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Find video protocols related to scientific articles indexed in Pubmed.
Nucleobindin-2 is a positive regulator for insulin-stimulated glucose transporter 4 translocation in fenofibrate treated E11 podocytes.
Endocr. J.
PUBLISHED: 08-27-2014
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The physiology of insulin signaling under normal and disease conditions is well studied in classical insulin target tissues, but not in podocytes. To examine insulin stimulation of podocyte GLUT4 translocation, we established a protocol involving treatment with the PPAR? agonist fenofibrate to induce E11 podocyte differentiation within 48 hours rather than 7-10 days, which is required for differentiation under the reported protocol. This allowed us to transiently introduce GLUT4 reporter cDNA and RNAi and thereby to examine the regulatory pathway involved. Here we demonstrate that treatment with 200 ?M fenofibrate for 36 hours following transfection had a dramatic effect on podocyte morphology, induced several podocyte specific protein expression markers (G protein-coupled receptor 137B, chloride intracellular channel 5, and nephrin) and resulted in insulin-stimulated GLUT4 translocation. In addition, Nucleobindin-2 was found to constitutively associate with Septin 7 (the repressor of GLUT4 translocation), and knockdown of Nucleobindin-2 was found to completely abrogate insulin-stimulated GLUT4 translocation. Together, these data suggest that Nucleobindin-2 may repress Septin7-induced inhibition of insulin-stimulated GLUT4 translocation in podocytes.
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Protection against high-fat diet-induced obesity in Helz2-deficient male mice due to enhanced expression of hepatic leptin receptor.
Endocrinology
PUBLISHED: 07-08-2014
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Obesity arises from impaired energy balance, which is centrally coordinated by leptin through activation of the long form of leptin receptor (Leprb). Obesity causes central leptin resistance. However, whether enhanced peripheral leptin sensitivity could overcome central leptin resistance remains obscure. A peripheral metabolic organ targeted by leptin is the liver, with low Leprb expression. We here show that mice fed a high-fat diet (HFD) and obese patients with hepatosteatosis exhibit increased expression of hepatic helicase with zinc finger 2, a transcriptional coactivator (Helz2), which functions as a transcriptional coregulator of several nuclear receptors, including peroxisome proliferator-activated receptor ? in vitro. To explore the physiological importance of Helz2, we generated Helz2-deficient mice and analyzed their metabolic phenotypes. Helz2-deficient mice showing hyperleptinemia associated with central leptin resistance were protected against HFD-induced obesity and had significantly up-regulated hepatic Leprb expression. Helz2 deficiency and adenovirus-mediated liver-specific exogenous Leprb overexpression in wild-type mice significantly stimulated hepatic AMP-activated protein kinase on HFD, whereas Helz2-deficient db/db mice lacking functional Leprb did not. Fatty acid-? oxidation was increased in Helz2-deficeint hepatocytes, and Helz2-deficient mice revealed increased oxygen consumption and decreased respiratory quotient in calorimetry analyses. The enhanced hepatic AMP-activated protein kinase energy-sensing pathway in Helz2-deficient mice ameliorated hyperlipidemia, hepatosteatosis, and insulin resistance by reducing lipogenic gene expression and stimulating lipid-burning gene expression in the liver. These findings together demonstrate that Helz2 deficiency ameliorates HFD-induced metabolic abnormalities by stimulating endogenous hepatic Leprb expression, despite central leptin resistance. Hepatic HELZ2 might be a novel target molecule for the treatment of obesity with hepatosteatosis.
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Coordinated regulation of transcription and alternative splicing by the thyroid hormone receptor and its associating coregulators.
Biochem. Biophys. Res. Commun.
PUBLISHED: 07-01-2014
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Emerging evidence has indicated that the transcription and processing of precursor mRNA (pre-mRNA) are functionally coupled to modulate gene expression. In collaboration with coregulators, several steroid hormone receptors have previously been shown to directly affect alternative pre-mRNA splicing coupled to hormone-induced gene transcription; however, the roles of the thyroid hormone receptor (TR) and its coregulators in alternative splicing coordinated with transcription remain unknown. In the present study, we constructed a luciferase reporter and CD44 alternative splicing (AS) minigene driven by a minimal promoter carrying 2 copies of the palindromic thyroid hormone-response element. We then examined whether TR could modulate pre-mRNA processing coupled to triiodothyronine (T3)-induced gene transcription using luciferase reporter and splicing minigene assays in HeLa cells. In the presence of cotransfected TR?1, T3 increased luciferase activities along with the inclusion of the CD44 variable exons 4 and 5 in a dose- and time-dependent manner. In contrast, cotransfected TR?1 did not affect the exon-inclusion of the CD44 minigene driven by the cytomegalovirus promoter. T3-induced two-exon inclusion was significantly increased by the cotransfection of the TR-associated protein, 150-kDa, a subunit of the TRAP/Mediator complex that has recently been shown to function as a splicing factor. In contrast, T3-induced two-exon inclusion was significantly decreased by cotransfection of the polypyrimidine tract-binding protein-associated splicing factor, which was previously shown to function as a corepressor of TR. These results demonstrated that liganded TR in cooperation with its associating cofactors could modulate alternative pre-mRNA splicing coupled to gene transcription.
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Safety and efficacy of high-dose leukocytapheresis in patients with refractory asthma.
Inflamm. Res.
PUBLISHED: 06-17-2014
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An open-label, non-randomized, single-arm study was performed to investigate the safety and efficacy of high-dose leukocytapheresis (pulse LCAP) for refractory asthma.
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A case of thyroid storm with a markedly elevated level of circulating soluble interleukin-2 receptor complicated by multiple organ failure and disseminated intravascular coagulation syndrome.
Endocr. J.
PUBLISHED: 05-20-2014
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Thyroid storm (TS) is a life-threatening endocrine emergency. However, the pathogenesis of TS is poorly understood. A 40-year-old man was admitted to a nearby hospital with body weight loss and jaundice. Five days after a contrasted abdominal computerized tomography (CT) scan, he exhibited high fever and disturbance of consciousness. He was diagnosed with TS originating from untreated Graves' disease and was transferred to the intensive care unit (ICU) of our hospital. The patient exhibited impaired consciousness (E4V1M4 in Glasgow coma scale), high fever (39.3 °C), and atrial flutter with a pulse rate 162/min, and was complicated by heart failure, acute hepatic failure, and disseminated intravascular coagulation syndrome (DIC). His circulating level of soluble interleukin-2 receptor (sIL-2R), a serum marker of an activated immune response, was highly elevated (7,416 U/mL, reference range: 135-483). Multiple organ failure (MOF) and DIC were successfully managed by multimodality treatments using inorganized iodide, glucocorticoids, anti-thyroid drugs, beta-blockers, and diuretics as well as an anticoagulant agent and the transfusion of platelet concentrate and fresh frozen plasma. sIL-2R levels gradually decreased during the initial treatment, but were still above the reference range even after thyroidectomy. Mild elevations in serum levels of sIL-2R have previously been correlated with thyroid hormone levels in non-storm Graves' disease. The present study demonstrated, for the first time, that circulating sIL-2R levels could be markedly elevated in TS. The marked increase in sIL-2R levels was speculated to represent an inappropriate generalized immune response that plays an unknown role in the pathogenesis of TS.
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A role of nesfatin-1/NucB2 in dehydration-induced anorexia.
Am. J. Physiol. Regul. Integr. Comp. Physiol.
PUBLISHED: 05-14-2014
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Nesfatin-1/NucB2, an anorexigenic molecule, is expressed mainly in the hypothalamus, particularly in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN). Nesfatin-1/NucB2 is also expressed in the subfornical organ (SFO). Because the SON and PVN are involved in body fluid regulation, nesfatin-1/NucB2 may be involved in dehydration-induced anorexia. To clarify the effects of endogenous nesfatin-1/NucB2, we studied changes in nesfatin-1/NucB2 mRNA levels in the SFO, SON, and PVN in adult male Wistar rats after exposure to osmotic stimuli by using in situ hybridization histochemistry. Significant increases in nesfatin-1/NucB2 mRNA levels, ?2- to 3-fold compared with control, were observed in the SFO, SON, and PVN following water deprivation for 48 h, consumption of 2% NaCl hypertonic saline in drinking water for 5 days, and polyethylene glycol-induced hypovolemia. In addition, nesfatin-1/NucB2 expression was increased in response to water deprivation in a time-dependent manner. These changes in nesfatin-1/NucB2 mRNA expression were positively correlated with plasma sodium concentration, plasma osmolality, and total protein levels in all of the examined nuclei. Immunohistochemistry for nesfatin-1/NucB2 revealed that nesfatin-1/NucB2 protein levels were also increased after 48 h of dehydration and attenuated by 24 h of rehydration. Moreover, intracerebroventricular administration of nesfatin-1/NucB2-neutralizing antibody after 48 h of water deprivation resulted in a significant increase in food intake compared with administration of vehicle alone. These results suggested that nesfatin-1/NucB2 is a crucial peptide in dehydration-induced anorexia.
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Synip phosphorylation is required for insulin-stimulated Glut4 translocation and glucose uptake in podocyte.
Endocr. J.
PUBLISHED: 04-05-2014
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Previously we reported that the phosphorylation of Synip on serine 99 is required for Synip dissociation from Syntaxin4 and insulin-stimulated Glut4 translocation in cultured 3T3-L1 adipocytes. We also reported that the dissociated Synip remains anchored to the plasma membrane by binding to Phosphatidylinositol (3,4,5)-triphosphate. Recently Synip was reported to arrest SNARE-dependent membrane fusion as a selective t-SNARE binding inhibitor. In this study, we have found that Synip is expressed in podocytes although at a somewhat lower level than in adipocytes. To determine whether phosphorylation of Synip on serine 99 is required for insulin-stimulated Glut4 translocation and glucose uptake in podocytes we expressed a phosphorylation deficient Synip mutant (S99A-Synip) that inhibited insulin-stimulated Glut4 translocation and 2-deoxyglucose uptake in adipocytes. We conclude that serine 99 phosphorylation of Synip is required for Glut4 translocation and glucose uptake in both adipocytes and podocytes, suggesting that defects in Synip phosphorylation may underlie insulin resistance and associated diabetic nephropathy.
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A Prospective Randomized Controlled Study of Endoscopic Sphincterotomy With the Endocut Mode or Conventional Blended Cut Mode.
J. Clin. Gastroenterol.
PUBLISHED: 03-04-2014
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Although the potential advantages of the Endocut mode (E-mode) of endoscopic sphincterotomy (EST) over the conventional blended cut mode (C-mode) have been reported, the problems, including the small sample size and retrospective analysis, that occurred in previous studies make it difficult to conclude the advantage of the E-mode regarding the safety and efficacy. We performed a prospective randomized controlled study to compare these modes.
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Vagal hyperactivity due to ventromedial hypothalamic lesions increases adiponectin production and release.
Diabetes
PUBLISHED: 01-31-2014
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In obese humans and animals, adiponectin production and release in adipose tissue are downregulated by feedback inhibition, resulting in decreased serum adiponectin. We investigated adiponectin production and release in ventromedial hypothalamic (VMH)-lesioned animals. VMH-lesioned mice showed significant increases in food intake and body weight gain, with hyperinsulinemia and hyperleptinemia at 1 and 4 weeks after VMH-lesioning. Serum adiponectin was elevated in VMH-lesioned mice at 1 and 4 weeks, despite adipocyte hypertrophy in subcutaneous and visceral adipose tissues and increased body fat. Adiponectin production and mRNA were also increased in both adipose tissues in VMH-lesioned mice at 1 week. These results were replicated in VMH-lesioned rats at 1 week. Daily atropine administration for 5 days or subdiaphragmatic vagotomy completely reversed the body weight gain and eliminated the increased adiponectin production and release in these rats, with reversal to a normal serum adiponectin level. Parasympathetic nerve activation by carbachol infusion for 5 days in rats increased serum adiponectin, with increased adiponectin production in visceral and subcutaneous adipose tissues without changes of body weight. These results demonstrate that activation of the parasympathetic nerve by VMH lesions stimulates production of adiponectin in visceral and subcutaneous adipose tissues and adiponectin release, resulting in elevated serum adiponectin.
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Oxidative stress potentially enhances Fc?RI-mediated leukotriene C4 release dependent on the late-phase increase of intracellular glutathione in mast cells.
Biochem. Biophys. Res. Commun.
PUBLISHED: 08-20-2013
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Cysteinyl leukotrienes (cysLTs), which include leukotriene C4 (LTC4), are the predominant class of LTs synthesized by mast cells. CysLTs can induce many of the abnormalities seen in asthma. LTC4 is generated by the conjugation of LTA4 with reduced glutathione (GSH) by LTC4 synthase. During screening of the effects of prostanoids on high-affinity IgE receptor (Fc?RI)-mediated LTC4 release from mast cells, we realized that some prostanoids, including ONO-AE1-259-01 and ONO-AE-248, inhibited LTC4 release, which was associated with a decrease in the amount of intracellular total GSH. We ascertained that l-buthionine-S,R-sulfoximine (BSO), a selective inhibitor of glutamate-cysteine ligase, inhibited LTC4 release. In addition, cell-permeable GSH, the glutathione reduced form ethyl ester (GSH-OEt), enhanced LTC4 release in accordance with the change in intracellular total GSH. Depletion of intracellular total GSH induced by ONO-AE-248 or BSO enhanced Fc?RI-mediated LTB4 release in contrast to LTC4. Oxidative stress contributes to many pathological conditions including asthma. GSH is a major soluble antioxidant and a cofactor for several detoxifying enzymes including GSH peroxidase. Exposure of mast cells to hydrogen peroxide (H2O2) or diamide to mimic oxidative stress unexpectedly increased rather than decreased the intracellular reduced GSH content as well as total GSH in the late phase (i.e., 24 or 48 h after exposure), which was accompanied by an increase in LTC4 release. In conclusion, Fc?RI-mediated LTC4 release from mast cells is mainly regulated by the amount of intracellular GSH. In some cases, oxidative stress may induce a late-phase increase in intracellular GSH, resulting in enhanced LTC4 release from mast cells.
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Carbon dioxide insufflation reduces the discomfort due to colonoscopy as objectively analyzed by salivary stress markers.
Acta Gastroenterol. Belg.
PUBLISHED: 08-01-2013
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Carbon dioxide (CO2) insufflation has been shown to reduce the procedure-related pain and discomfort during colonoscopy. However, the effects of CO2 insufflation on the improvement of participants stress had not been objectively analyzed.
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Functional gastrointestinal disorders in adolescents and quality of school life.
J. Gastroenterol. Hepatol.
PUBLISHED: 07-28-2013
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The prevalence of functional gastrointestinal disorders (FGID) in adolescents and their relationship to quality of school life (QOSL) are not fully understood. This study investigated the relationship between FGID and QOSL.
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Subclinical hypothyroidism and indices for metabolic syndrome in Japanese women: one-year follow-up study.
J. Clin. Endocrinol. Metab.
PUBLISHED: 06-04-2013
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Subclinical hypothyroidism (SCH) and metabolic syndrome (MetS) increase with age; however, their relationship remains unclear. Objective: Our objective was to investigate the relationship between SCH and indices of metabolic syndrome and follow up subjects for 1 year.
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A novel mechanism for the inhibition of type 2 iodothyronine deiodinase by tumor necrosis factor ?: involvement of proteasomal degradation.
Endocr. J.
PUBLISHED: 05-30-2013
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Thyroxine (T4) needs to be converted to 3,5,3-triiodothyronine (T3) by iodothyronine deiodinase to exert its biological activity. Recent studies revealed the presence of type 2 iodothyronine deiodinase (D2) in human thyroid tissue, human skeletal muscle and other tissues, suggesting that D2 is involved in maintaining plasma T3 level in human. Tumor necrosis factor ? (TNF?) is an inflammatory cytokine of which production is elevated in patients with nonthyroidal illness. Although several lines of evidence suggest the causal role of TNF? in nonthyroidal illness, detailed nature of the effect of TNF? on D2 remains unclear. In the present study, we identified D2 activity and D2 mRNA in TCO-1 cells, which were derived from human anaplastic thyroid carcinoma, and studied the mechanisms involved in the regulation of D2 expression by TNF?. The characteristics of the deiodinating activity in TCO-1 cells were compatible with those of D2 and Northern analysis demonstrated that D2 mRNA was expressed in TCO-1cells. D2 activity and D2 mRNA expression were rapidly increased by dibutyryl cAMP ((Bu)2cAMP). TNF? showed an inhibitory effect on (Bu)2cAMP-stimulated D2 activity in spite of little effect on (Bu)2cAMP-stimulated D2 mRNA expression. MG132, a proteasome inhibitor abolished TNF? suppression of D2 activity whereas BAY11-7082 or 6-Amino-4-(4-phenoxyphenylethylamino) quinazoline, inhibitors of nuclear factor-?B (NF-?B) failed to attenuate the effect of TNF? on D2 activity. These data suggest that a posttranslational mechanism through proteasomal degradation but not NF-?B activation is involved in the suppression of D2 by TNF?.
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Dilated cardiomyopathy as a presenting feature of Cushings syndrome.
Intern. Med.
PUBLISHED: 05-15-2013
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Cardiovascular complications, including cardiomegaly, myocardial ischemia and left ventricular hypertrophy, are some of the major determinants of the mortality rate in patients with Cushings syndrome. We herein report the case of a patient with Cushings syndrome caused by an adrenal adenoma who presented with congestive heart failure secondary to dilated cardiomyopathy. Follow-up echocardiography showed a marked improvement in the left ventricular cardiac function, and the plasma B-type natriuretic peptide (BNP) levels regressed after successful treatment. "Reversible" dilated cardiomyopathy is rarely associated with Cushings syndrome; however, it should be recognized. Administering appropriate treatment in a timely manner can reverse this cardiomyopathy along with the other symptoms of Cushings syndrome.
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Paraventricular nucleus nesfatin-1 neurons are regulated by pituitary adenylate cyclase-activating polypeptide (PACAP).
Neurosci. Lett.
PUBLISHED: 05-02-2013
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Nesfatin-1 is a neuropeptide localized in hypothalamic paraventricular nucleus (PVN). Previously, we have reported the mechanism of feeding suppression by nesfatin-1, and also reported the ability of nesfatin-1 in regulating stress response and the circadian feeding pattern. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide also related to the stress response, feeding, and regulation of cardiovascular and autonomic nervous systems. The neurons with receptors for PACAP are distributed in PVN. However, there are no reports showing the direct effect of PACAP on nesfatin-1 neurons. In order to explore the direct effect of PACAP on PVN nesfatin-1 neuron, we have measured the cytosolic free calcium ([Ca(2+)]i) using fura-2 microfluorometry in single neurons isolated from PVN of adult rats, followed by immunocytochemical identification of nesfatin-1 neurons. PACAP at 10(-15)M to 10(-9)M increased [Ca(2+)]i in dose dependent manner. PAC1 and VPAC2 receptor agonists also increased [Ca(2+)]i. Sixteen out of 40 neurons (40%) in PVN responded to 10(-9)M PACAP, and 12 out of 16 neurons (75%) which responded to 10(-9)M PACAP were found to be nesfatin-1 neurons. In this paper we show that PACAP directly activates nesfatin-1 neurons in PVN. The data suggest that nesfatin-1 controls feeding, stress response or autonomic response under PACAP regulation.
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[Characteristics and significance of criteria for obesity disease in Japan 2011].
Nippon Rinsho
PUBLISHED: 05-02-2013
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The Committee of Japan Society for the Study of Obesity reported the new criteria for obesity disease for Japanese in 2011. 1) Obesity: This is judged by body mass index (BMI) at initial screening and defined as a BMI > or = 25. 2) Definition of obesity disease: obesity disease is a clinical designation based on the presence of associated complications or their likely occurrence. A person in this situation needs to reduce their weight for medical reasons. 3) Criteria forobesity disease: a) obesity with complications that require weight reduction for their improvement or elimination. b) high-risk obesity as specified by an excess of visceral fat confirmed by CT scan (visceral fat obesity).
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Extended therapy duration for therapy-refractory hepatitis C patients with genotype 2.
World J. Gastroenterol.
PUBLISHED: 04-30-2013
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We devised an extended 72-wk peginterferon-?-2a/ribavirin therapy regimen for the retreatment of highly intractable cases, i.e., 48-wk peginterferon-?-2b/ribavirin therapy-intractable cases. Although 2 cases achieved a rapid virological response to 72-wk peginterferon-?-2a/ribavirin therapy, 1 case failed to achieve a sustained virological response. Although the reason for this difference in the effectiveness of 72-wk peginterferon-?-2a/ribavirin therapy between the cases was unclear, the rebound phenomenon of serum transaminase after 48-wk peginterferon-?-2b/ribavirin therapy and the resultant lower viral load compared to that before 48-wk peginterferon-?-2b/ribavirin therapy might have influenced the treatment outcome. Thus, it may be beneficial to consider the rebound phenomenon of serum transaminase and the changes in viral load resulting from previous interferon-based therapy and then cautiously determine the indication and the timing of the administration of 72-wk peginterferon-?-2a/ribavirin in highly intractable cases. Further studies should be performed to confirm this strategy.
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Clinical significance of L-type amino acid transporter 1 expression as a prognostic marker and potential of new targeting therapy in biliary tract cancer.
BMC Cancer
PUBLISHED: 04-27-2013
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The expression of L-type amino acid transporter 1 (LAT1) has been described to play essential roles in tumor cell growth and survival. However, it remains unclear about the clinicopathological significance of LAT1 expression in biliary tract cancer. This study was conducted to determine biological significance of LAT1 expression and investigate whether LAT1 could be a prognostic biomarker for biliary tract cancer.
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Transforming growth factor-? activates pancreatic stellate cells and may be involved in matrix metalloproteinase-1 upregulation.
Lab. Invest.
PUBLISHED: 04-22-2013
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The role that transforming growth factor-? (TGF-?) has in chronic pancreatitis and pancreatic cancer has not been fully elucidated. We evaluated the effects of TGF-? on the human pancreatic stellate cell (PSC) line RLT-PSC and primary human PSCs, and the expression levels of TGF-? and metalloproteinase-1 (MMP-1) in human chronic pancreatitis and pancreatic cancer tissues. TGF-? stimulated the proliferation and migration of PSCs. Although the mRNA expression levels of tissue inhibitor of metalloproteinase-1 and ?1(I) collagen were unchanged, the mRNA expression levels of MMP-1 increased concomitant with increases in MMP-1 protein levels and collagenase activity. TGF-?-stimulated migration of RLT-PSC cells was partially blocked by tissue inhibitor of metalloproteinase-1 protein and MMP-1 small interfering RNA. MMP-1 was also observed to stimulate the migration of PSCs. TGF-?-induced MMP-1 expression was completely blocked by gefitinib in PSCs. The Ras-ERK and PI3/Akt pathways appear to be involved in the activation of MMP-1 in PSCs. Immunohistochemical analyses showed that MMP-1 expression was significantly increased in the pancreatic interstitial tissues in case of chronic pancreatitis or pancreatic cancer compared with those in case of normal pancreas. In conclusion, TGF-? increased proliferation and migration of PSCs. TGF-?-induced migration of cells may be partly due to upregulation of MMP-1. TGF-? and MMP-1 upregulation may contribute to the pathogenesis of chronic pancreatitis and pancreatic cancer.
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Paraventricular NUCB2/nesfatin-1 rises in synchrony with feeding suppression during early light phase in rats.
Biochem. Biophys. Res. Commun.
PUBLISHED: 03-22-2013
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Obesity often results from hyperphagia and involves rhythm disorder. Circadian feeding pattern is suggested to be implicated in energy homeostasis while its disorder in obesity. However, the mechanism underlying circadian feeding is little known. PVN is considered a regulatory center for feeding and circadian activities of hormone release and autonomic nerve. Nucleobindin2 (NUCB2) and its processing product nesfatin-1 (NUCB2/nesfatin-1) are localized in the hypothalamic paraventricular nucleus (PVN) and implicated in regulation of feeding. This study aimed to clarify whether the PVN NUCB2/nesfatin-1 expression exhibits diurnal rhythm and, if so, whether it is related to circadian feeding. Here we show that NUCB2 mRNA expression in the PVN rises during early light phase (LP) in parallel with suppression of food intake. Immunoneutralization of PVN NUCB2/nesfatin-1 with anti-nesfatin-1 IgG during LP, but not dark phase, increased food intake. PVN-selective shRNA-induced knockdown of NUCB2 mRNA expression elevated food intake. Furthermore, the rise of PVN NUCB2 mRNA during LP was blunted in Zucker-fatty obese rats which exhibited LP-preferential hyperphagia. The increases in food intake during LP and 24h were significantly corrected by intracerebroventricular injection of nesfatin-1 during LP. These results reveal the diurnal rhythm of PVN NUCB2 mRNA expression characterized by early LP rise, which may serve as a factor to limit LP food intake, contributing to circadian feeding. Furthermore, impaired NUCB2/nesfatin-1 rhythm may be related to dysregulated feeding pattern and hyperphagia in Zucker-fatty rats.
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THRAP3 interacts with HELZ2 and plays a novel role in adipocyte differentiation.
Mol. Endocrinol.
PUBLISHED: 03-22-2013
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Using yeast two-hybrid screen, we previously isolated HELZ2 (helicase with zinc finger 2, transcriptional coactivator) that functions as a coregulator of peroxisome proliferator-activated receptor? (PPAR?). To further delineate its molecular function, we here identified thyroid hormone receptor-associated protein3 (THRAP3), a putative component of the Mediator complex, as a protein stably associating with HELZ2 using immunoprecipitation coupled with mass spectrometry analyses. In immunoprecipitation assays, Thrap3 could associate with endogenous Helz2 as well as Pparg in differentiated 3T3-L1 cells. HELZ2 interacts with the serine/arginine-rich domain and Bcl2 associated transcription factor1-homologous region in THRAP3, whereas THRAP3 directly binds 2 helicase motifs in HELZ2. HELZ2 and THRAP3 synergistically augment transcriptional activation mediated by PPAR?, whereas knockdown of endogenous THRAP3 abolished the enhancement by HELZ2 in reporter assays. Thrap3, similar to Helz2, is evenly expressed in the process of adipogenic differentiation in 3T3-L1 cells. Knockdown of Thrap3 in 3T3-L1 preadipocytes using short-interfering RNA did not influence the expression of Krox20, Klf5, Cebpb, or Cebpd during early stages of adipocyte differentiation, but significantly attenuated the expression of Pparg, Cebpa, and Fabp4/aP2 and accumulation of lipid droplets. Pharmacologic activation of Pparg by troglitazone could not fully restore the differentiation of Thrap3-knockdown adipocytes. In chromatin immunoprecipitation assays, endogenous Helz2 and Thrap3 could be co-recruited, in a ligand-dependent manner, to the PPAR?-response elements in Fabp4/aP2 and Adipoq gene enhancers in differentiated 3T3-L1 cells. These findings collectively suggest that Thrap3 could play indispensable roles in terminal differentiation of adipocytes by enhancing PPAR?-mediated gene activation cooperatively with Helz2.
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Hepatocyte growth factor promotes lung carcinogenesis in transgenic mice treated with diethylnitrosamine.
Anticancer Res.
PUBLISHED: 03-14-2013
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Hepatocyte growth factor (HGF) was initially discovered as a mitogen for hepatocytes, but it is also known to be related to carcinogenesis in many other organs. However, the role of HGF in lung carcinogenesis is not fully-understood. In this study, we investigated the role of HGF in lung carcinogenesis using HGF transgenic mice.
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A prospective study of long-term outcomes in female patients with nonalcoholic steatohepatitis using age- and body mass index-matched cohorts.
Acta Med. Okayama
PUBLISHED: 02-27-2013
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In patients with nonalcoholic steatohepatitis (NASH), the prevalence of cirrhosis is higher among women than men, and hepatocellular carcinoma (HCC) develops mainly in the cirrhotic stage among women. However, the long-term outcomes in female patients with NASH have not been fully elucidated, and age, gender and BMI were not simultaneously adjusted in previous studies on the prognosis of NASH. To elucidate the outcomes in female patients with NASH, we prospectively compared NASH patients with advanced fibrosis (advanced NASH) with hepatitis C virus-related advanced fibrosis (advanced CHC) patients and NASH patients with mild fibrosis (mild NASH) using study cohorts that were adjusted for body mass index (BMI) in addition to age. The median follow-up period was 92.5 months. Liver-related complication-free survival was significantly reduced in the advanced NASH group compared to the mild NASH group. No liver-related complications developed in the mild NASH group. The overall survival, liver-related complication- and cardiovascular/cerebrovascular disease-free survival were not significantly different between the advanced NASH and CHC groups. Female patients with NASH and advanced fibrosis may have a less favorable prognosis for liver-related complications than the matched cohorts with NASH and mild fibrosis, but may have a similar prognosis to the matched cohorts with CHC.
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Perfusion evaluation of lung cancer: assessment using dual-input perfusion computed tomography.
J Thorac Imaging
PUBLISHED: 02-06-2013
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The aim of this study was to investigate the feasibility of separately evaluating bronchial (BAP) and pulmonary arterial perfusion (PAP) of lung cancers using dual-input perfusion computed tomography.
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Discovery of nesfatin-1 and overview of biological actions and new developments.
Curr. Pharm. Des.
PUBLISHED: 02-01-2013
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Obesity arises from an impairment of energy homeostasis, which essentially involves the balance of food intake and energy dissipation. Some secreted molecules in the hypothalamus have become the focus of recent attention for their important roles in the regulation of food intake. One such molecule, nesfatin-1, is a novel molecule originally expressed in the hypothalamic nuclei of the brain, which exerts its satiety function in conjunction with other molecules, including oxytocin and pro-opiomelanocortin (POMC). Nesfatin-1 is processed from its precursor, DNA binding/EF-hand/acidic protein (NEFA)/nucleobindin 2 (NUCB2), and its mRNA is unexpectedly stabilized by troglitazone, a ligand for peroxisome proliferator-activated receptor ? (PPAR?). Subsequent analyses and observations have demonstrated that nesfatin-1 is also located in brain nuclei outside the hypothalamus and in peripheral tissues, and that nesfatin-1 neurons in the brain receive several signals. These findings imply that nesfatin-1 is an endogenous molecule important for the regulation of not only food intake but also other physiological functions. We discuss what is currently known about nesfatin-1, including new developments in our understanding of its distribution, regulation, and biological function.
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The anti-apoptotic effect of fucoxanthin on carbon tetrachloride-induced hepatotoxicity.
J Toxicol Sci
PUBLISHED: 01-30-2013
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This study evaluated the anti-apoptotic activity of fucoxanthin in carbon tetrachloride (CCl(4))-induced hepatotoxicity. An in vitro study using the 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay clearly demonstrated an attenuation of CCl(4)-induced hepatotoxicity with fucoxanthin. This effect was dose-dependent; 25 µM was more effective than 10 µM of fucoxanthin for attenuating the hepatotoxicity induced by 5 mM of CCl(4). Acute CCl(4)-hepatotoxicity in rats, with numerous cells positive for the terminal deoxynucleotidyl - transferase (TdT) -mediated deoxyuridine triphosphate-digoxigenin (dUTP) nick-end labeling (TUNEL) stain were seen in the pericentral area of the hepatic lobule. Oral pretreatment of CCl(4)- injected rats with fucoxanthin significantly reduced hepatocyte apoptosis. Fucoxanthin was immunohistochemically shown to increase heme oxygenase-1 expression in the cultured liver cells of Hc cells and TRL1215 cells. By oral pretreatment of CCl(4)-injected rats with fucoxanthin, the hepatic heme oxygenase-1 protein levels were significantly increased compared to those not pretreated with fucoxanthin. Heme oxygenase-1 mRNA expression after CCl(4 )injection was higher in the CCl(4)+fucoxanthin group than in the CCl(4 )group, although the difference was not significant. The findings suggest that fucoxanthin attenuates hepatocyte apoptosis through heme oxygenase-1 induction in CCl(4)-induced acute liver injury.
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Crosstalk between thyroid hormone receptor and liver X receptor in the regulation of selective Alzheimers disease indicator-1 gene expression.
PLoS ONE
PUBLISHED: 01-24-2013
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Selective Alzheimers disease (AD) indicator 1 (Seladin-1) has been identified as a gene down-regulated in the degenerated lesions of AD brain. Up-regulation of Seladin-1 reduces the accumulation of ?-amyloid and neuronal death. Thyroid hormone (TH) exerts an important effect on the development and maintenance of central nervous systems. In the current study, we demonstrated that Seladin-1 gene and protein expression in the forebrain was increased in thyrotoxic mice compared with that of euthyroid mice. However, unexpectedly, no significant decrease in the gene and protein expression was observed in hypothyroid mice. Interestingly, an agonist of liver X receptor (LXR), TO901317 (TO) administration in vivo increased Seladin-1 gene and protein expression in the mouse forebrain only in a hypothyroid state and in the presence of mutant TR-?, suggesting that LXR-? would compensate for TR-? function to maintain Seladin-1 gene expression in hypothyroidism and resistance to TH. TH activated the mouse Seladin-1 gene promoter (-1936/+21 bp) and site 2 including canonical TH response element (TRE) half-site in the region between -159 and -154 bp is responsible for the positive regulation. RXR-?/TR-? heterodimerization was identified on site 2 by gel-shift assay, and chromatin immunoprecipitation assay revealed the recruitment of TR-? to site 2 and the recruitment was increased upon TH administration. On the other hand, LXR-? utilizes a distinct region from site 2 (-120 to -102 bp) to activate the mouse Seladin-1 gene promoter. Taking these findings together, we concluded that TH up-regulates Seladin-1 gene expression at the transcriptional level and LXR-? maintains the gene expression.
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Incidence, mortality, and predictive factors of hepatocellular carcinoma in primary biliary cirrhosis.
Gastroenterol Res Pract
PUBLISHED: 01-18-2013
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Background. The study aims to analyze in detail the incidence, mortality using the standardized incidence ratio (SIR), and standardized mortality ratio (SMR) of hepatocellular carcinoma (HCC) in primary biliary cirrhosis (PBC), because no large case studies have focused on the detailed statistical analysis of them in Asia. Methods. The study cohorts were consecutively diagnosed at Gunma University and its affiliated hospitals. Age- or sex-specific annual cancer incidence and deaths were obtained from Japanese Cancer Registry and Death Registry as a reference for the comparison of SIR or SMR of HCC. Moreover, univariate analyses and multivariate analyses were performed to clarify predictive factors for the incidence of HCC. Results. The overall 179 patients were followed up for a median of 97 months. HCC had developed in 13 cases. SIR for HCC was 11.6 (95% confidence interval (CI), 6.2-19.8) and SMR for HCC was 11.2 (95% CI, 5.4-20.6) in overall patients. The serum albumin levels were a predictive factor for the incidence of HCC in overall patients. Conclusions. The incidence and mortality of HCC in PBC patients were significantly higher than those in Japanese general population. PBC patients with low serum albumin levels were populations at high risk for HCC.
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Thyroid hormone receptor and liver X receptor competitively up-regulate human selective Alzheimers disease indicator-1 gene expression at the transcriptional levels.
Biochem. Biophys. Res. Commun.
PUBLISHED: 01-11-2013
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Selective Alzheimers disease (AD) indicator-1 (Seladin-1) gene has been identified as a gene, whose expression is down-regulated in the vulnerable region in the brain of AD patients. Thyroid hormone (TH) is important to maintain the function of central nervous system and TH receptor (TR) is known to crosstalk with liver X receptor (LXR) on the lipid metabolism-related gene promoter. Recently, we have demonstrated that TR-? up-regulates the mouse Seladin-1 gene promoter at the transcriptional levels and LXR-? compensates the promoter activation only when the thyroid function is insufficient. In the current study, we have identified that TH and an LXR artificial agonist, TO901317 (TO) activated the human Seladin-1 promoter (-1024/+57 base pair (bp)) including consensus TH response element (TRE) half site (site A: -381 to -375 bp), and the site A mutation deteriorated the activation by TH and TO. Both TR-? and LXR-? heterodimerize with retinoid X receptor (RXR)-? on the site A, and chromatin immunoprecipitation (ChIP) assay revealed that TR-?, LXR-? and RXR-? are recruited to the site A. Moreover, TR-? and LXR-? functionally compete for the promoter activation in CV1 cells. Taken together, we concluded that TR-? and LXR-? competitively up-regulate the human Seladin-1 promoter, sharing the same response element, site A.
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Interferon treatment for patients with chronic hepatitis C complicated with chronic renal failure receiving hemodialysis.
J. Gastroenterol. Hepatol.
PUBLISHED: 01-11-2013
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The Japan Society for Dialysis Therapy established "Guidelines for the Treatment of Hepatitis C Virus Infection in Dialysis Patients." We evaluated the status of HCV infection and the treatment of hemodialysis patients in Gunma prefecture.
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Nesfatin-1: its role in the diagnosis and treatment of obesity and some psychiatric disorders.
Methods Mol. Biol.
PUBLISHED: 01-09-2013
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We discovered a new anorexigenic protein, nesfatin/nucleobindin-2 (NUCB2), which includes an EF-hand, calcium-binding motif. Nesfatin/NUCB2 is converted to nesfatin-1, which may be a physiologically active form in the body. Centrally and systemically administered nesfatin-1 inhibits appetite and body weight gain in rodents. The mid-segment of nesfatin-1 appears to be important in the inhibition of food intake. Intranasal administration of the mid-segment inhibits appetite. Nesfatin-1 may also be involved in the regulation of gastrointestinal function and insulin secretion. We have summarized the recent progress in the research of nesfatin-1.
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Proton-sensing ovarian cancer g protein-coupled receptor 1 on dendritic cells is required for airway responses in a murine asthma model.
PLoS ONE
PUBLISHED: 01-01-2013
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Ovarian cancer G protein-coupled receptor 1 (OGR1) stimulation by extracellular protons causes the activation of G proteins and subsequent cellular functions. However, the physiological and pathophysiological roles of OGR1 in airway responses remain largely unknown. In the present study, we show that OGR1-deficient mice are resistant to the cardinal features of asthma, including airway eosinophilia, airway hyperresponsiveness (AHR), and goblet cell metaplasia, in association with a remarkable inhibition of Th2 cytokine and IgE production, in an ovalbumin (OVA)-induced asthma model. Intratracheal transfer to wild-type mice of OVA-primed bone marrow-derived dendritic cells (DCs) from OGR1-deficient mice developed lower AHR and eosinophilia after OVA inhalation compared with the transfer of those from wild-type mice. Migration of OVA-pulsed DCs to peribronchial lymph nodes was also inhibited by OGR1 deficiency in the adoption experiments. The presence of functional OGR1 in DCs was confirmed by the expression of OGR1 mRNA and the OGR1-sensitive Ca(2+) response. OVA-induced expression of CCR7, a mature DC chemokine receptor, and migration response to CCR7 ligands in an in vitro Transwell assay were attenuated by OGR1 deficiency. We conclude that OGR1 on DCs is critical for migration to draining lymph nodes, which, in turn, stimulates Th2 phenotype change and subsequent induction of airway inflammation and AHR.
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Gastric ulcer bleeding from a variant left gastric artery accompanied by congenital absence of the splenic artery successfully treated with coil embolization: a case report and review of the literature.
J Gastrointestin Liver Dis
PUBLISHED: 12-22-2011
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Endoscopic hemostasis is a useful treatment modality for gastric ulcer bleeding. However, it is sometimes difficult to achieve hemostasis in cases with arterial bleeding, especially those complicated with vascular abnormalities. We describe a case with gastric ulcer bleeding from a variant left gastric artery accompanied by congenital absence of the splenic artery. A 50-year-old female was admitted to our hospital with dizziness and tarry stools. Upper gastrointestinal endoscopy revealed bleeding from a gastric ulcer, and endoscopic hemostasis by endoscopic clipping was carried out. Computed tomography and abdominal angiography revealed the variant left gastric artery running below the gastric ulcer. In spite of endoscopic hemostasis and medication, re-bleeding from the gastric ulcer occurred. A transcatheter coil embolization for the variant left gastric artery was performed and successfully achieved hemostasis. This case was accompanied by congenital absence of the splenic artery, which is an extremely rare condition. We herein describe this rare case and review previously reported cases.
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Haploinsufficient and predominant expression of multiple endocrine neoplasia type 1 (MEN1)-related genes, MLL, p27Kip1 and p18Ink4C in endocrine organs.
Biochem. Biophys. Res. Commun.
PUBLISHED: 10-01-2011
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Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominantly inherited syndrome characterized by parathyroid, gastro-entero-pancreatic and anterior pituitary tumors. Although the tissue selectivity of tumors in specific endocrine organs is the very essence of MEN1, the mechanisms underlying the tissue-selectivity of tumors remain unknown. The product of the Men1 gene, menin, and mixed lineage leukemia (MLL) have been found to cooperatively regulate p27(Kip1)/CDKN1B (p27) and p18(Ink4C)/CDKN2C (p18) genes. However, there are no reports on the tissue distribution of these MEN1-related genes. We investigated the expression of these genes in the endocrine and non-endocrine organs of wild-type, Men1 knockout and MLL knockout mice. Men1 mRNA was expressed at a similar level in endocrine and non-endocrine organs. However, MLL, p27 and p18 mRNAs were predominantly expressed in the endocrine organs. Notably, p27 and MLL mRNAs were expressed in the pituitary gland at levels approximately 12- and 17-fold higher than those in the liver. The heterozygotes of Men1 knockout mice the levels of MLL, p27 and p18 mRNAs did not differ from those in the wild-type mice. In contrast, heterozygotes of MLL knockout mice showed significant reductions in p27 mRNA as well as protein levels in the pituitary and p27 and p18 in the pancreatic islets, but not in the liver. This study demonstrated for the first time the predominant expression MEN1-related genes, particularly MLL and p27, in the endocrine organs, and a tissue-specific haploinsuffiency of MLL, but not menin, may lead to a decrease in levels of p27 and p18 mRNAs in endocrine organs. These findings may provide basic information for understanding the mechanisms of tissue selectivity of the tumorigenesis in patients with MEN1.
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Crosstalk of thyroid hormone receptor and liver X receptor in lipid metabolism and beyond [Review].
Endocr. J.
PUBLISHED: 09-09-2011
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Thyroid hormone receptors (TRs) and liver X receptors (LXRs) are members of the nuclear receptor superfamily. Although LXRs and TRs belong to two distinct receptor subgroups with respect to ligand-binding affinity, the two receptor systems show similarity with respect to molecular mechanism, target genes, and physiological roles. Since both TRs and LXRs play an important role in metabolic regulation, form heterodimers with retinoid X receptors (RXRs), and bind to direct repeat-4 (DR-4) with identical geometry and polarity, crosstalk between these two receptors has been reported, especially on lipid metabolism-related genes. Recently, several types of crosstalk between TRs and LXRs have been identified and crosstalk has also been observed in other physiological systems such as central nervous system rather than lipid metabolism. In this review, recent advances in elucidating the molecular mechanisms of the crosstalk between these two nuclear receptors are discussed, with the aim of finding a perspective on unknown roles of TRs and LXRs.
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Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells.
Biochem. Biophys. Res. Commun.
PUBLISHED: 08-12-2011
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Asthma is characterized by airway inflammation, hyper-responsiveness and remodeling. Extracellular acidification is known to be associated with severe asthma; however, the role of extracellular acidification in airway remodeling remains elusive. In the present study, the effects of acidification on the expression of connective tissue growth factor (CTGF), a critical factor involved in the formation of extracellular matrix proteins and hence airway remodeling, were examined in human airway smooth muscle cells (ASMCs). Acidic pH alone induced a substantial production of CTGF, and enhanced transforming growth factor (TGF)-?-induced CTGF mRNA and protein expression. The extracellular acidic pH-induced effects were inhibited by knockdown of a proton-sensing ovarian cancer G-protein-coupled receptor (OGR1) with its specific small interfering RNA and by addition of the G(q/11) protein-specific inhibitor, YM-254890, or the inositol-1,4,5-trisphosphate (IP(3)) receptor antagonist, 2-APB. In conclusion, extracellular acidification induces CTGF production through the OGR1/G(q/11) protein and inositol-1,4,5-trisphosphate-induced Ca(2+) mobilization in human ASMCs.
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Hepatocyte growth factor overexpression ameliorates liver inflammation and fibrosis in a mouse model of nonalcoholic steatohepatitis.
Hepatol Int
PUBLISHED: 08-05-2011
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BACKGROUND: Hepatocyte growth factor (HGF) is a potent growth factor involved in liver regeneration that has various effects on epithelial and nonepithelial cells. Although it has been demonstrated that HGF can reduce liver inflammation or fibrosis caused by pharmaceutical or chemical insult, no examination of its effect on liver injury in nonalcoholic steatohepatitis (NASH) has been reported. METHODS: To examine the effect of HGF on liver injury in NASH, we generated a murine steatohepatitis model on an HGF overexpression transgenic (Tg) background, and fed the mice a methionine- and choline-deficient diet (MCD). RESULTS: In mice fed the MCD diet, serum ALT levels and the inflammation score for the Tg mice were significantly lower than those for the wild-type (Wt) control mice (P < 0.01). The index of lipid peroxidation increased in the liver of the Wt mice as demonstrated by thiobarbituric acid-reactive substances. Furthermore, the liver fibrosis in Tg mice was dramatically suppressed in comparison to that in Wt mice. The gene expression of matrix metalloprotease-13 in the Tg mice was significantly increased in comparison to that of the Wt mice. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay showed the apoptotic cells to significantly decrease in number in the Tg mice in comparison to the Wt mice fed the MCD diet (P < 0.01). CONCLUSION: Hepatocyte growth factor ameliorated liver inflammation and fibrosis in a murine model of NASH as a result of the anti-oxidative and anti-apoptotic effect, and the induction of fibrinolysis.
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Cyclin-dependent kinase-5 is a key molecule in tumor necrosis factor-?-induced insulin resistance.
J. Biol. Chem.
PUBLISHED: 08-03-2011
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The mechanism of TNF-?-induced insulin resistance has remained unresolved with evidence for down-regulation of insulin effector targets effects or blockade of proximal as well as distal insulin signaling events depending upon the dose, time, and cell type examined. To address this issue we examined the acute actions of TNF-? in differentiated 3T3L1 adipocytes. Acute (5-15 min) treatment with 20 ng/ml (~0.8 nm) TNF-? had no significant effect on IRS1-associated phosphatidylinositol 3-kinase. In contrast, TNF-? increased insulin-stimulated cyclin-dependent kinase-5 (CDK5) phosphorylation on tyrosine residue 15 through an Erk-dependent pathway and up-regulated the expression of the CDK5 regulator protein p35. In parallel, TNF-? stimulation also resulted in the phosphorylation and GTP loading of the Rho family GTP-binding protein, TC10?. TNF-? enhanced the depolymerization of cortical F-actin and inhibited insulin-stimulated glucose transporter-4 (GLUT4) translocation. Treatment with the MEK inhibitor, PD98059, blocked the TNF-?-induced increase in CDK5 phosphorylation and the depolymerization of cortical F-actin. Conversely, siRNA-mediated knockdown of CDK5 or treatment with the MEK inhibitor restored the impaired insulin-stimulated GLUT4 translocation induced by TNF-?. Furthermore, siRNA-mediated knockdown of p44/42 Erk also rescued the TNF-? inhibition of insulin-stimulated GLUT4 translocation. Together, these data demonstrate that TNF-?-mediated insulin resistance of glucose uptake can occur through a MEK/Erk-dependent activation of CDK5.
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Glucagon plays an important role in the modification of insulin secretion by leptin.
Islets
PUBLISHED: 07-01-2011
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Obese people show marked hyerinsulinemia, but the exact mechanism has not been clarified. Hyperleptinemia is one of possible candidates, although there is an obvious difference in the effect of leptin on insulin secretion between isolated pancreatic islets and ?-cell line. Since glucagon may modulate the effect of leptin on insulin secretion, we determined the influences of glucagon in the leptin effect on insulin secretion. The influences of glucagon in the leptin effect on insulin secretion for 10 minutes were determined by using isolated mouse islets and HIT-T 15 cells. The influences of 3-isobutyl-1- methylxanthine (IBMX), forskolin, and dibutyryl cyclic AMP were investigated in the leptin effect on insulin secretion. Leptin-inhibited insulin and glucagon secretion in isolated mouse pancreatic islets. In contrast, leptin stimulated insulin secretion in isolated mouse islets previously incubated with monoclonal anti-glucagon antibodies for 18 hours. In HIT-T 15 cells, leptin dose-dependently increased insulin secretion, but this effect was attenuated by the addition of glucagon. The stimulatory effect of leptin on insulin secretion was attenuated by 48 hour pre-incubation with glucagon. In the presence of 100 mM IBMX, leptin decreased insulin secretion from HIT-T 15 cells. Leptin also reduced insulin secretion in the presence of 1mM forskolin or 1mM dibutyryl cyclic AMP. The leptin effects on insulin secretion were affected by the existence of glucagon. Intracellular cyclic AMP concentrations may determine the leptin effects on insulin secretion in pancreatic ?-cells.
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Prevalence of asthma symptoms based on the European Community Respiratory Health Survey questionnaire and FENO in university students: gender differences in symptoms and FENO.
Allergy Asthma Clin Immunol
PUBLISHED: 06-16-2011
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The fractional concentration of nitric oxide in exhaled air (FENO) is used as a biomarker of eosinophilic airway inflammation. FENO is increased in patients with asthma. The relationship between subjective asthma symptoms and airway inflammation is an important issue. We expected that the subjective asthma symptoms in women might be different from those in men. Therefore, we investigated the gender differences of asthma symptoms and FENO in a survey of asthma prevalence in university students.
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Topical application of glycyrrhizin preparation ameliorates experimentally induced colitis in rats.
World J. Gastroenterol.
PUBLISHED: 06-03-2011
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To examine the efficacy of glycyrrhizin preparation (GL-p) in the treatment of a rat model of ulcerative colitis (UC).
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Nuclear receptors CAR and PXR; therapeutic targets for cholestatic liver disease.
Front Biosci (Landmark Ed)
PUBLISHED: 05-31-2011
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Cholestasis results in the intrahepatic retention of cytotoxic bile acids (BA) and it can thus lead to liver injury. Hydrophilic BA ursodeoxycholic acid (UDCA) is currently used to treat cholestasis but its efficacy is limited. Nuclear receptors are key regulators of various processes including metabolism of xeno- and endobiotics such as BA and drugs. Recent studies have made significant progress in elucidating the mechanisms which regulate the BA metabolism by nuclear receptors. The nuclear receptor FXR plays the role of master regulator of BA homeostasis and is a promising drug target for cholestatic liver disease. In addition to FXR, the nuclear receptors CAR and PXR function as sensors of toxic byproducts and regulator of BA homeostasis. Ligands for both receptors including phenobarbital have been used to treat cholestatic liver diseases before the mechanisms of these receptors were revealed. Novel compounds targeting CAR and PXR with specific effects and fewer side effects will therefore be useful for the treatment of cholestatic liver diseases. This article will review the current knowledge of the xenobiotic-sensing nuclear receptors CAR and PXR, while also discussing their potential role in the treatment of cholestatic liver diseases.
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Different gastoroesophageal reflux symptoms of middle-aged to elderly asthma and chronic obstructive pulmonary disease (COPD) patients.
J Clin Biochem Nutr
PUBLISHED: 05-24-2011
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Symptomatic differences and the impact of gastroesophageal reflux disease (GERD) have not been clarified in patients with asthma and chronic obstructive pulmonary disease (COPD). The purpose of this study is to assess the differences of GERD symptoms among asthma, COPD, and disease control patients, and determine the impact of GERD symptoms on exacerbation of asthma or COPD by using a new questionnaire for GERD. A total of 120 subjects underwent assessment with the frequency scale for the symptoms of GERD (FSSG) questionnaire, including 40 age-matched patients in each of the asthma, COPD, and disease control groups. Asthma and control patients had more regurgitation-related symptoms than COPD patients (p<0.05), while COPD patients had more dysmotility-related symptoms than asthma patients (p<0.01) or disease control patients (p<0.01). The most distinctive symptom of asthma patients with GERD was an unusual sensation in the throat, while bloated stomach was the chief symptom of COPD patients with GERD, and these symptoms were associated with disease exacerbations. The presence of GERD diagnosed by the total score of FSSG influences the exacerbation of COPD. GERD symptoms differed between asthma and COPD patients, and the presence of GERD diagnosed by the FSSG influences the exacerbation of COPD.
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Cardiovascular complications of patients with aldosteronism associated with autonomous cortisol secretion.
J. Clin. Endocrinol. Metab.
PUBLISHED: 05-18-2011
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Primary aldosteronism (PA) is sometimes associated with the autonomous secretion of cortisol.
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Gastric ulcer revealed by computed tomography in a patient with tongue cancer after percutaneous gastrostomy.
Case Rep Gastroenterol
PUBLISHED: 04-06-2011
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With the advances in computed tomography (CT) imaging, CT can result in precise imaging, even of the gastrointestinal tract. However, the diagnostic quality of endoscopy is superior to CT because of precise mucosal observations or biopsy procedure. In the present case, CT was useful in the diagnosis of a gastric ulcer because endoscopy was deemed too difficult to perform due to tongue cancer occupying the oral space. Three-dimensional reconstruction of the CT images revealed an ulcerous lesion at the upper posterior wall of the stomach. CT may therefore be helpful for the diagnosis of gastric lesions when usual endoscopy is difficult to perform, as observed in the present patient.
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Gastroptosis is associated with less dyspepsia, rather than a cause of dyspepsia, in Japanese persons.
Intern. Med.
PUBLISHED: 04-01-2011
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Gastroptosis is recognized by its characteristic appearance on barium studies. The present prospective study assessed the relationship between gastroptosis and dyspeptic symptoms.
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Nesfatin-1 stimulates renal sympathetic nerve activity in rats.
Neuroreport
PUBLISHED: 04-01-2011
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Earlier examination reported that central injection of nesfatin-1 elevated blood pressure and suppressed food intake in conscious rats. In this study, we analyzed the effects of the intracerebroventricular injection of nesfatin-1 on the sympathetic nerve outflow to the kidney in urethane-anesthetized rats. An intracerebroventricular injection of nesfatin-1 significantly stimulated renal sympathetic nerve activity and blood pressure in a dose-dependent manner. Moreover, we examined the role of the melanocortin system on the sympathoexcitation caused by the nesfatin-1 injection. Pretreatment with the melanocortin-3/4 receptor antagonist, SHU9119, abolished the increase in nerve activity and blood pressure induced by nesfatin-1. Thus, the stimulating effects of nesfatin-1 administration on the sympathetic nerve activity of the kidney may depend on the central melanocortin system.
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Elemental analysis of lung tissue particles and intracellular iron content of alveolar macrophages in pulmonary alveolar proteinosis.
Respir. Res.
PUBLISHED: 03-31-2011
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Pulmonary alveolar proteinosis (PAP) is a rare disease occurred by idiopathic (autoimmune) or secondary to particle inhalation. The in-air microparticle induced X-ray emission (in-air micro-PIXE) system performs elemental analysis of materials by irradiation with a proton microbeam, and allows visualization of the spatial distribution and quantitation of various elements with very low background noise. The aim of this study was to assess the secondary PAP due to inhalation of harmful particles by employing in-air micro-PIXE analysis for particles and intracellular iron in parafin-embedded lung tissue specimens obtained from a PAP patient comparing with normal lung tissue from a non-PAP patient. The iron inside alveolar macrophages was stained with Berlin blue, and its distribution was compared with that on micro-PIXE images.
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Rapid gastric emptying, rather than delayed gastric emptying, might provoke functional dyspepsia.
J. Gastroenterol. Hepatol.
PUBLISHED: 03-30-2011
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It has been suggested that there could be three possible mechanisms of gastric dysfunction in patients with FD: (i) delayed gastric emptying, (ii) impaired gastric accommodation of food intake, and (iii) hypersensitivity to gastric distention. Postprandial fullness seems to be the most severe symptom in patients who report aggravation of their symptoms after meals. Therefore, it has been assumed that delayed gastric emptying and consequent prolonged antral distension could reduce hunger, increase satiety, and even cause gastric discomfort, all of which would pose a significant barrier to adequate nutrition. We previously reported that postprandial water intake inhibits gastric antral motility along with an increase of cholecystokinin (CCK) in normal subjects. We assumed that the rapid increase of CCK after water intake was initiated by a feedback mechanism related to the inflow of fatty chyme into the duodenum that inhibits gastric antral activity. This duodeno-gastric interaction is known as the "duodenal break." We also reported that total gastric emptying was more rapid after the intake of a high-viscosity liquid meal than after a low-viscosity meal, because the low-viscosity liquid meal inhibits gastric emptying after rapid initial inflow into the duodenum. Considering these results, we hypothesized that rapid gastric emptying, rather than delayed gastric emptying, could be a cause of FD. In some patients with postprandial distress syndrome (PDS), we have found a significant correspondence between PDS-related dyspepsia and accelerated gastric emptying in the early postprandial period. It is worth emphasizing that the duodenum and the duodeno-gastric interaction (duodenal break) could have an important role in the pathophysiology of FD. We consider that rapid gastric emptying might be a more important factor than delayed gastric emptying in patients with FD.
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Attenuated expression of menin and p27 (Kip1) in an aggressive case of multiple endocrine neoplasia type 1 (MEN1) associated with an atypical prolactinoma and a malignant pancreatic endocrine tumor.
Endocr. J.
PUBLISHED: 03-25-2011
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Tumors in multiple endocrine neoplasia type 1 (MEN1) are generally benign. Since information on the pathogenesis of MEN1 in malignant cases is limited, we conducted genetic analysis and compared the expression of menin, p27(Kip1)(p27)/CDKN1B and p18(Ink4C)(p18)/CDKN2C with levels in benign cases. We describe the case of a 56 year-old male with an atypical prolactinoma and malignant pancreatic neuroenocrine tumor. At age 50, he had undergone transsphenoidal surgery to remove a prolactinoma. However, the tumor relapsed twice. Histological analysis of the recurrent prolactinoma revealed the presence of prolactin, a high MIB-1 index (32.1 %), p53-positive cells (0.2%), and an unusual association with FSH-positive cells. A few years later, he was also found to have a non-functioning pancreatic tumor with probable metastasis to the extradullar region. The metastatic region tested positive for chromogranin and CD56, and negative for prolactin, with 1.2 % of cells p53-positive. Although genetic analyses of the MEN1, p27, and p18 genes demonstrated no mutation, numbers of menin, p27 and p18 immuno-positive cells were significantly down-regulated in the recurrent prolactinoma, but that of p18 was intact in the metastatic region. Furthermore, MEN1 and p27 mRNA levels of the recurrent prolactinoma were down-regulated, particularly the MEN1 mRNA level, compared to levels in 10 cases of benign prolactinoma, while the p18 mRNA level was similar to that of normal pituitary. The tumor in this case may be a subtype of MEN1 showing more aggressive and malignant features probably induced by low levels of menin and p27.
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A retrospective cohort study of partial splenic embolization for antiviral therapy in chronic hepatitis C with thrombocytopenia.
J. Gastroenterol.
PUBLISHED: 03-24-2011
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Although partial splenic embolization (PSE) is reportedly effective prior to interferon (IFN)-based therapy, the number of subjects in these studies is small, and the appropriate candidates and disease prognosis remain unknown.
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Analysis of ABC (D) stratification for screening patients with gastric cancer.
World J. Gastroenterol.
PUBLISHED: 02-21-2011
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To evaluate the value of ABC (D) stratification [combination of serum pepsinogen and Helicobacter pylori (H. pylori) antibody] of patients with gastric cancer.
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Nesfatin-1 enhances glucose-induced insulin secretion by promoting Ca(2+) influx through L-type channels in mouse islet ?-cells.
Endocr. J.
PUBLISHED: 02-17-2011
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Nucleobindin-2 (NUCB2)-derived nesfatin-1 located in the brain has been implicated in the satiety and control of energy metabolism. Nesfatin-1 is also produced in the periphery and present in the plasma. It has recently been reported that NUCB2/nesfatin-1 is localized in pancreatic islet ?-cells in mice and rats and released from islets. However, its function in islets remains largely unknown. This study examined direct effects of nesfatin-1 on insulin release from pancreatic islets and on cytosolic Ca(2+) concentration ([Ca(2+)](i)) in single ?-cells from ICR mice. In the presence of 8.3 mmol/L glucose, nesfatin-1 at 10(-10)-10(-9) mol/L tended to increase and at 10(-8) mol/L increased insulin release from isolated islets, while at 2.8 mmol/L glucose nesfatin-1 had no effect. Furthermore, nesfatin-1 at 10(-10)-10(-8) mol/L increased [Ca(2+)](i) in single ?-cells in the presence of 8.3 but not 2.8 mmol/L glucose. The nesfatin-1-induced [Ca(2+)](i) increase and insulin release were inhibited by removal of extracellular Ca(2+) and by addition of nitrendipine, a blocker of voltage-dependent L-type Ca(2+) channels. Unexpectedly, the [Ca(2+)](i) responses to nesfatin-1 were unaltered by inhibitors of protein kinase A (PKA) and phospholipase A(2) (PLA(2)). These results indicate that nesfain-1 potentiates glucose-induced insulin secretion by promoting Ca(2+) influx through L-type Ca(2+) channels independently of PKA and PLA(2) in mouse islet ?-cells.
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Transforming growth factor-? attenuates hepatic fibrosis: possible involvement of matrix metalloproteinase-1.
Liver Int.
PUBLISHED: 02-15-2011
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The effect of transforming growth factor (TGF)-? on fibrosis varies between cell types and the role of TGF-? in hepatic fibrosis has not been fully elucidated.
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Knockdown of oncogenic KRAS in non-small cell lung cancers suppresses tumor growth and sensitizes tumor cells to targeted therapy.
Mol. Cancer Ther.
PUBLISHED: 02-11-2011
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Oncogenic KRAS is found in more than 25% of lung adenocarcinomas, the major histologic subtype of non-small cell lung cancer (NSCLC), and is an important target for drug development. To this end, we generated four NSCLC lines with stable knockdown selective for oncogenic KRAS. As expected, stable knockdown of oncogenic KRAS led to inhibition of in vitro and in vivo tumor growth in the KRAS-mutant NSCLC cells, but not in NSCLC cells that have wild-type KRAS (but mutant NRAS). Surprisingly, we did not see large-scale induction of cell death and the growth inhibitory effect was not complete. To further understand the ability of NSCLCs to grow despite selective removal of mutant KRAS expression, we conducted microarray expression profiling of NSCLC cell lines with or without mutant KRAS knockdown and isogenic human bronchial epithelial cell lines with and without oncogenic KRAS. We found that although the mitogen-activated protein kinase pathway is significantly downregulated after mutant KRAS knockdown, these NSCLCs showed increased levels of phospho-STAT3 and phospho-epidermal growth factor receptor, and variable changes in phospho-Akt. In addition, mutant KRAS knockdown sensitized the NSCLCs to p38 and EGFR inhibitors. Our findings suggest that targeting oncogenic KRAS by itself will not be sufficient treatment, but may offer possibilities of combining anti-KRAS strategies with other targeted drugs.
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Liver X receptor-?/? expression ratio is increased in ACTH-secreting pituitary adenomas.
Neurosci. Lett.
PUBLISHED: 02-05-2011
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The liver X receptors (LXR-? and -?) are nuclear oxysterol receptors that play pivotal roles in regulating the expression of genes involved in cholesterol transport and metabolism. Recently, several groups have reported that the LXRs also regulate adrenal steroidogenesis. In the previous report, we demonstrated that LXR-? is dominantly expressed in the pituitary and that LXR-? positively regulates the proopiomelanocortin (POMC) gene promoter at the transcriptional level. In this report, we evaluated the expression levels of LXR-? and -? gene in the human pituitary tumor. Even though LXR-? mRNA levels are not significantly increased in ACTH-secreting adenomas, LXR-?/? expression ratio is significantly higher than other pituitary tumors including normal pituitaries. Furthermore, in At-T20 cells, which express POMC gene, overexpression of LXR-? decreased POMC gene promoter activities. Thus, we concluded that LXR-?/? gene expression ratio is a critical factor to activate POMC gene expression in ACTH-secreting pituitary adenomas.
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In-air microparticle induced X-ray emission analysis of particles in interstitial pneumonia lung tissue obtained by transbronchial biopsy.
J Clin Biochem Nutr
PUBLISHED: 01-19-2011
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Interstitial pneumonia develops in association with inhaled particles. In-air microparticle induced X-ray emission (in-air micro) analysis was previously employed to assess the spatial distribution and content of particles in surgical lung biopsy specimens. The aim of this study was to assess the efficacy of in-air micro-analysis for transbronchial lung biopsy specimens in patients with or without occupational exposure. The elements composing lung particles and their locations could be identified by in-air micro-analysis. Silicon was the major component of particles. Quantitative analysis revealed that the elements composing lung particles varied between patients. In a patient with suspected nickel exposure, aluminium, vanadium, and calcium were detected, but was not detected. In a patient without a work history (housewife), various elements were detected. In-air micro-analysis was useful for assessing the spatial distribution and content of particles in specimens from patients. Occupational exposure was not necessarily associated with deposition of particles in the lungs. Therefore, in the diagnosis of, elemental analysis of specimens by in-air micro-analysis could be useful for assessing exposure to particles objectively.
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Calcineurin inhibition by polaprezinc in rats with experimentally-induced colitis.
Life Sci.
PUBLISHED: 01-08-2011
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We investigated the therapeutic effect of polaprezinc (PZ), N-(3-aminopropionyl)-L-histidinato zinc, in rats with experimentally-induced colitis by focusing on calcineurin (CN) inhibition. CN plays a crucial role in T-cell activation and cytokine gene expression and is targeted by immunosuppressants such as cyclosporine and FK506.
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Oncogenic KRAS-induced interleukin-8 overexpression promotes cell growth and migration and contributes to aggressive phenotypes of non-small cell lung cancer.
Int. J. Cancer
PUBLISHED: 01-03-2011
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The CXC chemokine interleukin-8 (IL-8) is an angiogenic growth factor that is overexpressed in various cancers, including non-small cell lung cancer (NSCLC). Previously, IL-8 was shown as a transcriptional target of RAS signaling, raising the possibility of its role in oncogenic KRAS-driven NSCLC. Using microarray analysis, we identified IL-8 as the most downregulated gene by shRNA-mediated KRAS knockdown in NCI-H1792 NSCLC cells where IL-8 is overexpressed. NSCLC cell lines harboring KRAS or EGFR mutations overexpressed IL-8, while IL-8 levels were more prominent in KRAS mutants compared to EGFR mutants. IL-8 expression was downregulated by shRNA-mediated KRAS knockdown in KRAS mutants or by treatment with EGFR tyrosine kinase inhibitors and EGFR siRNAs in EGFR mutants. In our analysis of the relationship of IL-8 expression with clinical parameters and mutation status of KRAS or EGFR in 89 NSCLC surgical specimens, IL-8 expression was shown to be significantly higher in NSCLCs of males, smokers, and elderly patients and those with pleural involvement and KRAS mutated adenocarcinomas. In KRAS mutant cells, the MEK inhibitor markedly decreased IL-8 expression, while the p38 inhibitor increased IL-8 expression. Attenuation of IL-8 function by siRNAs or a neutralizing antibody inhibited cell proliferation and migration of KRAS mutant/IL-8 overexpressing NSCLC cells. These results indicate that activating mutations of KRAS or EGFR upregulate IL-8 expression in NSCLC; IL-8 is highly expressed in NSCLCs from males, smokers, elderly patients, NSCLCs with pleural involvement, and KRAS-mutated adenocarcinomas; and IL-8 plays a role in cell growth and migration in oncogenic KRAS-driven NSCLC.
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Inhibition of L-type amino acid transporter 1 has antitumor activity in non-small cell lung cancer.
Anticancer Res.
PUBLISHED: 12-29-2010
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L-type amino acid transporter 1 (LAT1) is highly expressed in various human neoplasms. Antitumor activity of inhibiting LAT1 was analyzed in non-small cell lung cancer (NSCLC).
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Stricture after endoscopic submucosal dissection for early gastric cancers and adenomas.
Dig Endosc
PUBLISHED: 12-24-2010
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?Stricture is a complication that may occur after endoscopic submucosal dissection (ESD) of gastric neoplasms. The goal of the present study was to investigate the incidence, risk factors and management of gastric stricture after ESD.
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Clinical characteristics and treatment for patients presenting with bleeding duodenal varices.
Dig Endosc
PUBLISHED: 12-24-2010
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Bleeding from ectopic varices, including duodenal varices, is uncommon, but it can be difficult to manage. The clinical data of patients diagnosed and treated for duodenal varices were reviewed to investigate the strategy for treatment.
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Attainment of glycaemic goals by step-up therapy with biphasic insulin aspart-70/30 in Japanese type 2 diabetic patients.
Endocr. J.
PUBLISHED: 12-21-2010
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We have made step-up titration protocol with biphasic insulin aspart-70/30 (BIAsp 30), and tried to achieve glycemic goals in poorly controlled Japanese type 2 diabetic patients. We summarized all results obtained to analyze the effectiveness of our protocol. The target of glycaemic control was defined as HbA1c over 7.0 %. In our insulin initiation protocol, all patients started a once-daily injection of BIAsp 30 before the breakfast in addition to their oral hypoglycaemic agents. The patients who could not achieve the target from 12 to 16 weeks after the start of insulin treatment proceeded to twice daily insulin injection before breakfast and dinner. Next, the patients who could not achieve the target from 12 to 16 weeks after the addition of another BIAsp injection proceeded to thrice daily insulin injection before each meal a day. The results of 39 patients were analyzed, and 10.3 % of all patients achieved the target after the start of once daily injection of BIAsp 30, 41.7 % achieved in twice daily injection of BIAsp, and 51.4 % achieved in thrice daily injection of BIAsp. Daily insulin dose at the end of each treatment was 9.3±4.1 U in once daily, 17.4±6.3 U in twice daily, and 28.4±10.4 U in thrice daily. Total body weight increase by 2.0±2.6 kg. The initiation and titration protocol with BIAsp 30 improved glycaemic control, and increased the number of patients with the achievement of glycaemic goals.
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Constitutive active/androstane receptor promotes hepatocarcinogenesis in a mouse model of non-alcoholic steatohepatitis.
Carcinogenesis
PUBLISHED: 12-20-2010
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The nuclear receptor constitutive active/androstane receptor (CAR) acts as a sensor of toxic byproducts derived from the endogenous metabolism and exogenous chemicals. We previously reported that CAR is responsible for exacerbating hepatic injury and fibrosis in a dietary model of non-alcoholic steatohepatitis (NASH) via upregulation of lipid peroxidation. In this study, we investigated the pathological roles of the CAR in the development of hepatocellular carcinoma in NASH model. CAR+/+ and CAR-/- mice were fed methionine- and choline-deficient (MCD) diet after tumor initiation with a single dose of the genotoxic carcinogen diethylnitrosamine (DEN) at 2 weeks of age. Interestingly, the MCD diet dramatically promoted DEN-induced hepatocarcinogenesis in CAR+/+ mice. However, the deletion of CAR leads to a significantly lower tumor incidence and smaller tumor diameter. Hepatocytes of MCD-treated-CAR+/+ mice showed a significantly higher staining frequency of Ki-67, a marker of cell proliferation, and exhibited a higher expression of c-Myc and FoxM1 transcripts compared with MCD-treated CAR-/- mice. Immunohistochemistry revealed the nuclear translocation of CAR thus suggesting that the activation of CAR signaling increased in the hepatocytes of CAR+/+ mice fed MCD diet. In addition, in vitro experiments using the CAR stably expressed cell line with TCPOBOP have suggested that CAR activation directly leads to cell proliferation. Survival was significantly lower in the CAR+/+ mice fed the MCD diet in comparison with the CAR-/- mice. Taken together, these results suggest that CAR may therefore play a critical role in the hepatocarcinogenesis of the murine NASH model via the upregulation of cell proliferation.
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[A case of non-small cell lung cancer responding to S-1 over a year].
Gan To Kagaku Ryoho
PUBLISHED: 11-19-2010
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A 71-year-old woman was admitted to our hospital, because of an abnormality on her chest radiograph findings. After extensive examination, she was diagnosed with primary lung adenocarcinoma (cT4N2M1, stage IV). She was treated by carboplatin+gemcitabine, gefitinib and docetaxel and the responses were stable disease in any treatment. As the fourth-line treatment, she received oral chemotherapy using S-1 at 100 mg/day (80 mg/m2 day) for 28 days, followed by withdrawal for 14 days. Tumor size was reduced 29.2% after 1 course, 62.5% after 5 courses and 83.3% after 10 courses (14 months). Hematologic and non-hematologic toxicities were mild with the S-1 administration. We experienced a case of continuation of tumor shrinkage over a year without serious adverse events by S-1 treatment. Therefore, oral administration of S-1 could be useful for the treatment of recurrent non-small cell lung cancer over a long time.
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Stressor-responsive central nesfatin-1 activates corticotropin-releasing hormone, noradrenaline and serotonin neurons and evokes hypothalamic-pituitary-adrenal axis.
Aging (Albany NY)
PUBLISHED: 10-23-2010
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A recently discovered satiety molecule, nesfatin-1, is localized in neurons of the hypothalamus and brain stem and colocalized with stress-related substances, corticotropin-releasing hormone (CRH), oxytocin, proopiomelanocortin, noradrenaline (NA) and 5-hydroxytryptamine (5-HT). Intracerebroventricular (icv) administration of nesfatin-1 produces fear-related behaviors and potentiates stressor-induced increases in plasma adrenocorticotropic hormone (ACTH) and corticosterone levels in rats. These findings suggest a link between nesfatin-1 and stress. In the present study, we aimed to further clarify the neuronal network by which nesfatin-1 could induce stress responses in rats. Restraint stress induced c-Fos expressions in nesfatin-1-immunoreactive neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus, and in the nucleus of solitary tract (NTS), locus coeruleus (LC) and dorsal raphe nucleus (DR) in the brain stem, without altering plasma nesfatin-1 levels. Icv nesfatin-1 induced c-Fos expressions in the PVN, SON, NTS, LC, DR and median raphe nucleus, including PVN-CRH, NTS-NA, LC-NA and DR-5-HT neurons. Nesfatin-1 increased cytosolic Ca2+ concentration in the CRH-immunoreactive neurons isolated from PVN. Icv nesfatin-1 increased plasma ACTH and corticosterone levels. These results indicate that the central nesfatin-1 system is stimulated by stress and activates CRH, NA and 5-HT neurons and hypothalamic-pituitary-adrenal axis, evoking both central and peripheral stress responses.
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Assessment of therapy response in lung cancer with ¹?F-?-methyl tyrosine PET.
AJR Am J Roentgenol
PUBLISHED: 10-23-2010
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PET with a novel tracer, L-[3-¹?F]-?-methyl tyrosine (¹?F-FMT), has been studied in lung cancer. We evaluated ¹?F-FMT PET for therapy response in comparison with ¹?F-FDG PET.
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Primary bilateral adrenal diffuse large B-cell lymphoma demonstrating adrenal failure.
Intern. Med.
PUBLISHED: 10-15-2010
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Primary adrenal lymphoma (PAL) is extremely rare although involvement of malignant lymphoma into adrenals is common. We report a case of a 58-year-old man with bilateral PAL who demonstrated adrenal insufficiency. Primary large B-cell lymphoma was proven by a computed tomography-guided needle biopsy of the adrenal tumor. Although a complete remission was once achieved by combination chemotherapy plus rituximab, a recurrence occurred with brain metastasis leading to his death. We concluded that PAL should be considered as a possible cause of bilateral adrenal incidentalomas with progressive adrenal insufficiency.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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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.