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Find video protocols related to scientific articles indexed in Pubmed.
Formation of a superatom monolayer using gas-phase-synthesized Ta@Si16 nanocluster ions.
Nanoscale
PUBLISHED: 10-07-2014
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The controlled assembly of superatomic nanocluster ions synthesized in the gas phase is a key technology for constructing a novel series of functional nanomaterials. However, it is generally difficult to immobilize them onto a conductive surface while maintaining their original properties owing to undesirable modifications of their geometry and charge state. In this study, it has been shown that this difficulty can be overcome by controlling the donor-acceptor interaction between nanoclusters and surfaces. Cations of Ta-atom-encapsulated Si16 cage nanoclusters (Ta@Si16) behaving as rare-gas-like superatoms are synthesized in the gas phase and deposited on conductive surfaces terminated with acceptor-like C60 and donor-like ?-sexithiophene (6T) molecules. Scanning tunneling microscopy and spectroscopy have demonstrated that Ta@Si16 cations can be densely immobilized onto C60-terminated surfaces while retaining their cage shape and positive charge, which is realized by creating binary charge transfer complexes (Ta@Si16(+)-C60(-)) on the surfaces. The Ta@Si16 nanoclusters exhibit excellent thermal stability on C60-teminated surfaces similar to those in the gas phase, whereas the nanoclusters destabilize at room temperature on 6T-terminated surfaces owing to the loss of electronic closure via a change in the charge state.
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Autoimmune pancreatitis associated with pancreatic cyst: how can we manage it?
J Hepatobiliary Pancreat Sci
PUBLISHED: 09-12-2014
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Autoimmune pancreatitis (AIP) with cyst formation (ACF) is often refractory to corticosteroid treatment (CST).
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Development of ultrafine multichannel microfluidic mixer for synthesis of bimetallic nanoclusters: catalytic application of highly monodisperse AuPd nanoclusters stabilized by poly(N-vinylpyrrolidone).
Langmuir
PUBLISHED: 08-22-2014
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On account of their novel properties, bimetallic nanoparticles and nanoclusters (NCs) are strong potential candidates for optical, magnetic, and catalytic functional materials. These properties depend on the chemical composition and size (number of constituent atoms) of the NCs. Control of size, structure, and composition is particularly important for fabricating highly functional materials based on bimetallic NCs. Size- and structure-controlled synthesis of two-element alloys can reveal their intrinsic electronic synergistic effects. However, because synergistic enhancement of activity is strongly affected by composition as well as by size and structure, controlled synthesis is a challenging task, particularly in catalytic applications. To investigate catalytic synergistic effects, we have synthesized highly monodisperse, sub-2 nm, solid-solution AuPd NCs stabilized with poly(N-vinylpyrrolidone) (AuPd:PVP) using a newly developed ultrafine microfluidic mixing device with 15 ?m wide multiple lamination channels. The synergistic enhancement for catalytic aerobic oxidation of benzyl alcohol exhibited a volcano-shaped trend, with a maximum at 20-65 at. % Pd. From X-ray photoelectron spectroscopic measurements, we confirmed that the enhanced activity originates from the enhanced electron density at the Au sites, donated by Pd sites.
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Comparison of intragastric balloon therapy and intensive lifestyle modification therapy with respect to weight reduction and abdominal fat distribution in super-obese Japanese patients.
Obes Res Clin Pract
PUBLISHED: 08-06-2014
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This study compared the impacts of intragastric balloon (IGB) therapy and intensive lifestyle modification therapy on abdominal fat distribution. Sixteen extremely obese Japanese patients were assigned to an intensive lifestyle modification therapy group with educational hospitalisation (8 patients) or an IGB therapy group (8 patients) and were followed up for 6 months. The main outcome measures were the differences at 6 months, relative to the baseline values, in the visceral fat area (VFA), subcutaneous fat area (SFA), and liver volume as measured using computed tomography. At 0 month, the body weights (BWs) were 121.3±19.0 kg and 127.1±24.4 kg and the VFAs were 299±55 cm2 and 257±56 cm2 in the intensive lifestyle modification therapy group and the IGB therapy group, respectively. No statistically significant differences in the baseline characteristics were observed between these two groups. At 6 months, no difference in the changes in BW from the baseline value (-11.5 [-16.4, -6.6] kg vs. -11.2 [-18.9, -3.4] kg) was seen between the two groups. However, a statistically significant difference in the change in the VFA (-66 [-87, -44] cm2 vs. -22 [-70, 26]cm(2) [P=0.027]) was observed; no significant changes in the SFA or liver volume were seen. In conclusion, IGB therapy was as effective as intensive lifestyle modification therapy for weight reduction but was less effective with respect to the improvement in abdominal visceral fat accumulation and liver steatosis in super-obese Japanese patients.
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Endoscopic nasobiliary drainage for obstructive jaundice using either a 5 Fr or 7 Fr catheter: a prospective, randomized trial.
BMC Gastroenterol
PUBLISHED: 07-10-2014
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The influence of size on the effectiveness of nasobiliary catheters has not yet been studied. We compared biliary drainage effectiveness and procedure-related discomfort and adverse events in 5 French (Fr) and 7 Fr nasobiliary catheters.
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Conditional knockout of the leptin receptor in the colonic epithelium revealed the local effects of leptin receptor signaling in the progression of colonic tumors in mice.
Carcinogenesis
PUBLISHED: 06-23-2014
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Leptin, secreted by the adipose tissue and known to be related to obesity, is considered to be involved in the onset and progression of colorectal cancer. However, the exact role of leptin in colorectal carcinogenesis is still unclear, as several controversial reports have been published on the various systemic effects of leptin. The aim of this study was to clarify the local and precise roles of leptin receptor (LEPR)-mediated signaling in colonic carcinogenesis using intestinal epithelium-specific LEPRb conditional knockout (cKO) mice. We produced and used colonic epithelium-specific LEPRb cKO mice to investigate the carcinogen-induced formation of aberrant crypt foci (ACF) and tumors in the colon, using their littermates as control. There were no differences in the body weight or systemic condition between the control and cKO mice. The tumor sizes and number of large-sized tumors were significantly lower in the cKO mice as compared with those in the control mice. On the other hand, there was no significant difference in the proliferative activity of the normal colonic epithelial cells or ACF formation between the control and cKO mice. In the control mice, marked increase of the LEPRb expression level was observed in the colonic tumors as compared with that in the normal epithelium; furthermore, signal transducer and activator of transcription (STAT3) was activated in the tumor cells. These findings suggest that STAT3 is one of the important molecules downstream of LEPRb, and LEPRb/STAT3 signaling controls tumor cell proliferation. We demonstrated the importance of local/regional LEPR-mediated signaling in colorectal carcinogenesis.
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Colorectal laterally spreading tumors show characteristic expression of cell polarity factors, including atypical protein kinase C ?/?, E-cadherin, ?-catenin and basement membrane component.
Oncol Lett
PUBLISHED: 06-20-2014
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Colorectal flat-type tumors include laterally spreading tumors (LSTs) and flat depressed-type tumors. The former of which shows a predominant lateral spreading growth rather than an invasive growth. The present study examined the morphological characteristics of LSTs, in comparison with polypoid- or flat depressed-type tumors, along with the expression of atypical protein kinase C (aPKC) ?/?, a pivotal cell polarity regulator, and the hallmarks of cell polarity, as well as with type IV collagen, ?-catenin and E-cadherin. In total, 37 flat-type (24 LSTs and 13 flat depressed-type tumors) and 20 polypoid-type colorectal tumors were examined. The LSTs were classified as 15 LST adenoma (LST-A) and nine LST cancer in adenoma (LST-CA). An immunohistochemical examination was performed on aPKC ?/?, type IV collagen, ?-catenin and E-cadherin. The LST-A and -CA showed a superficial replacing growth pattern, with expression of ?-catenin and E-cadherin in the basolateral membrane and type IV collagen along the basement membrane. In addition, 86.6% of LST-A and 55.6% of LST-CA showed aPKC ?/? expression of 1+ (weak to normal intensity staining in the cytoplasm compared with the normal epithelium). Furthermore, ~45% of the polypoid-type adenomas showed 2+ (moderate intensity staining in the cytoplasm and/or nucleus) and 66.7% of the polypoid-type cancer in adenoma were 3+ (strong intensity staining in the cytoplasm and nucleus). A statistically significant positive correlation was observed between the expression of aPKC ?/? and ?-catenin (r=0.842; P<0.001), or type IV collagen (r=0.823; P<0.001). The LSTs showed a unique growth pattern, different from the expanding growth pattern presented by a polypoid tumor and invasive cancer. The growth characteristics of LST appear to be caused by adequate coexpression of ?-catenin, type IV collagen and aPKC ?/?.
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PPAR?/? activation of CD300a controls intestinal immunity.
Sci Rep
PUBLISHED: 06-02-2014
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Macrophages are important for maintaining intestinal immune homeostasis. Here, we show that PPAR?/? (peroxisome proliferator-activated receptor ?/?) directly regulates CD300a in macrophages that express the immunoreceptor tyrosine based-inhibitory motif (ITIM)-containing receptor. In mice lacking CD300a, high-fat diet (HFD) causes chronic intestinal inflammation with low numbers of intestinal lymph capillaries and dramatically expanded mesenteric lymph nodes. As a result, these mice exhibit triglyceride malabsorption and reduced body weight gain on HFD. Peritoneal macrophages from Cd300a-/- mice on HFD are classically M1 activated. Activation of toll-like receptor 4 (TLR4)/MyD88 signaling by lipopolysaccharide (LPS) results in prolonged IL-6 secretion in Cd300a-/- macrophages. Bone marrow transplantation confirmed that the phenotype originates from CD300a deficiency in leucocytes. These results identify CD300a-mediated inhibitory signaling in macrophages as a critical regulator of intestinal immune homeostasis.
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Association of polymorphisms in GCKR and TRIB1 with nonalcoholic fatty liver disease and metabolic syndrome traits.
Endocr. J.
PUBLISHED: 05-01-2014
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In several genome-wide association studies, nonalcoholic fatty liver disease and alanine aminotransferase susceptibility variants have been identified in several genes, including LYPLAL1, ZP4, GCKR, HSD17B13, PALLD, PPP1R3B, FDFT1, TRIB1, COL13A1, CPN1, ERLIN1, CWF19L1, EFCAB4B, PZP, and NCAN. To investigate the relationship between these genes and nonalcoholic fatty liver disease in the Japanese population, we genotyped 540 patients and 1012 control subjects for 18 variations. We performed logistic regression analyses to characterize the association between the tested variations and nonalcoholic fatty liver disease. Metabolic syndrome and histological traits were also analyzed by linear regression. We also examined GCKR rs780094, TRIB1 rs2954021, and PNPLA3 rs738409 for epistatic effects. The A-allele of rs780094 in GCKR (P = 0.0024) and the A-allele of rs2954021 TRIB1 (P = 4.5 × 10(-5)) were significantly associated with nonalcoholic fatty liver disease. GCKR rs780094 was also associated with decreased plasma glucose, and increased triglycerides in the patient and control groups. GCKR rs780094 was also associated with an increased ratio of visceral to subcutaneous fat area in the patients with nonalcoholic fatty liver disease. Variations in GCKR, TRIB1, and PNPLA3 independently influenced nonalcoholic fatty liver disease and had no epistatic effects. Our data suggest variations in GCKR and TRIB1 are involved in the development of nonalcoholic fatty liver disease.
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Investigation of the electronic structures of organolanthanide sandwich complex anions by photoelectron spectroscopy: 4f orbital contribution in the metal-ligand interaction.
J Phys Chem A
PUBLISHED: 04-18-2014
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The electronic structures of lanthanide (Ln) ions sandwiched between 1,3,5,7-cyclooctatetraene (COT), Ln(COT)2(-), have been investigated by anion photoelectron spectroscopy. Complexes of 12 Ln atoms were investigated (excluding promethium (Pm), europium (Eu), and ytterbium (Yb)). The 213 nm photoelectron (PE) spectra of Ln(COT)2(-) exhibit two peaks assignable to the highest occupied molecular orbital (HOMO; e2u) and the next HOMO (HOMO-1; e2g) approximately at 2.6 and 3.6 eV, respectively, and their energy gap increases as the central metal atom progresses from lanthanum (La) to lutetium (Lu). Since lanthanide contraction shortens the distance between the Ln atom and the COT ligands, the widening energy gap represents the destabilization of the e2u orbital as well as the stabilization of the e2g orbital. Evidence for 4f orbital contribution in the metal-ligand interaction has been revealed by the Ln atom dependence in which the same e2u orbital symmetry enables an interaction between the 4f orbital of Ln atoms and the ? orbital of COT.
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Formation and electronic structures of organoeuropium sandwich nanowires.
J Phys Chem A
PUBLISHED: 04-14-2014
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Organoeuropium sandwich clusters, comprising europium (Eu) and 1,3,5,7-cyclooctatetraene (COT) (Eu(n)(COT)(m)), were produced in the gas phase using a laser vaporization synthesis method. Photoionization mass spectra revealed an exclusive Eu(n)(COT)(m) formation with three compositions: m = n + 1, m = n, and m = n - 1, which, we propose, correspond to full-sandwich, half-sandwich, and inverted-sandwich structures, respectively. The charge distributions, metal-ligand bonding characteristics, and electronic structures of the clusters were comprehensively investigated by photoionization measurements of Eu(n)(COT)(m) neutrals and by photoelectron spectroscopy of Eu(n)(COT)(m)(-) and isoelectronic Ba(n)(COT)(m)(-) anions. The results confirmed that (1) highly ionic metal-ligand bonding is formed between Eu(2+) and COT(2-) within the sandwich structure (at the termini, ionic forms are Eu(+) and COT(-)) and (2) size dependence of orbital energy can be explained by the Coulombic interaction of simple point charge models between the detaching electrons and dipoles/quadrupoles. When the terminus of the sandwich clusters is Eu(2+), COT(2-), or Eu(0), the orbital energy of the electron detachment channel at the opposite terminus strongly depends on the cluster size. In this case, the molecular stack behaves as a one-dimensionally aligned dipole; otherwise, it behaves as a quadrupole, and the relationship between cluster size and electron detachment energy is much weaker. The study also reports on the 4f orbital energy in Eu ions and the formation mechanism of organoeuropium sandwich nanowires up to 12 nm in length. The nanowires are formed by successive charge transfer at the terminal part, Eu(+) and COT(-), which reduces the ionization energy and increases the electron affinity, respectively.
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Metabolic factors accelerate colorectal adenoma recurrence.
BMC Gastroenterol
PUBLISHED: 03-14-2014
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Metabolic factors have been reported to increase the prevalence of colorectal adenomas, however, whether metabolic factors might also accelerate the recurrence after removal of adenomas has not yet been discussed. In this retrospective multicenter study, we clarified the risk factors for adenoma recurrence focusing on metabolic factors.
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Risk factors for small-bowel mucosal breaks in chronic low-dose aspirin users: data from a prospective multicenter capsule endoscopy registry.
Gastrointest. Endosc.
PUBLISHED: 03-14-2014
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To develop appropriate management strategies for patients who take low-dose aspirin, it is important to identify the risk factors for GI injury. However, few studies have described the risk factors for small-bowel injury in these patients.
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Pathophysiological analysis of primary biliary cirrhosis focusing on choline/phospholipid metabolism.
Liver Int.
PUBLISHED: 03-05-2014
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Injury to biliary epithelial cells caused by disorders in bile composition may be the initial step in the pathogenesis of primary biliary cirrhosis (PBC). We therefore examined choline/phospholipid metabolism in livers of patients with PBC.
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Accumulation of aberrant DNA methylation during colorectal cancer development.
World J. Gastroenterol.
PUBLISHED: 02-28-2014
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Despite the recent advances in the therapeutic modalities, colorectal cancer (CRC) remains to be one of the most common causes of cancer-related death. CRC arises through accumulation of multiple genetic and epigenetic alterations that transform normal colonic epithelium into adenocarcinomas. Among crucial roles of epigenetic alterations, gene silencing by aberrant DNA methylation of promoter regions is one of the most important epigenetic mechanisms. Recent comprehensive methylation analyses on genome-wide scale revealed that sporadic CRC can be classified into distinct epigenotypes. Each epigenotype cooperates with specific genetic alterations, suggesting that they represent different molecular carcinogenic pathways. Precursor lesions of CRC, such as conventional and serrated adenomas, already show similar methylation accumulation to CRC, and can therefore be classified into those epigenotypes of CRC. In addition, specific DNA methylation already occurs in the normal colonic mucosa, which might be utilized for prediction of the personal CRC risk. DNA methylation is suggested to occur at an earlier stage than carcinoma formation, and may predict the molecular basis for future development of CRC. Here, we review DNA methylation and CRC classification, and discuss the possible clinical usefulness of DNA methylation as biomarkers for the diagnosis, prediction of the prognosis and the response to therapy of CRC.
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Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.
World J. Gastroenterol.
PUBLISHED: 02-28-2014
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It is estimated that 30% of the adult population in Japan is affected by nonalcoholic fatty liver disease (NAFLD). Fatty changes of the liver are generally diagnosed using imaging methods such as abdominal ultrasonography (US) and computed tomography (CT), but the sensitivity of these imaging techniques is low in cases of mild steatosis. Alanine aminotransferase levels may be normal in some of these patients, warranting the necessity to establish a set of parameters useful for detecting NAFLD, and the more severe form of the disease, nonalcoholic steatohepatitis (NASH). Although liver biopsy is currently the gold standard for diagnosing progressive NASH, it has many drawbacks, such as sampling error, cost, and risk of complications. Furthermore, it is not realistic to perform liver biopsies on all NAFLD patients. Diagnosis of NASH using various biomarkers, scoring systems and imaging methods, such as elastography, has recently been attempted. The NAFIC score, calculated from the levels of ferritin, fasting insulin, and type IV collagen 7S, is useful for the diagnosis of NASH, while the NAFLD fibrosis score and the FIB-4 index are useful for excluding NASH in cases of advanced fibrosis. This article reviews the limitations and merits of liver biopsy and noninvasive diagnostic tests in the diagnosis of NAFLD/NASH.
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Protective mucosal immunity mediated by epithelial CD1d and IL-10.
Nature
PUBLISHED: 02-17-2014
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The mechanisms by which mucosal homeostasis is maintained are of central importance to inflammatory bowel disease. Critical to these processes is the intestinal epithelial cell (IEC), which regulates immune responses at the interface between the commensal microbiota and the host. CD1d presents self and microbial lipid antigens to natural killer T (NKT) cells, which are involved in the pathogenesis of colitis in animal models and human inflammatory bowel disease. As CD1d crosslinking on model IECs results in the production of the important regulatory cytokine interleukin (IL)-10 (ref. 9), decreased epithelial CD1d expression--as observed in inflammatory bowel disease--may contribute substantially to intestinal inflammation. Here we show in mice that whereas bone-marrow-derived CD1d signals contribute to NKT-cell-mediated intestinal inflammation, engagement of epithelial CD1d elicits protective effects through the activation of STAT3 and STAT3-dependent transcription of IL-10, heat shock protein 110 (HSP110; also known as HSP105), and CD1d itself. All of these epithelial elements are critically involved in controlling CD1d-mediated intestinal inflammation. This is demonstrated by severe NKT-cell-mediated colitis upon IEC-specific deletion of IL-10, CD1d, and its critical regulator microsomal triglyceride transfer protein (MTP), as well as deletion of HSP110 in the radioresistant compartment. Our studies thus uncover a novel pathway of IEC-dependent regulation of mucosal homeostasis and highlight a critical role of IL-10 in the intestinal epithelium, with broad implications for diseases such as inflammatory bowel disease.
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Association Between the Location of Diverticular Disease and the Irritable Bowel Syndrome: A Multicenter Study in Japan.
Am. J. Gastroenterol.
PUBLISHED: 02-01-2014
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OBJECTIVES:No previous reports have shown an association between location of diverticular disease (DD) and the irritable bowel syndrome (IBS).METHODS:We included 1,009 consecutive patients undergoing total colonoscopy in seven centers in Japan from June 2013 to September 2013. IBS was diagnosed using Rome III criteria, and diverticulosis was diagnosed by colonoscopy with transparent soft-short-hood. Left-sided colon was defined as sigmoid colon, descending colon, and rectum. Right-sided colon was defined as cecum, ascending colon, and transverse colon. We divided the patients into IBS and non-IBS groups and compared characteristics.RESULTS:Patient characteristics included mean age, 64.2±12.9 years and male:female ratio, 1.62:1. Right-sided DD was identified in 21.6% of subjects. Left-sided and bilateral DD was identified in 6.6 and 12.0% of subjects, respectively. IBS was observed in 7.5% of subjects. Multiple logistic regression analysis showed left-sided DD (odds ratio, 3.1; 95% confidence interval (CI): 1.4-7.1; P=0.0060) and bilateral DD (odds ratio, 2.6; 95% CI, 1.3-5.2; P=0.0070) were independent risk factors for IBS. Right-sided DD was not a risk factor for IBS.CONCLUSIONS:Our data showed that the presence of left-sided and bilateral DD, but not right-sided disease, was associated with a higher risk of IBS, indicating that differences in pathological factors caused by the location of the DD are important in the development of IBS. Clarifying the specific changes associated with left-sided DD could provide a better understanding of the pathogenic mechanisms of IBS (Trial registration # R000012739).Am J Gastroenterol advance online publication, 21 October 2014; doi:10.1038/ajg.2014.323.
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Gastroduodenal stenting with Niti-S stent: Long-term benefits and additional stent intervention.
Dig Endosc
PUBLISHED: 01-29-2014
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Self-expandable metallic stents have mainly been used for the palliation of malignant gastric outlet obstruction (GOO). However, their use in long-term survivors and the feasibility, safety and benefit of additional intervention for stent dysfunction remain controversial. The present study examined the long-term benefits of endoscopic gastroduodenal stenting.
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Probing of an adsorbate-specific excited state on an organic insulating surface by two-photon photoemission spectroscopy.
J. Am. Chem. Soc.
PUBLISHED: 01-22-2014
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In this study, we investigate the photoexcited electronic states of ferrocene (Fc) molecules adsorbed on an organic insulating surface by two-photon photoemission spectroscopy. This insulating layer, composed of a decanethiolate self-assembled monolayer formed on an Au(111) substrate, enables us to probe the electronically excited states localized at the adsorbed Fc molecules. The adsorbate-specific state is resonantly excited by photons at 4.57 eV, which is 0.5 eV smaller than the energy of the first molecular Rydberg state of free Fc in the gas phase. This result indicates that the electrons are bound to both the excited hole formed in the adsorbate and the positive image charge induced in the substrate. The hybridized electronic characteristics of the adsorbate-specific state are responsible for the strong transition selectivity and short lifetime of the excited state.
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Methylation epigenotypes and genetic features in colorectal laterally spreading tumors.
Int. J. Cancer
PUBLISHED: 01-15-2014
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Aberrant DNA methylation plays an important role in genesis of colorectal cancer (CRC). Previously, we identified Group 1 and Group 2 methylation markers through genome-wide DNA methylation analysis, and classified CRC and protruded adenoma into three distinct clusters: high-, intermediate- and low-methylation epigenotypes. High-methylation epigenotype strongly correlated with BRAF mutations and these aberrations were involved in the serrated pathway, whereas intermediate-methylation epigenotype strongly correlated with KRAS mutations. Here, we investigated laterally spreading tumors (LSTs), which are flat, early CRC lesions, through quantitative methylation analysis of six Group 1 and 14 Group 2 methylation markers using pyrosequencing. Gene mutations in BRAF, KRAS and PIK3CA, and immunostaining of TP53 and CTNNB1 as well as other clinicopathological factors were also evaluated. By hierarchical clustering using methylation information, LSTs were classified into two subtypes; intermediate-methylation epigenotype correlating with KRAS mutations (p = 9 × 10(-4)) and a granular morphology (LST-G) (p = 1 × 10(-7)), and low-methylation epigenotype correlating with CTNNB1 activation (p = 0.002) and a nongranular morphology (LST-NG) (p = 1 × 10(-7)). Group 1 marker methylation and BRAF mutations were barely detected, suggesting that high-methylation epigenotype was unlikely to be involved in LST development. TP53 mutations correlated significantly with malignant transformation, regardless of epigenotype or morphology type. Together, this may suggest that two molecular pathways, intermediate methylation associated with KRAS mutations and LST-G morphology, and low methylation associated with CTNNB1 activation and LST-NG morphology, might be involved in LST development, and that involvement of TP53 mutations could be important in both subtypes in the development from adenoma to cancer.
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Simple scoring system for predicting cirrhosis in nonalcoholic fatty liver disease.
World J. Gastroenterol.
PUBLISHED: 01-09-2014
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To investigate a simple noninvasive scoring system for predicting liver cirrhosis in nonalcoholic fatty liver disease (NAFLD) patients.
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Targeted next-generation sequencing and fine linkage disequilibrium mapping reveals association of PNPLA3 and PARVB with the severity of nonalcoholic fatty liver disease.
J. Hum. Genet.
PUBLISHED: 01-06-2014
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The genomic regions containing PNPLA3, SAMM50 and PARVB are susceptibility loci for the development and progression of nonalcoholic fatty liver disease (NAFLD). In order to search for all common variations in this region, we amplified the genomic DNA of 28 NAFLD patients by long-range PCR, covering the entire susceptibility region and sequenced the DNA using indexed multiplex next-generation sequencing. We found 329 variations, including four novel variations. Fine mapping of variations including insertion/deletions was performed for 540 NAFLD patients (488 with nonalcoholic steatohepatitis (NASH) and 52 with simple steatosis) and 1012 control subjects. HaploView analysis showed that linkage disequilibrium (LD) block 1 and 2 occurred in PNPLA3, block 3 in SAMM50 and block 4 in PARVB. Variations in LD blocks 1-4 were significantly associated with NAFLD as compared with control subjects (P<1 × 10(-8)). Variations in LD block 2 were significantly associated with the NAFLD activity score (NAS), aspartate aminotransferase and alanine aminotransferase. Variations in LD block 1 were significantly associated with the fibrosis stage. The strongest associations were observed for variations in LD block 4, with NASH as compared with simple steatosis (P=7.1 × 10(-6)) and NAS (P=3.4 × 10(-6)). Our results suggested that variations, including insertion/deletions, in PARVB, as well as those in PNPLA3, are important in the progression of NAFLD.
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[Pathophysiology of NAsh/NAFLD associated with high levels of serum triglycerides].
Nippon Rinsho
PUBLISHED: 11-12-2013
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The patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepa-titis(NASH) often have dyslipidemia along with other features of metabolic syndrome such as obesity, diabetes mellitus, and hypertension. The dyslipidemia in NAFLD is characterized by increased serum triglycerides, increased small dense low-density lipoprotein, and low high-density lipoprotein cholesterol. The pathogenesis of dyslipidemia in NAFLD is not well understood, but it is likely related to hepatic overproduction of the very low-density lipoprotein 1 and decreasing clearance of lipoproteins from the circulation. Recently it is showed that free fatty acids induce hepatocyte lipoapoptosis in vitro. In this manuscript we discuss about "hypertriglyceridemia and NASH/NAFLD".
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Endoscopic papillary large-balloon dilation versus endoscopic papillary regular-balloon dilation for removal of large bile-duct stones.
J Hepatobiliary Pancreat Sci
PUBLISHED: 10-14-2013
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Endoscopic papillary large-balloon dilation (EPLBD) became popular for the treatment of large common bile-duct stones (CBDS), and its feasibility has been reported in comparison to endoscopic sphincterotomy. However, the comparison between EPLBD and endoscopic papillary regular-balloon dilation (EPBD) has not been reported. In the present study, the efficacy and complications of EPLBD were compared with those of EPBD.
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Advanced nanocluster ion source based on high-power impulse magnetron sputtering and time-resolved measurements of nanocluster formation.
J Phys Chem A
PUBLISHED: 09-30-2013
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We developed a new nanocluster (NC) ion source based on the high-power impulse magnetron sputtering (HiPIMS) technique coupled with a gas flow cell reactor. Silver NC anions (Ag(n)(-)) with a maximum intensity of 5.5 nA (Ag11(-)) are generated with the size ranging from the atomic anion to the 70-mer, which is well-controlled by simply adjusting the peak power and repetition rate of the HiPIMS. By time-resolved density profiles of Ag(n)(-), we find that the ion beam generated by HiPIMS is characterized by individual 100 ms duration "bunches" below a repetition rate of 10 Hz, which is well-thermalized with a group velocity of 5 m/s. The high intensity of the NCs is attributable to the high ionization fraction by this HiPIMS ion source, while the underlying mechanism of the flexible size tuning of the ion source is understood by time-resolved mass spectrometry coupled with the sequential growth mechanism; the increment of the density of the target species in the bunches with the peak power and the overlapping of the bunches with the repetition rate cause the formation of large NCs.
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Rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.
Int J Mol Sci
PUBLISHED: 08-27-2013
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Research in nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), has been limited by the availability of suitable models for this disease. A number of rodent models have been described in which the relevant liver pathology develops in an appropriate metabolic context. These models are promising tools for researchers investigating one of the key issues of NASH: not so much why steatosis occurs, but what causes the transition from simple steatosis to the inflammatory, progressive fibrosing condition of steatohepatitis. The different rodent models can be classified into two large groups. The first includes models in which the disease is acquired after dietary or pharmacological manipulation, and the second, genetically modified models in which liver disease develops spontaneously. To date, no single rodent model has encompassed the full spectrum of human disease progression, but individual models can imitate particular characteristics of human disease. Therefore, it is important that researchers choose the appropriate rodent models. The purpose of the present review is to discuss the metabolic abnormalities present in the currently available rodent models of NAFLD, summarizing the strengths and weaknesses of the established models and the key findings that have furthered our understanding of the diseases pathogenesis.
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Positioning of nasobiliary tube using magnet-loaded catheters.
Endoscopy
PUBLISHED: 07-29-2013
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In endoscopic nasobiliary drainage (ENBD), repositioning the catheter from the mouth to the nose is complicated. We devised a method using catheters with magnets and verified its utility and safety.
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Emerging drugs for non-alcoholic steatohepatitis.
Expert Opin Emerg Drugs
PUBLISHED: 07-13-2013
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The prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is increasing along with the worldwide epidemic of obesity and their strong association with metabolic syndrome. Currently existing pharmacological therapies include anti-oxidants, insulin-sensitizing agents, lipid-lowering drugs and cytoprotective agents, but there is a lack of consensus regarding the most effective and appropriate pharmacologic therapies for NASH. Clinical trials examining new therapeutic drugs for NASH that act via various mechanisms are being performed in several countries, and these drugs may strongly influence current NASH treatment.
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Epidemiology and clinical experience of chronic intestinal pseudo-obstruction in Japan: a nationwide epidemiologic survey.
J Epidemiol
PUBLISHED: 07-09-2013
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We estimated the prevalence and incidence of chronic intestinal pseudo-obstruction (CIPO) in Japan, investigated the patterns of hospital visits among those with CIPO, and examined present knowledge of CIPO among medical professionals.
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Characteristics of the small bowel lesions detected by capsule endoscopy in patients with chronic kidney disease.
Gastroenterol Res Pract
PUBLISHED: 07-05-2013
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Obscure gastrointestinal bleeding (OGIB) is one of the common complications in patients with chronic kidney disease (CKD), especially those who are on maintenance hemodialysis (HD). However, little is known about the characteristics of the small-bowel lesions in these patients, or of the factors that could predict the presence of such lesions. Therefore we enrolled a total of 42 CKD patients (including 19 HD patients and 23 non-HD patients), and compared the incidence of the small-bowel lesions among two groups. Furthermore, to identify predictive factors for the presence of small-bowel lesions, we performed multivariate logistic-regression-analyses. The incidence of small-bowel vascular lesions was significantly higher in CKD patients than in age-and-sex matched non-CKD patients (P < 0.001). On the other hand, there was any significant difference of the incidence of small-bowel lesions between HD and non-HD patients. In CKD patients, past history of blood transfusion (OR 5.66; 95% CI 1.10-29.1, P = 0.04) was identified as an independent predictor of the presence of vascular lesions, and history of low-dose aspirin use (OR 6.00; 95% CI 1.13-31.9, P = 0.04) was identified as that of erosive/ulcerated lesions. This indicated that proactive CE examination would be clinically meaningful for these patients.
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Critical role of leukotriene B4 receptor signaling in mouse 3T3-L1 preadipocyte differentiation.
Lipids Health Dis
PUBLISHED: 07-05-2013
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Various inflammatory mediators related to obesity might be closely related to insulin resistance. Leukotrienes (LTs) are involved in inflammatory reactions. However, there are few reports regarding the role of LTs in adipocyte differentiation. Therefore, we investigated the role of leukotriene B4 (LTB4)-leukotriene receptor (BLT) signaling in mouse 3T3-L1 fibroblastic preadipocyte differentiation to mature adipocytes.
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The association of insomnia with gastroesophageal reflux symptoms in biopsy-proven nonalcoholic fatty liver disease.
J. Gastroenterol.
PUBLISHED: 06-27-2013
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It is suggested that nonalcoholic fatty liver disease (NAFLD), including nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), can be associated with insomnia and gastro-esophageal reflux disease (GERD). The relationship between GERD and insomnia in subjects with biopsy-proven NAFLD was investigated.
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Visceral obesity as a risk factor for left-sided diverticulitis in Japan: a multicenter retrospective study.
Gut Liver
PUBLISHED: 06-11-2013
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Left-sided diverticulitis is increasing in Japan, and many studies report that left-sided diverticulitis is more likely to be severe. Therefore, it is important to identify the features and risk factors for left-sided diverticulitis. We hypothesized that left-sided diverticulitis in Japan is related to obesity and conducted a study of the features and risk factors for this disorder in Japan.
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NUDT3 rs206936 is associated with body mass index in obese Japanese women.
Endocr. J.
PUBLISHED: 05-25-2013
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The predominant risk factor of metabolic syndrome is intra-abdominal fat accumulation, which is determined by waist circumference, waist-hip ratio measurements and visceral fat area (VFA); the latter can be accurately measured by performing computed tomography (CT). In addition to environmental factors, genetic factors play an important role in obesity and fat distribution. New genetic loci associated with body mass index (BMI) and adiposity have been identified by genome-wide association studies (GWASs). This study utilized CT to investigate whether single nucleotide polymorphisms (SNPs) that confer susceptibility to higher BMI are associated with VFA, subcutaneous fat area (SFA), and the ratio of VFA to SFA (V/S ratio). We measured the VFA and SFA of 1424 obese Japanese subjects (BMI ? 25 kg/m(2), 635 men and 789 women) who were genotyped for 13 single nucleotide polymorphisms (SNPs) reported by recent GWASs, namely, TNNI3K rs1514175, PTBP2 rs1555543, ADCY3 rs713586, IRS1 rs2943650, POC5 rs2112347, NUDT3 rs206936, LINGO2 rs10968576, STK33 rs4929949, MTIF3 rs4771122, SPRY2 rs534870, MAP2K5 rs2241423, QPCTL rs2287019, and ZC3H4 rs3810291. The G-allele of NUDT3 rs206936 was significantly associated with increased BMI (P = 5.3 × 10(-5)) and SFA (P = 0.00039) in the obese Japanese women. After adjustment with BMI, the association between rs206936 and SFA was not observed. This significant association was not observed in the men. The other SNPs analyzed were not significantly associated with BMI, VFA, SFA, or V/S ratio. Our results suggest that NUDT3 rs206936 is associated with BMI in Japanese women.
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Postpyloric decompression tube placement through a gastrostomy for malignant bowel obstruction.
BMC Res Notes
PUBLISHED: 05-23-2013
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Malignant bowel obstruction affect a patients quality of life, but, management of MBO is controversial.
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Microbiota and nonalcoholic steatohepatitis.
Semin Immunopathol
PUBLISHED: 04-07-2013
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The recent rise in obesity-related diseases, such as nonalcoholic fatty liver disease and its strong association with microbiota, has elicited interest in the underlying mechanisms of these pathologies. Experimental models have highlighted several mechanisms connecting microbiota to the development of liver dysfunction in nonalcoholic steatohepatitis (NASH) such as increased energy harvesting from the diet, small intestine bacterial overgrowth, modulation of the intestinal barrier by glucagon-like peptide-2 secretions, activation of innate immunity through the lipopolysaccharide-CD14 axis caused by obesity-induced leptin, periodontitis, and sterile inflammation. The manipulation of microbiota through probiotics, prebiotics, antibiotics, and periodontitis treatment yields encouraging results for the treatment of obesity, diabetes, and NASH, but data in humans is scarce.
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Gastric neuroendocrine carcinoma with non-islet cell tumor hypoglycemia associated with enhanced production of insulin-like growth factor II.
Intern. Med.
PUBLISHED: 04-01-2013
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A 75-year-old man was admitted to the hospital with a loss of consciousness. His blood glucose level was 24 mg/dL. Abdominal computed tomography revealed multiple metastatic lesions in the liver, while upper endoscopy disclosed advanced gastric cancer. The hypoglycemia was refractory despite the administration of glucose and steroid therapy. The patient died within one month of admission. An autopsy revealed neuroendocrine-type gastric cancer, which, on examination with immunohistochemistry, was found to be negative for insulin and insulin-like growth factor I and positive for insulin-like growth factor II (IGF-II). The patient was diagnosed as having gastric cancer with non-islet cell tumor hypoglycemia (NICTH) caused by IGF-II.
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Early Effect of Single-dose Sitagliptin Administration on Gastric Emptying: Crossover Study Using the (13)C Breath Test.
J Neurogastroenterol Motil
PUBLISHED: 02-21-2013
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The gastrointestinal motility effects of endogenous incretin hormones enhanced by dipeptidyl peptidase-IV (DPP-IV) inhibitors have not yet been sufficiently investigated. The aim of this study was to determine whether single pre-prandial sitagliptin, the DPP-IV inhibitor, administration might have an effect on the rate of liquid gastric emptying using the (13)C-acetic acid breath test.
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Efficacy of Lidocaine lontophoresis Using Either Alternating or Direct Current in Hairless Rats.
J. Med. Dent. Sci.
PUBLISHED: 02-19-2013
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The aim of this study was to determine transport of lidocaine ions through a hairless rat skin in vivo and to compare the efficacy of alternating current (AC) with that of direct current (DC) iontophoresis (IOP). We measured the concentration of lidocaine transported through a cellophane membrane or a hairless rat dorsal skin applying either AC-IOP or DC-IOP. The results revealed that lidocaine concentration increased in a time-dependent manner in vitro in both DC-IOP and AC-IOP. However, the in vivo study showed different tendencies in lidocaine concentration. In the DCIOP group, lidocaine concentration reached its maximum 20 min after current application and then decreased rapidly; the AC-IOP group showed an increase in lidocaine concentration in a timedependent manner. There were no side effects such as electrical burns in the rats. In conclusion, AC can be applied for long periods and DC for short periods, or their application time can be appropriately scheduled. Our study also suggests the mechanism by which voltage waveforms affect the skin when applied by IOP. In the future, these findings will be a solid foundation for developing various kinds of medical equipment such as scheduled drug delivery system that can easily deliver various types of drug.
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A novel scoring system for arterial invasion of pancreatic body and tail cancer based on multidetector row computed tomography and biomarkers.
Pancreatology
PUBLISHED: 01-22-2013
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The absence of major-vessel involvement is a crucial factor in the resectability and prognosis of pancreatic cancer. However, arterial invasion cannot be evaluated adequately using imaging findings alone. We therefore developed a scoring system to assess arterial invasion by pancreatic adenocarcinoma using multidetector row computed tomography (MDCT) and serum tumor markers.
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Covered self-expandable metal stent deployment promises safe neoadjuvant chemoradiation therapy in patients with borderline resectable pancreatic head cancer.
Dig Endosc
PUBLISHED: 01-17-2013
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Patients with borderline resectable pancreatic head cancer (BRPHC) have been treated with neoadjuvant chemoradiation therapy (NACRT) using metallic stents. The aim of the present study was to evaluate the efficacy and complications of covered self-expanding metallic stents (CSEMS) during the NACRT and surgical period.
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Improvement of pneumatosis cystoides intestinalis after steroid tapering in a patient with bronchial asthma: a case report.
J Med Case Rep
PUBLISHED: 01-15-2013
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We report the case of a patient who was diagnosed as having pneumatosis cystoides intestinalis while being treated with prednisolone for bronchial asthma. Even before we had experienced a case of this, the relationship between pneumatosis cystoides intestinalis and prednisolone was unclear. In this case, pneumatosis cystoides intestinalis was improved with the reduction of prednisolone, and therefore we thought a direct relationship between pneumatosis cystoides intestinalis and prednisolone might become clear, such as whether it is dose dependent.
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Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan.
Hum. Genet.
PUBLISHED: 01-14-2013
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We examined the genetic background of nonalcoholic fatty liver disease (NAFLD) in the Japanese population, by performing a genome-wide association study (GWAS). For GWAS, 392 Japanese NAFLD subjects and 934 control individuals were analyzed. For replication studies, 172 NAFLD and 1,012 control subjects were monitored. After quality control, 261,540 single-nucleotide polymorphisms (SNPs) in autosomal chromosomes were analyzed using a trend test. Association analysis was also performed using multiple logistic regression analysis using genotypes, age, gender and body mass index (BMI) as independent variables. Multiple linear regression analyses were performed to evaluate allelic effect of significant SNPs on biochemical traits and histological parameters adjusted by age, gender, and BMI. Rs738409 in the PNPLA3 gene was most strongly associated with NAFLD after adjustment (P = 6.8 × 10(-14), OR = 2.05). Rs2896019, and rs381062 in the PNPLA3 gene, rs738491, rs3761472, and rs2143571 in the SAMM50 gene, rs6006473, rs5764455, and rs6006611 in the PARVB gene had also significant P values (<2.0 × 10(-10)) and high odds ratios (1.84-2.02). These SNPs were found to be in the same linkage disequilibrium block and were associated with decreased serum triglycerides and increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in NAFLD patients. These SNPs were associated with steatosis grade and NAFLD activity score (NAS). Rs738409, rs2896019, rs738491, rs6006473, rs5764455, and rs6006611 were associated with fibrosis. Polymorphisms in the SAMM50 and PARVB genes in addition to those in the PNPLA3 gene were observed to be associated with the development and progression of NAFLD.
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aPKC?/? is a beneficial prognostic marker for pancreatic neoplasms.
Pancreatology
PUBLISHED: 01-13-2013
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Pancreatic cancer is a lethal disease. Overall survival is typically 6 months from diagnosis. Determination of prognostic factors in pancreatic cancer that would allow identification of patients who could potentially benefit from aggressive treatment is important. However, until date, there are no established reliable prognostic factors for pancreatic cancer patients. Herein, we propose a beneficial biomarker which is significantly correlated with the prognosis in pancreatic cancer patients. Atypical protein kinase C ?/? (aPKC?/?) is overexpressed and has been implicated in the progression of several cancers. We tested the expression levels of aPKC?/? in two types of pancreatic neoplasm, pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs), by immunohistochemistry. Examination of the aPKC?/? expression levels in surgically resected specimens of PDCA (n = 115) demonstrated that the expression levels of aPKC?/?in PDAC had prognostic implications, independent of the Tumor-Node-Metastasis classification and World Health Organization tumor grade. In the case of IPMNs (n = 46) also, the expression levels of aPKC?/?in IPMN were found to be of prognostic importance, independent of the World Health Organization histological grade or morphological type. Interestingly, high expression levels of aPKC?/? were significantly correlated with a worse histological grade (p = 0.010) and advanced stage of the tumor (p = 0.0050) in IPMN patients. These findings suggest that high expression levels of aPKC?/? could be involved in the malignant transformation of IPMNs. Based on these observations, we propose the expression level of aPKC?/? as a prognostic marker common to different types of pancreatic neoplasms.
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Hepatic triglyceride lipase plays an essential role in changing the lipid metabolism in genotype 1b hepatitis C virus replicon cells and hepatitis C patients.
Hepatol. Res.
PUBLISHED: 01-06-2013
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AIM: Recently, several studies have shown the existence of associations between lipoprotein profiles and hepatitis C virus (HCV), although only a limited amount of information is available about the mechanisms underlying the changes in the lipoprotein profiles associated with HCV. In this study, we investigated the association between lipoprotein profile, classified according to the particle size, and lipoprotein metabolism. METHODS: We used four kinds of cells for this experiment; full-length genome HCV RNA replicon cells (OR6), sub-genomic HCV RNA replicon cells (sO), and OR6c cells and sOc cells, which were the same cell lines treated with interferon-?. The triglyceride (TG) levels in the lipoprotein subclasses of the culture medium were measured by high-performance liquid chromatography. The mRNA expression levels of several molecules associated with lipoprotein metabolism were measured in the OR6, OR6c, sO and sOc cells. To confirm some of the results obtained using the in vitro system, liver biopsy samples obtained from the patients were also examined. RESULTS: The content of TG in the large low-density lipoprotein (LDL) and medium LDL in the culture medium was increased only in the OR6 cells. The hepatic triglyceride lipase (HTGL) mRNA expression levels were lower in the OR6 cells than in the OR6c cells (P?
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Alteration of the redox state with reactive oxygen species for 5-Fluorouracil-induced oral mucositis in hamsters.
PLoS ONE
PUBLISHED: 01-01-2013
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Oral mucositis is often induced in patients receiving cancer chemotherapy treatment. It has been reported that oral mucositis can reduce quality of life, as well as increasing the incidence of mortality. The participation of reactive oxygen species (ROS) in the pathogenesis of oral mucositis is well known, but no report has actually demonstrated the presence of ROS. Thus, the purpose of this study was thus to demonstrate the involvement of ROS and the alteration of the redox state in oral mucositis using an in vivo L-band electron spin resonance (ESR) technique. An oral mucositis animal model induced by treatment of 5-fluorouracil with 10% acetic acid in hamster cheek pouch was used. Lipid peroxidation was measured as the level of malondialdehyde determined by the thiobarbituric acid reaction. The rate constants of the signal decay of nitroxyl compounds using in vivo L-band ESR were calculated from the signal decay curves. Firstly, we established the oral mucositis animal model induced by treatment of 5-fluorouracil with acetic acid in hamster cheek pouch. An increased level of lipid peroxidation in oral mucositis was found by measuring malondialdehyde using isolated hamster cheek pouch ulcer. In addition, as a result of in vivo L-band ESR measurements using our model animals, the decay rate constants of carbamoyl-PROXYL, which is a reagent for detecting the redox balance in tissue, were decreased. These results suggest that a redox imbalance might occur by excessive generation of ROS at an early stage of oral mucositis and the consumption of large quantities of antioxidants including glutathione in the locality of oral mucositis. These findings support the presence of ROS involved in the pathogenesis of oral mucositis with anti-cancer therapy, and is useful for the development of novel therapies drugs for oral mucositis.
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Soluble CD14 levels reflect liver inflammation in patients with nonalcoholic steatohepatitis.
PLoS ONE
PUBLISHED: 01-01-2013
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Liver inflammation is a risk factor for the progression of nonalcoholic fatty liver disease (NAFLD). However, the diagnosis of liver inflammation is very difficult and invasive liver biopsy is still the only method to reliably detect liver inflammation. We previously reported that overexpression of CD14 in Kupffer cells may trigger the progression to nonalcoholic steatohepatitis (NASH) via liver inflammation following hyper-reactivity to low-dose lipopolysaccharide. Therefore, the aim of this study was to investigate the relationship between soluble type of CD14 (sCD14) and histological features in patients with NAFLD.
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Identification of preneoplastic lesions as mucin-depleted foci in patients with sporadic colorectal cancer.
Cancer Sci.
PUBLISHED: 11-28-2011
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In experimental models, mucin-depleted foci (MDF), formed by dysplastic crypts devoid of mucin production have been recognized to be correlated with colorectal carcinogenesis and to serve as preneoplastic lesions of colorectal cancer (CRC). In humans, there is only one report of identification of MDF in patients with familial adenomatous polyposis and CRC; however, the histological characteristics of human MDF are not discussed extensively in the report. In the present study, colonic samples from 53 patients with sporadic CRC were stained with Alcian blue and examined for the presence of MDF. Subsequently, the samples were examined for the presence of aberrant crypt foci (ACF) by methylene blue staining. We classified MDF into two categories: flat-MDF and protruded-MDF (having the characteristics of both ACF and MDF). We found a total of 354, 41 and 19 colonic mucosal lesions with a mean multiplicity of 44, 38.9 and 66.9 crypts (ACF, flat-MDF and protruded-MDF, respectively). The density of MDF was 0.0082 lesions/cm(2) . The ACF identified in sporadic CRC patients corresponded to hyperplastic or non-dysplasic lesions. However, MDF identified in these patients corresponded to low-grade dysplasia. In addition, we found that Paneth cell metaplasia and inflammatory cell infiltration were specific histological features of MDF. These histological characteristics are reported to be associated with the development of CRC. Therefore, our results indicate that MDF might represent preneoplastic lesions in human colorectal carcinogenesis.
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Genetic variations in the CYP17A1 and NT5C2 genes are associated with a reduction in visceral and subcutaneous fat areas in Japanese women.
J. Hum. Genet.
PUBLISHED: 11-10-2011
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Visceral fat accumulation has an important role in increasing the morbidity and mortality rates, by increasing the risk of developing several metabolic disorders, such as type 2 diabetes, dyslipidemia and hypertension. New genetic loci that are associated with increased systolic and diastolic blood pressures have been identified by genome-wide association studies in Caucasian populations. This study investigates whether single nucleotide polymorphisms (SNPs) that confer susceptibility to high blood pressure are also associated with visceral fat obesity. We genotyped 1279 Japanese subjects (556 men and 723 women) who underwent computed tomography for measuring the visceral fat area (VFA) and subcutaneous fat area (SFA) at the following SNPs: FGF5 rs16998073, CACNB2 rs11014166, C10orf107 rs1530440, CYP17A1 rs1004467, NT5C2 rs11191548, PLEKHA7 rs381815, ATP2B1 rs2681472 and rs2681492, ARID3B rs6495112, CSK rs1378942, PLCD3 rs12946454, and ZNF652 rs16948048. In an additive model, risk alleles of the CYP17A1 rs1004467 and NT5C2 rs11191548 were found to be significantly associated with reduced SFA (P=0.00011 and 0.0016, respectively). When the analysis was performed separately in men and women, significant associations of rs1004467 (additive model) and rs11191548 (recessive model) with reduced VFA (P=0.0018 and 0.0022, respectively) and SFA (P=0.00039 and 0.00059, respectively) were observed in women, but not in men. Our results suggest that polymorphisms in the CYP17A1 and NT5C2 genes influence a reduction in both visceral and subcutaneous fat mass in Japanese women.
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A case of rectal cancer arising from long-standing prolapsed mucosa of the rectum.
Intern. Med.
PUBLISHED: 11-01-2011
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Mucosal prolapse syndrome (MPS) has been recognized as a chronic benign inflammatory disorder, characterized mainly by rectal mucosal prolapse. Disorders representing this condition include solitary rectal ulcer syndrome (SRUS), rectal prolapse, proctitis cystica profunda, and inflammatory cap polyps. The gross appearance of rectal MPS can be occasionally misinterpreted as rectal cancer. In contrast, there have been a few reports of colorectal cancer originating from prolapsed mucosa. Herein, we report a case of MPS associated with two independent rectal cancers extending into the submucosal layer. We speculate that long-standing MPS may increase the risk of malignant transformation.
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Soft- and reactive-landing of Cr(aniline)2 sandwich complexes onto self-assembled monolayers: separation between functional and binding sites.
J. Am. Chem. Soc.
PUBLISHED: 10-27-2011
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Soft- and reactive-landing of gas-phase synthesized cationic Cr(aniline)(2) complexes onto self-assembled monolayers of methyl-terminated (CH(3)-SAM) and carboxyl-terminated (COOH-SAM) organothiolates coated on gold were performed at hyperthermal collision energy (5-20 eV). The properties of the Cr(aniline)(2) complexes on the SAM surfaces were characterized using infrared reflection absorption spectroscopy (IRAS) and temperature-programmed desorption (TPD), together with theoretical calculations based on density functional theory (DFT). For the CH(3)-SAM, the Cr(aniline)(2) complexes were embedded inside the SAM matrix in a neutral charge state, keeping a sandwich structure. For the COOH-SAM, the IRAS and TPD study revealed that the amine-containing Cr(aniline)(2) complexes were bound to the SAM surface in two forms of physisorption and chemical linking through an amide bond. In the desorption, the latter form appeared as the reaction product between organothiolates and Cr(aniline)(2) above 400 K, where the organothiolate molecules, forming the SAM, were desorbed from the gold surface. The results show that the hyperthermal depositions onto a COOH-SAM bring about reactive-landing followed by covalent linking of an amide bond between the amine-containing Cr(aniline)(2) complexes to the carboxyl-terminated SAM surface, in which the binding sites can be separated from the functional sites of the d-? interaction.
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Sitagliptin as a novel treatment agent for non-alcoholic Fatty liver disease patients with type 2 diabetes mellitus.
Hepatogastroenterology
PUBLISHED: 10-26-2011
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Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury, and is considered as the hepatic manifestation of metabolic syndrome. However, no effective drug therapy for NAFLD has been established yet. In the present study, we evaluated the efficacy of 4 months of treatment with sitagliptin in NAFLD patients with type 2 diabetes mellitus (DM).
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Semaphorin 4D, a lymphocyte semaphorin, enhances tumor cell motility through binding its receptor, plexinB1, in pancreatic cancer.
Cancer Sci.
PUBLISHED: 09-13-2011
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Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor, for which the development of new biomarkers and therapeutic targets has become critical. The main cause of poor prognosis in PDAC patients is the high invasive and metastatic potential of the cancer. In the present study, we report a new signaling pathway that was found to mediate the enhanced tumor cell motility in pancreatic cancer. Semaphorin 4D (Sema4D) is a ligand known to be expressed on different cell types, and has been reported to be involved in the regulation of immune functions, epithelial morphogenesis, and tumor growth and metastasis. In this study, we revealed for the first time that the cancer tissue cells expressing Sema4D in PDAC are tumor-infiltrating lymphocytes. The overexpression of Sema4D and of its receptor, plexinB1, was found to be significantly correlated with clinical factors, such as lymph node metastasis, distant metastasis, and poor prognosis in patients with PDAC. Through in vitro analysis, we demonstrated that Sema4D can potentiate the invasiveness of pancreatic cancer cells and we identified the downstream molecules. The binding of Sema4D to plexinB1 induced small GTPase Ras homolog gene family, member A activation and resulted in the phosphorylation of MAPK and Akt. In addition, in terms of potential therapeutic application, we clearly demonstrated that the enhanced-cell invasiveness induced by Sema4D could be inhibited by knockdown of plexinB1, suggesting that blockade of plexinB1 might diminish the invasive potential of pancreatic cancer cells. Our findings provide new insight into possible prognostic biomarkers and therapeutic targets in PDAC patients.
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Role of endothelin receptor signalling in squamous cell carcinoma.
Int. J. Oncol.
PUBLISHED: 09-12-2011
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Endothelin plays important roles in various physiological functions including vascular constriction. Recent studies reported that the endothelin receptors ETA and ETB are highly expressed in lung and skin tumor tissues. In contrast, there are few reports on endothelin signalling in the proliferation of head and neck cancer. We found that both ETA and ETB endothelin receptors were overexpressed in tumor cells of tongue cancer samples by immunohistochemistry. ETA and ETB were expressed in cultured lingual and esophageal squamous cell carcinoma (SCCs) cell lines. When both cultured cell lines were treated with an ETA selective antagonist (BQ123) or an ETB selective antagonist (BQ788), inhibition of cell growth was observed. Similar results were observed when SCCs were treated with specific siRNA for the suppression of ETA or ETB. Furthermore, inhibition of the mitogen-activated protein (MAP) kinase pathway by the treatments with ET receptor antagonists and siRNA was also observed. These results indicate that endothelin signalling may, in part, play important roles in cell growth in SCCs through the MAP kinase pathway.
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Intermediate methylation epigenotype and its correlation to KRAS mutation in conventional colorectal adenoma.
Am. J. Pathol.
PUBLISHED: 07-30-2011
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A subset of colorectal cancer shows significant accumulation of aberrant promoter methylation. Previously, we developed two groups of methylation markers that classified colorectal cancer into three epigenotypes: i) high-, ii) intermediate-, and iii) low-methylation epigenotypes. High-methylation epigenotype, with methylation of both group 1 and group 2 markers, correlates to BRAF-mutation((+)). Intermediate-methylation epigenotype, with methylation of group 2 markers, but not group 1, correlates to KRAS-mutation((+)). To gain insight into epigenotype development in colorectal carcinogenesis, especially intermediate-methylation epigenotype and its correlation to KRAS-mutation((+)) in adenoma, we analyzed methylation levels of group 1 and group 2 markers quantitatively by matrix assisted laser desorption ionization-time of flight mass spectrometry, in 51 adenomas, 13 aberrant crypt foci, and 26 normal mucosa samples, and we compared them to 149 previously analyzed colorectal cancer samples. Three serrated adenomas were all BRAF-mutation((+)), showing great methylation of group 1 and group 2 markers, thus high-methylation epigenotype. Forty-eight conventional adenomas were not methylated in group 1 markers and were classified into two clusters with higher and lower methylation of group 2 markers, thus into intermediate- and low-methylation epigenotypes, respectively. Adenoma with intermediate-methylation epigenotype correlated to KRAS-mutation((+)). Methylation levels of group 2 markers in adenoma were higher than aberrant crypt foci and normal samples, but similar to cancer. These data suggested that epigenotype development occur at an earlier stage than carcinoma formation, and already be completed at the adenoma stage. Intermediate methylation epigenotype and its correlation to KRAS-mutation((+)) were developed in conventional adenoma.
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Computed tomography analysis of the association between the SH2B1 rs7498665 single-nucleotide polymorphism and visceral fat area.
J. Hum. Genet.
PUBLISHED: 07-28-2011
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Visceral fat accumulation has an important role in increasing morbidity and mortality rate by increasing the risk of developing several metabolic disorders, such as type 2 diabetes, dyslipidemia and hypertension. New genetic loci that contribute to the development of obesity have been identified by genome-wide association studies in Caucasian populations. We genotyped 1279 Japanese subjects (556 men and 723 women), who underwent computed tomography (CT) for measuring visceral fat area (VFA) and subcutaneous fat area (SFA), for the following single-nucleotide polymorphisms (SNPs): NEGR1 rs2815752, SEC16B rs10913469, TMEM18 rs6548238, ETV5 rs7647305, GNPDA2 rs10938397, BDNF rs6265 and rs925946, MTCH2 rs10838738, SH2B1 rs7498665, MAF rs1424233, and KCTD15 rs29941 and rs11084753. In the additive model, none of the SNPs were significantly associated with body mass index (BMI). The SH2B1 rs7498665 risk allele was found to be significantly associated with VFA (P=0.00047) but not with BMI or SFA. When the analysis was performed in men and women separately, no significant associations with VFA were observed (P=0.0099 in men and P=0.022 in women). None of the other SNPs were significantly associated with SFA. Our results suggest that there is a VFA-specific genetic factor and that a polymorphism in the SH2B1 gene influences the risk of visceral fat accumulation.
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Association of variations in the FTO, SCG3 and MTMR9 genes with metabolic syndrome in a Japanese population.
J. Hum. Genet.
PUBLISHED: 07-28-2011
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Metabolic syndrome is defined as a cluster of multiple risk factors, including central obesity, dyslipidemia, hypertension and impaired glucose tolerance, that increase cardiovascular disease morbidity and mortality. Genetic factors are important in the development of metabolic syndrome, as are environmental factors. However, the genetic background of metabolic syndrome is not yet fully clarified. There is evidence that obesity and obesity-related phenotypes are associated with variations in several genes, including NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, SH2B1, FTO, MAF, MC4R, KCTD15, SCG3, MTMR9, TFAP2B, MSRA, LYPLAL1, GCKR and FADS1. To investigate the relationship between metabolic syndrome and variations in these genes in the Japanese population, we genotyped 33 single-nucleotide polymorphisms (SNPs) in 19 genes from 1096 patients with metabolic syndrome and 581 control individuals who had no risk factors for metabolic syndrome. Four SNPs in the FTO gene were significantly related to metabolic syndrome: rs9939609 (P=0.00013), rs8050136 (P=0.00011), rs1558902 (P=6.6 × 10(-5)) and rs1421085 (P=7.4 × 10(-5)). rs3764220 in the SCG3 gene (P=0.0010) and rs2293855 in the MTMR9 gene (P=0.0015) were also significantly associated with metabolic syndrome. SNPs in the FTO, SCG3 and MTMR9 genes had no SNP × SNP epistatic effects on metabolic syndrome. Our data suggest that genetic variations in the FTO, SCG3 and MTMR9 genes independently influence the risk of metabolic syndrome.
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Effects of Histamine-2 Receptor Antagonists and Proton Pump Inhibitors on the Rate of Gastric Emptying: A Crossover Study Using a Continuous Real-Time C Breath Test (BreathID System).
J Neurogastroenterol Motil
PUBLISHED: 07-13-2011
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The effects of Histamine-2 receptor antagonists and proton pump inhibitors on the gastrointestinal motility have not yet been sufficiently investigated. The aim of this study was to determine the effects of intravenous bolus administration of famotidine and omeprazole on the rate of gastric emptying using the continuous (13)C breath test (BreathID system, Exalenz Bioscience Ltd, Israel).
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Investigation of the prevalence and number of aberrant crypt foci associated with human colorectal neoplasm.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 07-12-2011
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Aberrant crypt foci (ACF) are considered to be useful as surrogate biomarker for colorectal cancer (CRC), but the biological significance of ACF remains controversial. We attempted to investigate the relationship between the presence of ACF and human colorectal carcinogenesis using a relatively large sample size.
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Mosapride accelerates the delayed gastric emptying of high-viscosity liquids: a crossover study using continuous real-time C breath test (BreathID System).
J Neurogastroenterol Motil
PUBLISHED: 07-09-2011
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The administration of liquid nutrients to patients is often accompanied by complications such as gastroesophageal reflux. To prevent gastroesophageal reflux, high-viscosity liquid meals are used widely, however, it still remains controversial whether high-viscosity liquid meals have any effect on the rate of gastric emptying. The present study was conducted with the aim of determining whether high-viscosity liquid meals had any effect on the rate of gastric emptying and mosapride might accelerate the rate of gastric emptying of high-viscosity liquid meals.
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Solitary Peutz-Jeghers type hamartomatous polyps in the duodenum are not always associated with a low risk of cancer: two case reports.
J Med Case Rep
PUBLISHED: 06-27-2011
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A hamartomatous polyp without associated mucocutaneous pigmentation or a family history of Peutz-Jeghers Syndrome is diagnosed as a solitary Peutz-Jeghers type hamartomatous polyp. As compared with Peutz-Jeghers Syndrome, Peutz-Jeghers type hamartomatous polyps are diagnosed with a lower risk of cancer and are regarded as a different disorder.
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The collagen-binding protein of Streptococcus mutans is involved in haemorrhagic stroke.
Nat Commun
PUBLISHED: 06-22-2011
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Although several risk factors for stroke have been identified, one-third remain unexplained. Here we show that infection with Streptococcus mutans expressing collagen-binding protein (CBP) is a potential risk factor for haemorrhagic stroke. Infection with serotype k S. mutans, but not a standard strain, aggravates cerebral haemorrhage in mice. Serotype k S. mutans accumulates in the damaged, but not the contralateral hemisphere, indicating an interaction of bacteria with injured blood vessels. The most important factor for high-virulence is expression of CBP, which is a common property of most serotype k strains. The detection frequency of CBP-expressing S. mutans in haemorrhagic stroke patients is significantly higher than in control subjects. Strains isolated from haemorrhagic stroke patients aggravate haemorrhage in a mouse model, indicating that they are haemorrhagic stroke-associated. Administration of recombinant CBP causes aggravation of haemorrhage. Our data suggest that CBP of S. mutans is directly involved in haemorrhagic stroke.
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Effects of domperidone on gastric emptying: a crossover study using a continuous real-time 13C breath test (BreathID system).
Hepatogastroenterology
PUBLISHED: 06-14-2011
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To determine the correlation between domperidone and gastric emptying using the continuous real time 13C breath-test (BreathID system), a novel non-invasive technique for measuring gastric emptying.
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Risk factors for mortality in patients with Mallory-Weiss syndrome.
Hepatogastroenterology
PUBLISHED: 06-14-2011
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Although the majority of patients with Mallory-Weiss syndrome (MWS) have a benign course, in some patients MWS results in a fatal outcome. Therefore, this study was carried out to analyze the risk factors for mortality in patients with MWS.
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Capsule-endoscopic findings of ulcerative colitis patients.
Digestion
PUBLISHED: 05-16-2011
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Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by diffuse mucosal inflammation, traditionally regarded as being limited to the colorectum. Although several gastroduodenal lesions have also been reported recently in cases of UC, in general, small-bowel lesions in UC are believed to be extremely rare. The aim of this study was to examine the small bowel by capsule endoscopy in patients with UC.
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Effective treatment for duodenal variceal bleeding using endoscopic ligation.
Hepatogastroenterology
PUBLISHED: 05-13-2011
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Duodenal variceal rupture is rare, and there is little agreement on the best therapeutic option. A 72-year old man treated for liver cirrhosis with HCV visited the emergency room complaining of dizziness and tarry stool. Fiberscope images showed varices (F2CbRC+) with white plaques at the horizontal region of the duodenum. The patient was treated using endoscopic variceal ligation (EVL), and no more bleeding has been detected.
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Tests for serum levels of trefoil factor family proteins can improve gastric cancer screening.
Gastroenterology
PUBLISHED: 05-12-2011
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Improving methods for early detection of gastric cancer could reduce mortality. Measurements of serum pepsinogen levels have been used for screening in Japan without satisfactory levels of sensitivity or specificity. Trefoil factor family (TFF) proteins (TFF1, TFF2, and TFF3) are small and stable molecules secreted by the mammalian gastrointestinal tract. Foveolar hyperplasia, spasmolytic polypeptide (TFF2)-expressing metaplasia, and intestinal metaplasia are histologic changes observed in patients with atrophic gastritis; they express TFF1, TFF2, and TFF3, respectively. We investigated whether serum levels of TFF can be used as markers for gastric cancer screening.
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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.