the expression of maturation markers such as CD80 and CD86 and increases the expression of thrombomodulin on the DC surface. Treatment of DCs with neutralizing anti-HMGB1 antibody acted synergistically with thrombomodulin in increasing thrombomodulin expression on DCs. Treatment with thrombomodulin can still reduce the expression of surface markers on DCs derived from mice that are deficient in RAGE showing that thrombomodulin can affect DCs by an alternative mechanism. Conclusions: The results of this study show that thrombomodulin modulates DCs both by antagonizing the interaction of HMGB1 with RAGE and by an independent mechanism.
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Stratified phase II trial to establish the usefulness of the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) for advanced gastric cancer.
Gastric Cancer
PUBLISHED: 06-13-2013
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We conducted a multicenter phase II trial to assess the suitability of three types of chemotherapy (docetaxel plus S-1, irinotecan plus S-1, or S-1 alone) for patients with advanced gastric cancer by means of the collagen gel droplet embedded culture-drug sensitivity test (CD-DST). To our knowledge, this is the first multicenter clinical trial that has employed CD-DST to choose anticancer agents for the treatment of advanced gastric cancer.
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Effects of School Closure during Influenza A/H1N1 Pandemic in 2009 in Japan.
Nihon Eiseigaku Zasshi
PUBLISHED: 05-31-2013
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Schools were closed worldwide during the 2009 influenza A/H1N1 pandemic to prevent the viral spread; however, to date, there has been insufficient evidence to conclude that the closures were beneficial. Therefore, in the present review, we evaluated the effects of school closure during the 2009 influenza A/H1N1 pandemic in Japan. A search of PubMed and Japanese journals identified 24 articles that evaluated the effects of school closure using the following methods: descriptive epidemiology, changes in absenteeism rate, a simulation model, and reproductive number. Almost all of the retrieved studies showed that school closure effectively reduced the number of new infections and thus subsequently suppressed the epidemic. On the other hand, two major sets of confounding variables were identified. First, the effect of school closure was confounded by the methods used to measure, viral infectivity, subject characteristics, increased immunization rates, nonpharmaceutical interventions, antiviral administration, student contact patterns during school closure, and individual household environments. Secondly, school closure implementation was affected by differences between proactive and reactive closures, differences between seasonal and pandemic influenza, decision factors regarding school closure, socioeconomic cost, and ethics of imposing restrictions on individuals. Therefore, a comprehensive, longitudinal study is necessary to clarify the effects of school closure during viral pandemics.
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Utility of a microwave surgical instrument in sealing lymphatic vessels.
Am. J. Surg.
PUBLISHED: 05-28-2013
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This study assessed the ability of a novel microwave coagulation surgical instrument (MWCX) to seal lymphatic vessels when compared with LigaSure (Valleylab, Boulder, CO), the Harmonic Scalpel (HS; Ethicon Endo-Surgery, Cincinnati, OH), and electric cautery.
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CCDC3 is specifically upregulated in omental adipose tissue in subjects with abdominal obesity.
Obesity (Silver Spring)
PUBLISHED: 05-27-2013
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Objective The aim of this study was to search for novel markers of visceral adiposity. Design and Methods Visceral (omental) and subcutaneous adipose tissues were obtained from 43 Japanese men. We first conducted microarray analysis using total RNA from visceral and subcutaneous adipose tissues obtained from five men with abdominal obesity and five non-obese men. We then examined the expression pattern of candidate genes identified in the human study in mouse models of adiposity. Results Among 30,500 genes evaluated, the mRNA expression of CCDC3 (encoding coiled-coil domain-containing protein 3) was upregulated in omental adipose tissues from abdominally obese subjects (3.07-fold) but not in subcutaneous adipose tissues (0.89-fold). Similar expression patterns were found in two distinct mouse models of obesity. In the analysis of all 43 men, CCDC3 mRNA levels in omental, but not in subcutaneous adipose tissue, were positively correlated with waist circumference and body mass index. CCDC3 was predicted to be a secretory protein, which was confirmed by western blotting, as overexpressed CCDC3 was secreted into the culture media. Conclusions The expression of CCDC3 is specifically increased in visceral adipose tissues in abdominally obese subjects. These results suggest that CCDC3 is a potential biomarker for estimating visceral adiposity.
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Clinical characteristics and outcomes of patients with small cell lung cancer detected by CT screening.
Med. Oncol.
PUBLISHED: 05-15-2013
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The present study was performed to evaluate the clinical characteristics and survival outcomes in patients with small cell lung cancer (SCLC) detected by low-dose computed tomography (CT). We retrospectively reviewed clinical records of patients with SCLC treated at our hospital between 1997 and 2011 and selected patients with SCLC detected by CT screening. We identified 12 patients (male/female 11/1; mean age 67.8 years old. Nine patients had limited disease (LD), and 3 had extensive disease (ED). Five LD patients underwent thoracic surgery, and the pathological staging information included stage IA (n = 1), IB (n = 1), IIA (n = 1), and IIIB (n = 2). Although 2 patients with pathological stages IA and IB had >10-year survival, the median survival times (MST) in LD and ED were 25 months (95 % CI 17.0-32.9) and 16 months (95 % CI; not evaluated), respectively. In addition, MST in 12 patients was not significantly different from that in SCLC patients in general care in our hospital. This analysis suggested that CT screening contributes to the detection of early-stage SCLC in patients that are potentially suitable for surgery, but it remains unclear how to improve clinical outcome in patients with SCLC.
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IL6 trans-signaling promotes functional recovery of hypofunctional phagocytes through STAT3 activation during peritonitis.
Inflamm. Res.
PUBLISHED: 05-14-2013
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The role of high interleukin 6 (IL6) levels has not been clearly explained in severe sepsis. We show that the augmentation of the IL6 signal by recombinant IL6 receptors (rIL6R) delivery allows the functional recovery of phagocytes in a peritonitis mouse model.
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Long-term Outcomes of Coil Packing for Visceral Aneurysms: Correlation between Packing Density and Incidence of Coil Compaction or Recanalization.
J Vasc Interv Radiol
PUBLISHED: 04-26-2013
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To evaluate the correlation between packing density and the incidence of coil compaction or recanalization of visceral artery aneurysms (VAAs) after coil packing.
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Budd-Chiari Syndrome with Multiple Thrombi due to a Familial Arg42Ser Mutation in the Protein C Gene.
Case Rep Med
PUBLISHED: 04-22-2013
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A 34-year-old Japanese woman was admitted to our hospital complaining of developing bilateral pedal edema. Imaging studies led to a diagnosis of Budd-Chiari syndrome combined with internal jugular vein thrombus. We investigated the cause of thrombosis and found that the anticoagulant activity of protein C was decreased. Genetic analysis showed the presence of a c.125C>A (Arg42Ser) substitution in the protein C gene (PROC) of the proband, which generates an Arg42Ser mutation that replaces the scissile bond Arg42-Ala43 normally cleaved by a furin-like processing protease. Her father and younger brother also carried this mutation, although they had no evidence of thrombosis.
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Amino acid profile index for early detection of endometrial cancer: verification as a novel diagnostic marker.
Int. J. Clin. Oncol.
PUBLISHED: 04-18-2013
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BACKGROUND: Plasma amino acid profiles (PAAPs) vary in individual cancer patients, and it has been suggested that they may be useful for early detection of several types of cancer. We evaluated the diagnostic performance of a profile index for endometrial cancer composed of multiple plasma amino acids as a novel biomarker and compared its diagnostic performance with that of CA125. METHODS: Plasma amino acid levels of 80 patients with endometrial cancer, 122 with benign gynecological diseases, and 240 age- and body mass index-matched control subjects were measured using liquid chromatography and mass spectrometry. After univariate analysis, we applied a multiplex model based on the PAAP multivariate analysis to distinguish patients with endometrial cancer from control subjects. We compared the diagnostic performance of the multiple PAAP index (API) with that of CA125. RESULTS: The levels of several plasma amino acids were significantly different in patients with endometrial cancer. The area under the receiver operating characteristic curves (AUC) used to distinguish endometrial cancer patients from control subjects was 0.94. The AUC for API was significantly larger than that for CA125 (P = 0.0068). For the same specificity of 98.3 %, API showed a significantly higher sensitivity (60.0 %, 95 % CI, 43.3-75.1) than that of CA125 (22.5 %, 95 % CI, 10.1-38.5). In stage I cases, API showed significantly higher positivity than that of CA125 (P = 0.0002). CONCLUSIONS: The sensitivity and disease specificity of API for early-stage detection of endometrial cancer was superior to CA125. This novel plasma biomarker has the potential to become a diagnostic and screening marker for endometrial cancer.
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Two-pass dual-energy CT imaging for simultaneous detection, characterization, and volume measurement of urinary stones with excretory-phase CT urography alone: a phantom study.
Jpn J Radiol
PUBLISHED: 04-10-2013
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To evaluate if two-pass dual-energy CT imaging--i.e., simultaneous three-material and two-material decomposition analysis--can depict and characterize urinary stones in various concentrations of iodine solution in vitro.
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Octreotide improves early dumping syndrome potentially through incretins: a case report.
Endocr. J.
PUBLISHED: 04-03-2013
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Dumping syndrome, or rapid gastric emptying, is a frequent complication after gastric surgery. In this case, the patient was a 47-year-old woman who 10 years previously had undergone distal gastrectomy with Billroth I reconstruction for early-stage gastric cancer. She presented with symptoms of weakness, headache, palpitation, sweating, dizziness and significant fatigue between one and two hours after a meal. Because a 75 g oral glucose tolerance test (75 g-OGTT) induced both acute postprandial tachycardia (within 1 hour) and postprandial hypoglycemia, we diagnosed this patient with early and late dumping syndrome. Dietary measures and acarbose improved symptoms of late dumping syndrome but did not prevent the symptoms of early dumping syndrome such as postprandial tachycardia, weakness, headache, palpitation, and dizziness. We therefore used the somatostatin analogue octreotide, which has been reported as an effective therapy for early dumping syndrome. Octreotide prevented the symptoms of early dumping syndrome, especially postprandial tachycardia, but caused postprandial hyperglycemia. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were completely suppressed during the 75 g-OGTT following subcutaneous injection of octreotide. No change was observed in vasoactive intestinal polypeptide (VIP), which is the gastrointestinal peptide hormone generally responsible for early dumping syndrome, suggesting possible contribution of incretins in early dumping syndrome of this patient.
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Long-term monitoring of serum p53 antibody after neoadjuvant chemotherapy and surgery for esophageal adenocarcinoma: report of a case.
Surg. Today
PUBLISHED: 02-25-2013
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We monitored serum p53 antibody (s-p53-Ab) titers in a 76-year-old man with esophageal adenocarcinoma, clinical stage III (T2N2M0), for over 4 years, including during the perioperative period and throughout follow-up after surgery. Screening tests for CA19-9 (205 IU/ml) and s-p53-Abs (381 U/ml) were positive before treatment. After neoadjuvant chemotherapy with 5-FU and cisplatin, CA19-9 decreased to the normal range, but the s-p53-Ab titer remained positive (224 U/ml). Pathological findings of surgically resected specimens showed stage T1b disease and no lymph node metastases. After surgery, s-p53-Ab titers consistently decreased, with no disease recurrence. Although the s-p53-Ab titer remained positive even after 4 years, it decreased to 8.66, 3.59, 2.38, and 1.92 U/ml, 1, 2, 3, and 4 years after surgery, respectively. Thus, monitoring perioperative changes in s-p53-Ab titers proved useful for detecting the presence of residual cancer cells in a patient with superficial esophageal adenocarcinoma.
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Effect of sleeve gastrectomy on body weight, food intake, glucose tolerance, and metabolic hormone level in two different rat models: Goto-Kakizaki and diet-induced obese rat.
J. Surg. Res.
PUBLISHED: 02-22-2013
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It is still an important question whether sleeve gastrectomy (SG) is appropriate only in the context of obesity-the condition for which it was originally developed-or whether lean people with insulin-deficient diabetes might also benefit. The aim of this study is to evaluate the effects of SG in Goto-Kakizaki (GK) and diet-induced obese (DIO) rats that have distinct characteristics in beta-cell function and fat mass.
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Cetuximab as salvage monotherapy in chemotherapy-refractory metastatic colorectal cancer: A single-center report.
Oncol Lett
PUBLISHED: 02-08-2013
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In July 2008, cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGFR), was approved in Japan for clinical use against chemotherapy-refractory metastatic colorectal cancer (mCRC). At Shiga University of Medical Science, between December 2007 and April 2012, a total of 24 EGFR-positive mCRC cases were administered immunohistochemistry with cetuximab as salvage monotherapy. The safety, side-effects and clinical efficacy of the treatment, including response rate, time to treatment failure, progression-free and overall survival, K-ras mutation status and impact on outcome, were investigated. The patient tumor growth control rate (TCR) was 38%, the mean time to progression (TTP) was 9.8 weeks [95% confidence interval (CI), 7.2-12.4] and the mean overall survival (OS) was 49.4 weeks (95% CI, 30.1-68.8). The most common adverse reactions reported were skin reactions, including acne (67%), hand-foot syndrome (16.7%) and paronychia (16.7%), followed by hypocalcemia (50%), hypomagnesemia (16%), stomatitis (20%) and gastrointestinal disorders (12%). The results of the present single-center study demonstrated that cetuximab monotherapy is beneficial for the treatment of chemotherapy-refractory patients with mCRC and that it has an acceptable level of safety and manageable side-effects.
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Performing simple and safe dunking pancreaticojejunostomy using mattress sutures in pure laparoscopic pancreaticoduodenectomy.
Surg Endosc
PUBLISHED: 01-29-2013
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Although recent technological developments and improved endoscopic procedures have further spread the application of laparoscopic pancreatic resection, laparoscopic pancreaticoduodenectomy still presents major technical difficulties, such as when performing pancreatic-enteric anastomosis.
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Strongly driven electron spins using a K(u) band stripline electron paramagnetic resonance resonator.
J. Magn. Reson.
PUBLISHED: 01-28-2013
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This article details our work to obtain strong excitation for electron paramagnetic resonance (EPR) experiments by improving the resonators efficiency. The advantages and application of strong excitation are discussed. Two 17 GHz transmission-type, stripline resonators were designed, simulated and fabricated. Scattering parameter measurements were carried out and quality factor were measured to be around 160 and 85. Simulation results of the microwaves magnetic field distribution are also presented. To determine the excitation field at the sample, nutation experiments were carried out and power dependence were measured using two organic samples at room temperature. The highest recorded Rabi frequency was rated at 210 MHz with an input power of about 1 W, which corresponds to a ?/2 pulse of about 1.2 ns.
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RAGE-Mediated Inflammation, Type 2 Diabetes, and Diabetic Vascular Complication.
Front Endocrinol (Lausanne)
PUBLISHED: 01-01-2013
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Obesity is associated with inflammation and type 2 diabetes. Innate immune system comprised of cellular and molecular components plays an important role in the inflammatory reactions. Immune cells like macrophages and their cell surface pattern-recognition receptors (PRRs) are representative for innate immunity promoting inflammatory reactions. The receptor for advanced glycation end-products (RAGE) is a member of PRRs and a proinflammatory molecular device that mediates danger signals to the body. The expression of RAGE is observed in adipocytes as well as immune cells, endothelial cells, and pancreatic ? cells under certain conditions. It has been reported that RAGE is implicated in adipocyte hypertrophy and insulin resistance. RAGE-mediated regulation of adiposity and inflammation may attribute to type 2 diabetes and diabetic vascular complications.
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Enhanced Intestinal Motility during Oral Glucose Tolerance Test after Laparoscopic Sleeve Gastrectomy: Preliminary Results Using Cine Magnetic Resonance Imaging.
PLoS ONE
PUBLISHED: 01-01-2013
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Enhanced secretion of glucagon-like peptide-1 (GLP-1) has been suggested as a possible mechanism underlying the improvement in type 2 diabetes mellitus (T2DM) after laparoscopic sleeve gastrectomy (LSG). However, the reason for enhanced GLP-1 secretion during glucose challenge after LSG remains unclear because LSG does not include intestinal bypass. In this study, we focused on the effects of LSG on GLP-1 secretion and intestinal motility during the oral glucose tolerance test (OGTT) using cine magnetic resonance imaging (MRI) before and 3 months after LSG.
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IgG4-related airway involvement which developed in a patient receiving corticosteroid therapy for autoimmune pancreatitis.
Intern. Med.
PUBLISHED: 12-15-2011
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A 66-year-old man was diagnosed with autoimmune pancreatitis in February 2009 and started 40 mg of oral prednisolone followed by a maintenance dose of 5 mg daily. The patient developed a cough in October 2010 and visited our division. He had a high serum concentration of immunoglobulin (Ig) G4 and his chest computed tomography showed airway stenosis without bilateral hilar lymphadenopathy (BHL). The bronchial biopsy specimens revealed lymphoplasmacytic infiltrations with IgG4-positive/IgG-positive plasma cells of more than 50%. Thus, we diagnosed the airway lesion with IgG4-related airway involvement. This is the first report of a patient with IgG4-related airway involvement without BHL.
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Diabetes alters subsets of endothelial progenitor cells that reside in blood, bone marrow, and spleen.
Am. J. Physiol., Cell Physiol.
PUBLISHED: 12-07-2011
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Circulating endothelial progenitor cells (EPCs) derived from the bone marrow (BM) participate in maintaining endothelial integrity and vascular homeostasis. Reduced EPC number and function result in vascular complications in diabetes. EPCs are a population of cells existing in various differentiation stages, and their cell surface marker profiles change during the process of mobilization and maturation. Hence, a generally accepted marker combination and a standardized protocol for the quantification of EPCs remain to be established. To determine the EPC subsets that are affected by diabetes, we comprehensively analyzed 32 surface marker combinations of mouse peripheral blood (PB), BM, and spleen cells by multicolor flow cytometry. Ten subsets equivalent to previously reported mouse EPCs significantly declined in number in the PB of streptozotocin-induced diabetic mice, and this reduction was reversed by insulin treatment. The PI(-)Lin(-)c-Kit(-)Sca-1(+)Flk-1(-)CD34(-)CD31(+) EPC cluster, which can differentiate into mature endothelial cells in vitro, was the highest population in the PB, BM, and spleen and occurred 61 times more in the spleen than in the PB. The cell number significantly decreased in the BM as well as in the PB but paradoxically increased in the spleen under diabetic conditions. Insulin treatment reversed the decrease of EPC subsets in the BM and PB and reversed their increase in spleen. A similar tendency was observed in some of the major cell populations in db/db mice. To the best of our knowledge, we are the first to report spatial population changes in mouse EPCs by diabetes in the blood and in the BM across the spleen. Diminished circulating EPC supply by diabetes may be ascribed to impaired EPC production in the BM and to decreased EPC mobilization from the spleen, which may contribute to vascular dysfunction in diabetic conditions.
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[Long term oxygen therapy and mechanical ventilation for patients with COPD].
Nippon Rinsho
PUBLISHED: 11-12-2011
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Non-drug treatments such as long term oxygen therapy (LTOT) and non-invasive positive pressure ventilation (NPPV) are thought important for patients with chronic obstructive pulmonary disease (COPD). It is reported that LTOT can improve the prognosis of patients with COPD, particularly who have severe respiratory failure. NPPV attracted attention to avoid endotracheal intubation and high efficacy in patients with acute exacerbation of COPD. In chronic phase of COPD, NPPV may improve the quality of life in patients with hypercapnia, selected carefully.
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Pure laparoscopic distal pancreatectomy with en bloc celiac axis resection.
J Laparoendosc Adv Surg Tech A
PUBLISHED: 11-04-2011
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Recent technological developments and improved endoscopic procedures have greatly enlarged the applications of laparoscopic pancreatic resection.
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Fibrosis and adipogenesis originate from a common mesenchymal progenitor in skeletal muscle.
J. Cell. Sci.
PUBLISHED: 11-01-2011
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Accumulation of adipocytes and collagen type-I-producing cells (fibrosis) is observed in muscular dystrophies. The origin of these cells had been largely unknown, but recently we identified mesenchymal progenitors positive for platelet-derived growth factor receptor alpha (PDGFR?) as the origin of adipocytes in skeletal muscle. However, the origin of muscle fibrosis remains largely unknown. In this study, clonal analyses show that PDGFR?(+) cells also differentiate into collagen type-I-producing cells. In fact, PDGFR?(+) cells accumulated in fibrotic areas of the diaphragm in the mdx mouse, a model of Duchenne muscular dystrophy. Furthermore, mRNA of fibrosis markers was expressed exclusively in the PDGFR?(+) cell fraction in the mdx diaphragm. Importantly, TGF-? isoforms, known as potent profibrotic cytokines, induced expression of markers of fibrosis in PDGFR?(+) cells but not in myogenic cells. Transplantation studies revealed that fibrogenic PDGFR?(+) cells mainly derived from pre-existing PDGFR?(+) cells and that the contribution of PDGFR?(-) cells and circulating cells was limited. These results indicate that mesenchymal progenitors are the main origin of not only fat accumulation but also fibrosis in skeletal muscle.
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Hesr1 and Hesr3 are essential to generate undifferentiated quiescent satellite cells and to maintain satellite cell numbers.
Development
PUBLISHED: 10-13-2011
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Satellite cells, which are skeletal muscle stem cells, divide to provide new myonuclei to growing muscle fibers during postnatal development, and then are maintained in an undifferentiated quiescent state in adult skeletal muscle. This state is considered to be essential for the maintenance of satellite cells, but their molecular regulation is unknown. We show that Hesr1 (Hey1) and Hesr3 (Heyl) (which are known Notch target genes) are expressed simultaneously in skeletal muscle only in satellite cells. In Hesr1 and Hesr3 single-knockout mice, no obvious abnormalities of satellite cells or muscle regenerative potentials are observed. However, the generation of undifferentiated quiescent satellite cells is impaired during postnatal development in Hesr1/3 double-knockout mice. As a result, myogenic (MyoD and myogenin) and proliferative (Ki67) proteins are expressed in adult satellite cells. Consistent with the in vivo results, Hesr1/3-null myoblasts generate very few Pax7(+) MyoD(-) undifferentiated cells in vitro. Furthermore, the satellite cell number gradually decreases in Hesr1/3 double-knockout mice even after it has stabilized in control mice, and an age-dependent regeneration defect is observed. In vivo results suggest that premature differentiation, but not cell death, is the reason for the reduced number of satellite cells in Hesr1/3 double-knockout mice. These results indicate that Hesr1 and Hesr3 are essential for the generation of adult satellite cells and for the maintenance of skeletal muscle homeostasis.
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RAGE mediates vascular injury and inflammation after global cerebral ischemia.
Neurochem. Int.
PUBLISHED: 10-12-2011
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The receptor for advanced glycation end products (RAGE) is a multi-ligand receptor involved in a diverse range of pathological conditions. To analyze the roles of RAGE and its decoy receptor, endogenous secretory RAGE (esRAGE), in the global cerebral ischemia, three different mouse cohorts, wild-type, RAGE?/?, and esRAGE transgenic (Tg) mice were subjected to bilateral common carotid artery occlusion (BCCAO). RT-PCR and immunohistochemical analysis revealed that expression of RAGE was induced in the vascular cells at 12 h, and then in the neurons and glia from 3 to 7 days in the hippocampus after BCCAO. The numbers of surviving neurons in the hippocampal CA1 region were significantly higher in RAGE?/? and esRAGE Tg mice than those in wild-type mice in the periods between 24 h and 7 days after BCCAO. Lower levels of 3-nitrotyrosine (3-NT) and higher levels of endothelial nitric oxide synthase (eNOS), together with enlarged vascular areas were observed in RAGE?/? and esRAGE Tg mice at 12 h after BCCAO. In the later periods, expressions of glia-derived inflammatory mediators TNF? and inducible nitric oxide synthase (iNOS) were reduced in RAGE?/? and esRAGE Tg mice. These results suggest that RAGE may contribute to delayed neuronal death after global cerebral ischemia by enhancing vascular injury and deleterious glia-mediated inflammation.
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Epidemiology of hepatitis E virus in indoor-captive cynomolgus monkey colony.
J. Vet. Med. Sci.
PUBLISHED: 10-12-2011
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A serological survey of hepatitis E virus (HEV) antibody was conducted using 202 adult captive cynomolgus monkeys, who did not show any clinical signs of acute hepatitis. Out of these, 44 monkeys were sero-positive for anti-HEV IgG and all monkeys were negative for anti-HEV IgM. All positive monkeys came from either Vietnam or China, but none from the Philippines, Indonesia, or our facility. Selected 12 monkeys out of positive monkeys from Vietnam, including 9 positive and 3 negative, revealed mostly within the reference ranges for alanine aminotransferase (ALT) and asparatate aminotransferase (AST) by serum biochemistries. Their titers of anti-HEV IgG did not correlate with the concentrations of ALT and AST. Moreover, HEV-RNA could not be detected from any fecal specimens of the 12 monkeys. Thus, monkeys with anti-HEV IgG sero-positive did not seem to be source of the HEV-pollution, because 1) sero-positive monkeys did not excrete HEV-RNA from their feces, and 2) monkeys from the Philippines and Indonesia have remained to be sero-negative for anti-HEV IgG, even if the monkeys were kept in same animal room of our facility. From these results, it could be inferred that primary infection of HEV occurred in the exported countries, but not in our colony. The contamination of HEV in indoor-captive monkeys could be prevented by precise quarantine tests, including ELISA for detecting anti-HEV and RT-PCR for HEV RNA.
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A case of organizing pneumonia induced by tocilizumab.
Intern. Med.
PUBLISHED: 10-01-2011
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A 66-year-old woman rheumatoid arthritis was treated with methotrexate and tocilizumab. Chest radiography revealed bilateral consolidation of an upper lesion in the lung. Laboratory data indicated a hepatic disorder and increased eosinophils. Transbronchial lung biopsy specimens showed organizing pneumonia. Infection was unfavorable based on culture and PCR. Drug lymphocyte stimulation test showed positive results both for methotrexate and tocilizumab. We were concerned that her pneumonitis was drug-induced. And the symptoms appeared after the infusion of tocilizumab. Here, we report a case of tocilizumab-induced organizing pneumonia.
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Congenital dermatofibrosarcoma protuberans in a newborn infant with a massive back tumor: favorable effects of oral imatinib on the control of residual tumor growth.
J. Pediatr. Hematol. Oncol.
PUBLISHED: 09-24-2011
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Dermatofibrosarcoma protuberans (DFSP) is known as a very rare malignant tumor of the deep dermis and subcutaneous tissue. It typically develops during adolescence and adulthood, with pediatric and infantile cases, particularly congenital ones, being much less frequent. We report a neonate with congenital DFSP. A newborn girl presented with a massive back tumor at birth. The tumor was at first suspected to be infantile fibrosarcoma (IFS) after immunohistochemical analysis of biopsy material, although the results were not fully compatible with IFS. She received chemotherapy under a tentative diagnosis of IFS, but this was unsuccessful. Partial resection was therefore performed at the age of 8 months to reduce the tumor mass and to reexamine its immunohistochemical characteristics. Positive CD34 staining and Collagen ?1?/platelet-derived growth factor beta chimera gene signals on analysis of the excised tumor tissues enabled a definitive diagnosis of DFSP. She then underwent local irradiation and was given a daily dose of oral tyrosine kinase inhibitor (imatinib). After almost 1 year, the patient is doing well without enlargement of the residual tumor.
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Combination chemotherapy with doxorubicin, vincristine, cyclophosphamide, and platinum compounds for advanced thymic carcinoma.
J Thorac Oncol
PUBLISHED: 09-06-2011
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Thymic carcinoma is a rare epithelial neoplasm that tends to be aggressive and metastasize widely. The optimal chemotherapy for unresectable advanced thymic carcinoma has not yet been established because of its rare occurrence. The purpose of this study was to evaluate the efficacy and tolerability of combination chemotherapy with doxorubicin, vincristine, cyclophosphamide, and platinum compounds for advanced thymic carcinoma.
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Outcomes after curative treatment for cryptogenic cirrhosis-associated hepatocellular carcinoma satisfying the Milan criteria.
J. Gastroenterol. Hepatol.
PUBLISHED: 09-03-2011
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The prognosis of cryptogenic cirrhosis-associated hepatocellular carcinoma (CC-HCC) was reported to be poor because many of them were discovered at the advanced stage. The aim of this study is to reveal the clinical features of early CC-HCC.
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Acute occlusion of the abdominal aorta with concomitant internal iliac artery occlusion.
Ann Thorac Cardiovasc Surg
PUBLISHED: 09-02-2011
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Acute aortic occlusion is a rare but catastrophic pathology with high mortality even after revascularization. We describe four patients who underwent thrombectomy or bypass surgery for acute aortic occlusion with concomitant internal iliac artery occlusion. Two patients (82- and 75-year-old men), who had insufficient reperfusion of bilateral internal iliac arteries after treatment (thrombectomy alone and axillobifemoral bypass, respectively), died on postoperative day three of uncontrollable hyperkalemia and multiple organ failure, respectively (mortality: 50%). The third patient (74-year-old man), in whom the left internal iliac artery was reperfused after an axillobifemoral bypass, underwent right lower limb amputation but survived. The fourth patient (63-year-old man) with sufficient internal iliac artery reperfusion bilaterally after aortobifemoral and right internal iliac artery reconstruction, had an uneventful postoperative course. Elevated creatine phosphokinase and myoglobinuria levels were observed in all four patients but were notably higher in the two patients with no reperfusion in either of the internal iliac arteries. Our results suggest that reperfusion of one or more internal iliac arteries may be a crucial factor in reducing mortality in revascularization treatment of acute aortic occlusion with concomitant internal iliac artery occlusion.
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Factors predicting progression in early degenerative lumbar scoliosis.
J Orthop Surg (Hong Kong)
PUBLISHED: 08-23-2011
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To review early radiographs of patients with de novo degenerative lumbar scoliosis to determine factors predicting early scoliosis progression.
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Regulation of RAGE for attenuating progression of diabetic vascular complications.
Exp Diabetes Res
PUBLISHED: 07-23-2011
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Diabetic angiopathy including micro- and macroangiopathy is concerned with high rate of morbidity and mortality in patients with long-standing diabetes. Receptor for advanced glycation end products (RAGE) and its ligands have been considered as important pathogenic triggers for the progression of the vascular injuries in diabetes. The deleterious link between RAGE and diabetic angiopathy has been demonstrated in animal studies. Preventive and therapeutic strategies focusing on RAGE and its ligand axis may be of great importance in relieving diabetic vascular complications and reducing the burden of disease.
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Conserved GC-boxes, E-box and GATA motif are essential for GATA-4 gene expression in P19CL6 cells.
Biochem. Biophys. Res. Commun.
PUBLISHED: 07-20-2011
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The promoter of the GATA-4 gene was analyzed in P19CL6 cells. A 124bp segment containing conserved two GC-boxes and E-box was essential for the basal promoter activity, as determined with a transient luciferase reporter gene assay. However, an extended 1312 bp reporter construct but not the 124 bp segment, when ligated to the GFP gene and stably inserted into the chromosome, showed regulated promoter activity since GFP was expressed upon DMSO addition. Mutations of the two GC-boxes and/or E-box significantly impaired the GFP expression. Furthermore, mutation of the distal conserved GATA motif in the 1312 bp sequence decreased the expression of GFP. Chromatin immuno-precipitation assay showed that GATA-6 binds to this conserved GATA motif. These results suggest that the distal GATA motif recognized by GATA-6 together with the GC- and E-boxes may be important for transcriptional activation of the GATA-4 gene in the chromosome.
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An inter-networking mechanism with stepwise synchronization for wireless sensor networks.
Sensors (Basel)
PUBLISHED: 07-12-2011
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To realize the ambient information society, multiple wireless networks deployed in the region and devices carried by users are required to cooperate with each other. Since duty cycles and operational frequencies are different among networks, we need a mechanism to allow networks to efficiently exchange messages. For this purpose, we propose a novel inter-networking mechanism where two networks are synchronized with each other in a moderate manner, which we call stepwise synchronization. With our proposal, to bridge the gap between intrinsic operational frequencies, nodes near the border of networks adjust their operational frequencies in a stepwise fashion based on the pulse-coupled oscillator model as a fundamental theory of synchronization. Through simulation experiments, we show that the communication delay and the energy consumption of border nodes are reduced, which enables wireless sensor networks to communicate longer with each other.
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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.

How does it work?

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.