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Find video protocols related to scientific articles indexed in Pubmed.
Melanopsin mediates light-dependent relaxation in blood vessels.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-19-2014
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Melanopsin (opsin4; Opn4), a non-image-forming opsin, has been linked to a number of behavioral responses to light, including circadian photo-entrainment, light suppression of activity in nocturnal animals, and alertness in diurnal animals. We report a physiological role for Opn4 in regulating blood vessel function, particularly in the context of photorelaxation. Using PCR, we demonstrate that Opn4 (a classic G protein-coupled receptor) is expressed in blood vessels. Force-tension myography demonstrates that vessels from Opn4(-/-) mice fail to display photorelaxation, which is also inhibited by an Opn4-specific small-molecule inhibitor. The vasorelaxation is wavelength-specific, with a maximal response at ?430-460 nm. Photorelaxation does not involve endothelial-, nitric oxide-, carbon monoxide-, or cytochrome p450-derived vasoactive prostanoid signaling but is associated with vascular hyperpolarization, as shown by intracellular membrane potential measurements. Signaling is both soluble guanylyl cyclase- and phosphodiesterase 6-dependent but protein kinase G-independent. ?-Adrenergic receptor kinase 1 (?ARK 1 or GRK2) mediates desensitization of photorelaxation, which is greatly reduced by GRK2 inhibitors. Blue light (455 nM) regulates tail artery vasoreactivity ex vivo and tail blood blood flow in vivo, supporting a potential physiological role for this signaling system. This endogenous opsin-mediated, light-activated molecular switch for vasorelaxation might be harnessed for therapy in diseases in which altered vasoreactivity is a significant pathophysiologic contributor.
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Development of [11C]MFTC for PET Imaging of Fatty Acid Amide Hydrolase in Rat and Monkey Brains.
ACS Chem Neurosci
PUBLISHED: 11-15-2014
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We developed 2-methylpyridin-3-yl-4-(5-(2-fluorophenyl)-4H-1,2,4-triazol-3-yl)piperidine-1-[11C]carboxylate ([11C]MFTC) as a promising PET tracer for in vivo imaging of fatty acid amide hydrolase (FAAH) in rat and monkey brains. [11C]MFTC was synthesized by reacting 3-hydroxy-2-methylpyridine (2) with [11C]phosgene ([11C]COCl2), followed by reacting with 4-(5-(2-fluorophenyl)-4H-1,2,4-triazol-3-yl)piperidine (3), with a 20 ± 4.6% radiochemical yield (decay-corrected, n = 30) based on [11C]CO2 and 40 min synthesis time from the end of bombardment. A biodistribution study in mice showed high uptake of radioactivity in FAAH-rich organs, including the lung, liver, and kidneys. PET summation images of rat brains showed high radioactivity in the frontal cortex, cerebellum, and hippocampus, which was consistent with the regional distribution pattern of FAAH in rodent brain. Pretreatment with MFTC or FAAH-selective URB597 significantly reduced the uptake in the brain. PET imaging of monkey brain showed relatively high uptake in the whole brain, particularly in the occipital cortex, which was also inhibited by treatment with MFTC or URB597. More than 96% of the total radioactivity was irreversible in the brain homogenate of rats 5 min after the radiotracer injection. The specific in vivo FAAH binding indicates that [11C]MFTC is a promising PET tracer for visualizing FAAH in the brain.
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Loss-of-TET2 has dual roles in murine myeloproliferative neoplasms: disease sustainer and disease accelerator.
Blood
PUBLISHED: 11-15-2014
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Acquired mutations of JAK2 and TET2 are frequent in myeloproliferative neoplasms (MPNs). We examined the individual and cooperative effects of these mutations on MPN development. Recipients of JAK2V617F cells developed primary myelofibrosis-like features; the addition of loss-of-TET2 worsened this JAK2V617F-induced disease, causing prolonged leukocytosis, splenomegaly, extramedullary hematopoiesis, and modestly shorter survival. Double mutant (JAK2V617F and loss-of-TET2) myeloid cells were more likely to be in a proliferative state than JAK2V617F single mutant myeloid cells. In a serial competitive transplantation assay, JAK2V617F cells resulted in decreased chimerism in the 2nd recipients, which did not develop MPNs. In marked contrast, cooperation between JAK2V617F and loss-of-TET2 developed and maintained MPNs in the 2nd recipients by compensating for impaired hematopoietic stem cell (HSC) functioning. In vitro sequential colony formation assays also supported the observation that JAK2V617F did not maintain HSC functioning over the long term, but concurrent loss-of-TET2 mutation restored it. Transcriptional profiling revealed that loss-of-TET2 affected the expression of many HSC signature genes. We conclude that loss-of-TET2 has two different roles in MPNs; one is as a disease accelerator, while the other is as a disease initiator and sustainer in combination with JAK2V617F.
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Insulin requirement profiles in Japanese hospitalized subjects with type 2 diabetes treated with basal-bolus insulin therapy.
Endocr. J.
PUBLISHED: 11-14-2014
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To assess the total daily inulin dose (TDD) and contribution of basal insulin to TDD and to identify the predictive factors for insulin requirement profiles in subjects with type 2 diabetes, we retrospectively examined insulin requirement profiles of 275 hospitalized subjects treated with basal-bolus insulin therapy (BBT) (mean age, 60.1 ± 12.9 years; HbA1c, 10.2 ± 4.5%). Target plasma glucose level was set between 80 and 129 mg/dL before breakfast and between 80 and 179 mg/dL at 2-hour after each meal without causing hypoglycemia. We also analyzed the relationship between the insulin requirement profiles (TDD and basal/total daily insulin ratio [B/TD ratio]) and insulin-associated clinical parameters. The mean TDD was 0.463 ± 0.190 unit/kg/day (range, 0.16-1.13 unit/kg/day). The mean B/TD ratio was 0.300 ± 0.099 (range, 0.091-0.667). A positive correlation of TDD with B/TD ratio was revealed by linear regression analysis (r=0.129, p=0.03). Stepwise multiple regression analysis identified post-breakfast glucose levels before titrating insulin as an independent determinant of the insulin requirement profile [Std ? (standard regression coefficient) = 5.71E-4, p<0.01 for TDD, Std ? = -2.39E-4, p <0.01 for B/TD ratio]. The TDD was <0.6 unit/kg/day and the B/TD ratio was <0.4 in the majority (70.2%) of subjects in the present study. These findings may have relevance in improving glycemic control and decreasing the risk of hypoglycemia and weight gain in subjects with type 2 diabetes treated with BBT.
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Improvement of gamete quality and its short-term storage: an approach for biotechnology in laboratory fish.
Animal
PUBLISHED: 11-14-2014
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In fish, in vitro fertilization is an important reproductive tool used as first step for application of others biotechniques as chromosome and embryo manipulation. In this study, we aimed to optimize gamete quality and their short-term storage from the yellowtail tetra Astyanax altiparanae, for future application in laboratory studies. Working with sperm, we evaluated the effects of spawning inducers (carp pituitary gland and Ovopel® [(D-Ala6, Pro9-NEt) - mGnRH+metoclopramide]) and the presence of female on sperm motility. Additionally, we developed new procedures for short-term storage of sperm and oocytes. Briefly, sperm motility was higher when male fish were treated with carp pituitary gland (73.1±4.0%) or Ovopel® (79.5±5.5%) when compared with the control group treated with 0.9% NaCl (55.6±27.2%; P=0.1598). Maintenance of male fish with an ovulating female fish also improved sperm motility (74.4±7.4%) when compared with untreated male fish (42.1±26.1%; P=0.0018). Storage of sperm was optimized in modified Ringer solution, in which the sperm was kept motile for 18 days at 2.5°C. The addition of antibiotics or oxygen decreased sperm motility, but partial change of supernatant and the combination of those conditions improve storage ability of sperm. Fertilization ability of oocytes decreased significantly after storage for 30, 60 90 and 120 min at 5, 10, 15 and 20°C when compared with fresh oocytes (P=0.0471), but considering only the stored samples, the optimum temperature was 15°C. Those data describe new approaches to improve semen quality and gametes short-term storage in yellowtail tetra A. altiparanae and open new possibilities in vitro fertilization.
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[Successful acute endovascular therapy of cerebral embolism for a patient with ventricular assist device: a case report].
No Shinkei Geka
PUBLISHED: 10-30-2014
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The number of patients with a ventricular assist device(VAD)will increase with the spread of heart transplantation in Japan. On the other hand, it is likely that VADs could cause cerebral embolism. However, there are few reports about endovascular therapy for intracranial embolic infarction from VAD. The authors report successful acute endovascular therapy for cerebral embolism. A 19-year-old woman with a VAD who received anti-coagulant treatment by warfarin sodium presented disturbance of consciousness and right hemiparesis. CT scan showed early CT sign in the left middle cerebral artery(MCA)area. 3D-CTA demonstrated occlusion of the left MCA and basilar artery(BA). We first performed endovascular recanalization in the left MCA, because IV tPA was ineligible. The left MCA was recanalized with TICI 2b perfusion and her symptoms were significantly improved. The treatment of the VAD patient reveals important issues. First, the femoral puncture requires ultrasound due to pulseless femoral artery. Second, the access route is an intact artery because of the anatomy of the VAD. Third, even if the patient has a hemorrhagic complication by intervention, the patient must be kept on anti-coagulant treatment because the VAD requires it. Careful consideration should be given to recanalization of occlusive vessels.
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Profiling psychiatric inpatient suicide attempts in Japan.
Int J Emerg Ment Health
PUBLISHED: 10-28-2014
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Suicide is an adverse event that can occur even when patient are hospitalized in psychiatric facilities. This study delineates the demographic characteristics of suicide attempts in mental hospitals and psychiatric wards of general hospitals in Japan, a country where the suicide rate is remarkably high. Analyses of incident reports on serious suicide attempts in psychiatric inpatients were performed using prefectural incident records between April 1, 2001, and December 31, 2012. Suicide reports were included for 35 incidents that occurred over 11 years, and demonstrated that 83% of patients (n = 29) committed suicide and 17% (n = 6) survived their attempt with serious aftereffects, such as cognitive impairment or persistent vegetative state. The male/female ratio of inpatient suicide was 1.5:1. The mean age of the attempters was 50.5 years (SD = 18.2). The most common psychiatric diagnoses for those with suicide incident reports were schizophrenia spectrum disorders (51.4%) and affective disorders (40%). Hanging (60%) was the most common method of suicide attempt, followed by jumping in front of moving objects (14.3%) and jumping from height (11.4%). Fifty-four percent of suicides (n = 19) occurred within hospital sites and the remainder (46%; n = 16) occurred outside hospital sites (e.g., on medical leave or elopement) while they were still inpatients.
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Synthesis and evaluation of new (18)F-labelled acetamidobenzoxazolone-based radioligands for imaging of the translocator protein (18 kDa, TSPO) in the brain.
Org. Biomol. Chem.
PUBLISHED: 10-23-2014
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The visualization of the activated microglia/TSPO is one of the main aspects of neuroimaging. Here we describe two new (18)F-labelled molecules, 2-[5-(4-[(18)F]fluoroethoxyphenyl)- ([(18)F]2) and 2-[5-(4-[(18)F]fluoropropyloxyphenyl)- ([(18)F]3) -2-oxo-1,3-benzoxazol-3(2H)-yl]-N-methyl-N-phenylacetamide as novel PET ligands for imaging the translocator protein (18 kDa, TSPO) in the brain. The three-D pharmacophore evaluation and docking studies suggested their high affinity for the TSPO and in vitro binding assays of the TSPO showed binding affinities 6.6 ± 0.7 nM and 16.7 ± 2.5 nM for 2 and 3, respectively. The radiochemical yields for [(18)F]2 and [(18)F]3 were found to be 22 ± 4% (n = 8) and 5 ± 2% (n = 5), respectively at EOB. The radiochemical purity for both was found ?98% and the specific activity was in the range of 98-364 GBq ?mol(-1) at EOS. In vitro autoradiography with an ischemic rat brain showed significantly increased binding on the ipsilateral side compared to the contralateral side. The specificity of [(18)F]2 and [(18)F]3 for binding TSPO was confirmed using the TSPO ligands PK11195 and MBMP. The biodistribution patterns of both PET ligands were evaluated in normal mice by 1 h dynamic PET imaging. In the brain, regional radioactivity reached the maximum very rapidly within 0-4 min for both ligands, similar to (R)[(11)C]PK11195. The metabolite study of [(18)F]2 also favoured a more favourable profile for quantification in comparison to (R)[(11)C]PK11195. In summary, these data indicated that [(18)F]2 and [(18)F]3 have good potential to work as PET ligands, therefore there are merits to use these radioligands for the in vivo evaluation in animal models to see their efficacy in the living brain.
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Harmonic curved shears system prevent of bile leakage after liver resection in a pig model.
Int Surg
PUBLISHED: 09-13-2014
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Abstract We evaluated the efficacy of TachoComb (TC) collagen fleece and Harmonic Focus (HF) shears in a pig liver resection model. Pigs were divided into 3 groups of 7, in which vessels were tied with silk and TC was applied to the cut surfaces (Silk+TC group), sealed and sheared with HF and TC (HF+TC group), or sealed using HF alone (HF-TC group). After 1 month, we conducted a histologic evaluation and recorded the incidence of bile leakage with infected collections at the liver cut surface. Six pigs were evaluated in each group. In the Silk+TC group, 4 of the 6 pigs had infected collections at the cut surface. Histologically, the silk had remained under the fibrotic tissue, which contained remnants of TC fragments. In the HF+TC group, 5 of the 6 pigs also had infected collections, and histologically, TC had remained in the hard fibrotic tissues. In the HF-TC group, none of the 6 pigs had infected collections, and the histologic findings were normal. Use of the HF alone may be an effective method for preventing bile leakage in infected collections after liver resection.
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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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Loss of the Timp gene family is sufficient for the acquisition of the CAF-like cell state.
Nat. Cell Biol.
PUBLISHED: 08-24-2014
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Cancer-associated fibroblasts (CAFs) drive tumour progression, but the emergence of this cell state is poorly understood. A broad spectrum of metalloproteinases, controlled by the Timp gene family, influence the tumour microenvironment in human cancers. Here, we generate quadruple TIMP knockout (TIMPless) fibroblasts to unleash metalloproteinase activity within the tumour-stromal compartment and show that complete Timp loss is sufficient for the acquisition of hallmark CAF functions. Exosomes produced by TIMPless fibroblasts induce cancer cell motility and cancer stem cell markers. The proteome of these exosomes is enriched in extracellular matrix proteins and the metalloproteinase ADAM10. Exosomal ADAM10 increases aldehyde dehydrogenase expression in breast cancer cells through Notch receptor activation and enhances motility through the GTPase RhoA. Moreover, ADAM10 knockdown in TIMPless fibroblasts abrogates their CAF function. Importantly, human CAFs secrete ADAM10-rich exosomes that promote cell motility and activate RhoA and Notch signalling in cancer cells. Thus, Timps suppress cancer stroma where activated-fibroblast-secreted exosomes impact tumour progression.
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Comparative analysis of autistic traits and behavioral disorders in Prader-Willi syndrome and Asperger disorder.
Am. J. Med. Genet. A
PUBLISHED: 08-22-2014
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Prader-Willi syndrome (PWS) is a neuro-genetic disorder caused by the absence/loss of expression of one or more paternally expressed genes on chromosome 15 (q11-13). In this study, a comparative analysis of intelligence level and autistic traits was conducted between children with PWS (n?=?30; 18 males, 12 females; age?=?10.6?±?2.8 years) and those with Asperger disorder (AD; n?=?31; 24 males, 7 females; age?=?10.5?±?3.1 years). The children were compared by age group: lower elementary school age (6-8 years), upper elementary school age (9-12 years), and middle school age (13-15 years). As results, the intelligence levels of children with PWS were significantly lower than those with AD across all age groups. Autistic traits, assessed using the Pervasive Developmental Disorders Autism Society Japan Rating Scale (PARS), revealed that among elementary school age children, those with PWS had less prominent autistic traits than those with AD, however, among middle school age children, those with PWS and AD showed similar prominence. An analysis of the PARS subscale scores by age group showed that while the profiles of autistic traits for children with PWS differed from those of children with AD at elementary school age, the profiles showed no significant differences between the groups at middle school age. The findings suggest that autistic traits in PWS become gradually more prominent with increasing of age and that these autistic traits differ in their fundamental nature from those observed in AD. © 2014 Wiley Periodicals, Inc.
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Analysis of DNA methylation in bowel lavage fluid for detection of colorectal cancer.
Cancer Prev Res (Phila)
PUBLISHED: 08-19-2014
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Aberrant DNA methylation could potentially serve as a biomarker for colorectal neoplasms. In this study, we assessed the feasibility of using DNA methylation detected in bowel lavage fluid (BLF) for colorectal cancer screening. A total of 508 BLF specimens were collected from patients with colorectal cancer (n = 56), advanced adenoma (n = 53), minor polyp (n = 209), and healthy individuals (n = 190) undergoing colonoscopy. Methylation of 15 genes (miR-1-1, miR-9-1, miR-9-3, miR-34b/c, miR-124-1, miR-124-2, miR-124-3, miR-137, SFRP1, SFRP2, APC, DKK2, WIF1, LOC386758, and ZNF582) was then analyzed in MethyLight assays, after which receiver operating characteristic (ROC) curves were analyzed to assess the diagnostic performance of BLF methylation. Through analyzing BLF specimens in a training set (n = 345), we selected the three genes showing the greatest sensitivity for colorectal cancer detection (miR-124-3, 71.8%; LOC386758, 79.5%; and SFRP1, 74.4%). A scoring system based on the methylation of those three genes (M-score) achieved 82% sensitivity and 79% specificity, and the area under the ROC curve (AUC) was 0.834. The strong performance of this system was then validated in an independent test set (n = 153; AUC = 0.808). No significant correlation was found between M-score and the clinicopathologic features of the colorectal cancers. Our results demonstrate that DNA methylation in BLF specimens may be a useful biomarker for the detection of colorectal cancer.
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Pancreatic ductal perfusion at organ procurement enhances islet yield in human islet isolation.
Pancreas
PUBLISHED: 07-25-2014
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Pancreas preservation is a major factor influencing the results of islet cell transplantation. This study evaluated the effects of 2 different solutions for pancreatic ductal perfusion (PDP) at organ procurement.
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[A case report of gastrointestinal stromal tumor of the small intestine presenting with liver abscesses caused by Streptococcus constellatus].
Nihon Shokakibyo Gakkai Zasshi
PUBLISHED: 07-08-2014
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A 49-year-old woman visited a local hospital in October 2007 with complaint of fever and melena. Abdominal ultrasonography and abdominal computed tomography revealed an irregular mass in the lower abdomen, together with multiple masses in the liver. She was admitted because of anemia, and the high fever was determined to be an inflammatory response. Blood tests revealed elevated biliary enzyme levels. Percutaneous biopsy of the liver mass was performed, which revealed liver abscesses caused by Streptococcus constellatus. On abdominal angiography, the mass was suspected to be a tumor of the small intestine. In late November 2007, laparoscopy-assisted partial small bowel resection was performed, and pathological examination of the surgical specimen confirmed gastrointestinal stromal tumor (GIST) of the small bowel. Because reports of small intestinal GIST with liver abscesses caused by Streptococcus constellatus are rare, this case description could provide valuable information.
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Retinal ganglion cell analysis in multiple evanescent white dot syndrome.
BMC Ophthalmol
PUBLISHED: 07-04-2014
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Multiple evanescent white dot syndrome (MEWDS) is an acute and usually unilateral retinopathy that occurs predominantly in young adults. This report presents the outcomes of ganglion cell analysis (GCA) in MEWDS.
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Inflammation-based prognostic score predicts biliary stent patency in patients with unresectable malignant biliary obstruction.
Anticancer Res.
PUBLISHED: 07-02-2014
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An inflammation-based prognostic score, the modified Glasgow prognostic score (mGPS), has been reported to be useful for predicting postoperative survival in patients with various types of cancer. However, no studies have investigated whether the mGPS can predict biliary stent (BS) patency in patients undergoing BS placement for unresectable malignant biliary obstruction (UMBO).
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Estimation of subepithelial lateral extent in submucosal early gastric cancer: retrospective histological analysis.
Gastric Cancer
PUBLISHED: 07-01-2014
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Endoscopic full-thickness resection (EFTR) is expected to make possible minimally invasive local resection of early gastric cancer (EGC). However, no consensus exists regarding how far an optimal safety margin should be set in determining the resection area by endoscopy. We aimed to investigate the optimal lateral margin of EGC which could be a candidate for EFTR by measuring the subepithelial extent (SE) of tumors.
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Impact of a single nucleotide polymorphism upstream of the IL28B gene in patients positive for anti-HCV antibody in an HCV hyperendemic area in Japan.
J. Med. Virol.
PUBLISHED: 07-01-2014
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The influence of genetic variation at the interleukin-28B (IL28B) locus on the natural course of hepatitis C virus (HCV) infection has not been fully investigated. The goal of this study was to examine whether an IL28B polymorphism (rs8099917) is associated with natural clearance of HCV and with disease parameters of HCV infection in an HCV hyperendemic area of Japan. The patients were 502 anti-HCV antibody-positive residents who participated in liver disease screening program from 2002 to 2004. Patients who underwent interferon-based therapy or had hepatocellular carcinoma were excluded. Of these patients, 149 were negative for HCV RNA (prior infection) and 353 were positive for HCV RNA or HCV core antigen (HCV carriers). In multivariate analysis, the IL28B TT genotype was a predictor for prior HCV infection. In addition, nine of the patients with prior HCV infection were positive for anti-HCV antibody with positive for HCV core antigen or HCV RNA before 2001, and these nine patients all had the IL28B TT genotype. Furthermore, the IL28B TT genotype was associated independently with higher HCV core antigen levels in HCV carriers. In contrast, the IL28B genotype did not affect the biochemical markers, such as alanine aminotransferase, hepatic fibrosis markers, and ?-fetoprotein, and the degree of hepatic fibrosis assessed by transient elastography in HCV carriers. We concluded that IL28B polymorphism (TT genotype) is associated with spontaneous clearance of HCV and conversely with high viral loads in HCV carriers. In contrast, the IL28B genotype does not affect disease progression such as hepatic fibrosis.
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[Clinical outcome and clinicopathological prognostic factors in adenoid cystic carcinoma of the head and neck].
Nippon Jibiinkoka Gakkai Kaiho
PUBLISHED: 06-25-2014
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We retrospectively reviewed the records of the 30 patients with adenoid cystic carcinoma of the head and neck (ACCHN) who had undergone initial treatment in the Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine between 1988 and 2007. The primary tumor site was the parotid gland in 10 patients and the submandibular gland in 4 patients, which account for about a half of the subjects. Thirty patients underwent surgical resection with curative intent as the primary treatment, of which 10 patients had post-operative radiotherapy. The 5-and 10-year disease-specific survival (DSS) was 73.9% and 62.4%, respectively, whereas the 5-and 10-year disease-free survival (DFS) was 64.3% and 59.7%, respectively. A univariate analysis revealed that DSS was significantly correlated with perineural invasion (p = 0.010) and lymphatic invasion (p = 0.036), while DFS was significantly correlated with higher T-stage (p = 0.044), a positive surgical margin (p = 0.012) and perineural invasion (p = 0.019). A multivariate analysis demonstrated that perineural invasion (p = 0.034, risk ratio = 9.530) was the independent prognostic factor for DSS, whereas for DFS it was a positive surgical margin (p = 0.038, risk ratio = 8.897). The histological grade classification, defined specifically for ACC, showed no correlation with the survival. Extended resection with wider margin and additional resection in cases with positive margin may improve treatment results, however, surgical resection alone can prevent neither the development of local recurrence mainly attributed to undetectable perineural invasion, nor that of delayed distant metastasis. Therefore, the roles of adjuvant radiotherapy and effective systemic therapies are also significant in ACCHN, although a reliable regimen for the latter has not yet been established. Development of a personalized strategy for the adjuvant therapy, which should be based on the accurate prediction of the long-term prognosis in combination with dependable molecular biomarkers, would be indispensable in the future to improve the clinical outcome of the patients with ACCHN.
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Aspartate aminotransferase-to-platelet ratio index is associated with liver cirrhosis in patients undergoing surgery for hepatocellular carcinoma.
J. Surg. Res.
PUBLISHED: 06-04-2014
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Among various preoperative evaluations of liver function, accurate assessment of liver cirrhosis (LC) is especially important in patients undergoing surgery for hepatocellular carcinoma (HCC).
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Analysis of hypoxia-induced metabolic reprogramming.
Meth. Enzymol.
PUBLISHED: 05-28-2014
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Hypoxia is a common finding in advanced human tumors and is often associated with metastatic dissemination and poor prognosis. Cancer cells adapt to hypoxia by utilizing physiological adaptation pathways that promote a switch from oxidative to glycolytic metabolism. This promotes the conversion of glucose into lactate while limiting its transformation into acetyl coenzyme A (acetyl-CoA). The uptake of glucose and the glycolytic flux are increased under hypoxic conditions, mostly owing to the upregulation of genes encoding glucose transporters and glycolytic enzymes, a process that depends on hypoxia-inducible factor 1 (HIF-1). The reduced delivery of acetyl-CoA to the tricarboxylic acid cycle leads to a switch from glucose to glutamine as the major substrate for fatty acid synthesis in hypoxic cells. In addition, hypoxia induces (1) the HIF-1-dependent expression of BCL2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3) and BNIP3-like (BNIP3L), which trigger mitochondrial autophagy, thereby decreasing the oxidative metabolism of both fatty acids and glucose, and (2) the expression of the sodium-hydrogen exchanger NHE1, which maintains an alkaline intracellular pH. Here, we present a compendium of methods to study hypoxia-induced metabolic alterations.
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Comparison of the efficacy of sitagliptin and glimepiride dose-up in Japanese patients with type 2 diabetes poorly controlled by sitagliptin and glimepiride in combination.
J Diabetes Investig
PUBLISHED: 05-21-2014
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The goal of the study was to examine the effects of sitagliptin dose-up or glimepiride dose-up in Japanese patients with type 2 diabetes who were controlled inadequately by sitagliptin and glimepiride in combination.
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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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Tyk2-dependent bystander activation of conventional and nonconventional Th1 cell subsets contributes to innate host defense against Listeria monocytogenes infection.
J. Immunol.
PUBLISHED: 04-11-2014
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IL-12, which is produced in response to intracellular bacteria, such as Listeria monocytogenes, promotes the development of pathogen-specific Th1 cells that play an important role in host defense. However, it has also been known that CD44(high) memory-phenotype CD4 T cells with Th1 functions naturally occur in naive mice, and that lymphopenia-induced proliferation of naive CD4 T cells generates memory-phenotype CD4 T cells with Th1 functions, although their differentiation mechanism and contribution to host defense are unclear. In this study, we analyzed the development and the functions of the different subsets of Th1 cells by using mice lacking tyrosine kinase 2 (Tyk2), a member of the Janus kinase family critically involved in IL-12 signaling. In contrast with the case of conventional Ag-specific Th1 cells, the development of naturally occurring Th1 cells was not impaired in Tyk2-deficient mice. In addition, Th1 cells were normally generated from Tyk2-deficient naive CD4 T cells via lymphopenia-induced proliferation. Nevertheless, all these Th1 subsets, including conventional Ag-induced Th1 cells, produced IFN-? in response to IL-12 in a Tyk2-dependent manner. Importantly, such Tyk2-dependent bystander IFN-? production of any Th1 subsets conferred early protection against L. monocytogenes infection. Thus, Tyk2-mediated IL-12 signaling is differentially required for the development of different Th1 cell subsets but similarly induces their bystander IFN-? production, which contributes to innate host defense against infection with intracellular bacteria.
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[(11)C-carbonyl]CEP-32496: radiosynthesis, biodistribution and PET study of brain uptake in P-gp/BCRP knockout mice.
Bioorg. Med. Chem. Lett.
PUBLISHED: 03-31-2014
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CEP-32496 is a novel, orally active serine/threonine-protein kinase B-raf (BRAF) (V600E) kinase inhibitor that is being investigated in clinical trials for the treatment of some cancers in patients. In this study, we developed [(11)C-carbonyl]CEP-32496 as a novel positron emission tomography (PET) probe to study its biodistribution in the whole bodies of mice. [(11)C]CEP-32496 was synthesized by the reaction of 5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-amine hydrochloride (1·HCl) with [(11)C]phosgene, followed by treatment with 3-(6,7-dimethoxyquinozolin-4-yloxy)aniline (2). Small-animal PET studies with [(11)C]CEP-32496 indicated that radioactivity levels (AUC0-90 min, SUV×min) accumulated in the brains of P-gp/BCRP knockout mice at a 8-fold higher rate than in the brains of wild-type mice.
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Outcome of hepatectomy for hepatocellular carcinoma in elderly patients with portal hypertension.
Int Surg
PUBLISHED: 03-28-2014
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Abstract The outcome of liver resection (LR) for elderly hepatocellular carcinoma (HCC) patients with portal hypertension (PHT) who may be excluded as liver transplantation candidates has not been fully evaluated. One hundred ninety-five patients who underwent initial curative LR for HCC with PHT were divided into 2 groups: age <70 years (n = 131) and age ?70 years (n = 64). Clinicopathologic data and postoperative complications were compared. Preoperative characteristics and postoperative complications were similar in both groups. However, in-hospital mortality was significantly more frequent in elderly than in younger patients (11% versus 1%, P = 0.002). No significant intergroup differences were observed in the 5-year disease-free survival rate or recurrence rate (19.7% versus 17.2%; P = 0.338, 63% versus 56%; P = 0.339). Although LR for elderly HCC patients with PHT can be performed with curative intent and gives results comparable with those in younger patients, it is associated with higher in-hospital mortality.
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Laparoscopic mesh repair of a Morgagni hernia using the double-crown technique: A case study.
Asian J Endosc Surg
PUBLISHED: 03-27-2014
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We report a case of Morgagni hernia in which the patient underwent laparoscopic mesh repair. A 65-year-old woman presented with an abnormal shadow in the right lower lung field on a routine medical checkup. CT showed that the transverse colon passed between the liver and abdominal wall, and herniated into the thoracic cavity. Simple closure was precluded by the large hernial orifice. We therefore performed laparoscopic repair using a Parietex Optimized Composite Mesh. The double-crown technique was used to fix the margin of the mesh to the region around the hernial orifice. Our procedure for repair of a Morgagni hernia with a large hernial orifice is safe and minimally invasive, and it may effectively prevent recurrence.
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Development of acute pancreatitis caused by sodium valproate in a patient with bipolar disorder on hemodialysis for chronic renal failure: a case report.
BMC Psychiatry
PUBLISHED: 03-25-2014
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Cases of acute pancreatitis caused by sodium valproate (VPA) have been reported by many authors thus far. However, most of these were cases with epilepsy. Chronic renal failure is also regarded as a risk factor for acute pancreatitis. Here, we report a case of acute pancreatitis development due to VPA in a patient with bipolar disorder on hemodialysis for chronic renal failure.
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When hepatic-side ductal margin is positive in N+ cases, additional resection of the bile duct is not necessary to render the negative hepatic-side ductal margin during surgery for extrahepatic distal bile duct carcinoma.
Med. Sci. Monit.
PUBLISHED: 03-25-2014
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The current standard treatment for extrahepatic distal bile duct carcinoma (EDBDC) is surgical resection, as no effective alternative treatment exists. In this study, we investigated the treatment strategies and outcomes for 90 cases of EDBDC at our department.
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Bernard Lerer: recipient of the 2014 inaugural Werner Kalow Responsible Innovation Prize in Global Omics and Personalized Medicine (Pacific Rim Association for Clinical Pharmacogenetics).
OMICS
PUBLISHED: 03-20-2014
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This article announces the recipient of the 2014 inaugural Werner Kalow Responsible Innovation Prize in Global Omics and Personalized Medicine by the Pacific Rim Association for Clinical Pharmacogenetics (PRACP): Bernard Lerer, professor of psychiatry and director of the Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. The Werner Kalow Responsible Innovation Prize is given to an exceptional interdisciplinary scholar who has made highly innovative and enduring contributions to global omics science and personalized medicine, with both vertical and horizontal (transdisciplinary) impacts. The prize is established in memory of a beloved colleague, mentor, and friend, the late Professor Werner Kalow, who cultivated the idea and practice of pharmacogenetics in modern therapeutics commencing in the 1950s. PRACP, the prize's sponsor, is one of the longest standing learned societies in the Asia-Pacific region, and was founded by Kalow and colleagues more than two decades ago in the then-emerging field of pharmacogenetics. In announcing this inaugural prize and its winner, we seek to highlight the works of prize winner, Professor Lerer. Additionally, we contextualize the significance of the prize by recalling the life and works of Professor Kalow and providing a brief socio-technical history of the rise of pharmacogenetics and personalized medicine as a veritable form of 21(st) century scientific practice. The article also fills a void in previous social science analyses of pharmacogenetics, by bringing to the fore the works of Kalow from 1995 to 2008, when he presciently noted the rise of yet another field of postgenomics inquiry--pharmacoepigenetics--that railed against genetic determinism and underscored the temporal and spatial plasticity of genetic components of drug response, with invention of the repeated drug administration (RDA) method that estimates the dynamic heritabilities of drug response. The prize goes a long way to cultivate transgenerational capacity and broader cognizance of the concept and practice of responsible innovation as an important criterion of 21(st) century omics science and personalized medicine. A new call is presently in place for the 2016 PRACP Werner Kalow prize. Nominations can be made in support of an exceptional individual interdisciplinary scholar, or alternatively, an entire research team, from any region in the world with a record of highly innovative contributions to global omics science and/or personalized medicine, in the spirit of responsible innovation. The application process is straightforward, requiring a signed, 1500-word nomination letter (by the applicant or sponsor) submitted not later than May 31, 2015.
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Intraductal papillary neoplasm of the bile duct developing in a patient with primary sclerosing cholangitis: A case report.
World J. Gastroenterol.
PUBLISHED: 03-18-2014
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We report a case of intraductal papillary neoplasm of the bile duct (IPNB) that developed in a patient with primary sclerosing cholangitis. A 46-year-old woman was admitted to our hospital with obstructive jaundice. The liver function tests demonstrated increased serum liver enzyme levels. Computed tomography showed dilatation of the intrahepatic bile ducts. Abdominal ultrasonography revealed a highly echoic protruding lesion in the posterior bile duct near the right lobe of the liver. The lesion was suspected to be IPNB, but we were unable to confirm whether it was a carcinoma. A right hepatectomy was performed, and this showed that the dilated bile duct was filled with mucin and contained several yellowish papillary tumors. Histologically, the neoplastic biliary epithelium showed papillary growth in the dilated lumen. The tumor was diagnosed as IPNB, high-grade intraepithelial neoplasia secreting abundant mucin. No recurrence has been detected 3 years after surgery.
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Use of Short-term Circulatory Support as a Bridge in Pediatric Heart Transplantation.
Arq. Bras. Cardiol.
PUBLISHED: 03-06-2014
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Background: Heart transplantation is considered the gold standard therapy for the advanced heart failure, but donor shortage, especially in pediatric patients, is the main limitation for this procedure, so most sick patients die while waiting for the procedure. Objective: To evaluate the use of short-term circulatory support as a bridge to transplantation in end-stage cardiomyopathy. Methods: Retrospective clinical study. Between January 2011 and December 2013, 40 patients with cardiomyopathy were admitted in our Pediatric Intensive Care Unit, with a mean age of 4.5 years. Twenty patients evolved during hospitalization with clinical deterioration and were classified as Intermacs 1 and 2. One patient died within 24 hours and 19 could be stabilized and were listed. They were divided into 2 groups: A, clinical support alone and B, implantation of short-term circulatory support as bridge to transplantation additionally to clinical therapy. Results: We used short-term mechanical circulatory support as a bridge to transplantation in 9. In group A (n=10), eight died waiting and 2 patients (20%) were transplanted, but none was discharged. In group B (n=9), 6 patients (66.7%) were transplanted and three were discharged.The mean support time was 21,8 days (6 to 984h). The mean transplant waiting list time was 33,8 days. Renal failure and sepsis were the main complication and causeof death in group A while neurologic complications were more prevalent en group B. Conclusion: Mechanical circulatory support increases survival on the pediatric heart transplantation waiting list in patients classified as Intermacs 1 and 2.
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Impact of cognitive reserve on the progression of mild cognitive impairment to Alzheimer's disease in Japan.
Geriatr Gerontol Int
PUBLISHED: 03-04-2014
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The present study aimed to investigate whether cognitive reserve (CR), referring here to education and premorbid intelligence (IQ), is associated with the risk for progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD).
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Simultaneous determination of N(G)-monomethyl-L-arginine, N(G),N(G)-dimethyl-L-arginine, N(G),N(G')-dimethyl-L-arginine, and L-arginine using monolithic silica disk-packed spin columns and a monolithic silica column.
J Sep Sci
PUBLISHED: 03-03-2014
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We have developed and validated a high-performance liquid chromatography method that uses monolithic silica disk-packed spin columns and a monolithic silica column for the simultaneous determination of N(G)-monomethyl-L-arginine, N(G),N(G)-dimethyl-L-arginine, and N(G),N(G')-dimethyl-L-arginine in human plasma. For solid-phase extraction, our method employs a centrifugal spin column packed with monolithic silica bonded to propyl benzenesulfonic acid as a cation exchanger. After pretreatment, the methylated arginines are converted to fluorescent derivatives with 4-fluoro-7-nitro-2,1,3-benzoxadiazole, and then the derivatives are separated on a monolithic silica column. L-arginine concentration was also determined in diluted samples. Standard calibration curves revealed that the assay was linear in the concentration range 0.2-1.0 ?M for methylated arginines and 40-200 ?M for L-arginine. Linear regression of the calibration curve yielded equations with correlation coefficients of 0.999 (r(2)). The sensitivity was satisfactory, with a limit of detection ranging from 3.75 to 9.0 fmol for all four compounds. The RSDs were 4.3-4.8% (intraday) and 3.0-6.8% (interday). When this method was applied to samples from six healthy donors, the detected concentrations of N(G)-monomethyl-L-arginine, N(G),N(G)-dimethyl-L-arginine, N(G),N(G')-dimethyl-L-arginine and L-arginine were 0.05 ± 0.01, 0.41 ± 0.07, 0.59 ± 0.11, and 83.8 ± 30.43 ?M (n = 6), respectively.
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Loss of NDRG2 expression activates PI3K-AKT signalling via PTEN phosphorylation in ATLL and other cancers.
Nat Commun
PUBLISHED: 02-06-2014
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Constitutive phosphatidylinositol 3-kinase (PI3K)-AKT activation has a causal role in adult T-cell leukaemia-lymphoma (ATLL) and other cancers. ATLL cells do not harbour genetic alterations in PTEN and PI3KCA but express high levels of PTEN that is highly phosphorylated at its C-terminal tail. Here we report a mechanism for the N-myc downstream-regulated gene 2 (NDRG2)-dependent regulation of PTEN phosphatase activity via the dephosphorylation of PTEN at the Ser380, Thr382 and Thr383 cluster within the C-terminal tail. We show that NDRG2 is a PTEN-binding protein that recruits protein phosphatase 2A (PP2A) to PTEN. The expression of NDRG2 is frequently downregulated in ATLL, resulting in enhanced phosphorylation of PTEN at the Ser380/Thr382/Thr383 cluster and enhanced activation of the PI3K-AKT pathway. Given the high incidence of T-cell lymphoma and other cancers in NDRG2-deficient mice, PI3K-AKT activation via enhanced PTEN phosphorylation may be critical for the development of cancer.
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Effects of recombinant human soluble thrombomodulin treatment for disseminated intravascular coagulation at a single institution--an analysis of 62 cases caused by infectious diseases and 30 cases caused by hematological diseases.
Intern. Med.
PUBLISHED: 02-05-2014
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Disseminated intravascular coagulation (DIC) is a clinical condition with high mortality that is characterized by the systemic activation of coagulation pathways resulting in multiple organ failure. Although no standard treatment for DIC has been established, recent reports have indicated that recombinant human soluble thrombomodulin (rTM) is effective against DIC.
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Usefulness of a new inflammation-based scoring system for prognostication of patients with hepatocellular carcinoma after hepatectomy.
Am. J. Surg.
PUBLISHED: 02-04-2014
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We investigated whether a preoperative scoring system (the "CRP-AFP Score [CAS]") based on the serum levels of C-reactive protein and alpha-fetoprotein would predict outcome in patients undergoing hepatectomy for hepatocellular carcinoma.
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Characterization of a novel acetamidobenzoxazolone-based PET ligand for translocator protein (18 kDa) imaging of neuroinflammation in the brain.
J. Neurochem.
PUBLISHED: 01-11-2014
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We developed the novel positron emission tomography (PET) ligand 2-[5-(4-[(11)C]methoxyphenyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]-N-methyl-N-phenylacetamide ([(11)C]MBMP) for translocator protein (18 kDa, TSPO) imaging and evaluated its efficacy in ischemic rat brains. [(11)C]MBMP was synthesized by reacting desmethyl precursor (1) with [(11)C]CH3 I in radiochemical purity of ? 98% and specific activity of 85 ± 30 GBq/?mol (n = 18) at the end of synthesis. Biodistribution study on mice showed high accumulation of radioactivity in the TSPO-rich organs, e.g., the lungs, heart, kidneys, and adrenal glands. The metabolite analysis in mice brain homogenate showed 80.1 ± 2.7% intact [(11)C]MBMP at 60 min after injection. To determine the specific binding of [(11)C]MBMP with TSPO in the brain, in vitro autoradiography and PET studies were performed in an ischemic rat model. In vitro autoradiography indicated significantly increased binding on the ipsilateral side compared with that on the contralateral side of ischemic rat brains. This result was supported firmly by the contrast of radioactivity between the ipsilateral and contralateral sides in PET images. Displacement experiments with unlabelled MBMP or PK11195 minimized the difference in uptake between the two sides. In summary, [(11)C]MBMP is a potential PET imaging agent for TSPO and, consequently, for the up-regulation of microglia during neuroinflammation.
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Factors affecting discontinuation of initial treatment with paroxetine in panic disorder and major depressive disorder.
Neuropsychiatr Dis Treat
PUBLISHED: 01-01-2014
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The aims of the present study were to analyze the association between discontinuation of paroxetine (PAX) and the genetic variants of the polymorphism in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) in Japanese patients with panic disorder (PD) and major depressive disorder (MDD).
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QT is longer in drug-free patients with schizophrenia compared with age-matched healthy subjects.
PLoS ONE
PUBLISHED: 01-01-2014
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The potassium voltage-gated channel KCNH2 is a well-known gene in which mutations induce familial QT interval prolongation. KCNH2 is suggested to be a risk gene for schizophrenia. Additionally, the disturbance of autonomic control, which affects the QT interval, is known in schizophrenia. Therefore, we speculate that schizophrenic patients have characteristic features in terms of the QT interval in addition to the effect of antipsychotic medication. The QT interval of patients with schizophrenia not receiving antipsychotics (n?=?85) was compared with that of patients with schizophrenia receiving relatively large doses of antipsychotics (n?=?85) and healthy volunteers (n?=?85). The QT interval was corrected using four methods (Bazett, Fridericia, Framingham or Hodges method). In ANCOVA with age and heart rate as covariates, patients not receiving antipsychotic treatment had longer QT intervals than did the healthy volunteers, but antipsychotics prolonged the QT interval regardless of the correction method used (P<0.01). Schizophrenic patients with and without medication had a significantly higher mean heart rate than did the healthy volunteers, with no obvious sex-related differences in the QT interval. The QT interval prolongation may be manifestation of a certain biological feature of schizophrenia.
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Psychiatrists' attitudes toward metabolic adverse events in patients with schizophrenia.
PLoS ONE
PUBLISHED: 01-01-2014
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There is growing concern about the metabolic abnormalities in patients with schizophrenia.
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Tyk2 is a therapeutic target for psoriasis-like skin inflammation.
Int. Immunol.
PUBLISHED: 12-17-2013
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Tyrosine kinase 2 (Tyk2), a member of the Jak kinase family, mediates signals triggered by various cytokines, which are related to the pathogenesis of psoriasis. In this study, we investigated the role of Tyk2 in IL-23-induced psoriasis-like skin inflammation. Tyk2(-/-) mice when injected with IL-23 showed significantly reduced ear skin swelling with epidermal hyperplasia and inflammatory cell infiltration compared with wild-type mice. In addition, Tyk2 deficiency reduced production of pro-inflammatory cytokines and psoriasis-relevant anti-microbial peptides. More noteworthy is that Tyk2 directly regulated IL-22-dependent inflammation and epidermal hyperplasia. Taken together with the inhibition of IL-23-induced inflammation by treatment with neutralizing antibodies against IL-17 or IL-22, Tyk2 participates in both IL-23 and IL-22 signal transduction to mediate psoriasis-like skin inflammation. On the basis of these findings, we demonstrated for the first time that a small-molecule Tyk2 inhibitor significantly inhibited IL-23-induced inflammation and cytokine production in the skin. These observations demonstrate the important role of Tyk2 in experimental skin inflammation and indicate the therapeutic potential of Tyk2 inhibition in human psoriasis.
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HIF and pulmonary vascular responses to hypoxia.
J. Appl. Physiol.
PUBLISHED: 12-12-2013
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In the lung, acute reductions in oxygen lead to hypoxic pulmonary vasoconstriction, whereas prolonged exposures to hypoxia result in sustained vasoconstriction, pulmonary vascular remodeling and the development of pulmonary hypertension. Data from both human subjects and animal models implicates a role for hypoxia-inducible factors (HIFs), oxygen-sensitive transcription factors, in pulmonary vascular responses to both acute and chronic hypoxia. In this review, we discuss work from our lab and others supporting a role for HIF in modulating hypoxic pulmonary vasoconstriction and mediating hypoxia-induced pulmonary hypertension, identify some of the downstream targets of HIF, and assess the potential to pharmacologically target the HIF system.
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Concurrent loss of Ezh2 and Tet2 cooperates in the pathogenesis of myelodysplastic disorders.
J. Exp. Med.
PUBLISHED: 11-11-2013
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Polycomb group (PcG) proteins are essential regulators of hematopoietic stem cells. Recent extensive mutation analyses of the myeloid malignancies have revealed that inactivating somatic mutations in PcG genes such as EZH2 and ASXL1 occur frequently in patients with myelodysplastic disorders including myelodysplastic syndromes (MDSs) and MDS/myeloproliferative neoplasm (MPN) overlap disorders (MDS/MPN). In our patient cohort, EZH2 mutations were also found and often coincided with tet methylcytosine dioxygenase 2 (TET2) mutations. Consistent with these findings, deletion of Ezh2 alone was enough to induce MDS/MPN-like diseases in mice. Furthermore, concurrent depletion of Ezh2 and Tet2 established more advanced myelodysplasia and markedly accelerated the development of myelodysplastic disorders including both MDS and MDS/MPN. Comprehensive genome-wide analyses in hematopoietic progenitor cells revealed that upon deletion of Ezh2, key developmental regulator genes were kept transcriptionally repressed, suggesting compensation by Ezh1, whereas a cohort of oncogenic direct and indirect polycomb targets became derepressed. Our findings provide the first evidence of the tumor suppressor function of EZH2 in myeloid malignancies and highlight the cooperative effect of concurrent gene mutations in the pathogenesis of myelodysplastic disorders.
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Intermittent hypoxia impairs glucose homeostasis in C57BL6/J mice: partial improvement with cessation of the exposure.
Sleep
PUBLISHED: 10-02-2013
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Obstructive sleep apnea is associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Although several studies have suggested that intermittent hypoxia in obstructive sleep apnea may induce abnormalities in glucose homeostasis, it remains to be determined whether these abnormalities improve after discontinuation of the exposure. The objective of this study was to delineate the effects of intermittent hypoxia on glucose homeostasis, beta cell function, and liver glucose metabolism and to investigate whether the impairments improve after the hypoxic exposure is discontinued.
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Intramedullary and retroperitoneal melanocytic tumor associated with congenital blue nevus and nevus flammeus: an uncommon combination of neurocutaneous melanosis and phacomatosis pigmentovascularis--case report.
Neurol. Med. Chir. (Tokyo)
PUBLISHED: 09-27-2013
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Neurocutaneous melanosis (NCM) is a rare condition characterized by central nervous system melanocytic tumors associated with congenital melanocytic nevi. Phacomatosis pigmentovascularis (PPV) is an association of vascular nevus with pigmentary nevus. Aberrant maturation of neural crest-derived cells is considered to be related to pathogenesis in both conditions. However, association of NCM and PPV has not been reported to the best of our knowledge. Melanocytoma, which usually involves the leptomeninges or spinal cord, is extremely rare in the retroperitoneum. We present here a case of a patient with NCM, PPV, and melanocytic tumors in the spinal cord and retroperitoneum, which were treated surgically. A 40-year-old woman had a 2-year history of dysesthesia and weakness in the left leg. History included congenital giant blue nevus-like lesion in the trunk, a port-wine stain in the sacral area, and Caesarean section performed 8 years before, when diffuse pigmentation in the peritoneum was noted. Magnetic resonance (MR) imaging of the spine revealed an intramedullary tumor at T10 level with paramagnetic signal characteristics. The spinal cord tumor was totally removed, and the histological diagnosis was melanocytoma. Three months later, a left retroperitoneal mass with histological features of melanocytic tumor was removed. Neither tumors recurred and the patient stays ambulatory 4 years after the surgery. Multiple subtypes of melanocytic tumors with distinctive features of NCM and PPV can develop simultaneously, mimicking malignant melanoma. Gross total resection of each tumor, when indicated, is beneficial.
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Clinical characteristics and outcomes of 11 patients with pure red cell aplasia at a single institution over a 13-year period.
Intern. Med.
PUBLISHED: 09-18-2013
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Pure red cell aplasia (PRCA) is a rare clinical entity characterized by anemia due to severe suppression of erythroid precursors, where the other cell lineages in the bone marrow remain morphologically normal. A standard treatment has not yet been established for PRCA due to the rarity of this condition. Recently, however, the administration of either cyclosporine (CSP) or prednisolone (PSL) has been reported to be an effective treatment for PRCA.
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Association between circulating leukocyte subtype counts and carotid intima-media thickness in Japanese subjects with type 2 diabetes.
Cardiovasc Diabetol
PUBLISHED: 09-17-2013
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An increased leukocyte count is an independent risk factor for cardiovascular events, but the association between leukocyte subtype counts and carotid atherosclerosis in patients with diabetes has not been determined. We therefore investigated the correlation between leukocyte subtype counts and intima-media thickness of the common carotid artery (CCA-IMT) in subjects with type 2 diabetes.
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Jun activation domain-binding protein 1 (JAB1) is required for the optimal response to interferons.
J. Biol. Chem.
PUBLISHED: 09-16-2013
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Degradation of IFN receptor (IFNR) protein is one of the mechanisms to limit the extent of cellular responses to interferons. Tyrosine kinase 2 (TYK2), a JAK family kinase, has been reported to bind to and stabilize IFNR, indicating that TYK2 is a fundamental component of IFNR complex. Herein, we identified Jun activation domain-binding protein 1 (JAB1) as a new TYK2 binding partner and investigated its role in the regulation of IFN responses. siRNA knockdown of JAB1 resulted in suppression of IFN-induced phosphorylation of STAT proteins and their transcriptional activation. Importantly, JAB1 knockdown induced the activation of SCF ubiquitin ligase complex containing Cullin 1 (CUL1), as judged by the enhancement of covalent modification of CUL1 with the ubiquitin-like protein NEDD8, and markedly reduced the basal protein level of IFNR. In contrast, NEDD8 knockdown or inhibition of NEDD8 modification by NEDD8-activating enzyme inhibitor resulted in increased IFNR protein concomitantly with a reduction of NEDD8-modified CUL1. Furthermore, NEDD8-activating enzyme inhibitor treatment enhanced the susceptibility to IFN-? in HeLa cells. These data suggest that the NEDD8 modification pathway is involved in the proteolysis of IFNR and that JAB1 acts as a positive regulator of IFN responses by stabilizing IFNR through antagonizing the NEDD8 pathway.
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Portal vein thrombosis during eltrombopag treatment for immune thrombocytopenic purpura in a patient with liver cirrhosis due to hepatitis C viral infection.
J Clin Exp Hematop
PUBLISHED: 09-03-2013
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Portal vein thrombosis is a rare, aggressive and life-threatening complication of liver cirrhosis (LC). Eltrombopag is effective for the treatment of chronic hepatitis with thrombocytopenia, and portal vein thrombosis at this time has rarely been reported. We describe the case of a 78-year-old woman who suffered from LC due to hepatitis C viral infection. The patient developed immune thrombocytopenic purpura (ITP) that was diagnosed on the basis of nasal bleeding, progressive severe thrombocytopenia, elevation of platelet-associated IgG (PAIgG), no response to the transfusion of platelets and no abnormal findings on bone marrow biopsy. Although we first administered prednisolone (0.5 mg/kg/day), there was no recovery of platelet function and the nasal bleeding persisted. Subsequently, we administered eltrombopag for refractory ITP at a dose of 12.5 mg/day, and the thrombocytopenia gradually improved. Fifty-four days after the start of eltrombopag therapy, she developed portal vein thrombosis. Eltrombopag was stopped immediately, and antithrombin III was administered for prophylaxis against further portal vein thrombosis. Despite these treatments, there were subsequent deep vein and pulmonary artery thromboses. We then administered heparin for recanalization of the thrombi. One month after the initiation of heparin, there was recanalization as well as improvements of the portal vein, deep vein and pulmonary artery thromboses. There was no further thrombosis progression after switching from heparin to warfarin therapy. Our case suggests that eltrombopag may increase the risk of portal vein thrombosis ; therefore, this drug must be used carefully in the treatment of ITP in patients with LC due to hepatitis C viral infection.
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Association of the Hermansky--Pudlak syndrome type 4 (HPS4) gene variants with cognitive function in patients with schizophrenia and healthy subjects.
BMC Psychiatry
PUBLISHED: 08-27-2013
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The Hermansky--Pudlak Syndrome Type 4 (HPS4) gene, which encodes a subunit protein of the biogenesis of lysosome-related organelles complex (BLOC)-3, which is involved in late endosomal trafficking, is associated with schizophrenia; however, its clinical relevance in schizophrenia remains unknown. The purpose of the present study was to investigate whether HPS4 is associated with cognitive functions in patients with schizophrenia and healthy controls and with the clinical profiles of patients with schizophrenia.
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Binding potential of (E)-[(11)C]ABP688 to metabotropic glutamate receptor subtype 5 is decreased by the inclusion of its (11)C-labelled Z-isomer.
Nucl. Med. Biol.
PUBLISHED: 08-09-2013
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[(11)C]ABP688 is a promising positron emission tomography (PET) ligand for imaging of metabotropic glutamate receptor subtype 5 (mGlu5 receptor). Of the two geometric isomers of ABP688, (E)-ABP688 has a greater affinity towards mGlu5 receptors than (Z)-ABP688. Therefore, a high ratio of E-isomer is required when using [(11)C]ABP688 as a PET probe for imaging and quantification of mGlu5 receptors. The aim of this study was to evaluate the effect (Z)-[(11)C]ABP688 on the synthesis of [(11)C]ABP688 to be used for binding (E)-[(11)C]ABP688 in the brain.
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Efficacy and safety of sitagliptin as add-on therapy on glycemic control and blood glucose fluctuation in Japanese type 2 diabetes subjects ongoing with multiple daily insulin injections therapy.
Endocr. J.
PUBLISHED: 08-03-2013
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To assess the efficacy and safety of adding sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, in subjects with type 2 diabetes inadequately controlled with multiple daily insulin injections therapy (MDI). HbA1c, 1,5-anhydroglucitol (1,5-AG), body mass index (BMI), insulin doses, six-point self-measured plasma glucose (SMPG) profiles were assessed before, after 12 weeks, and after 24 weeks of MDI with 50 mg/day of sitagliptin in 40 subjects with type 2 diabetes. Safety endpoints included hypoglycemia and any adverse events. HbA1c significantly decreased during the first 12 weeks ( -0.64±0.60%), and was sustained over 24 weeks ( -0.69±0.85%). 1,5-AG increased significantly from 7.5±4.5 ?g/mL at baseline to 9.6±5.5 ?g/mL after 24 weeks. The bolus insulin dose at 12 weeks was decreased, and the mean plasma glucose, the SD of daily glucose, M-value, and the mean amplitude of glycemic excursions (MAGE) also decreased significantly as compared with baseline values. BMI and frequency of hypoglycemia were not changed significantly. Univariate linear regression analyses revealed that % change in HbA1c was significantly associated with BMI, and % changes in the indexes of glycemic instability (SD of daily glucose and MAGE) were significantly associated with age. In conclusion, adding sitagliptin to MDI significantly improved glycemic control and decreased the daily glucose fluctuation in subjects with type 2 diabetes inadequately controlled with MDI, without weight gain or an increase in the incidence of hypoglycemia. This trial was registered with UMIN (no. UMIN000010157).
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Usefulness of an inflammation-based prognostic score (mGPS) for predicting survival in patients with unresectable malignant biliary obstruction.
World J Surg
PUBLISHED: 05-10-2013
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An inflammation-based prognostic score, the modified Glasgow Prognostic Score (mGPS), has been established as a useful tool for predicting postoperative outcome in patients with cancer. However, no studies have investigated the usefulness of the mGPS for prognostication in patients undergoing palliative surgery for unresectable malignant biliary obstruction (UMBO). The present study was conducted to investigate whether the mGPS is useful for predicting the postoperative survival of patients undergoing intraoperative placement of an expandable metal stent for UMBO, or not.
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Synthesis and evaluation of 1-[2-(4-[(11)C]methoxyphenyl)phenyl]piperazine for imaging of the serotonin 5-HT7 receptor in the rat brain.
Bioorg. Med. Chem.
PUBLISHED: 04-24-2013
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1-[2-(4-Methoxyphenyl)phenyl]piperazine (4) is a potent serotonin 5-HT7 receptor antagonist (Ki=2.6nM) with a low binding affinity for the 5-HT1A receptor (Ki=476nM). As a potential positron emission tomography (PET) radiotracer for the 5-HT7 receptor, [(11)C]4 was synthesized at high radiochemical yield and specific activity, by O-[(11)C]methylation of 2-(piperazin-1-yl)-[1,1-biphenyl]-4-ol (6) with [(11)C]methyl iodide. Autoradiography revealed that [(11)C]4 showed in vitro specific binding with 5-HT7 in the rat brain regions, such as the thalamus which is a region with high 5-HT7 expression. Metabolite analysis indicated that intact [(11)C]4 in the brain exceeded 90% of the radioactive components at 15min after the radiotracer injection, although two radiolabeled metabolites were found in the rat plasma. The PET study of rats showed moderated uptake of [(11)C]4 in the brain (1.2SUV), but no significant regional difference in radioactivity in the brain. Pretreatment with 5-HT7-selective antagonist SB269970 (3) did not decrease the uptake of [(11)C]4 in the rat brain. Further studies are warranted that focus on the development of PET ligand candidates with higher binding affinity for 5-HT7 and higher in vivo stability in brain than 4.
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Effect of billroth II or Roux-en-Y reconstruction for the gastrojejunostomy on delayed gastric emptying after pancreaticoduodenectomy: a randomized controlled study.
Ann. Surg.
PUBLISHED: 04-13-2013
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Delayed gastric emptying (DGE) is one of the major complications after pancreaticoduodenectomy (PD), occurring in 14% to 61% of cases. There have been no studies that compare the incidence of DGE in terms of the reconstruction method of gastrojejunostomy performed in subtotal stomach-preserving pancreaticoduodenectomy (SSPPD). The objective of this study was to evaluate the superiority of Billroth II (B-II) to Roux-en Y (R-Y) reconstruction on decreasing the incidence of delayed gastric emptying DGE after SSPPD by a prospective randomized controlled trial.
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An association study of the Hermansky-Pudlak syndrome type 4 gene in schizophrenic patients.
Psychiatr. Genet.
PUBLISHED: 04-09-2013
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We encountered two Japanese siblings who had Hermansky-Pudlak syndrome (HPS) and major mental disorders (schizophrenia and major depression) as well. As it is known that HPS is caused by a local mutation in one of the human genes, named HPS1 to HPS8 and PLDN (HPS9), encoding subunit proteins involved in endosomal trafficking pathways, here, we report the mutation causing the siblings disease and a case-control association study of schizophrenia using polymorphisms of a gene to be screened in the mutation analysis.
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Frequent alteration of the protein synthesis of enzymes for glucose metabolism in hepatocellular carcinomas.
J. Gastroenterol.
PUBLISHED: 04-04-2013
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Cancer cells show enhanced glycolysis and inhibition of oxidative phosphorylation, even in the presence of sufficient oxygen (aerobic glycolysis). Glycolysis is much less efficient for energy production than oxidative phosphorylation, and the reason why cancer cells selectively use glycolysis remains unclear.
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Survival after surgery for hepatocellular carcinoma in relation to presence or absence of viral infection.
Am. J. Surg.
PUBLISHED: 03-30-2013
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The aim of this study was to compare postoperative survival between hepatocellular carcinoma (HCC) patients with and without viral infection.
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Activation of hypoxia-inducible factor-1 in pulmonary arterial smooth muscle cells by endothelin-1.
Am. J. Physiol. Lung Cell Mol. Physiol.
PUBLISHED: 02-15-2013
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Numerous cellular responses to hypoxia are mediated by the transcription factor hypoxia-inducible factor-1 (HIF-1). HIF-1 plays a central role in the pathogenesis of hypoxic pulmonary hypertension. Under certain conditions, HIF-1 may utilize feedforward mechanisms to amplify its activity. Since hypoxia increases endothelin-1 (ET-1) levels in the lung, we hypothesized that during moderate, prolonged hypoxia ET-1 might contribute to HIF-1 signaling in pulmonary arterial smooth muscle cells (PASMCs). Primary cultures of rat PASMCs were treated with ET-1 or exposed to moderate, prolonged hypoxia (4% O(2) for 60 h). Levels of the oxygen-sensitive HIF-1? subunit and expression of HIF target genes were increased in both hypoxic cells and cells treated with ET-1. Both hypoxia and ET-1 also increased HIF-1? mRNA expression and decreased mRNA and protein expression of prolyl hydroxylase 2 (PHD2), which is the protein responsible for targeting HIF-1? for O(2)-dependent degradation. The induction of HIF-1? by moderate, prolonged hypoxia was blocked by BQ-123, an antagonist of ET-1 receptor subtype A. The effects of ET-1 were mediated by increased intracellular calcium, generation of reactive oxygen species, and ERK1/2 activation. Neither ET-1 nor moderate hypoxia induced the expression of HIF-1? or HIF target genes in aortic smooth muscle cells. These results suggest that ET-1 induces a PASMC-specific increase in HIF-1? levels by upregulation of HIF-1? synthesis and downregulation of PHD2-mediated degradation, thereby amplifying the induction of HIF-1? in PASMCs during moderate, prolonged hypoxia.
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Impact of antibody to hepatitis B core antigen on the clinical course of hepatitis C virus carriers in a hyperendemic area in Japan: A community-based cohort study.
Hepatol. Res.
PUBLISHED: 01-14-2013
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AIM: Subjects positive for antibody to hepatitis B core antigen (HBcAb) and negative for hepatitis B surface antigen (HBsAg) are considered to have occult hepatitis B virus (HBV) infection. The aim of this study was to determine the impact of occult HBV infection on aggravation of the clinical course in hepatitis C virus (HCV) carriers. METHODS: A prospective cohort study was performed in 400 subjects who were positive for anti-HCV antibody and negative for HBsAg. Among these subjects, 263 were HCV core antigen positive or HCV RNA positive (HCV carriers). We examined whether the presence of HBcAb affected the clinical course in these HCV carriers from 1996-2005. RESULTS: The HBcAb positive rates were 53.6% and 52.6% in HCV carriers and HCV RNA negative subjects, respectively. There were no differences in the incidence of hepatocellular carcinoma (HCC) and cumulative mortality associated with liver-related death between HCV carriers who were positive and negative for HBcAb. In multivariate analysis, age (?65 years) and alanine aminotransferase level (?31?IU/L) emerged as independent risk factors for HCC development and liver-related death, but the HBcAb status was not a risk factor. In addition, increased serum hepatic fibrosis markers (measured from 2001-2004) were not associated with HBcAb status. CONCLUSION: In our cohort study, the presence of HBcAb had no impact on HCC development, liver-related death and hepatic fibrosis markers in HCV carriers. Thus, our results indicate that occult HBV infection has no impact on the clinical course in HCV carriers.
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Vascular remodeling in pulmonary hypertension.
J. Mol. Med.
PUBLISHED: 01-08-2013
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Pulmonary hypertension is a complex, progressive condition arising from a variety of genetic and pathogenic causes. Patients present with a spectrum of histologic and pathophysiological features, likely reflecting the diversity in underlying pathogenesis. It is widely recognized that structural alterations in the vascular wall contribute to all forms of pulmonary hypertension. Features characteristic of the remodeled vasculature in patients with pulmonary hypertension include increased stiffening of the elastic proximal pulmonary arteries, thickening of the intimal and/or medial layer of muscular arteries, development of vaso-occlusive lesions, and the appearance of cells expressing smooth muscle-specific markers in normally non-muscular small diameter vessels, resulting from proliferation and migration of pulmonary arterial smooth muscle cells and cellular transdifferentiation. The development of several animal models of pulmonary hypertension has provided the means to explore the mechanistic underpinnings of pulmonary vascular remodeling, although none of the experimental models currently used entirely replicates the pulmonary arterial hypertension observed in patients. Herein, we provide an overview of the histological abnormalities observed in humans with pulmonary hypertension and in preclinical models and discuss insights gained regarding several key signaling pathways contributing to the remodeling process. In particular, we will focus on the roles of ion homeostasis, endothelin-1, serotonin, bone morphogenetic proteins, Rho kinase, and hypoxia-inducible factor 1 in pulmonary arterial smooth muscle and endothelial cells, highlighting areas of cross-talk between these pathways and potentials for therapeutic targeting.
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Contribution of bone marrow-derived hematopoietic stem/progenitor cells to the generation of donor-marker? cardiomyocytes in vivo.
PLoS ONE
PUBLISHED: 01-01-2013
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Definite identification of the cell types and the mechanism relevant to cardiomyogenesis is essential for effective cardiac regenerative medicine. We aimed to identify the cell populations that can generate cardiomyocytes and to clarify whether generation of donor-marker(+) cardiomyocytes requires cell fusion between BM-derived cells and recipient cardiomyocytes.
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Clinical features and outcomes of 35 disseminated intravascular coagulation cases treated with recombinant human soluble thrombomodulin at a single institution.
J Clin Exp Hematop
PUBLISHED: 11-23-2011
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Disseminated intravascular coagulation (DIC) is a clinical entity with high mortality and is characterized by multiple organ failure caused by activation of systemic intravascular coagulation. Although a standard treatment for DIC has not been established owing to the absence of randomized controlled trials, recent reports have indicated that recombinant human soluble thrombomodulin (rTM) is effective against DIC. To elucidate the clinical characteristics and outcomes of DIC, we retrospectively analyzed 35 DIC patients treated with rTM at our institution over a 2-year period (infectious disease: 21 cases; hematological disease: 14 cases). Diagnosis of DIC was based on the diagnostic criteria for DIC of the Japanese Ministry of Health and Welfare. In addition to the treatment of underlying diseases, we administered rTM for 6 consecutive days. Twenty-one (60.0%) of the DIC patients attained resolution of DIC at 7 days after administration (infectious disease: 61.9%; hematological disease: 57.1%). Furthermore, 7 of the remaining 14 DIC patients (who did not attain resolution at 7 days) attained resolution at an average of 12.1 days. Consequently, 28 (80.0%) of the 35 patients were alive with resolution of DIC after a 28-day observation period (infectious disease: 76.2%; hematological disease: 85.7%). Among them, for 7 (70%) of the 10 DIC patients with severe life-threatening bleeding symptoms without hemorrhagic shock, treatment with heparin was contraindicated; these patients were successfully treated with rTM without the progression of hemorrhage. In the majority of DIC patients, rTM administration may be an effective, safe, and feasible therapeutic modality producing a good outcome.
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Early diagnosis and surgical revascularization for a predictive case of moyamoya disease in a boy born to a moyamoya mother.
J. Child Neurol.
PUBLISHED: 11-22-2011
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Among patients with moyamoya disease, familial occurrence is observed in about 20%, suggesting the involvement of genetic factors. In this report, we describe the first predictive case of moyamoya disease in a boy born to a woman who underwent surgical revascularization for moyamoya disease when she was 3 years old. We educated the mother and her family not to miss his initial signs of the disease. His family could easily notice his brief episode of ischemic attack when he was 6 years old. He underwent superficial temporal artery-to-middle cerebral artery anastomosis and indirect bypass on both sides. The postoperative course was uneventful. In conclusion, it is quite important to educate the family not to miss the initial signs of disease in their offspring, at least when they have a genetic background of the disease, because early diagnosis and effective treatment are essential to improve the long-term outcome in pediatric patients.
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A critical role for the protein apoptosis repressor with caspase recruitment domain in hypoxia-induced pulmonary hypertension.
Circulation
PUBLISHED: 11-14-2011
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Pulmonary hypertension (PH) is a lethal syndrome associated with the pathogenic remodeling of the pulmonary vasculature and the emergence of apoptosis-resistant cells. Apoptosis repressor with caspase recruitment domain (ARC) is an inhibitor of multiple forms of cell death known to be abundantly expressed in striated muscle. We show for the first time that ARC is expressed in arterial smooth muscle cells of the pulmonary vasculature and is markedly upregulated in several experimental models of PH. In this study, we test the hypothesis that ARC expression is essential for the development of chronic hypoxia-induced PH.
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Establishment of a prolonged pancreas preservation model for islet isolation research in mice.
Islets
PUBLISHED: 11-03-2011
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Establishing a prolonged pancreas preservation model in a small animal is important for islet isolation research. Use of a rat pancreas model has been reported, but no published reports have used a mouse pancreas for prolonged cold preservation prior to islet isolation. For the model, a mouse is preferred over a rat because of its small size, well-known immune characterization, and variety of gene-modulated models. In the present study, we established a prolonged pancreas preservation model in a mouse for islet isolation research. The collagenase solution was injected successfully after 24 and 48 h cold preservations in University of Wisconsin solution, and islets could be isolated from both groups of preserved pancreata. The islet yields from the control, 24 h preserved, and 48 h preserved pancreata were 183.9 ± 13.9, 128.5 ± 15.5, and 24.6 ± 12.9 per pancreas, respectively. The propidium iodide-positive area assay was significantly increased in both preserved groups, and insulin secretion levels in response to 20.0 mM glucose and stimulation indices were significantly decreased in the 48 h preserved group. Inflammation-related genes mRNA levels were significantly upregulated in the 24 h preserved group, as previously shown in the human model. Thus, this model might be useful for prehuman islet isolation screening research, reserving research using human pancreata for the most promising approaches.
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[A case of hemifacial spasm in a juglar foramen tumor patient treated by microvascular decompression].
No Shinkei Geka
PUBLISHED: 11-01-2011
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Hemifacial spasm is a movement disorder characterized by involuntary paroxysmal chronic contractions of the facial musculature. The usual cause is simple vascular compression of the facial nerve, at its root exit zone of the brain stem. Previously only a case of hemifacial spasm associated with a juglar foramen tumor has been reported in the literature. In this article, we report a case in which hemifacial spasm accompanied an ipsilateral juglar foramen tumor in a 62-year-old woman. The sole use of arterial decompression of the facial nerve at the root exit zone resulted in complete resolution of the patients symptoms.
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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.