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Find video protocols related to scientific articles indexed in Pubmed.
A8, An Anti-uPA Agonistic Antibody, Promotes Metastasis of Cancer Cells Via ERK Pathway.
Monoclon Antib Immunodiagn Immunother
PUBLISHED: 10-31-2014
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Urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) are expressed in many tumors and have been reported to be correlated to protein expression and poor prognosis in malignant tumors. In a previous study, we reported on the selection of human single-chain variable fragment (scFv) A8 specific to uPA from phage-displayed human naïve scFv library. In this study, scFv A8 was converted to minibody form and evaluated for its functional ability on the uPA system involved in cellular signaling and cancer cell metastasis. A8 minibody increased enzyme activity of uPA and enhanced the migration and invasion of HT1080 colon cancer cells in a dose-dependent manner. A8 increased ERK phosphorylation, and enhanced migration was blocked by U0126, but not by LY0294002, SB2203580, and SP600125. A8 minibody also enhanced migration of MDA-MB231 by mediated expressing surface uPA, but not that of MCF-7 non-expressing surface uPA. Taken together, the A8 anti-uPA antibody is a uPA agonistic antibody, enhancing migration and invasion of cancer cells that express uPA via activation of ERK pathway.
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Nephrotoxic potential and toxicokinetics of melamine combined with cyanuric Acid in rats.
J. Toxicol. Environ. Health Part A
PUBLISHED: 10-25-2014
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To investigate the nephrotoxic potential of melamine (MEL) and cyanuric acid (CA) in male Sprague-Dawley rats, 7-d repeated-dose studies were performed. The experimental groups of MEL100 and CA100 were orally administered with MEL and CA at 100 mg/kg/d for 7 d, respectively. In groups dosed with MEL-CA mixtures, melamine and cyanuric acid (1:1) were simultaneously administered at 4, 20, or 100 mg/kg/d for 7 d (i.e., MEL-CA4, MEL-CA20, or MEL-CA100, respectively). Body weights were not markedly affected in MEL100, CA100, and MEL-CA4 groups, but significantly reduced in MEL-CA 20 and 100 rats. Most parameters determined in sera and tissues were not markedly altered in MEL100, CA100, and MEL-CA4-treated rodents. However, BUN, creatinine, total protein, and kidney weights were significantly increased in MEL-CA20- and MEL-CA100-treated animals. Renal histopathologic findings also revealed signs of toxicity, including tubular dilatation, crystal deposition, granulomatous tubulo-interstitial inflammation, and tubular necrosis with regeneration. Data suggested that the combination of MEL and CA might be responsible for observed nephrotoxicity that was not seen following individual exposure to either MEL or CA alone. Subsequently, the concentrations of MEL and CA were determined in serum, urine, and kidney tissues by using liquid chromatography-mass spectrometry. Toxicokinetic studies indicated that MEL or CA alone might be eliminated almost completely within 24 h after dosing showing no accumulation in kidney. However, the combined MEL-CA dose produced marked accumulation of chemicals in blood and kidneys. These results suggested that combined MEL and CA might produce renal toxicity due to significant chemical accumulation in kidney accompanied by low excretion.
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Accelerated disease progression after discontinuation of sorafenib in a patient with metastatic papillary thyroid cancer.
Endocrinol Metab (Seoul)
PUBLISHED: 09-25-2014
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Distant metastases from papillary thyroid carcinoma (PTC) are rare and are associated with a poor prognosis. Here, we describe a patient with metastatic PTC who was treated with a tyrosine kinase inhibitor (TKI, sorafenib) for several months that was acutely exacerbated by discontinuation. A 43-year-old male was diagnosed with PTC in February 2004 and underwent total thyroidectomy followed by two courses of high-dose radioactive iodine (RAI) therapy. Despite two additional courses of high-dose RAI therapy, lung and muscle metastases were developed. Treatment with sorafenib was begun in September 2010. After 11 months treatment of sorafenib, newly developed metastatic lesions were found in mediastinal lymph nodes, liver, and bones. Considered as treatment failure, the administration of sorafenib was discontinued. Two weeks after sorafenib treatment was stopped, the disease progressed abruptly and caused death of the patient by respiratory failure. In our patient, PTC progressed rapidly after the cessation of sorafenib treatment. Patients with several other types of cancer have also experienced such rapid disease progression, termed "flare-ups." Physicians should be aware that flare-ups may occur in advanced PTC patients following the cessation of TKI therapy.
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Herniated intervertebral disk induces hypertrophy and ossification of ligamentum flavum.
J Spinal Disord Tech
PUBLISHED: 09-25-2014
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In vitro experiment using degenerated human ligamentum flavum (LF) and herniated intervertebral disk (IVD).
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Intratumoral heterogeneity impacts the response to anti-neu antibody therapy.
BMC Cancer
PUBLISHED: 09-01-2014
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Along with de novo resistance, continued exposure to trastuzumab, an anti-human epidermal growth factor receptor 2 (HER2/neu) antibody, can lead to acquired resistance. In this study, we characterize a new anti-HER2/neu antibody resistant and metastatic mouse breast carcinoma cell line, TUBO-P2J. This cell line was developed during in vivo experiments using the antibody sensitive and non-metastatic tumor line TUBO. In addition, TUBO-P2J was used to establish an intratumoral HER2 heterogenous animal tumor model to evaluate the therapeutic effects of anti-HER2/neu antibody.
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Inhibition of adenylyl cyclase type 5 prevents L-DOPA-induced dyskinesia in an animal model of Parkinson's disease.
J. Neurosci.
PUBLISHED: 08-29-2014
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The dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) is widely used as a therapeutic choice for the treatment of patients with Parkinson's disease. However, the long-term use of L-DOPA leads to the development of debilitating involuntary movements, called L-DOPA-induced dyskinesia (LID). The cAMP/protein kinase A (PKA) signaling in the striatum is known to play a role in LID. However, from among the nine known adenylyl cyclases (ACs) present in the striatum, the AC that mediates LID remains unknown. To address this issue, we prepared an animal model with unilateral 6-hydroxydopamine lesions in the substantia nigra in wild-type and AC5-knock-out (KO) mice, and examined behavioral responses to short-term or long-term treatment with L-DOPA. Compared with the behavioral responses of wild-type mice, LID was profoundly reduced in AC5-KO mice. The behavioral protection of long-term treatment with L-DOPA in AC5-KO mice was preceded by a decrease in the phosphorylation levels of PKA substrates ERK (extracellular signal-regulated kinase) 1/2, MSK1 (mitogen- and stress-activated protein kinase 1), and histone H3, levels of which were all increased in the lesioned striatum of wild-type mice. Consistently, FosB/?FosB expression, which was induced by long-term L-DOPA treatment in the lesioned striatum, was also decreased in AC5-KO mice. Moreover, suppression of AC5 in the dorsal striatum with lentivirus-shRNA-AC5 was sufficient to attenuate LID, suggesting that the AC5-regulated signaling cascade in the striatum mediates LID. These results identify the AC5/cAMP system in the dorsal striatum as a therapeutic target for the treatment of LID in patients with Parkinson's disease.
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A novel pyrido-thieno-pyrimidine derivative activates p53 through induction of phosphorylation and acetylation in colorectal cancer cells.
Int. J. Oncol.
PUBLISHED: 08-19-2014
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The tumor suppressor p53 plays a key role in regulation of the cell cycle, apoptosis and senescence in response to various stresses. We screened a library of 7920 chemical compounds for the p53 activator and identified N-[2-(dimethylamino)ethyl]-2,3-dimethyl-4-oxo-4H-pyrido[1,2-a]thieno[2,3-d]pyrimidine-9-carboxamide (PTP), which significantly increased p53-mediated reporter activity in colorectal cancer cells. PTP was found to induce p53 protein and activated transcription of downstream genes, such as p21 and PUMA, in HCT116 cells, leading to growth delay, G1-phase cell cycle arrest, cell senescence and cell death. Proximity ligation assay revealed that PTP weakened the interaction between p53 and murine double minute 2 (MDM2) in situ, thereby inhibiting MDM2-mediated p53 degradation. Although DNA damage has been known to promote phosphorylation of p53 and MDM2, thereby preventing their interaction and stabilizing p53, PTP did not cause DNA damage or activate any DNA damage response signaling. Instead, phosphorylation of p53 was mediated by Erk1/2 MAP kinase. In addition, PTP induced acetylation of p53 at Lys382 in a p300-dependent manner, but sirtuin (SIRT)1 and histone deacetylase (HDAC)1, a well-known p53-regulating deacetylase, were not involved. In the present study, the novel anticancer agent PTP was shown to cause the accumulation of p53 by inducing multiple post-translational modifications, as well as cell cycle arrest, senescence and cell death.
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The prevalence of duck hepatitis A virus types 1 and 3 on Korean duck farms.
Arch. Virol.
PUBLISHED: 08-16-2014
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This study reports the prevalence of duck hepatitis A virus (DHAV) types 1 and 3 on Korean duck farms. By RT-nested PCR assays specific for DHAV-1 or DHAV-3, DHAV-1 was detected in 9 of 157 liver samples (5.7 %) from 2 of 30 farms (6.7 %), and DHAV-3 was positive in 104 of 157 liver samples (66.2 %) from 23 of 30 farms (76.7 %). Dual infections with DHAV-1 and DHAV-3 were detected in 23 of 157 samples (14.6 %) from 5 of 30 farms (16.7 %). The data indicate that DHAV-3 infections are prevalent and that DHAV-1 reemerged in Korea, resulting in dual infections on several farms. Our data will help to establish a vaccination policy against DHAV-1 and DHAV-3 in Korea.
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Simultaneous ionization and analysis of 84 anabolic androgenic steroids in human urine using liquid chromatography-silver ion coordination ionspray/triple-quadrupole mass spectrometry.
Drug Test Anal
PUBLISHED: 07-16-2014
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Metal ion coordination ionspray (M(+) CIS) ionization is a powerful technique to enhance ionization efficiency and sensitivity. In this study, we developed and validated an analytical method for simultaneous ionization and analysis of 84 anabolic androgenic steroids (65 exogenous and 19 endogenous) using liquid chromatography-silver ion coordination ionspray/triple-quadrupole mass spectrometry (LC-Ag(+) CIS/MS/MS). The concentrations of silver ions and organic solvents have been optimized to increase the amount of silver ion coordinated complexes. A combination of 25??M of silver ions and methanol showed the best sensitivity. The validation results showed the intra- (0.8-9.2%) and inter-day (2.5-14.9%) precisions, limits of detection (0.0005-5.0?ng/mL), and matrix effect (71.8-100.3%) for the screening analysis. No significant ion suppression was observed. In addition, this method was successfully applied to analysis of positive samples from suspected abusers and useful for the detection of the trace levels of anabolic steroids in human urine samples. Copyright © 2014 John Wiley & Sons, Ltd.
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Intra-articular delivery of kartogenin-conjugated chitosan nano/microparticles for cartilage regeneration.
Biomaterials
PUBLISHED: 07-16-2014
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We developed an intra-articular (IA) drug delivery system to treat osteoarthritis (OA) that consisted of kartogenin conjugated chitosan (CHI-KGN). Kartogenin, which promotes the selective differentiation of mesenchymal stem cells (MSCs) into chondrocytes, was conjugated with low-molecular-weight chitosan (LMWCS) and medium-molecular-weight chitosan (MMWCS) by covalent coupling of kartogenin to each chitosan using an ethyl(dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) catalyst. Nanoparticles (NPs, 150 ± 39 nm) or microparticles (MPs, 1.8 ± 0.54 ?m) were fabricated from kartogenin conjugated-LMWCS and -MMWCS, respectively, by an ionic gelation using tripolyphosphate (TPP). The in vitro release profiles of kartogenin from the particles showed sustained release for 7 weeks. When the effects of the CHI-KGN NPs or CHI-KGN MPs were evaluated on the in vitro chondrogenic differentiation of human bone marrow MSCs (hBMMSCs), the CHI-KGN NPs and CHI-KGN MPs induced higher expression of chondrogenic markers from cultured hBMMSCs than unconjugated kartogenin. In particular, hBMMSCs treated with CHI-KGN NPs exhibited more distinct chondrogenic properties in the long-term pellet cultures than those treated with CHI-KGN MPs. The in vivo therapeutic effects of CHI-KGN NPs or CHI-KGN MPs were investigated using a surgically-induced OA model in rats. The CHI-KGN MPs showed longer retention time in the knee joint than the CHI-KGN NPs after IA injection in OA rats. The rats treated with CHI-KGN NPs or CHI-KGN MPs by IA injection showed much less degenerative changes than untreated control or rats treated with unconjugated kartogenin. In conclusion, CHI-KGN NPs or CHI-KGN MPs can be useful polymer-drug conjugates as an IA drug delivery system to treat OA.
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Gel Phantom Study with High-Intensity Focused Ultrasound: Influence of Metallic Stent Containing Either Air or Fluid.
Ultrasound Med Biol
PUBLISHED: 07-13-2014
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We aimed to investigate whether a cylindrical structure containing either air or fluid and with or without a metallic stent affects the volume and density of cavitation produced by high-intensity focused ultrasound via a gel phantom study. Sixteen tissue-mimicking phantoms based on a polyacrylamide gel mixed with bovine serum albumin with a cylindrical hole 1 cm in diameter and 7.5 cm in length were divided into four groups of four phantoms with air in the holes (group 1), four phantoms with fluid in the holes (group 2), four phantoms with air-containing metallic stents (group 3) and four phantoms with fluid-containing metallic stents (group 4). A pulsed high-intensity focused ultrasound beam (50% duty cycle, 40-Hz pulse repetition frequency) at 75 W of acoustic power was directed perpendicularly to the longitudinal axis of the hole, with its focus at the posterior wall of the hole. The size of the cavitation on the x-, y-, and z-axes was measured, and the volumes of cavitation and coagulation were calculated using the formula for the volume of an elliptical cone. The density of cavitation was measured in the tissue phantom anterior to the hole with a 1 × 1-cm square region of interest. For statistical analysis, the Kruskal-Wallis test and Mann-Whitney U-test were used. The phantoms with air-containing holes (groups 1 and 3) developed larger and denser cavitations anterior to the focus, without unnecessary coagulation posterior to the focus, compared with the phantoms with fluid-containing holes (groups 2 and 4), regardless of the presence of stents. All of the axes and volumes of the anterior cavitations were significantly larger than those of the posterior cavitations in groups 1 and 3 (all p-values <0.05). The results of this study might be applied to maximize cavitation to enhance drug delivery into tumors.
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Effect of Smad3/4 on chemotherapeutic drug sensitivity in colorectal cancer cells.
Oncol. Rep.
PUBLISHED: 07-11-2014
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Smad3 and Smad4 are signaling mediators in the transforming growth factor ? (TGF?) pathway and play a major role in the progression and migration of many types of cancers. The TGF? pathway is correlated with resistance against both targeted and conventional chemotherapeutic drugs. The aim of this study was to determine the effect of Smad3/4 on drug sensitivity in chemotherapy-resistant colorectal cancer (CRC) cells. We isolated the TGF?-mediated chemoresistant CRC cell line DLD1-5FU-C10, which showed high expression of Smad3/4 and p21. In order to analyze the influence of Smad3/4 on drug sensitivity in DLD1-5FU-C10 cells, we knocked down Smad3/4 using small interfering RNAs (siRNA). The results showed similar drug sensitivity between the DLD1?5FU-C10 and the DLD1 control cells and reduced p21 expression. In addition, we found a significant increase in the levels of 3 TGF? downstream factors: interleukin 6 (IL6), plasminogen activator (PLAU) and prostaglandin-endoperoxide synthase 2 (PTGS2). Furthermore, we showed that Smad3/4 regulated the JAK1/STAT3 pathway via IL6 in the chemoresistant CRC cell line. In conclusion, we identified Smad3/4 as a novel drug sensitivity regulator in TGF?-mediated chemotherapy-resistant CRC cells. Our results suggest that Smad3/4 regulate p-STAT3 signaling by IL6 and p21 and highlight an important role for STAT3 signaling in Smad3/4 regulated drug sensitivity in chemoresistant CRC cells.
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Comparative study on the hypoglycemic and antioxidative effects of fermented paste (doenjang) prepared from soybean and brown rice mixed with rice bran or red ginseng marc in mice fed with high fat diet.
Nutrients
PUBLISHED: 06-23-2014
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The effects of fermented paste made from soybean, brown rice, or brown rice in combination with rice bran or red ginseng marc on the glucose metabolism and antioxidative defense system in high fat-fed mice were investigated. The mice were given experimental diets for eight weeks: Normal control, high fat, and high fat supplemented with soybean fermented paste, brown rice fermented paste, brown rice-rice bran fermented paste, or brown rice-red ginseng marc fermented paste. The high fat group showed markedly higher blood glucose level and erythrocyte lipid peroxidation than the normal control group. Diet supplementation of fermented paste inhibited the high fat-induced hyperglycemia and oxidative stress via regulation of the glucose-regulating and antioxidant enzymes activities. The soybean and brown rice-red ginseng marc fermented pastes were the most effective in improving the glucose metabolism and antioxidant defense status in mice under high fat diet condition. These findings illustrate that brown rice, in combination with red ginseng marc, may be useful in the development of fermented paste with strong hypoglycemic and antioxidative activities.
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Both ?2,3- and ?2,6-linked sialic acids on o-linked glycoproteins act as functional receptors for porcine sapovirus.
PLoS Pathog.
PUBLISHED: 06-01-2014
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Sapovirus, a member of the Caliciviridae family, is an important cause of acute gastroenteritis in humans and pigs. Currently, the porcine sapovirus (PSaV) Cowden strain remains the only cultivable member of the Sapovirus genus. While some caliciviruses are known to utilize carbohydrate receptors for entry and infection, a functional receptor for sapovirus is unknown. To characterize the functional receptor of the Cowden strain of PSaV, we undertook a comprehensive series of protein-ligand biochemical assays in mock and PSaV-infected cell culture and/or piglet intestinal tissue sections. PSaV revealed neither hemagglutination activity with red blood cells from any species nor binding activity to synthetic histo-blood group antigens, indicating that PSaV does not use histo-blood group antigens as receptors. Attachment and infection of PSaV were markedly blocked by sialic acid and Vibrio cholerae neuraminidase (NA), suggesting a role for ?2,3-linked, ?2,6-linked or ?2,8-linked sialic acid in virus attachment. However, viral attachment and infection were only partially inhibited by treatment of cells with sialidase S (SS) or Maackia amurensis lectin (MAL), both specific for ?2,3-linked sialic acid, or Sambucus nigra lectin (SNL), specific for ?2,6-linked sialic acid. These results indicated that PSaV recognizes both ?2,3- and ?2,6-linked sialic acids for viral attachment and infection. Treatment of cells with proteases or with benzyl 4-O-?-D-galactopyranosyl-?-D-glucopyranoside (benzylGalNAc), which inhibits O-linked glycosylation, also reduced virus binding and infection, whereas inhibition of glycolipd synthesis or N-linked glycosylation had no such effect on virus binding or infection. These data suggest PSaV binds to cellular receptors that consist of ?2,3- and ?2,6-linked sialic acids on glycoproteins attached via O-linked glycosylation.
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Induction of galectin-1 by TGF-?1 accelerates fibrosis through enhancing nuclear retention of Smad2.
Exp. Cell Res.
PUBLISHED: 05-26-2014
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Fibrosis is one of the most serious side effects in cancer patients undergoing radio-/ chemo-therapy, especially of the lung, pancreas or kidney. Based on our previous finding that galectin-1 (Gal-1) was significantly increased during radiation-induced lung fibrosis in areas of pulmonary fibrosis, we herein clarified the roles and action mechanisms of Gal-1 during fibrosis. Our results revealed that treatment with TGF-?1 induced the differentiation of fibroblast cell lines (NIH3T3 and IMR-90) to myofibroblasts, as evidenced by increased expression of the fibrotic markers smooth muscle actin-alpha (?-SMA), fibronectin, and collagen (Col-1). We also observed marked and time-dependent increases in the expression level and nuclear accumulation of Gal-1. The TGF-?1-induced increases in Gal-1, ?-SMA and Col-1 were decreased by inhibitors of PI3-kinase and p38 MAPK, but not ERK. Gal-1 knockdown using shRNA decreased the phosphorylation and nuclear retention of Smad2, preventing the differentiation of fibroblasts. Gal-1 interacted with Smad2 and phosphorylated Smad2, which may accelerate fibrotic processes. In addition, up-regulation of Gal-1 expression was demonstrated in a bleomycin (BLM)-induced mouse model of lung fibrosis in vivo. Together, our results indicate that Gal-1 may promote the TGF-?1-induced differentiation of fibroblasts by sustaining nuclear localization of Smad2, and could be a potential target for the treatment of pulmonary fibrotic diseases.
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Bacillus Calmette-Guérin Suppresses Asthmatic Responses via CD4(+)CD25(+) Regulatory T Cells and Dendritic Cells.
Allergy Asthma Immunol Res
PUBLISHED: 05-21-2014
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Bacillus Calmette-Guérin (BCG) is known to suppress the asthmatic responses in a murine model of asthma and to induce dendritic cells (DCs) maturation. Mature DCs play a crucial role in the differentiation of regulatory T cells (Tregs), which are known to regulate allergic inflammatory responses. To investigate whether BCG regulates Tregs in a DCs-mediated manner, we analyzed in a murine model of asthma.
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The effect of perinatal anxiety on bronchiolitis is influenced by polymorphisms in ROS-related genes.
BMC Pulm Med
PUBLISHED: 05-13-2014
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Exposure to perinatal anxiety affects disease susceptibility in offspring but studies on the association between perinatal anxiety and gene polymorphisms are lacking. This study aimed to elucidate the interaction between perinatal anxiety and polymorphisms in antioxidant defense and innate immunity genes on the development of respiratory tract infections (RTIs) during early infancy.
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Influencing factor on the prognosis of arthrocentesis.
J Korean Assoc Oral Maxillofac Surg
PUBLISHED: 04-23-2014
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The purpose of this article is to evaluate factors influencing prognosis of arthrocentesis in patients with temporomandibular joint (TMJ) disorder.
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Short-term outcomes of immediate breast reconstruction using an implant or tissue expander after mastectomy in breast cancer patients.
Breast Cancer
PUBLISHED: 04-18-2014
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Mastectomy is an optional surgical management of breast cancer, but it can cause significant adverse reactions. Breast reconstruction is a concern in post-mastectomy recovery. We assessed the oncologic safety and patient satisfaction following immediate breast reconstruction using an implant or tissue expander.
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Comparison of pathogenicities and nucleotide changes between porcine and bovine reassortant rotavirus strains possessing the same genotype constellation in piglets and calves.
Vet. Microbiol.
PUBLISHED: 04-11-2014
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Although reassortment is one of the most important characteristics of group A rotavirus (RVA) evolution, the host range restriction and/or virulence of reassortant RVAs remain largely unknown. The porcine 174-1 strain isolated from a diarrheic piglet was identified as a reassortant strain, harboring the same genotype constellation as the previously characterized bovine strain KJ56-1. Owing to its same genotype constellation, the pathogenicity of the porcine strain 174-1 in piglets and calves was examined for comparison with that of the bovine reassortant KJ56-1 strain, whose pathogenicity has already been demonstrated in piglets and calves. The porcine 174-1 strain induced diarrhea and histopathological changes in the small intestine of piglets and calves, whereas KJ56-1 had been reported to be virulent only in piglets, but not in calves. Therefore, full genomic sequences of 174-1 and KJ56-1 strains were analyzed to determine whether specific mutations might be associated with clinical and pathological phenotypes. Sequence alignment between the 174-1 and KJ56-1 strains detected one nucleotide substitution at the 3' untranslated region of the NSP3 gene and 16 amino acid substitutions at the VP7, VP4, VP1, VP3, NSP1 and NSP4 genes. These mutations may be critical molecular determinants for different virulence and/or pathogenicity of each strain. This study presents new insights into the host range restriction and/or virulence of RVAs.
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Effect of antibiotic use and mold exposure in infancy on allergic rhinitis in susceptible adolescents.
Ann. Allergy Asthma Immunol.
PUBLISHED: 04-01-2014
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Antibiotic use in infancy induces alteration in intestinal microbiota and is associated with the development of allergic diseases. Mold exposure is also associated with allergic diseases. Genetic susceptibility may interact with specific environmental factors in allergic disease development.
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Influence of Aging Process on the Bioactive Components and Antioxidant Activity of Ginseng (Panax ginseng L.).
J. Food Sci.
PUBLISHED: 03-27-2014
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The effects of aging process on the ginsenosides and antioxidant activity of ginseng was investigated. Fresh ginseng roots were aged in oven at 70 or 80 °C for 7, 14, 21, or 28 d. Their ginsenosides, phenolics, and antioxidant activity were analyzed. Ginseng aged at 80 °C for 14 d exhibited the highest amounts of total saponins and phenolics. It also showed markedly higher free radical scavenging activity, reducing power, and ferrous ion chelating ability than the other aged ginsengs. The ginsenosides Rb1 , Rb3 , Rg3 , Re, Rg1 , and Rg2 were generated during aging. The Rg2 was the most abundant ginsenoside in aged ginseng, with samples treated at 80 °C for 14 d having the highest amount. These findings provide the first evidence that aging, particularly at 80 °C for 14 d, could increase the bioactive compounds, indicating that this heating process may be useful in enhancing the biological activity of ginseng.
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Characterization of a novel otubain-like cysteine protease of Cryptosporidium parvum.
Parasitol. Int.
PUBLISHED: 03-22-2014
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Otubains are a recently discovered family of cysteine proteases that participate in the ubiquitin pathway. Here, we partially characterized the biochemical properties of a cysteine protease of Cryptosporidium parvum, which is closely related to otubains. The gene encoding otubain-like cysteine protease of C. parvum (CpOTU) contained the aspartate, cysteine and histidine residues that form the catalytic triad of otubains. The modified ubiquitin-associated domain and LxxL motif were identified in CpOTU. The recombinant CpOTU showed the isopeptidase activity at neutral pH values and its activity was effectively inhibited by ubiquitin aldehyde, N-ethylmaleimide and iodoacetic acid. Interestingly, CpOTU had an unusual C-terminal extension of 217 amino acids compared to mammalian otubains, and the C-terminal extension is essential for the activity of the enzyme. Expression of CpOTU peaked in the oocyst stage of the parasite, which suggested its potential physiological role for the oocyst stage.
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Molecular analysis of Anisakis type I larvae in marine fish from three different sea areas in Korea.
Korean J. Parasitol.
PUBLISHED: 03-21-2014
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Anisakiasis, a human infection of Anisakis L3 larvae, is one of the common foodborne parasitic diseases in Korea. Studies on the identification of anisakid larvae have been performed in the country, but most of them have been focused on morphological identification of the larvae. In this study, we analyzed the molecular characteristics of 174 Anisakis type I larvae collected from 10 species of fish caught in 3 different sea areas in Korea. PCR-RFLP and sequence analyses of rDNA ITS and mtDNA cox1 revealed that the larvae showed interesting distribution patterns depending on fish species and geographical locations. Anisakis pegreffii was predominant in fish from the Yellow Sea and the South Sea. Meanwhile, both A. pegreffii and A. simplex sensu stricto (A. simplex s.str.) larvae were identified in fish from the East Sea, depending on fish species infected. These results suggested that A. pegreffii was primarily distributed in a diverse species of fish in 3 sea areas around Korea, but A. simplex s.str. was dominantly identified in Oncorhynchus spp. in the East Sea.
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Simple quantitation of formoterol and 11-nor-?(9)-tetrahydrocannabinol-9-carboxylic acid in human urine by liquid chromatography-tandem mass spectrometry in doping control.
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.
PUBLISHED: 03-18-2014
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11-nor-?(9)-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) and formoterol are newly revised prohibited threshold substances (150 ng/mL for THC-COOH and 40 ng/mL for formoterol) by the World Anti-Doping Agency (WADA). In continuation of our direct quantitation work of the prohibited threshold substances, direct LC-MS/MS methods combined with a simple sample preparation procedure have been developed and validated for the measurement of these two threshold substances in urine samples. After the enzymatic hydrolysis of urine samples, the resulting samples were diluted with acetonitrile and centrifuged. The supernatant was directly analyzed by LC-MS/MS using the selected reaction monitoring mode. The calibration curve range of the assay was ranged over 50-200% of the threshold value according to WADA guidelines. The limit of detection and limit of quantification were 6.1 and 18.4 ng/mL for THC-COOH and 2.0 and 6.2 ng/mL for formoterol, respectively. Intra- and inter-day precisions were between 2.08% and 7.28% and the accuracies ranged from 95.16% to 104.49%. The present methods were successfully applied to the analysis of the proficiency test samples.
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Anti-rotavirus effects by combination therapy of stevioside and Sophora flavescens extract.
Res. Vet. Sci.
PUBLISHED: 03-13-2014
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Anti-rotaviral activities of Sophora flavescens extract (SFE) and stevioside (SV) from Stevia rebaudiana Bertoni either singly or in various combinations were examined in vitro and in vivo using a porcine rotavirus G5[P7] strain. Combination of SFE and SV inhibited in vitro virus replication more efficiently than each single treatment. In the piglet model, SV had no effect on rotavirus enteritis, whereas SFE improved but did not completely cure rotaviral enteritis. Interestingly, combination therapy of SFE and SV alleviated diarrhea, and markedly improved small intestinal lesion score and fecal virus shedding. Acute toxicity tests including the piglet lethal dose 50, and body weight, organ weight and pathological changes for the combination therapy did not show any adverse effect on the piglets. These preliminary data suggest that the combination therapy of SV and SFE is a potential curative medication for rotaviral diarrhea in pigs. Determination of the efficacy of this combination therapy in other species including humans needs to be addressed in the future.
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Association between recent acetaminophen use and asthma: modification by polymorphism at TLR4.
J. Korean Med. Sci.
PUBLISHED: 03-11-2014
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The risk of asthma has been increasing in parallel with use of acetaminophen, which is a potential source of oxidative stress. Toll-like receptor 4 (TLR4) plays a critical role not only in innate immunity, but also in mediating reactive oxygen species induced inflammation. Therefore, we investigated associations between acetaminophen usage and TLR4 polymorphism on asthma and bronchial hyperresponsiveness (BHR). The number of 2,428 elementary school children in Seoul and Jeongeup cities was recruited. Subjects who used acetaminophen with a family history of asthma had an increased risk of both asthma diagnosis ever and current asthma. Individuals with CT+TT genotypes at the TLR4 polymorphism, in combination with acetaminophen usage, also demonstrated an increased risk of asthma diagnosis ever (aOR, 2.08; 95% confidence interval [CI], 1.10-3.92). Family history of asthma and acetaminophen usage were risk factors for BHR. Although TLR4 was not an independent risk factor for BHR, individuals with CT+TT genotypes at the TLR4 polymorphism had an increased risk of BHR when combined with acetaminophen usage (aOR, 1.74; 95% CI, 1.03-2.94). In conclusion, acetaminophen usage may be associated with asthma and BHR in genetically susceptible subjects. This effect may be modified by polymorphism at TLR4.
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Effect of instant cooked giant embryonic rice on body fat weight and plasma lipid profile in high fat-fed mice.
Nutrients
PUBLISHED: 02-18-2014
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The comparative effects of instant cooked rice made from giant embryo mutant or ordinary normal rice on body weight and lipid profile in high fat-fed mice were investigated. The animals were given experimental diets for seven weeks: normal control (NC), high fat (HF), and HF supplemented with instant normal white (HF-NW), normal brown (HF-NB), giant embryonic white (HF-GW), or giant embryonic brown (HF-GB) rice. The HF group showed markedly higher body weight, body fat, plasma and hepatic triglyceride and cholesterol concentrations, and atherogenic index relative to NC group. However, instant rice supplementation counteracted this high fat-induced hyperlipidemia through regulation of lipogenesis and adipokine production. The GB rice exhibited greater hypolipidemic and body fat-lowering effects than the GW or NB rice. These findings illustrate that the giant embryo mutant may be useful as functional biomaterial for the development of instant rice with strong preventive action against high fat diet-induced hyperlipidemia and obesity.
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Magnifying endoscopy of gastric epithelial dysplasia based on the morphologic characteristics.
World J. Gastroenterol.
PUBLISHED: 02-16-2014
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To investigate the difference in magnifying endoscopic findings of gastric epithelial dysplasias (GEDs) according to the morphologic characteristics.
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An immunosufficient murine model for the study of human islets.
Xenotransplantation
PUBLISHED: 02-16-2014
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For the sake of therapy of diabetes, it is critical to understand human beta cell function in detail in health and disease. Current studies of human beta cell physiology in vivo are mostly limited to immunodeficient mouse models, which possess significant technical limitations. This study aimed to create a new model for the study of human islets through induction of transplant tolerance in immunosufficient mice. B6 diabetic mice were transplanted with human islets and treated with anti-CD45RB. To assess whether anti-CD45RB-induced transplant tolerance requires B cells, B6 recipients received additional anti-CD20 or B6?MT-/- mice were used. For some anti-CD45RB-treated B6?MT-/- mice, additional anti-CD25 mAb was applied at the early or late stage post-transplant. Immunohistology was performed to show the Foxp3 cells in grafted anti-CD45RB/anti-CD20-treated Foxp3-GFP B6 mice. The results showed that anti-CD45RB alone allowed indefinite graft survival in 26.6% of B6 mice, however 100% of xenografts were accepted in mice treated simultaneously with anti-CD20, and 88.9% of xenografts accepted in anti-CD45RB-treated ?MT-/- mice. These ?MT-/- mice accepted the islets from another human donor but rejected the islets from baboon. Additional administration of anti-CD25 mAb at the time of transplantation resulted in 100% rejection, whereas 40% of grafts were rejected while the antibody was administrated at days 60 post-transplant. Immunohistologic examination showed Foxp3+ cells accumulated around grafts. We conclude that induction of tolerance to human islets in an immunosufficient mouse model could be generated by targeting murine CD45RB and CD20. This new system will facilitate study of human islets and accelerate the dissection of the critical mechanisms underlying islet health in human disease.
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TGF-?-producing regulatory B cells induce regulatory T cells and promote transplantation tolerance.
Eur. J. Immunol.
PUBLISHED: 02-12-2014
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Regulatory B (Breg) cells have been shown to play a critical role in immune homeostasis and in autoimmunity models. We have recently demonstrated that combined anti-T cell immunoglobulin domain and mucin domain-1 and anti-CD45RB antibody treatment results in tolerance to full MHC-mismatched islet allografts in mice by generating Breg cells that are necessary for tolerance. Breg cells are antigen-specific and are capable of transferring tolerance to untreated, transplanted animals. Here, we demonstrate that adoptively transferred Breg cells require the presence of regulatory T (Treg) cells to establish tolerance, and that adoptive transfer of Breg cells increases the number of Treg cells. Interaction with Breg cells in vivo induces significantly more Foxp3 expression in CD4(+) CD25(-) T cells than with naive B cells. We also show that Breg cells express the TGF-? associated latency-associated peptide and that Breg-cell mediated graft prolongation post-adoptive transfer is abrogated by neutralization of TGF-? activity. Breg cells, like Treg cells, demonstrate preferential expression of both C-C chemokine receptor 6 and CXCR3. Collectively, these findings suggest that in this model of antibody-induced transplantation tolerance, Breg cells promote graft survival by promoting Treg-cell development, possibly via TGF-? production.
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Protective Effects of Diallyl Sulfide against Thioacetamide-Induced Toxicity: A Possible Role of Cytochrome P450 2E1.
Biomol Ther (Seoul)
PUBLISHED: 02-07-2014
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Effects of diallyl sulfide (DAS) on thioacetamide-induced hepatotoxicity and immunotoxicity were investigated. When male Sprague-Dawley rats were treated orally with 100, 200 and 400 mg/kg of DAS in corn oil for three consecutive days, the activity of cytochrome P450 (CYP) 2E1-selective p-nitrophenol hydroxylase was dose-dependently suppressed. In addition, the activities of CYP 2B-selective benzyloxyresorufin O-debenzylase and pentoxyresorufin O-depentylase were significantly induced by the treatment with DAS. Western immunoblotting analyses also indicated the suppression of CYP 2E1 protein and/or the induction of CYP 2B protein by DAS. To investigate a possible role of metabolic activation by CYP enzymes in thioacetamide-induced hepatotoxicity, rats were pre-treated with 400 mg/kg of DAS for 3 days, followed by a single intraperitoneal treatment with 100 and 200 mg/kg of thioacetamide in saline for 24 hr. The activities of serum alanine aminotransferase and aspartate aminotransferase significantly elevated by thioacetamide were protected in DAS-pretreated animals. Likewise, the suppressed antibody response to sheep erythrocytes by thioacetamide was protected by DAS pretreatment in female BALB/c mice. Taken together, our present results indicated that thioacetamide might be activated to its toxic metabolite(s) by CYP 2E1, not by CYP 2B, in rats and mice.
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Comparison of the Efficacy and Tolerability between Same-day Picosulfate and Split-dose Polyethylene Glycol Bowel Preparation for Afternoon Colonoscopy: A Prospective, Randomized, Investigator-blinded Trial.
Intest Res
PUBLISHED: 01-28-2014
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In the present study, we evaluated the efficacy and tolerability between same-day bowel preparation protocols using 2 sachets of Picosulfate and a 4 L split-dose polyethylene glycol (PEG) bowel preparation for afternoon colonoscopy.
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A case of ampullary gangliocytic paraganglioma.
Korean J. Intern. Med.
PUBLISHED: 01-24-2014
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Gangliocytic paragangliomas (GPs) are rare tumors of the duodenum, presenting as single sessile or pedunculated polypoid masses. Clinical manifestations of duodenal GPs can vary from an incidental finding at endoscopy to frequent upper gastrointestinal bleeding caused by mucosal ulceration and abdominal pain. GPs are considered benign, but the disease can recur and spread to regional lymph nodes. A 41-year-old female presented with abdominal pain. Upper gastrointestinal endoscopy revealed a subepithelial tumor of the ampulla of Vater in the second portion of the duodenum. The tumor was resected using the endoscopic mucosal resection technique. The tumor was diagnosed as benign GP of the duodenum using histological and immunohistochemical staining procedures.
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Spontaneous obliteration of right ventricular pseudoaneurysm after blunt chest trauma: diagnosis and follow-up with multidetector CT.
Korean J Radiol
PUBLISHED: 01-24-2014
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Right ventricular (RV) pseudoaneurysm caused by trauma is very rare. We report a case of RV pseudoaneurysm which resolved without surgical treatment in a patient who survived a falling accident. Echocardiography failed to identify the pseudoaneurysm. Electrocardiography-gated CT showed a 17-mm-sized saccular pseudoaneurysm arising from the RV outflow tract with a narrow neck. Follow-up CT after two months showed spontaneous obliteration of the lesion.
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Pitx3 deficient mice as a genetic animal model of co-morbid depressive disorder and parkinsonism.
Brain Res.
PUBLISHED: 01-15-2014
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Approximately 40-50% of all patients with Parkinson?s disease (PD) show symptoms and signs of depressive disorders, for which neither pathogenic understanding nor rational treatment are available. Using Pit3x-deficient mice, a model for selective nigrostriatal dopaminergic neurodegeneration, we tested depression-related behaviors and acute stress responses to better understand how a nigrostriatal dopaminergic deficit increases the prevalence of depressive disorders in PD patients. Pitx3-deficient mice showed decreased sucrose consumption and preference in the two-bottle free-choice test of anhedonia. Acute restraint stress increased c-Fos (known as a neuronal activity marker) expression levels in various brain regions, including the prefrontal cortex, striatum, nucleus accumbens, and paraventricular nucleus of the hypothalamus (PVN), in both Pitx3+/+ and -/- mice. However, the stress-induced increases in c-Fos levels in the cortex, dorsal striatum, and PVN were significantly greater in Pitx3-/- than +/+ mice, suggesting that signs of depressive disorders in parkinsonism are related to altered stress vulnerability. Based on these results, we propose that Pitx3-/- mice may serve as a useful genetic animal model for co-morbid depressive disorder and parkinsonism.
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Relationship between 15-hydroxyprostaglandin dehydrogenase and gastric adenocarcinoma.
Ann Surg Treat Res
PUBLISHED: 01-14-2014
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Prostaglandin E2 (PGE2) is a contributory carcinogen in gastric adenocarcinoma. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) catabolizes PGE2 by oxidizing its 15(s)-hydroxy group. The aim of this study was to investigate the expression of 15-PGDH in gastric adenocarcinoma tissue and the relationship between 15-PGDH expression and clinicopathologic features of gastric adenocarcinoma.
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A novel synthetic mycolic Acid inhibits bronchial hyperresponsiveness and allergic inflammation in a mouse model of asthma.
Allergy Asthma Immunol Res
PUBLISHED: 01-10-2014
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Recognition of microbes is important to trigger the innate immune system. Mycolic acid (MA) is a component of the cell walls of mycobacteria such as Mycobacterium bovis Bacillus Calmette-Guerin. MA has immunogenic properties, which may modulate the innate and adaptive immune response. This study aimed to investigate whether a novel synthetic MA (sMA) inhibits allergic inflammatory responses in a mouse model of asthma.
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Polymorphic patterns of the merozoite surface protein-3? in Korean isolates of Plasmodium vivax.
Malar. J.
PUBLISHED: 01-02-2014
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The merozoite surface protein-3? of Plasmodium vivax (PvMSP-3?) is one of the candidate antigens for blood stage malaria vaccine development. The polymorphisms in PvMSP-3? have been reported in certain P. vivax isolates. However, the diversity of PvMSP-3? throughout its global distribution has not been well understood. In this study, the genetic diversity and the effects of natural selection in PvMSP-3? among P. vivax Korean isolates were analysed.
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Full-length genomic analysis of Korean porcine Sapelovirus strains.
PLoS ONE
PUBLISHED: 01-01-2014
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Porcine sapelovirus (PSV), a species of the genus Sapelovirus within the family Picornaviridae, is associated with diarrhea, pneumonia, severe neurological disorders, and reproductive failure in pigs. However, the structural features of the complete PSV genome remain largely unknown. To analyze the structural features of PSV genomes, the full-length nucleotide sequences of three Korean PSV strains were determined and analyzed using bioinformatic techniques in comparison with other known PSV strains. The Korean PSV genomes ranged from 7,542 to 7,566 nucleotides excluding the 3' poly(A) tail, and showed the typical picornavirus genome organization; 5'untranslated region (UTR)-L-VP4-VP2-VP3-VP1-2A-2B-2C-3A-3B-3C-3D-3'UTR. Three distinct cis-active RNA elements, the internal ribosome entry site (IRES) in the 5'UTR, a cis-replication element (CRE) in the 2C coding region and 3'UTR were identified and their structures were predicted. Interestingly, the structural features of the CRE and 3'UTR were different between PSV strains. The availability of these first complete genome sequences for PSV strains will facilitate future investigations of the molecular pathogenesis and evolutionary characteristics of PSV.
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Additive effect between IL-13 polymorphism and cesarean section delivery/prenatal antibiotics use on atopic dermatitis: a birth cohort study (COCOA).
PLoS ONE
PUBLISHED: 01-01-2014
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Although cesarean delivery and prenatal exposure to antibiotics are likely to affect the gut microbiome in infancy, their effect on the development of atopic dermatitis (AD) in infancy is unclear. The influence of individual genotypes on these relationships is also unclear. To evaluate with a prospective birth cohort study whether cesarean section, prenatal exposure to antibiotics, and susceptible genotypes act additively to promote the development of AD in infancy.
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Predicting the development of diabetes using the product of triglycerides and glucose: the Chungju Metabolic Disease Cohort (CMC) study.
PLoS ONE
PUBLISHED: 01-01-2014
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To determine whether the TyG index, a product of the levels of triglycerides and fasting plasma glucose (FPG) might be a valuable marker for predicting future diabetes.
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Drug delivery systems for intra-articular treatment of osteoarthritis.
Expert Opin Drug Deliv
PUBLISHED: 12-06-2013
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Introduction: Intra-articular (IA) drug delivery is very useful in the treatment of osteoarthritis (OA), the most common chronic joint affliction. However, the therapeutic effect of IA administration depends mostly on the efficacy of drug delivery. Areas covered: The present article reviews the current status of IA therapy for OA treatment as well as its rationale. Outlines of drug delivery parameters such as release profile, retention time, distribution, size and transport that influence the drugs biological performance in the joints are summarized. New delivery systems, currently under investigation, including liposome, nanoparticle, microparticle and hydrogel formulations are introduced. Functionalized drug delivery systems by targeting and thermoresponsiveness that are being investigated for OA treatment via IA therapy are also addressed. Expert opinion: Several delivery systems, including liposome, microparticles, nanoparticles and hydrogels, have been investigated for the sustained drug delivery to the joints. These can be advanced by the use of functionalized drug delivery systems that can lead targeting to specific regions and thermoresponsiveness for prolonged drug release in the joints. Further advances will bring forth new biocompatible and biodegradable materials as a drug carrier or new combination regimens. Future innovations in this field should be directed toward the development of adapted delivery systems that can induce tissue regeneration in OA patients.
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Intravoxel Incoherent Motion Diffusion-weighted MR Imaging for Characterization of Focal Pancreatic Lesions.
Radiology
PUBLISHED: 10-28-2013
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Purpose:To evaluate the diagnostic potential of apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM)-derived parameters for differentiation of common pancreatic tumors, chronic pancreatitis, and normal pancreas and for characterization of the malignancy potential of intraductal papillary mucinous neoplasms (IPMNs).Materials and Methods:The institutional review board approved this retrospective study, and informed consent was waived. Ninety-three consecutive patients with surgically resected and pathologically confirmed pancreatic tumors (39 pancreatic adenocarcinomas [PACs], 17 neuroendocrine tumors [NETs], and 37 IPMNs), seven patients with chronic pancreatitis, and 26 patients with a normal pancreas were included in this study. All patients underwent pancreatic 3.0-T magnetic resonance imaging, including IVIM diffusion-weighted imaging with 10 b values used (from 0 to 1000 sec/mm(2)). The ADC, slow component of diffusion (Dslow), incoherent microcirculation (Dfast), and perfusion fraction (f) were calculated. Steel-Dwass and Mann-Whitney U tests were used for comparison. The diagnostic performance of the parameters was evaluated by using receiver operating characteristic (ROC) analysis with Bonferroni correction.Results:Among ADC- and IVIM-derived parameters, Dfast and f values of PACs were significantly lower than those of normal pancreas, chronic pancreatitis, and NETs (all P < .05 in post hoc analyses). For differentiation of PACs from NETs, f and Dfast showed a significant difference (P < .0001 for both) and were more useful parameters than ADC and Dslow in ROC analysis (all P < .05). Malignant IPMNs had significantly lower ADC and Dslow values and higher Dfast and f values when compared with benign IPMNs (all P < .05). In ROC analysis, f showed the highest area under the ROC curve value for distinguishing malignant from benign IPMNs.Conclusion:IVIM-derived perfusion-related parameters could be helpful for the differentiation of common malignant tumors in the pancreas and for distinguishing malignant from benign IPMNs. Dfast and f were more valuable parameters in the differentiation of PACs from NETs than were ADC and Dslow.© RSNA, 2013Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13122712/-/DC1.
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Non-FDG-avid primary papillary thyroid carcinoma may not differ from FDG-avid papillary thyroid carcinoma.
Thyroid
PUBLISHED: 09-19-2013
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FDG (2-[(18)F]Fluoro-2-D-deoxyglucose-positron emission tomography (PET)/computed tomography (CT), which can detect a change in glucose metabolism in cancer cells, has been introduced as a diagnostic and prognostic tool in papillary thyroid carcinoma (PTC). However, differences in the clinicopathological and biological characteristics between primary PTCs with FDG uptake and those without FDG uptake are not well established.
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Anti-inflammatory effect of platelet-rich plasma on nucleus pulposus cells with response of TNF-? and IL-1.
J. Orthop. Res.
PUBLISHED: 08-25-2013
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The purpose of this study was to investigate the anti-inflammatory effect of platelet-rich plasma (PRP) with collagen matrix on human nucleus pulposus (NP) cell in response to pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-?) and interleukin-1 (IL-1). NP cells from human disks were cultured in a monolayer and maintained in the collagen matrix prior to the addition of recombinant human IL-1 and TNF-?. After applying IL-1 and TNF-?, PRP prepared by using a commercially available platelet concentration system was added. The response was investigated using real-time PCR for mRNA expression of type II collagen, aggrecan, matrix metalloproteinase-3 (MMP-3), and cyclooxygenase-2 (COX-2). The combination of IL-1? and TNF-? led to decrease of matrix synthesis gene expression such as collagen type II and aggrecan and increase of the degradation gene expression of COX-2 and MMP-3, compared to the control. Consecutive PRP exposure significantly recovered the down-regulated gene expression of collagen type II and aggrecan and significantly reduced the increased MMP-3 and COX-2 gene expression, compared to that of control groups with pro-inflammatory cytokines. The administration of PRP with collagen matrix markedly suppressed cytokine-induced pro-inflammatory degrading enzymes and mediators in the NP cell. It also rescued gene expression concerning matrix synthesis, thereby stabilizing NP cell differentiation. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
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Inflammatory cytokines induce fibrosis and ossification of human ligamentum flavum cells.
J Spinal Disord Tech
PUBLISHED: 08-02-2013
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In vitro experiment using degenerated human ligamentum flavum (LF) and various inflammatory cytokines.
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Identification and characterization of the second cysteine protease inhibitor of Clonorchis sinensis (CsStefin-2).
Parasitol. Res.
PUBLISHED: 07-09-2013
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CsStefin-2, the second cysteine protease inhibitor of Clonorchis sinensis, was identified and characterized. CsStefin-2 is a cysteine protease inhibitor that belongs to family 1 stefins based on its phylogenetic and structural properties. However, CsStefin-2 had a QIVSG cystatin motif distinct from the common QVVAG cystatin motif that is well conserved in family 1 stefins. Mutagenesis analysis revealed that the two amino acid substitutions in the QIVSG cystatin motif of CsStefin-2 did not affect its inhibitory activity. Molecular modeling also indicated that no critical change was induced in the interaction between CsStefin-2 and its target enzyme. CsStefin-2 showed broad inhibitory activities against several cysteine proteases, including human cathepsins B and L, papain, and cathepsin Fs of C. sinensis (CsCFs), and effectively inhibited the autocatalytic maturation of CsCF-6. Native CsStefin-2 was assembled into a homo-tetramer, in which intermolecular disulfide bonds are not involved in the assembly of the tetramer. CsStefin-2 was expressed throughout the various developmental stages of the parasite and was localized in the intestinal epithelium, where CsCFs are actively synthesized. These results suggest that CsStefin-2 is the second active cysteine protease inhibitor of C. sinensis that shares functional redundancy with CsStefin-1 to modulate the activity and processing of CsCFs.
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The effect of gut microbiota on drug metabolism.
Expert Opin Drug Metab Toxicol
PUBLISHED: 06-12-2013
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Numerous drugs and toxicants must be metabolized to an active form. Metabolic activation by host tissues, such as the liver, has been well studied. However, drug and toxicant metabolism by the intestinal microbiota is an unexplored, but essential, field of study in pharmacology and toxicology. The taxonomic diversity and sheer numbers of the intestinal microbiota, and their capacity to metabolize xenobiotics, underscore the importance of this mode of metabolism.
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Gastrointestinal stromal tumors in children and young adults: a clinicopathologic and molecular genetic study of 22 Korean cases.
APMIS
PUBLISHED: 06-12-2013
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Studies on gastrointestinal stromal tumors (GISTs) in young patients are limited due to their rarity, and none have been conducted in Asian populations. GISTs from patients under the age of 30 were retrospectively reviewed and were analyzed for clinicopathologic features, immunohistochemistry for SDHB (succinate dehydrogenase subunit B), and mutations for exon 9, 11, 13, and 17 of KIT gene and exon 12, 14, and 18 of PDGFRA gene. We found two pediatric (<18 years old) and 20 young adult (18-30 years old) GIST cases. Pediatric GISTs occurred in two girls, both as solitary masses with epithelioid histology in the stomach. Both GISTs were wild type for KIT and PDGFRA genes, were negative for SDHB, and there was no recurrence during follow-up. Of the 20 GISTs in young adults, 12 (60%) were from extra-gastric locations (six duodenum, five jejunum, and one esophagus), and 16 (80%) showed a spindle cell morphology. Mutations of KIT or PDGFRA genes were identified in 14 (78%) of the 18 cases. One patient with multiple gastric GISTs with perigastric lymph node metastases at presentation developed multiple distant metastases and died of the disease 7.3 years after diagnosis. Of the 19 R0-resected young adult patients, one patient with small intestinal GIST harboring KIT exon 11 deletion mutation developed recurrence and showed partial responses for imatinib. In summary, compared with pediatric GIST cases, young adult GISTs are heterogeneous and share the characteristics of both pediatric and adult GISTs. When a mesenchymal tumor is clinically suspected in the small intestine of young adults, a GIST should be included in the differential diagnoses. Further mutation studies and extensive treatments are recommended for these cases.
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Adaptive 4D volume perfusion CT of lung cancer: effects of computerized motion correction and the range of volume coverage on measurement reproducibility.
AJR Am J Roentgenol
PUBLISHED: 05-25-2013
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The purpose of this study was to determine whether measurement reproducibility can be improved using computerized motion correction and whole-tumor coverage in adaptive 4D perfusion CT of lung cancer.
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Proteomic changes in rat gastrocnemius muscle after botulinum toxin a injection.
Ann Rehabil Med
PUBLISHED: 04-30-2013
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To observe the changes in protein expression induced by botulinum toxin A (BoNT-A) injection and to characterize the molecular and cellular action of mechanisms of BoNT-A injection on skeletal muscles using proteomic elements as biomarkers.
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Defining the regulatory and inhibitory elements within the prodomain of CsCF-6, a cathepsin F cysteine protease of Clonorchis sinensis.
Mol. Biochem. Parasitol.
PUBLISHED: 04-20-2013
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CsCF-6 is a member of the multigene family of cathepsin F cysteine proteases of Clonorchis sinensis. Similar to other papain family proteases, CsCF-6 is synthesized as a proenzyme and is converted to the mature form by autocatalytic removal of the prodomain. Here, we analyzed the regulatory and inhibitory elements within the CsCF-6 prodomain to understand the regulatory mechanism of CsCF-6 by its prodomain. The CsCF-6 prodomain played an essential role in the folding of CsCF-6. Particularly, the ERFNAQ motif within the prodomain was essential, and the minimum segment required for this event was the C-terminal part of the prodomain, including Asn(58) and downstream residues. The CsCF-6 prodomain effectively inhibited CsCF-6, in which the ERFNAQ motif played a critical role in the inhibition, but the GTFD motif was also required for complete inhibition of CsCF-6. The CsCF-6 prodomain showed broad inhibitory activity against several cysteine proteases. These results suggest that the CsCF-6 prodomain plays bi-functional roles in correct folding and inhibition of its cognate enzyme.
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Breastfeeding Might Have Protective Effects on Atopy in Children With the CD14C-159T CT/CC Genotype.
Allergy Asthma Immunol Res
PUBLISHED: 04-12-2013
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Breastfeeding is widely recommended to reduce risk of sensitization, eczema and asthma. However, the role of breastfeeding in prevention of allergic diseases is uncertain. We aimed to investigate whether the relationship between breastfeeding and sensitization to aeroallergens is modified by cluster of differentiation 14 (CD14) genotype. This study included 1,828 school children aged 9-12. We administered a detailed questionnaire and genotyped the CD14C-159T polymorphism. Skin prick tests for 12 aeroallergens were performed. School children who had been breastfed were less likely sensitized to aeroallergens (adjusted odds ratio [aOR] 0.712, 95% confidence interval [CI]: 0.555-0.914). There was no significant association between CD14C-159T genotype and atopy. Breastfeeding was associated with a decreased risk of atopic sensitization in children with CT/CC genotype (aOR 0.667, 95% CI: 0.463-0.960). Our data might identify the gene-environment interaction between the CD14C-159T polymorphism and breastfeeding in relation to aeroallergen sensitization.
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Down-regulation of collagen synthesis and matrix metalloproteinase expression in myofibroblasts from dupuytren nodule using adenovirus-mediated relaxin gene therapy.
J. Orthop. Res.
PUBLISHED: 04-01-2013
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Dupuytrens disease is a fibroproliferative connective tissue disorder characterized by contracture of the palmer fascia of the hand. Relaxin (RLN) is a multifunctional factor which contributes to the remodeling of the pelvic ligament by inhibiting fibrosis and inflammatory activities. The aim of this study was to investigate the effect of the RLN gene on the inhibition of fibrosis in myofibroblastic cells. Myofibroblast cells with adenovirus LacZ (Ad-LacZ) as a marker gene or adenovirus relaxin (Ad-RLN) as therapeutic gene showed transgene expressions in beta-galactosidase assay and Western blot analysis. Myofibroblastic cells with Ad-RLN demonstrated a 22% and 48% reduction in collagen I and III mRNA expressions respectively, a 50% decrease in MMP-1, 70% decrease in MMP-2, 80% decrease in MMP-9, and a 15% reduction in MMP-13 protein expression compared with cultures with viral control and saline control. In addition, myofibroblastic cells with Ad-RLN showed a 40% decrease in TIMP 1 and a 15% increase in TIMP 3 protein expression at 48?h compared to cultures with viral control and saline control. Also, myofibroblastic cell with Ad-RLN demonstrated a 74% inhibition of fibronectin and a 52% decrease in total collagen synthesis at 48?h compared with cultures with viral control and saline control. In conclusion, the RLN gene render antifibrogenic effect on myofibroblastic cells from Dupuytrens nodule via direct inhibition of collagen synthesis not through collagenolytic pathway such as MMP-1, -13, TIMP 1, and 3. Therefore relaxin can be an alternative therapeutic strategy in initial stage of Dupuytrens disease by its antifibrogenic effect. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
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Role of metabolism by intestinal microbiota in pharmacokinetics of oral baicalin.
Arch. Pharm. Res.
PUBLISHED: 03-22-2013
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Baicalin (baicalein-7-glucuronide) is a flavonoid purified from Scutellaria baicalensis Georgi that has traditionally been used for treatment of hypertension, cardiovascular diseases, and viral hepatitis. In this study, the effects of intestinal microbiota on the pharmacokinetics of baicalin were investigated in normal and antibiotic-pretreated rats following p.o. administration of 100 mg/kg baicalin by using liquid chromatography/ion trap mass spectrometry. When rats were pretreated orally with cefadroxil, oxytetracycline and erythromycin for 3 days to control the number of intestinal bacteria, the pharmacokinetic parameters of oral baicalin were significantly affected by antibiotics: Cmax, T1/2(?), Kel and AUC values were significantly changed compared to those in normal rats. These results indicate that intestinal microbiota might play a key role in the oral pharmacokinetics of baicalin.
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Mutations in the Filaggrin are Predisposing Factor in Korean Children With Atopic Dermatitis.
Allergy Asthma Immunol Res
PUBLISHED: 03-20-2013
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Filaggrin (FLG) is a key protein that facilitates the terminal differentiation of the epidermis and the formation of the skin barrier. Recent studies showed that atopic dermatitis (AD) associates closely with loss-of-function mutations in the FLG gene. Asian and European populations differ in the frequencies of FLG mutations. Several FLG mutations, including 3321delA, E2422X, K4671X, S2554X, and R501X, occur frequently in Chinese and Japanese populations. The association between three FLG null mutations and AD in Korean children was investigated.
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Effects of crosslinked dextran in hydroxylpropyl methylcellulose on soft tissue augmentation in rats.
J. Biomed. Mater. Res. Part B Appl. Biomater.
PUBLISHED: 03-18-2013
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This study compared crosslinked dextrans in hydroxylpropyl methycellulose (DiHMs, pH 5 or 7) with polymethylmethacrylate in bovine collagen (PMMA) and hyaluronic acid (HA) fillers on soft tissue augmentation and safety in rats. HA tended to maintain its size throughout the experimental period but was moveable and friable because of a lack of thick fibroconnective tissue formation. Although, PMMA induced moderately thick fibroconnective tissue formation, its size was decreased markedly from 3-week postimplantation (PI) and became the smallest at 24-month PI. DiHM (pH 7) elicited strong fibrous encapsulation around the filler. Its size decreased slowly but was still considerably maintained at 24-month PI. In contrast, the rate of the DiHM (pH 5) size decrease was slower than that of PMMA, faster DiHM (pH 7), but comparable to HA. Immunohistochemically, types I and III collagens were deposited inside and outside DiHMs (pH 5 and 7). DiHMs (pH 5 and 7), PMMA, and HA showed no adverse reactions. These results suggest that DiHM (pH 7) assures efficacy and safety and is a good candidate for soft tissue augmentation in both humans and animals. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.
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Limited sequence polymorphisms of four transmission-blocking vaccine candidate antigens in Plasmodium vivax Korean isolates.
Malar. J.
PUBLISHED: 02-13-2013
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Transmission-blocking vaccines (TBVs), which target the sexual stages of malaria parasites to interfere with and/or inhibit the parasites development within mosquitoes, have been regarded as promising targets for disrupting the malaria transmission cycle. In this study, genetic diversity of four TBV candidate antigens, Pvs25, Pvs28, Pvs48/45, and PvWARP, among Plasmodium vivax Korean isolates was analysed.
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Added value of diffusion-weighted imaging to MR cholangiopancreatography with unenhanced mr imaging for predicting malignancy or invasiveness of intraductal papillary mucinous neoplasm of the pancreas.
J Magn Reson Imaging
PUBLISHED: 02-06-2013
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To investigate the added value of diffusion-weighted imaging (DWI) to magnetic resonance cholangiopancreatography (MRCP) with unenhanced MR imaging for predicting the malignancy or invasiveness of intraductal papillary mucinous neoplasms (IPMNs).
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Pathogenicity of porcine G9P[23] and G9P[7] rotaviruses in piglets.
Vet. Microbiol.
PUBLISHED: 01-27-2013
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G9 group A rotaviruses (RVAs) are considered important pathogens in pigs and humans, and pigs are hypothesized to be a potential host reservoir for human. However, intestinal and extra-intestinal pathogenicity and viremia of porcine G9 RVAs has remained largely unreported. In this study, colostrum-deprived piglets were orally infected with a porcine G9P[23] or G9P[7] strain. Histopathologically, both strains induced characteristic small intestinal lesions. Degeneration and necrosis of parenchymal cells were observed in the extra-intestinal tissues, but most predominantly in the mesenteric lymph nodes (MLNs). RVA antigen was continuously detected in the small intestinal mucosa and MLNs, but only transiently in cells of the liver, lung, and choroid plexus. Viral RNA levels were much higher in the feces and the MLNs compared to other tissues. The onset of viremia occurred at day post infection (DPI) 1 with the amount of viral RNA reaching its peak at DPI 3 or 5, before decreasing significantly at DPI 7 and remaining detectable until DPI 14. Our data suggest that porcine G9 RVAs have a strong small intestinal tropism, are highly virulent for piglets, have the ability to escape the small intestine, spread systemically via viremia, and replicate in extra-intestinal tissues. In addition, MLNs might act as a secondary site for viral amplification and the portal of systemic entry. These results add to our understanding of the pathogenesis of human G9 RVAs, and the validity of the pig model for use with both human and pig G9 RVAs in further studies.
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Tetraarsenic oxide and cisplatin induce apoptotic synergism in cervical cancer.
Oncol. Rep.
PUBLISHED: 01-18-2013
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Tetraarsenic oxide (As4O6, TAO) is a new arsenic compound that inhibits cell growth and induces apoptosis in human cervical cancer cell lines. In the present study, we report that the growth of tumor cells (CaSki) was inhibited by treatment with TAO alone or in combination with cisplatin or paclitaxel in vitro and in vivo. Proliferation was assessed by WST-1 assay, and apoptosis was assessed by Annexin-V/PI FACS analysis in the CaSki cell line treated with a single agent or with the combinations of two agents. Expression of apoptosis-related proteins was analyzed by western blot analysis. A mouse xenograft model using CaSki cells was used to determine the in vivo activity of tetraarsenic oxide alone and in combination with cisplatin or paclitaxel by estimation of tumor size. At the end of the experiment, tumor tissue from each mouse was removed and processed for TUNEL analysis for confirmation of apoptotic cells. TAO was able to inhibit cell proliferation in a time- and dose-dependent manner. A combination of TAO and cisplatin effectively induced apoptosis by activating caspase-3. Using a mouse xenograft model, the sizes of tumors which were treated with a single agent and with a combination of agents decreased in a time-dependent manner. A combination of TAO and cisplatin resulted in a significantly reduced tumor size (P<0.05). The data for the histochemical staining of TUNEL-positive cells showed that the number of apoptotic cells was significantly increased by the combination of TAO and cisplatin. Thus, TAO is a good candidate for use in a combined regimen with cisplatin for patients with cervical cancer.
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Protective effect of phlorotannins from Eisenia bicyclis against lipopolysaccharide-stimulated inflammation in HepG2 cells.
Environ. Toxicol. Pharmacol.
PUBLISHED: 01-14-2013
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In this study, four bioactive phloroglucinol derivates including phloroglucinol (1), eckol (2), dioxinodehydroeckol (3), and dieckol (4) were isolated from Eisenia bicyclis and characterized by nuclear magnetic resonance (NMR) spectroscopic methods. Moreover, the anti-inflammatory activity of these compounds was investigated on human hepatoma cell line HepG2 cells stimulated by lipopolysaccharide (LPS). It was demonstrated that LPS can induce the production of pro-inflammatory cytokines such as interleukin-1? (IL-1?), interleukin-6 (IL-6), and tumor necrosis factor-? (TNF-?) as well as the expression of inflammatory mediators as cyclooxygenase-2 (COX-2), and inducible nitric oxide synthases (iNOS) from HepG2 cells. Among isolated compounds, compound (1) exhibited significant inhibition on LPS-stimulated inflammatory responses in HepG2 cells without any cytotoxicity. Herein, compound (1) suppresses the production of pro-inflammatory cytokines such as IL-1?, IL-6, and TNF-? and the expression of COX-2 and iNOS. Thus, these results indicated that phlorotannins isolated from E. bicyclis, especially compound (1), can be used as a beneficial source for preventing and treating inflammation response.
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Different virulence of porcine and porcine-like bovine rotavirus strains with genetically nearly identical genomes in piglets and calves.
Vet. Res.
PUBLISHED: 01-11-2013
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Direct interspecies transmissions of group A rotaviruses (RVA) have been reported under natural conditions. However, the pathogenicity of RVA has never been directly compared in homologous and heterologous hosts. The bovine RVA/Cow-tc/KOR/K5/2004/G5P[7] strain, which was shown to possess a typical porcine-like genotype constellation similar to that of the G5P[7] prototype RVA/Pig-tc/USA/OSU/1977/G5P9[7] strain, was examined for its pathogenicity and compared with the porcine G5P[7] RVA/Pig-tc/KOR/K71/2006/G5P[7] strain possessing the same genotype constellation. The bovine K5 strain induced diarrhea and histopathological changes in the small intestine of piglets and calves, whereas the porcine K71 strain caused diarrhea and histopathological changes in the small intestine of piglets, but not in calves. Furthermore, the bovine K5 strain showed extra-intestinal tropisms in both piglets and calves, whereas the porcine K71 strain had extra-intestinal tropisms in piglets, but not in calves. Therefore, we performed comparative genomic analysis of the K71 and K5 RVA strains to determine whether specific mutations could be associated with these distinct clinical and pathological phenotypes. Full-length sequencing analyses for the 11 genomic segments for K71 and K5 revealed that these strains were genetically nearly identical to each other. Two nucleotide mutations were found in the 5 untranslated region (UTR) of NSP5 and the 3 UTR of NSP3, and eight amino acid mutations in VP1-VP4 and NSP2. Some of these mutations may be critical molecular determinants for RVA virulence and/or pathogenicity.
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Induction of neuronal differentiation of rat muscle-derived stem cells in vitro using basic fibroblast growth factor and ethosuximide.
Int J Mol Sci
PUBLISHED: 01-11-2013
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Several studies have demonstrated that basic fibroblast growth factor (bFGF) can induce neural differentiation of mesenchymal stem cells. In this study, we investigated the neural differentiation of muscle-derived stem cells (MDSCs) following treatment with bFGF and ethosuximide, a small molecule used as an anticonvulsant in humans. Stem cells isolated from rat skeletal muscle (rMDSCs) were pre-induced by culturing with 25 ng/mL bFGF for 24 h and then were transferred to a medium supplemented with or without 4 mM ethosuximide. Neuronal differentiation was assessed by immunocytochemical and western blotting analyses of marker expression. Immunocytochemistry of rMDSCs treated with bFGF and ethosuximide identified abundant cells expressing neuronal markers (TuJ1, neuron-specific class III ?-tubulin; NeuN, neuronal nuclear antigen; and NF-MH; neurofilament M and H). Olig2 (oligodendrocyte transcription factor 2)-positive cells were also observed, indicating the presence of oligodendrocyte lineage cells. These findings were substantiated by western blotting analysis of marker proteins. In particular, the expression of NeuN and TuJ1 was significantly higher in rMDSCs treated with ethosuximide and bFGF than in cells stimulated with bFGF alone (NeuN, p < 0.05 and TuJ1, p < 0.001). Expression of the astrocyte marker GFAP (glial fibrillary acidic protein) was not detected in this study. Collectively, the results showed that treatment with bFGF and ethosuximide induced effective transdifferentiation of rMDSCs into cells with a neural-like phenotype. Notably, rMDSCs treated with a combination of bFGF plus ethosuximide showed enhanced differentiation compared with cells treated with bFGF alone, implying that ethosuximide may stimulate neuronal differentiation.
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Elevated Levels of Interferon-? Production by Memory T Cells Do Not Promote Transplant Tolerance Resistance in Aged Recipients.
PLoS ONE
PUBLISHED: 01-01-2013
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Immunosenescence predisposes the elderly to infectious and autoimmune diseases and impairs the response to vaccination. We recently demonstrated that ageing also impedes development of transplantation tolerance. Unlike their young counterparts (8-12 weeks of age) aged male recipients (greater than 12 months of age) transplanted with a full MHC-mismatched heart are resistant to tolerance mediated by anti-CD45RB antibody. Surprisingly, either chemical or surgical castration restored tolerance induction to levels observed using young recipients. Based on the strong impact of endocrine modulation on transplant tolerance, we explored the impact of ageing and castration on the immune system. Here we report a significant increase in the percentage of T cells that produce interferon-? (IFN-?) in aged male versus young male animals and that the overall increase in IFN-? production was due to an expansion of IFN-?-producing memory T cells in aged animals. In contrast to IFN-? production, we did not observe differences in IL-10 expression in young versus old male mice. We hypothesized that endocrine modulation would diminish the elevated levels of IFN-? production in aged recipients, however, we observed no significant reduction in the percentage of IFN-?+ T cells upon castration. Furthermore, we neutralized interferon-? by antibody and did not observe an effect on graft survival. We conclude that while elevated levels of interferon-? serves as a marker of tolerance resistance in aged mice, other as yet to be identified factors are responsible for its cause. Defining these factors may be relevant to design of tolerogenic strategies for aged recipients.
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Early changes in 25-hydroxyvitamin D levels and bone markers after monthly risedronate with cholecalciferol in Korean patients with osteoporosis.
Clin Interv Aging
PUBLISHED: 01-01-2013
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This study investigated the efficacy and safety of monthly risedronate, with and without cholecalciferol, on 25-hydroxyvitamin D (25[OH]D) levels and bone markers in Korean patients with osteoporosis.
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Antidiabetic effects of rice hull smoke extract in alloxan-induced diabetic mice.
J. Agric. Food Chem.
PUBLISHED: 12-16-2011
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This study investigated the protective effect of a liquid rice hull smoke extract (RHSE) against diabetes in alloxan-induced diabetic mice. Antidiabetic effects of RHSE were evaluated in both the rat insulinoma-1 cell line (INS-1) and diabetic ICR mice induced by intraperitoneal (ip) injection of alloxan. Alloxan treatment (10 mM) increased cellular reactive oxygen species (ROS) levels in the INS-1 cells, which were inversely related to cell viabilities. RHSE inhibited alloxan-induced nitric oxide (NO) generation through inhibition of inducible nitric oxide synthase (iNOS) gene expression and suppressed the inflammatory reaction in INS-1 cells through inhibition of expression of pro-inflammatory genes, including tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?), and interleukin-6 (IL-6). Dietary administration of 0.5 or 1% RHSE to alloxan-induced diabetic mice caused a decrease in blood glucose and increases in both serum insulin and hepatic glycogen levels. RHSE induced decreases in glucose-6-phosphatase (G6 Pase) and phosphoenolpyruvate carboxykinase (PEPCK) levels and an increase in the glucokinase (GCK) level. These changes resulted in restoring glucose-regulating enzyme levels to control values. Histopathology showed that alloxan also induced damage of Langerhans islet cells of the pancreas and liver necrosis associated with diabetes. Oral administration of RHSE restored the islet and liver cells to normal levels. RHSE-supplemented functional food could protect insulin-producing islet cells against damage triggered by oxidative stress and local inflammation associated with diabetes.
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