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Find video protocols related to scientific articles indexed in Pubmed.
A phase I study of TRC105 anti-CD105 (endoglin) antibody in metastatic castration-resistant prostate cancer.
BJU Int.
PUBLISHED: 11-03-2014
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? TRC105 is a chimeric IgG1 monoclonal antibody that binds endoglin (CD105). ? This phase I open-label study evaluated the safety, pharmacokinetics, and pharmacodynamics of TRC105 in patients with metastatic castration-resistant prostate cancer (mCRPC).
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Cynandione A attenuates lipopolysaccharide-induced production of inflammatory mediators via MAPK inhibition and NF-?B inactivation in RAW264.7 macrophages and protects mice against endotoxin shock.
Exp. Biol. Med. (Maywood)
PUBLISHED: 11-02-2014
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Cynanchum wilfordii has been traditionally used in eastern Asia for the treatment of various diseases such as gastrointestinal diseases and arteriosclerosis. Cynandione A (CA), an acetophenone, is one of major constituents from roots of C. wilfordii. In the present study, the anti-inflammatory activities of CA were investigated in lipopolysaccharide (LPS)-treated RAW264.7 macrophages and LPS-administered C57BL/6?N mice. CA significantly decreased LPS-induced production of nitric oxide and prostaglandin E2 in a dose-dependent manner, while CA up to 200??M did not exhibit cytotoxic activity. Our data also showed that CA significantly attenuated expression of iNOS and COX-2 in LPS-stimulated macrophages. CA inhibited phosphorylation of I?B-? and MAP kinases such as ERK and p38. Furthermore, we demonstrated that CA inhibited translocation of NF-?B to the nucleus, transcription of the NF-?B minimal promoter and NF-?B DNA binding activity. Administration of CA significantly decreased the plasma levels of pro-inflammatory cytokines such as TNF-?, IL-6, and IL-1? in LPS-injected mice and improved survival of septic mice with lethal endotoxemia. These results demonstrate that CA has effective inhibitory effects on production of inflammatory mediators via suppressing activation of NF-?B and MAPK signaling pathways, suggesting that CA may be used as a potential anti-inflammatory agent for the prevention and treatment of inflammatory diseases.
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Correlation between the size of the solid component on thin-section CT and the invasive component on pathology in small lung adenocarcinomas manifesting as ground-glass nodules.
J Thorac Oncol
PUBLISHED: 09-27-2014
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We aimed to evaluate the correlation between the size of the solid component on thin-section computed tomography (CT) and invasive component on pathology in small lung adenocarcinomas manifesting as subsolid nodules.
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Positron emission tomography/magnetic resonance imaging evaluation of lung cancer: current status and future prospects.
J Thorac Imaging
PUBLISHED: 09-10-2014
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Various designs of positron emission tomography/magnetic resonance imaging (PET/MRI) systems have been recently introduced to clinical practice, which have overcome preexisting technical challenges concerning the fusion of PET and MRI systems. Although further improvements are still necessary especially for bony lesions, quantification using current MRI-based attenuation correction techniques has been shown to be comparable to that of PET/computed tomography (CT) systems. On the basis of the results of previous whole-body MRI studies, PET/MRI is expected to show even better performance than PET/CT in M-staging especially for brain and liver metastases. Another advantage of PET/MRI over PET/CT, in addition to good soft tissue contrast, is the potential reduction in radiation dose. The next important hurdle to overcome for its clinical application is the development of time-efficient protocols for lung cancer evaluation and interpretation of discordant results from both modalities. Multiparametric imaging through PET/MRI will help radiologists better understand tumor biology and better evaluate treatment response.
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A Phase I/II Trial of Belinostat in Combination with Cisplatin, Doxorubicin, and Cyclophosphamide in Thymic Epithelial Tumors: A Clinical and Translational Study.
Clin. Cancer Res.
PUBLISHED: 09-04-2014
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This phase I/II study sought to determine the safety and maximum tolerated dose (MTD) of a novel schedule of belinostat, a histone deacetylase inhibitor (HDAC) administered before and in combination with cisplatin (P), doxorubicin (A), and cyclophosphamide (C) in thymic epithelial tumors (TET). Antitumor activity, pharmacokinetics, and biomarkers of response were also assessed.
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Neuroinflammatory and Amyloidogenic Activities of IL-32? in Alzheimer's Disease.
Mol. Neurobiol.
PUBLISHED: 08-27-2014
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Interleukin (IL)-32? can act as either pro-inflammatory or anti-inflammatory cytokines with being dependent on the status of disease development. Herein, we investigated whether IL-32? overexpression changes cytokine levels and affects amyloid-beta (A?)-induced pro-inflammation in the brain. IL-32? transgenic (Tg) mice and non-Tg mice were intracerebroventricularly infused with A?1-42 once a day for 14 days, and then cognitive function was assessed by the Morris water maze test and passive avoidance test. Our data showed that IL-32? Tg mice increased memory impairment, glia activation, amyloidogenesis, and neuroinflammation. The expression of glial fibrillary acid protein (GFAP), Iba1, and ?-secretase 1 (BACE1) in the cortex and hippocampus was much higher in the A?1-42-infused IL-32? Tg mice brain. The activation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappa B (NF-?B) was much higher in A?1-42-infused IL-32? Tg mice brain. We also found that cytokines including IP-10, GM-CSF, JE, IL-13, and interferone-inducible T cell ? chemoattractant (I-TAC) were elevated in A?1-42-infused IL-32? Tg mice brain. These results suggest that IL-32? could activate NF-?B and STAT3, and thus affect neuroinflammation as well as amyloidogenesis, leading to worsening memory impairment.
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Shp/Npas2 axis in regulating the oscillation of liver lipid metabolism.
Hepatology
PUBLISHED: 08-06-2014
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In mammals, circadian rhythms are essential for coordinating the timing of various metabolic processes. The Clock gene regulates diurnal plasma triglyceride fluctuation through nuclear receptor small heterodimer partner (Shp, Nr0b2). Given that SHP is a critical regulator of metabolism in the liver, it is unknown whether SHP is necessary to coordinate metabolism and circadian rhythms. Methods: Shp(+/+) and Shp(-/-) mice on a C57BL/6 background (n=3-5/group) were fed a standard chow diet and water ad libitum. Serum and livers were collected at zeitgeber time (ZT) 2, 6, 10, 14, 18 and 22. In vivo and in vitro assays include: RNA-sequencing (RNA-seq), qPCR, VLDL production, adenovirus overexpression and siRNA knockdown, serum parameters, circadian locomotor activity, oil-red O staining, transient transfection, luciferase reporter assay, ChIP assay, gel-shift assay, Co-IP, Western blots. Results: Shp-deficiency had a robust global impact on major liver metabolic genes. Several components of the liver clock including Pgc-1?, Npas2 and Ror?/? were sharply induced in Shp(-/-) liver. At the molecular level, SHP inhibited Npas2 gene transcription and promoter activity through interaction with Ror? to repress Ror? transactivation and by interacting with Rev-erb? to enhance its inhibition of Ror? activity. Conversely, Npas2 controlled the circadian rhythm of Shp expression by binding rhythmically to the Shp promoter, which was enhanced by NADH, but not NADPH. Phenotypically, Npas2-deficiency induced severe steatosis in Shp(-/-) mice, which was attributed to the dysregulation of lipoprotein metabolism. Conclusion: Shp and Npas2 crosstalk is essential to maintain hepatic lipid homeostasis. (Hepatology 2014).
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Cynandione A from Cynanchum wilfordii attenuates the production of inflammatory mediators in LPS-induced BV-2 microglial cells via NF-?B inactivation.
Biol. Pharm. Bull.
PUBLISHED: 08-05-2014
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Cynanchum wilfordii is one of most widely used medicinal plants in Oriental medicine for the treatment of various conditions. In the present study, we isolated cynandione A (CA) from an extract of Cynanchum wilfordii roots (CWE) and investigated the effects of CA on the expression of inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines in lipopolysaccharide (LPS)-induced BV-2 microglial cells. CWE and CA significantly decreased LPS-induced nitric oxide production and the expression of iNOS in a concentration-dependent manner, while they (CWE up to 500 µg/mL and CA up to 80 µM) did not exhibit cytotoxic activity. Results from reverse transcription-polymerase chain reaction (RT-PCR) analysis and enzyme-linked immunosorbent assay (ELISA) showed that CA significantly attenuated the expression of tumor necrosis factor-alpha (TNF-?), interleukin-6 (IL-6), and IL-1? in LPS-stimulated BV-2 cells. Furthermore, CA inhibited the phosphorylation of inhibitor kappa B-alpha (I?B-?) and translocation of nuclear factor-kappa B (NF-?B) to the BV-2 cell nucleus, indicating that CWE and CA may have effective anti-inflammatory activities via NF-?B inactivation in stimulated microglial cells.
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Identification of orai1 channel inhibitors by using minimal functional domains to screen small molecule microarrays.
Chem. Biol.
PUBLISHED: 08-03-2014
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Store-operated calcium (SOC) channels are vital for activation of the immune cells, and mutations in the channel result in severe combined immunodeficiency in human patients. In lymphocytes, SOC entry is mediated by the Orai1 channel, which is activated by direct binding of STIM1. Here we describe an alternative approach for identifying inhibitors of SOC entry using minimal functional domains of STIM1 and Orai1 to screen a small-molecule microarray. This screen identified AnCoA4, which inhibits SOC entry at submicromolar concentrations and blocks T cell activation in vitro and in vivo. Biophysical studies revealed that AnCoA4 binds to the C terminus of Orai1, directly inhibiting calcium influx through the channel and also reducing binding of STIM1. AnCoA4, unlike other reported SOC inhibitors, is a molecule with a known binding site and mechanism of action. These studies also provide proof of principle for an approach to ion channel drug discovery.
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Computerized texture analysis of persistent part-solid ground-glass nodules: differentiation of preinvasive lesions from invasive pulmonary adenocarcinomas.
Radiology
PUBLISHED: 08-01-2014
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To retrospectively investigate the value of computerized three-dimensional texture analysis for differentiation of preinvasive lesions from invasive pulmonary adenocarcinomas (IPAs) that manifest as part-solid ground-glass nodules (GGNs).
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Value of temporary stents for the management of perivaterian perforation during endoscopic retrograde cholangiopancreatography.
World J Clin Cases
PUBLISHED: 07-28-2014
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Endoscopic retrograde cholangiopancreatography (ERCP) has become the mainstay of treatment in hepato-pancreato-biliary disease. However, ERCP requires a high level of technical skills and experience in therapeutic endoscopy, there is always a risk of complications. Especially, the perforation per se affects the patient adversely, and the clinical course may lead to a poor prognosis, even with appropriate management. The treatments for ERCP-related perforation are diverse, depending on the location and mechanism of the bowel perforation and the time of diagnosis. Thus, we reviewed the appropriate surgical and non-surgical management options for therapeutic ERCP-related perforations, especially, evaluating metallic stenting as a treatment modality in perivaterian perforation.
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Organ-specific distribution of gold nanoparticles by their surface functionalization.
J Appl Toxicol
PUBLISHED: 07-14-2014
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The behavior and fate of intravenously (i.v.) injected nanoparticles (NPs) can be controlled by several physicochemical factors including size, shape and surface charge. To evaluate the role of surface charge on distribution of NPs, we used neutral-charged 15-nm-sized polyethylene glycol-coated gold nanoparticles (AuNPPEG ) as a core NP and carboxyl or amine groups were conjugated to AuNPPEG to generate negative (AuNPCOOH ) or positive AuNP (AuNPNH2 ), respectively. Each type of AuNP was i.v. injected into mice (1?mg?kg(-1) ) and the concentration of Au was measured in different organs at 30?min, 4, 24?h, 7, 14?days, 1, 3 and 6?months post-injection. The organ distribution also showed the higher deposition rate depending on their functional groups: AuNPPEG for mesenteric lymph node, kidney, brain and testis; AuNPCOOH for liver; AuNPNH2 for spleen, lung and heart. The blood circulation time and the major excretion route were different depending on their functional groups. In conclusion, functional groups conjugated on the surface of AuNPs produce differences in blood kinetics, organ distribution and elimination pattern which can be important information for directing NPs to specific organs or improving the kinetic properties. Copyright © 2014 John Wiley & Sons, Ltd.
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A 36 month naturalistic retrospective study of clinic-treated youth with attention-deficit/hyperactivity disorder.
J Child Adolesc Psychopharmacol
PUBLISHED: 06-23-2014
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The purpose of this study was to investigate factors for pharmacotherapy adherence in patients with attention-deficit/hyperactivity disorder (ADHD), with an emphasis on medication possession ratio (MPR).
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Genome-wide identification of nuclear receptor (NR) superfamily genes in the copepod Tigriopus japonicus.
BMC Genomics
PUBLISHED: 06-20-2014
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Nuclear receptors (NRs) are a large superfamily of proteins defined by a DNA-binding domain (DBD) and a ligand-binding domain (LBD). They function as transcriptional regulators to control expression of genes involved in development, homeostasis, and metabolism. The number of NRs differs from species to species, because of gene duplications and/or lineage-specific gene losses during metazoan evolution. Many NRs in arthropods interact with the ecdysteroid hormone and are involved in ecdysone-mediated signaling in arthropods. The nuclear receptor superfamily complement has been reported in several arthropods, including crustaceans, but not in copepods. We identified the entire NR repertoire of the copepod Tigriopus japonicus, which is an important marine model species for ecotoxicology and environmental genomics.
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Volume and mass doubling times of persistent pulmonary subsolid nodules detected in patients without known malignancy.
Radiology
PUBLISHED: 06-14-2014
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To evaluate volume doubling time (VDT) and mass doubling time (MDT) of persistent pulmonary subsolid nodules (SSNs) followed-up with low-dose (LD) computed tomography (CT) in patients without a history of malignancy.
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Holmium Laser Enucleation of the Prostate is Effective in the Treatment of Symptomatic Benign Prostatic Hyperplasia of Any Size Including a Small Prostate.
Korean J Urol
PUBLISHED: 05-29-2014
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Although transurethral resection of the prostate (TURP) is considered the standard surgical treatment for benign prostatic hyperplasia (BPH), Holmium laser enucleation of the prostate (HoLEP) is replacing TURP. We compared TURP with HoLEP with matching for prostate size.
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Pulmonary adenocarcinomas appearing as part-solid ground-glass nodules: Is measuring solid component size a better prognostic indicator?
Eur Radiol
PUBLISHED: 05-15-2014
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To assess whether measuring the solid portion of adenocarcinomas appearing as part-solid ground-glass nodules (GGNs) can predict a patient's prognosis accurately and how the prognosis corresponds to that of solid nodules.
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Reproducibility of histogram and texture parameters derived from intravoxel incoherent motion diffusion-weighted MRI of FN13762 rat breast Carcinomas.
Anticancer Res.
PUBLISHED: 04-30-2014
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To determine the reproducibility of histogram and texture parameters derived from intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (MRI) of FN13762 rat breast carcinomas.
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Detailed analysis of the density change on chest CT of COPD using non-rigid registration of inspiration/expiration CT scans.
Eur Radiol
PUBLISHED: 04-18-2014
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One objective was to evaluate the air trapping index (ATI), measured by inspiration/expiration CT, in COPD patients and nonsmokers. Another objective was to assess the association between the pulmonary function test (PFT) and CT parameters such as ATI or other indices, separately in the whole lung, in emphysema, and in hyperinflated and normal lung areas.
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Morphological and molecular changes associated with Pitchfork during mouse palate development.
Cell Tissue Res.
PUBLISHED: 04-08-2014
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Mammalian palate development is regulated by complex processes. Many cellular and molecular events, such as cell proliferation, apoptosis, cell migration and the epithelial mesenchymal transition, regulate proper palate development and some abnormalities in palate development lead to cleft palate. Various developmental disorders, such as cleft palate and disorders of the lung, kidney and heart, are known to be associated with ciliary defects. Pitchfork, a mouse embryonic node gene, is associated with ciliary targeting complexes located at the basal body during primary cilia disassembly. To determine the function of Pitchfork during palate development, we examine Pitchfork expression patterns and morphological changes in the developing secondary palate after Pitchfork over-expression. From embryonic day 12.5 (E12.5) to E13.5 in mice, Pitchfork was highly expressed in the developing mouse secondary palate. Morphological differences were observed in vitro in cultured palates in the Pitchfork over-expression group compared with the control group. Pitchfork over-expression induced primary cilia disassembly during palate development. Sonic hedgehog and Patched1 expression levels and palatine rugae morphology were altered in the over-expressed Pitchfork group during palate development. Thus, the proper expression levels of Pitchfork might play a pivotal role in normal secondary palate morphogenesis.
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Thoracic cavity segmentation algorithm using multiorgan extraction and surface fitting in volumetric CT.
Med Phys
PUBLISHED: 04-04-2014
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To develop and validate a semiautomatic segmentation method for thoracic cavity volumetry and mediastinum fat quantification of patients with chronic obstructive pulmonary disease.
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Transient subsolid nodules in patients with extrapulmonary malignancies: their frequency and differential features.
Acta Radiol
PUBLISHED: 03-12-2014
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For pulmonary subsolid nodules (SSNs) in patients with extrapulmonary malignancies, it is still unclear what proportion of SSNs is transient and how we can more accurately diagnose these transient SSNs.
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Comparison of sputum and nasopharyngeal swabs for detection of respiratory viruses.
J. Med. Virol.
PUBLISHED: 03-04-2014
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Diagnostic tests for respiratory viral infections use traditionally either nasopharyngeal washes or swabs. Sputum is representative of the lower respiratory tract but is used rarely for viral testing. The aim of this study was to compare the detection rates of respiratory viruses from nasopharyngeal swabs and sputum using a multiplex real-time reverse transcription-polymerase chain reaction (RT-PCR). Adults who were admitted or presented to the clinics of Gil Medical Center with acute respiratory symptoms were recruited from 1 November 2012 to 31 March 2013. Paired specimens of nasopharyngeal swabs and sputum were obtained from 154 subjects, and RNA was extracted and tested for 16 different respiratory viruses using the Anyplex II RV16 Detection kit (Seegene, Seoul, Korea). The positive rate was 53% (81/154) for nasopharyngeal swabs and 68% (105/154) for sputum (P?
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Protective effect of Disporum sessile D.Don extract against UVB-induced photoaging via suppressing MMP-1 expression and collagen degradation in human skin cells.
J. Photochem. Photobiol. B, Biol.
PUBLISHED: 03-04-2014
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In the present study, we report that Disporum sessile D.Don herbal extract (DDE) possesses anti-skin photoaging effect through inhibition of MMP-1 mRNA and protein expression levels and increase collagen production in UVB-irradiated human dermal fibroblast cells (NHDF). To delineate the molecular mechanism by which DDE inhibited MMP-1 expression, immortal human keratinocytes cells (HaCaT) have been used. We have found that DDE inhibited UVB-induced MMP-1 mRNA and protein expression levels in HaCaT cells through inhibition of UVB-induced activation of NF-?B in HaCaT cells. Inhibitors of NF-?B (Bay11-7082), and mitogen-activated protein kinases such as extracellular regulated kinase (PD98059), c-Jun N-terminal kinase (SP600125), and p38 (SB203580) suppressed expression of MMP-1, and phosphorylation of these signaling molecules were attenuated by DDE. DDE also inhibited phosphorylation of IKK? and I?B?, and reduced nuclear translocation of NF-?B. Our results also demonstrated that DDE inhibited NF-?B driven expression of luciferase reporter gene and the DNA binding of NF-?B to its cognate binding site in UV-irradiated cells. Therefore, these results strongly suggest that DDE can be utilized as a potential agent for prevention and treatment of skin photoaging.
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Burnout syndrome in psychotherapists: a comparative analysis of five nations.
Psychol Serv
PUBLISHED: 02-26-2014
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Burnout is a common phenomenon among psychotherapists. The purpose of this study was to test the Counselor Burnout Inventory (CBI; Lee et al., 2007) measurement invariance, as well as compare means of five latent variables (i.e., CBI subscales of Exhaustion, Incompetence, Negative Work Environment, Devaluing Client, and Deterioration in Personal Life) across five nations (United States, Korea, Japan, Philippines, and Hong Kong) using structural equation modeling. The results indicated that the assumptions of configural, factor loading, and intercept invariance were satisfied across the five nations. When comparing means of five latent variables, the results indicated differential burnout tendencies across the five nations. Implications for psychotherapists' burnout prevention and future research are discussed.
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Pigmented villonodular synovitis on lumbar spine : a case report and literature review.
J Korean Neurosurg Soc
PUBLISHED: 02-24-2014
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Pigmented villonodular synovitis (PVNS) is a benign proliferative joint disease with an uncertain etiology that uncommonly involves the spine. We present a case of PVNS involving the lumbar spine. A 38-year-old male developed back pain and pain in both legs caused by a mass in the L4 region of the right lamina. After gross total tumor removal, the symptoms improved. The pathological finding was synovial hyperplasia with accumulation of hemosiderin-laden macrophages. He was diagnosed with PVNS and experienced no recurrence for up to 2 years after surgery. In this report, we review the previous literature and discuss etiology, clinical manifestations, diagnosis, and treatment.
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Efficacy of bronchoscopic lung volume reduction by endobronchial valves in patients with heterogeneous emphysema: report on the first asian cases.
J. Korean Med. Sci.
PUBLISHED: 02-24-2014
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Although many patients with severe emphysema have benefited from bronchoscopic lung volume reduction (BLVR) worldwide, experience of BLVR in Asian emphysema patients is scarce. Between July 2012 and March 2013, seven patients with advanced heterogeneous emphysema underwent BLVR in the Asan Medical Center. They had severe dyspnea and poor lung function (Modified Medical Research Council dyspnea scale 3-4; median forced expiratory volume in 1 sec [FEV1], 0.59 L [19.0 % predicted]; median 6-min walk distance [6MWD], 195 m). Endobronchial valves were inserted into the target lobe which was most hyperinflated and least perfused, and had no collateral ventilation with other lobes. Six patients showed clinical improvement after 1 month. Of them, 2 patients improved to dyspnea scale 1 and 4 patients did to scale 2 (P = 0.026). The median FEV1 increased from 0.59 to 0.89 L (51%; P = 0.028) and the median 6MWD increased from 195 to 252 m (29.2%; P = 0.028). Two patients developed a pneumothorax (one requiring drainage) and one patient experienced slight hemoptysis; however, there were no other serious adverse events. BLVR is effective in Asian advanced emphysema patients, with noted clinical improvements in lung function and exercise capacity.
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Effect of sodium butyrate on the assembly, charge variants, and galactosylation of antibody produced in recombinant Chinese hamster ovary cells.
Appl. Microbiol. Biotechnol.
PUBLISHED: 02-04-2014
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Sodium butyrate (NaBu) is known to increase the specific productivity of recombinant Chinese hamster ovary (rCHO) cells. To understand the effects of NaBu on the product quality, rCHO cells producing monoclonal antibody (Mab) were cultivated at various concentrations of NaBu (0 to 4 mM). NaBu increased correctly assembled Mab. In the absence of NaBu, the proportions of intact Mab (2H2L) and heavy chain dimer (2H) were 81 and 15 %. At 1 mM NaBu, the proportion of 2H2L increased to 93 %, whereas the proportion of 2H decreased to 2 %. No further increase in the proportion of 2H2L was obtained at a higher NaBu concentration. NaBu also affected the charge heterogeneity of Mab, which may affect the efficacy of Mab. The basic charge variants of Mabs increased with an increase in the NaBu concentration. In addition, NaBu affected the galactosylation of Mab negatively. Overall, the data obtained here show that NaBu used in rCHO cell cultures for improved Mab production affects certain quality aspects of Mab, in this case, the charge heterogeneity and galactosylation.
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C-arm cone-beam CT-guided percutaneous transthoracic needle biopsy of lung nodules: clinical experience in 1108 patients.
Radiology
PUBLISHED: 01-31-2014
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To retrospectively evaluate the diagnostic performance and complications of C-arm cone-beam computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) in 1108 patients.
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Persistent pulmonary subsolid nodules: model-based iterative reconstruction for nodule classification and measurement variability on low-dose CT.
Eur Radiol
PUBLISHED: 01-29-2014
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To compare the pulmonary subsolid nodule (SSN) classification agreement and measurement variability between filtered back projection (FBP) and model-based iterative reconstruction (MBIR).
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Asymmetric Hsp90 N domain SUMOylation recruits Aha1 and ATP-competitive inhibitors.
Mol. Cell
PUBLISHED: 01-28-2014
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The stability and activity of numerous signaling proteins in both normal and cancer cells depends on the dimeric molecular chaperone heat shock protein 90 (Hsp90). Hsp90's function is coupled to ATP binding and hydrolysis and requires a series of conformational changes that are regulated by cochaperones and numerous posttranslational modifications (PTMs). SUMOylation is one of the least-understood Hsp90 PTMs. Here, we show that asymmetric SUMOylation of a conserved lysine residue in the N domain of both yeast (K178) and human (K191) Hsp90 facilitates both recruitment of the adenosine triphosphatase (ATPase)-activating cochaperone Aha1 and, unexpectedly, the binding of Hsp90 inhibitors, suggesting that these drugs associate preferentially with Hsp90 proteins that are actively engaged in the chaperone cycle. Importantly, cellular transformation is accompanied by elevated steady-state N domain SUMOylation, and increased Hsp90 SUMOylation sensitizes yeast and mammalian cells to Hsp90 inhibitors, providing a mechanism to explain the sensitivity of cancer cells to these drugs.
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Is the environment of the endoscopy unit a reservoir of pathogens?
Intest Res
PUBLISHED: 01-25-2014
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Given the characteristic procedures involved in the endoscopy unit, the spread of pathogens is much more frequent in this unit than in other environments. However, there is a lack of data elucidating the existence of pathogens in the endoscopy unit. The aim of this study was to detect the presence of possible pathogens in the endoscopy unit.
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Influence of radiation dose and iterative reconstruction algorithms for measurement accuracy and reproducibility of pulmonary nodule volumetry: A phantom study.
Eur J Radiol
PUBLISHED: 01-24-2014
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To evaluate the influence of radiation dose settings and reconstruction algorithms on the measurement accuracy and reproducibility of semi-automated pulmonary nodule volumetry.
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Longitudinal Analysis of Academic Burnout in Korean Middle School Students.
Stress Health
PUBLISHED: 01-24-2014
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The purpose of the study was to investigate the longitudinal relationships between the initial values and slopes of three dimensions of burnout syndrome (i.e. emotional exhaustion, cynicism and academic inefficacy). The study utilized four-wave longitudinal data from a total of 367 (81.6% response rate) middle school students in South Korea. Comprising a 6-month interval survey, the first survey was conducted in June 2010, the second in December 2010, the third in June 2011 and the fourth in December 2011. All participants were 13-year-olds at the first and second surveys, and 14-year-olds at the third and fourth surveys. The Maslach Burnout Inventory-Student Survey was used for each survey to assess the level of academic burnout. The longitudinal data were analysed using latent growth modelling. The results of the study indicated that high initial values (intercept) for emotional exhaustion were associated with a higher rate of increase (slope) in cynicism and academic inefficacy. On the other hand, high initial values for cynicism and academic inefficacy were associated with a lower rate of increase in the other dimensions. This longitudinal study should promote understanding of burned-out students and contribute to the literature by informing the design of prevention programmes for academic burnout. Copyright © 2014 John Wiley & Sons, Ltd.
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Success rate and risk factors for failure of empirical antifungal therapy with itraconazole in patients with hematological malignancies: a multicenter, prospective, open-label, observational study in Korea.
J. Korean Med. Sci.
PUBLISHED: 01-17-2014
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We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462).
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Cixutumumab for patients with recurrent or refractory advanced thymic epithelial tumours: a multicentre, open-label, phase 2 trial.
Lancet Oncol.
PUBLISHED: 01-15-2014
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No standard treatment exists for refractory or relapsed advanced thymic epithelial tumours. We investigated the efficacy of cixutumumab, a fully human IgG1 monoclonal antibody targeting the insulin-like growth factor 1 receptor in thymic epithelial tumours after failure of previous chemotherapy.
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Assessment of perfusion pattern and extent of perfusion defect on dual-energy CT angiography: correlations between the causes of pulmonary hypertension and vascular parameters.
Korean J Radiol
PUBLISHED: 01-10-2014
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To assess perfusion patterns on a dual-energy pulmonary CT angiography (DECTA) of pulmonary hypertension (PHT) with variable causes and to assess whether the extent of perfusion defect can be used in the severity assessment of PHT.
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Early response-based intensification of primary therapy in newly diagnosed multiple myeloma patients who are eligible for autologous stem cell transplantation: phase II study.
Ann. Hematol.
PUBLISHED: 01-09-2014
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This phase II study prospectively evaluated the efficacy and tolerability of an early change in induction therapy before autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients who failed to achieve more than a partial response (PR) after two cycles of a cyclophosphamide, thalidomide, and dexamethasone (CTD) regimen. Patients aged 18-65 years received two cycles of CTD therapy, and then the patients who achieved more than a PR received two additional cycles of CTD therapy, while those who failed to achieve more than a PR were given intensified therapy with four cycles of a Vel-CD regimen (bortezomib, cyclophosphamide, and dexamethasone). After completing primary chemotherapy, the patients underwent ASCT. This study initially enrolled 64 patients, although four were excluded. Of the patients, 60 were treated with CTD regimen and 8 patients also had the intensified Vel-CD regimen, of whom five showing improved responses. The overall response rate before ASCT in 59 patients was 94.9 %, including 27.1 % with a stringent complete response/complete response, 23.7 % with a very good partial response (VGPR), and 44.1 % with a PR. The median time to progression (TTP) was 33.2 months (95 % CI, 26.6-34.8). Patients who attained a VGPR or better after ASCT tended to have a longer TTP than the patients who did not (not reached vs. 24.2 months, P?=?0.04). In conclusion, early response-adapted intensification with a Vel-CD regimen was a well-tolerated, effective strategy for improving the response before ASCT in patients with newly diagnosed MM.
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Inhibitory effect of ent-Sauchinone on amyloidogenesis via inhibition of STAT3-mediated NF-?B activation in cultured astrocytes and microglial BV-2 cells.
J Neuroinflammation
PUBLISHED: 01-08-2014
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ent-Sauchinone is a polyphenolic compound found in plants belonging to the lignan family. ent-Sauchinone has been shown to modulate the expression of inflammatory factors through the nuclear factor-kappa B (NF-?B) signaling pathway. It is well known that neuroinflammation is associated with amyloidogenesis. Thus, in the present study, we investigated whether ent-Sauchinone could have anti-amyloidogenic effects through the inhibition of NF-?B pathways via its anti-inflammatory property.
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High-throughput screening for the identification of new therapeutic options for metastatic pheochromocytoma and paraganglioma.
PLoS ONE
PUBLISHED: 01-01-2014
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Drug repurposing or repositioning is an important part of drug discovery that has been growing in the last few years for the development of therapeutic options in oncology. We applied this paradigm in a screening of a library of about 3,800 compounds (including FDA-approved drugs and pharmacologically active compounds) employing a model of metastatic pheochromocytoma, the most common tumor of the adrenal medulla in children and adults. The collection of approved drugs was screened in quantitative mode, testing the compounds in compound-titration series (dose-response curves). Analysis of the dose-response screening data facilitated the selection of 50 molecules with potential bioactivity in pheochromocytoma cells. These drugs were classified based on molecular/cellular targets and signaling pathways affected, and selected drugs were further validated in a proliferation assay and by flow cytometric cell death analysis. Using meta-analysis information from molecular targets of the top drugs identified by our screening with gene expression data from human and murine microarrays, we identified potential drugs to be used as single drugs or in combination. An example of a combination with a synergistic effect is presented. Our study exemplifies a promising model to identify potential drugs from a group of clinically approved compounds that can more rapidly be implemented into clinical trials in patients with metastatic pheochromocytoma or paraganglioma.
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Usefulness of texture analysis in differentiating transient from persistent part-solid nodules(PSNs): a retrospective study.
PLoS ONE
PUBLISHED: 01-01-2014
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Early discrimination between transient and persistent par-solid ground-glass nodules (PSNs) at CT is essential for patient management. The objective of our study was to retrospectively investigate the value of texture analysis in differentiating pulmonary transient and persistent PSNs in addition to clinical and CT features.
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Co-culture with NK-92MI cells enhanced the anti-cancer effect of bee venom on NSCLC cells by inactivation of NF-?B.
Arch. Pharm. Res.
PUBLISHED: 01-01-2014
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In the present study we experimented on a multimodal therapeutic approach, such as combining chemotherapy agent (Bee venom) with cellular (NK-92MI) immunotherapy. Previously bee venom has been found to show anti-cancer effect in various cancer cell lines. In lung cancer cells bee venom showed an IC(50) value of 3 ?g/ml in both cell lines. The co-culture of NK-92MI cell lines with lung cancer cells also show a decrease in viability upto 50 % at 48 h time point. Hence we used bee venom treated NK-92MI cells to co-culture with NSCLC cells and found that there is a further decrease in cell viability upto 70 and 75 % in A549 and NCI-H460 cell lines respectively. We further investigated the expression of various apoptotic and anti-apoptotic proteins and found that Bax, cleaved caspase-3 and -8 were increasing where as Bcl-2 and cIAP-2 was decreasing. The expression of various death receptor proteins like DR3, DR6 and Fas was also increasing. Concomitantly the expression of various death receptor ligands (TNFalpha, Apo3L and FasL) was also increasing of NK-92MI cells after co-culture. Further the DNA binding activity and luciferase activity of NF-?B was also inhibited after co-culture with bee venom treated NK-92MI cell lines. The knock down of death receptors with si-RNA has reversed the decrease in cell viability and NF-?B activity after co-culture with bee venom treated NK-92MI cells. Thus this new approach can enhance the anti-cancer effect of bee venom at a much lower concentration.
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Synthesis and structure-activity relationship studies of novel dihydropyridones as androgen receptor modulators.
J. Med. Chem.
PUBLISHED: 10-30-2013
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A library of 3-hydroxy-2,3-dihydropyridones was synthesized, and their activities as antiandrogens were tested in the human prostate cancer cell line LNCaP. Structure-activity relationship (SAR) studies resulted in the identification of a potent compound whose activity is comparable to that of MDV3100. Homology modeling and molecular mechanics were used to build a structural model of the androgen receptor-ligand binding domain and to investigate the structural basis of the antagonism. The model is qualitatively consistent with the observed SAR. Moreover, the enrichment plot shows that screening with the model performs significantly better than random screening. Therefore, the model probably represents a realistic conformation of the antagonist form and can be utilized for structure-based design of novel antiandrogens.
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Digital mRNA profiling of N-glycosylation gene expression in recombinant Chinese hamster ovary cells treated with sodium butyrate.
J. Biotechnol.
PUBLISHED: 09-26-2013
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To understand the effects of sodium butyrate (NaBu) on protein glycosylation, recombinant Chinese hamster ovary (rCHO) cells producing Fc-fusion glycoprotein were subjected to 3mM NaBu. The addition of NaBu to the cultures reduced the relative proportion of acidic isoforms and sialic acid content of the glycoprotein. Fifty-two N-glycosylation-related gene expressions were also assessed by the NanoString nCounter system, which can provide a direct digital readout using custom-designed color-coded probes. Among them, ten genes (ugp, slc35a2, ganc, man1a, man1c, mgat5a, st3gal5, glb1, neu1, and neu3) were up-regulated and three genes (b4galt2, st3gal3, and neu2) were down-regulated significantly. Altered expression patterns in st3gal3, neu1, and neu3, which have roles in the sialic acid biosynthesis pathway, correlated with reduced sialic acid content of the glycoprotein by NaBu. Taken together, the results obtained in this study provide a better understanding of the detrimental effect of NaBu on N-glycosylation in rCHO cells.
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Tumor cells loaded with ?-galactosylceramide promote therapeutic NKT-dependent anti-tumor immunity in multiple myeloma.
Immunol. Lett.
PUBLISHED: 09-17-2013
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Tumor cells have been used as the tumor antigen sources for developing cancer vaccines. Due to their low immunogenicity, tumor antigens are combined with various adjuvants to enhance immunogenicity of cancer vaccines. Among them, a natural killer T cell (NKT)-ligand, ?-galactosylceramide (?GC) has been reported as a powerful adjuvant showing therapeutic effects in solid tumors as well as hematological malignancies including lymphoma. In this study, we applied ?GC-based tumor cell vaccine in mouse multiple myeloma model. The ?GC-loaded MOPC315BM myeloma cell vaccine efficiently retarded tumor growth, induced regression of established tumors, and protected surviving mice from tumor rechallenge. Therapeutic responses were associated with induction of strong humoral immune responses, including myeloma-specific antibodies, and cellular immune responses, including myeloma-specific CD8(+) cytotoxic T lymphocytes and memory T cells. In addition, regulatory T cells were significantly decreased in mice that received the ?GC-loaded myeloma cell vaccine. Thus, our results demonstrated that ?GC-loaded myeloma vaccine efficiently promoted NKT-dependent anti-tumor immunity in a mouse model. These findings are informative for improving the efficacy of tumor-cell-based immunotherapy for patients with MM and other CD1d-expressing tumors.
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The diagnostic sensitivity of dynamic contrast-enhanced magnetic resonance imaging and breast-specific gamma imaging in women with calcified and non-calcified DCIS.
Acta Radiol
PUBLISHED: 09-16-2013
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Early detection of breast cancer reduces mortality. Therefore, diagnosis of ductal carcinoma in situ (DCIS) is important.
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Effect of kVp on image quality and accuracy in coronary CT angiography according to patient body size: a phantom study.
Int J Cardiovasc Imaging
PUBLISHED: 09-08-2013
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The aim is to investigate the effect of tube voltage and chest wall thickness on image quality, stenosis measurement, and radiation dose in coronary CT angiography (CCTA) in a phantom study. A phantom with tubes in a box at its center and concentric cylindrical plastic chambers of three layers at its periphery was constructed. The concentric cylinders were filled with oil or left empty to simulate different degrees of obesity. Retrospective CT scanning was performed at different kVps and mAs. Image noise, contrast to noise ratio (CNR), stenosis measurement, and radiation dose were obtained. A CNR higher than 10 was considered to be acceptable for clinical practice. Mean image noise was 51.7 at 80 kVp, 31.6 at 100 kVp, and 24.7 at 120 kVp (P < 0.001). A CNR greater than 10 could be achieved with all the images using 80 kVp as well as using 100 or 120 kVp. However, CNRs at 100 and 120 kVp were significantly higher than the CNR at 80 kVp (P < 0.001). There were no significant differences between 100 and 120 kVp. All stenosis measurements were overestimated. Accuracy of stenosis measurement was significantly correlated with CNR (P < 0.05), but not with kVps. Mean doses were 2.07 mSv at 80 kVp, 3.37 mSv at 100 kVp, and 5.17 mSv at 120 kVp (P < 0.001). CNR per radiation dose was highest at 80 kVp, regardless of chest wall thickness. For CCTA, using 80 kVp with high mAs is the best choice, regardless of chest wall thickness, for minimal radiation dose and sufficient image quality.
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Experimental direct estimation of nonlinear functionals of photonic quantum states via interferometry with a controlled-swap operation.
Opt Express
PUBLISHED: 08-14-2013
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We propose a multi-photon interferometer with a generalized C-SWAP operation that can estimate Tr[?(1)?(2)···?(n)], a nonlinear functional of n photonic density matrices. The scheme is demonstrated for three single-photon states whose overlap is experimentally measured as the interference visibility of a control qubit encoded into photonic paths. The validity of this method is verified by comparing the visibility with the results of Hong-Ou-Mandel experiments.
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The transcription factor protein Sox11 enhances early osteoblast differentiation by facilitating proliferation and the survival of mesenchymal and osteoblast progenitors.
J. Biol. Chem.
PUBLISHED: 07-25-2013
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Sox11 deletion mice are known to exhibit developmental defects of craniofacial skeletal malformations, asplenia, and hypoplasia of the lung, stomach, and pancreas. Despite the importance of Sox11 in the developing skeleton, the role of Sox11 in osteogenesis has not been studied yet. In this study, we identified that Sox11 is an important transcription factor for regulating the proliferation and survival of osteoblast precursor cells as well as the self-renewal potency of mesenchymal progenitor cells via up-regulation of Tead2. Furthermore, Sox11 also plays an important role in the segregation of functional osteoblast lineage progenitors from osteochondrogenic progenitors. Facilitation of osteoblast differentiation from mesenchymal cells was achieved by enhanced expression of the osteoblast lineage specific transcription factors Runx2 and Osterix. Morpholino-targeted disruption of Sox11 in zebrafish impaired organogenesis, including the bones, which were under mineralized. These results indicated that Sox11 plays a crucial role in the proliferation and survival of mesenchymal and osteoblast precursors by Tead2, and osteogenic differentiation by regulating Runx2 and Osterix.
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Posttranslational modification and conformational state of heat shock protein 90 differentially affect binding of chemically diverse small molecule inhibitors.
Oncotarget
PUBLISHED: 07-23-2013
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Heat shock protein 90 (Hsp90) is an essential molecular chaperone in eukaryotes that facilitates the conformational maturation and function of a diverse protein clientele, including aberrant and/or over-expressed proteins that are involved in cancer growth and survival. A role for Hsp90 in supporting the protein homeostasis of cancer cells has buoyed interest in the utility of Hsp90 inhibitors as anti-cancer drugs. Despite the fact that all clinically evaluated Hsp90 inhibitors target an identical nucleotide-binding pocket in the N domain of the chaperone, the precise determinants that affect drug binding in the cellular environment remain unclear, and it is possible that chemically distinct inhibitors may not share similar binding preferences. Here we demonstrate that two chemically unrelated Hsp90 inhibitors, the benzoquinone ansamycin geldanamycin and the purine analog PU-H71, select for overlapping but not identical subpopulations of total cellular Hsp90, even though both inhibitors bind to an amino terminal nucleotide pocket and prevent N domain dimerization. Our data also suggest that PU-H71 is able to access a broader range of N domain undimerized Hsp90 conformations than is geldanamycin and is less affected by Hsp90 phosphorylation, consistent with its broader and more potent anti-tumor activity. A more complete understanding of the impact of the cellular milieu on small molecule inhibitor binding to Hsp90 should facilitate their more effective use in the clinic.
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Low-dose chest computed tomography with sinogram-affirmed iterative reconstruction, iterative reconstruction in image space, and filtered back projection: studies on image quality.
J Comput Assist Tomogr
PUBLISHED: 07-19-2013
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This study aimed to determine optimal strength of sinogram-affirmed iterative reconstruction (SAFIRE) and to evaluate image quality (IQ) of low-dose chest computed tomography (LDCT) using SAFIRE compared with iterative reconstruction in image space (IRIS) and filtered back projection (FBP).
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A comparison of two commercial volumetry software programs in the analysis of pulmonary ground-glass nodules: segmentation capability and measurement accuracy.
Korean J Radiol
PUBLISHED: 07-17-2013
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To compare the segmentation capability of the 2 currently available commercial volumetry software programs with specific segmentation algorithms for pulmonary ground-glass nodules (GGNs) and to assess their measurement accuracy.
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Pure and part-solid pulmonary ground-glass nodules: measurement variability of volume and mass in nodules with a solid portion less than or equal to 5 mm.
Radiology
PUBLISHED: 07-17-2013
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To prospectively assess and compare the measurement variability of volume and mass for pure and part-solid ground-glass nodules (GGNs) with solid portions less than or equal to 5 mm by using a commercially available volumetric software program.
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Adverse events of non-ablative fractional laser photothermolysis: a retrospective study of 856 treatments in 362 patients.
J Dermatolog Treat
PUBLISHED: 07-11-2013
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Background: Non-ablative fractional laser photothermolysis (NAFP) has been used effectively in the treatment of photodamaged skin and scars, with short post-operative recovery times; but, studies evaluating its adverse events and complication rates in Asian population have been limited. Objective: To determine the frequency and range of adverse events associated with NAFP treatment in Korean patients. Materials and methods: We retrospectively evaluated the outcomes of 754 1550-nm erbium-doped and 102 1927-nm thulium fiber fractional laser treatments in patients with skin phototypes III-IV treated at a single center. Adverse events were identified and tabulated, as were patient demographics and laser parameters. Results: From 856 treatments, there were 43 adverse events (5.0%), the most frequent being prolonged erythema (1.8%), post-inflammatory hyperpigmentation (1.1%) and aggravation of melasma (0.9%). Less frequently observed adverse events included herpes simplex outbreak (0.6%) and acneiform eruption (0.2%). There were no reports of long-term adverse events. Conclusion: Non-ablative fractional laser skin treatment has a relatively low complication rate. The adverse events found were temporary and did not result in long-term or severe sequelae such as hypertrophic scarring, atrophic scarring or permanent pigmentary alteration.
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Automatic reconstruction of the arterial and venous trees on volumetric chest CT.
Med Phys
PUBLISHED: 07-05-2013
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This paper introduces a novel approach to classify pulmonary arteries and veins from volumetric chest computed tomography (CT) images. Although there is known to be a relationship between the alteration of vessel distributions and the progress of various pulmonary diseases, there has been relatively little research on the quantification of pulmonary vessels in vivo due to morphological difficulties. In particular, there have been few efforts to quantify the morphology and distribution of only arteries or veins through automated algorithms despite the clinical importance of such work. In this study, the authors classify different types of vessels by constructing a tree structure from vascular points while minimizing the construction cost using the vascular geometries and features of CT images.
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Promoter methylation status of the FHIT gene and Fhit expression: association with HER2/neu status in breast cancer patients.
Oncol. Rep.
PUBLISHED: 06-18-2013
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Aberrant DNA methylation has been recognized to contribute to breast carcinogenesis, and promoter hypermethylation of several tumor suppressor genes has been correlated with decreased gene expression. The fragile histidine triad (FHIT) gene is a putative tumor suppressor gene in breast and other types of cancer, and loss of Fhit expression has been observed in breast cancer. The aim of the present study was to evaluate the association between methylation of the FHIT gene and its expression in breast cancer, and to investigate whether methylation and expression of the FHIT gene correlates with clinicopathological characteristics in relation to human epidermal growth factor receptor 2 (HER2) status. Pyrosequencing of bisulfite-treated DNA was performed to study the methylation status of the FHIT gene in 60 breast cancer samples. We examined the expression of Fhit using tissue microarrays by immunohistochemical staining. FHIT methylation was detected in 96.7% and the positive expression rate of Fhit was 87.3% of the patients. The mean methylation level of the FHIT gene was associated with intratumoral inflammation. Methylation level of the FHIT gene had no significant differences according to molecular subtypes. Loss of Fhit expression was associated with large tumor size, basal-like subtype and positive expression of EGFR. In HER2-negative breast cancer, loss of Fhit expression was significantly associated with tumor size, estrogen receptor status and Ki-67 proliferation index. No significant correlation between methylation of the FHIT gene and its expression was observed in the present study. Our results suggest that loss of Fhit expression in breast cancer is associated with poor prognostic features, and it is also relevant to the results in HER2-negative breast cancer. Further studies with larger sample sizes and longer follow-up are required to clarify the predictive and prognostic value of Fhit expression and the FHIT gene methylation status in breast cancer.
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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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Tbc1d15-17 regulates synaptic development at the Drosophila neuromuscular junction.
Mol. Cells
PUBLISHED: 05-13-2013
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Members of the Tre-2/Bub2/Cdc16 (TBC) family of proteins are believed to function as GTPase-activating proteins (GAPs) for Rab GTPases, which play pivotal roles in intracellular membrane trafficking. Although membrane trafficking is fundamental to neuronal morphogenesis and function, the roles of TBC-family Rab GAPs have been poorly characterized in the nervous system. In this paper, we provide genetic evidence that Tbc1d15-17, the Drosophila homolog of mammalian Rab7-GAP TBC1d15, is required for normal presynaptic growth and postsynaptic organization at the neuromuscular junction (NMJ). A loss-of-function mutation in Tbc1d15-17 or its presynaptic knockdown leads to an increase in synaptic bouton number and NMJ length. Tbc1d15-17 mutants are also defective in the distribution of the postsynaptic scaffold Discs-large (Dlg) and in the level of the postsynaptic glutamate subunit GluRIIA. These postsynaptic phenotypes are recapitulated by postsynaptic knockdown of Tbc1d15-17. We also show that presynaptic overexpression of a constitutively active Rab7 mutant in a wild-type background causes a synaptic overgrowth phenotype resembling that of Tbc1d15-17 mutants, while a dominant-negative form of Rab7 has the opposite effect. Together, our findings establish a novel role for Tbc1d15-17 and its potential substrate Rab7 in regulating synaptic development.
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Adult T-cell leukemia cells overexpress Wnt5a and promote osteoclast differentiation.
Blood
PUBLISHED: 05-09-2013
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Adult T-cell leukemia/lymphoma (ATL) is etiologically linked to infection with the human T-cell leukemia/lymphoma virus type 1 (HTLV-I). ATL is classified into 4 distinct clinical diseases: acute, lymphoma, chronic, and smoldering. Acute ATL is the most aggressive form, representing 60% of cases and has a 4-year survival of < 5%. A frequent complication and cause of death in acute ATL patients is the presence of lytic bone lesions and hypercalcemia. We analyzed the Wnt/?-catenin pathway because of its common role in cancer and bone remodeling. Our study demonstrated that ATL cells do not express high levels of ?-catenin but displayed high levels of LEF-1/TCF genes along with elevated levels of ?-catenin (LEF-1/TCF target genes) responsive genes. By profiling Wnt gene expression, we discovered that ATL patient leukemia cells shifted expression toward the noncanonical Wnt pathway. Interestingly, ATL cells overexpressed the osteolytic-associated genes-Wnt5a, PTHLH, and RANKL. We further show that Wnt5a secreted by ATL cells favors osteoclast differentiation and expression of RANK. Our results suggest that Wnt5a is a major contributing factor to the increase in osteolytic bone lesions and hypercalcemia found in ATL patients. Anti-Wnt5a therapy may prevent or reduce osteolytic lesions found in ATL patients and improve therapy outcome.
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Liver X receptor activation inhibits osteoclastogenesis by suppressing NF-?B activity and c-Fos induction and prevents inflammatory bone loss in mice.
J. Leukoc. Biol.
PUBLISHED: 05-08-2013
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LXRs are nuclear receptors that function as important regulators of lipid homeostasis and inflammatory responses. LXR activation has been shown to suppress RANKL-induced osteoclast differentiation, but its underlying mechanisms and its influence on inflammatory bone destruction remain unclear. In this study, we report that the LXR agonists T0901317 and GW3965 inhibit osteoclastogenesis from primary BMMs in a dose-dependent manner. LXR activation suppressed RANKL-induced transcriptional activity of NF-?B without affecting I?B? degradation and the phosphorylation of p38. LXR agonists significantly suppressed RANKL-induced expression of c-Fos and NFATc1, which are crucial transcription factors for osteoclastogenesis. The activation of LXRs also inhibited RANKL-mediated AP-1 transcriptional activity. Furthermore, LXR activation attenuated PPAR? ligand-induced c-Fos expression, and LXR suppressed AP-1 promoter activity by PPAR?. The inhibitory effect of LXR activation on osteoclastogenesis was reversed by overexpression of c-Fos, suggesting that c-Fos is a downstream target of the antiosteoclastogenic action of LXRs. In addition to osteoclast differentiation, LXR activation accelerated apoptosis in mature osteoclasts by the induction of caspase-3 and -9 activity and Bim expression. Consistent with the in vitro effects we observed, the administration of a LXR agonist protected from bone loss induced by LPS in vivo. Together, our data provide evidence that LXRs may have potential as therapeutic targets for bone resorption-associated diseases.
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Ultrasonographic evaluation of needle insertion site for the flexor pollicis longus.
Ann Rehabil Med
PUBLISHED: 04-30-2013
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To establish the safest approach to needle electrode insertion into the flexor pollicis longus (FPL) regarding possible needle injury to the superficial radial nerve (SRN) or radial artery by ultrasonography.
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Gait freezing and speech disturbance in Parkinsons disease.
Neurol. Sci.
PUBLISHED: 04-12-2013
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Gait freezing and speech disturbance are disabling axial features of Parkinsons disease (PD). However, the pathogenesis of these features remains unclear. We investigated the relation between changes in gait freezing and speech disturbance using visual and auditory cues in PD. 18 PD patients, comprising of 9 patients with freezing (PDGF) and 9 without gait freezing were studied. Patients performed a 7-m back-and-forth walk in a baseline state and with visual and auditory cues. Gait velocity, stride length and cadence were evaluated using a three-dimensional gait analysis system. For speech evaluation, patients read ten sentences in a baseline state and with visual and auditory cues. The time delay of speech initiation, speech rate and the number of repetitions per sentence were quantified. In PDGF patients, the increase in gait velocity positively correlated with the decrease in the time delay of the speech initiation. Also, the increase in the gait velocity and cadence positively correlated with the decrease in the number of repetitions per sentence. The increase in the stride length positively correlated with the increase in speech rate. Lastly, the increase in stride length positively correlated with the decrease in the number of repetitions per sentence. These findings suggest that there is a common pathomechanism of gait freezing and speech disturbance in PD.
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Molecular chaperone TRAP1 regulates a metabolic switch between mitochondrial respiration and aerobic glycolysis.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-05-2013
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TRAP1 (TNF receptor-associated protein), a member of the HSP90 chaperone family, is found predominantly in mitochondria. TRAP1 is broadly considered to be an anticancer molecular target. However, current inhibitors cannot distinguish between HSP90 and TRAP1, making their utility as probes of TRAP1-specific function questionable. Some cancers express less TRAP1 than do their normal tissue counterparts, suggesting that TRAP1 function in mitochondria of normal and transformed cells is more complex than previously appreciated. We have used TRAP1-null cells and transient TRAP1 silencing/overexpression to show that TRAP1 regulates a metabolic switch between oxidative phosphorylation and aerobic glycolysis in immortalized mouse fibroblasts and in human tumor cells. TRAP1-deficiency promotes an increase in mitochondrial respiration and fatty acid oxidation, and in cellular accumulation of tricarboxylic acid cycle intermediates, ATP and reactive oxygen species. At the same time, glucose metabolism is suppressed. TRAP1-deficient cells also display strikingly enhanced invasiveness. TRAP1 interaction with and regulation of mitochondrial c-Src provide a mechanistic basis for these phenotypes. Taken together with the observation that TRAP1 expression is inversely correlated with tumor grade in several cancers, these data suggest that, in some settings, this mitochondrial molecular chaperone may act as a tumor suppressor.
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Thoracic magnetic resonance imaging for the evaluation of pulmonary emphysema.
J Thorac Imaging
PUBLISHED: 04-03-2013
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Pulmonary emphysema is a pathologic condition characterized by permanently enlarged airspaces distal to the terminal bronchiole with destruction of the alveolar walls. Functional information of the lungs is important to understand the pathophysiology of emphysema and that of chronic obstructive pulmonary disease. With the recent developments in magnetic resonance imaging (MRI) techniques, functional MRI with variable MR sequences can be used for the evaluation of different physiological and anatomic changes seen in cases of pulmonary emphysema. In this review article, we will focus on a brief description of each method, results of some of the most recent work, and the clinical application of such knowledge.
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Association between genetic polymorphisms of Toll-like receptor 2 (TLR2) and schizophrenia in the Korean population.
Gene
PUBLISHED: 03-19-2013
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Immunological dysregulation has been suggested to be involved in the pathogenesis of schizophrenia. Accumulating evidences further implicate that activated inflammatory processes may be particularly relevant for the precipitation of negative and cognitive symptoms of schizophrenia. Toll-like receptor 2 (TLR2) plays an important role in innate immunity by sensing a variety of pathogens and inducing an acquired immunity. In the present study, we investigated whether the coding region of single nucleotide polymorphisms (SNPs) of the TLR2 gene was associated with schizophrenia as well as with clinical symptoms in schizophrenia patients. The study population consisted of 286 Korean schizophrenia patients and 305 Korean control subjects. The assessment of the Scale for the Assessment of Negative Symptoms was used to evaluate the negative symptoms of schizophrenia; the operational criteria checklist was used to measure general psychopathology. We selected two cSNPs [rs3804099 (Asn199Asn) and rs3804100 (Ser450Ser)] considering their heterozygosity and minor allele frequency. SNP genotyping was conducted using direct sequencing. We did not find any significant associations between SNPs and schizophrenia in the genotype and allelic frequencies. On the other hand, in the analysis of cognitive symptoms, rs3804099 showed significant differences in schizophrenia patients with poor concentration in the dominant model (TC/CC vs. TT, p=0.0099). Also, rs3804100 showed a significant association with poor concentration in the co-dominant (TC vs. TT, p=0.014) and the dominant models (TC/CC vs. TT, p=0.0035). We obtained no significant support for the association of the TLR2 gene with susceptibility to schizophrenia in the Korean population. However, our results provide possibility that C allele of rs3804099 and rs3804100 may be associated with poor concentration in schizophrenia patients. Further studies with larger samples are required to confirm our results.
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Escalated daunorubicin dosing as an induction treatment for Philadelphia-negative adult acute lymphoblastic leukemia.
Ann. Hematol.
PUBLISHED: 03-09-2013
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The dose intensity of daunorubicin (DNR) delivered during the induction period represented the major prognostic factor for the outcome of adult acute lymphoblastic leukemia (ALL). The aim of this study was to determine the survival or toxicity of escalated doses of DNR in induction treatment of adult patients with acute lymphoblastic leukemia who are at least 15 years of age. For induction chemotherapy, all patients were given 90 mg/m(2)/day of DNR by continuous intravenous (IV) infusion over 24 h daily on days 1-3, 2 mg of vincristine IV push on days 1 and 8, and 60 mg/m(2)/day of prednisolone per oral (PO) on days 1-14 in conjunction with 4,000 units/m(2)/day of L-asparaginase intramuscular or subcutaneous on days 17-28. The median patient age was 32 years (range, 15-69). Complete remission (CR) was achieved in 169 (88.5 %) patients, while 4 died before CR was reached. Additionally, 11 patients died from leukemia progression, 4 had refractory disease, and 3 had follow-up loss. The median follow-up time was 697 days (range, 12-2,270). The 3-year cumulative incidence of relapse was 49.3 %. The probabilities of disease-free survival and overall survival at 3 years were 46.1 and 43.1 %, respectively. The dose of DNR was 100 % of the target dose, and there were no additional specific toxicities. The results show that escalated doses of DNR in induction chemotherapy are similar with the standard dose in response and toxicities. Our study indicates that a more effective regimen or better chemotherapy agents are needed to improve the CR rate and prolong survival in Philadelphia-negative adult ALL.
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Mycobacterium intracellulare Pulmonary Disease with Endobronchial Caseation in a Patient Treated with Methotrexate.
Tuberc Respir Dis (Seoul)
PUBLISHED: 03-07-2013
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Methotrexate (MTX) has been established as a standard disease-modifying anti-rheumatic drug. If adequate disease control is achieved for a reasonable period of time, tapering the MTX dosage is recommended because the chronic use of MTX can result in opportunistic infection. We present here a case of a woman with rheumatoid arthritis taking MTX, and the woman developed actively caseating endobronchial Mycobacterium intracellulare disease with pulmonary infiltrations. After discontinuing the MTX, the patient was able to tolerate 18 months of antimycobacterial treatment without flare ups of rheumatoid arthritis, and she completely recovered from nontuberculous mycobacterial respiratory disease.
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Invasive pulmonary adenocarcinomas versus preinvasive lesions appearing as ground-glass nodules: differentiation by using CT features.
Radiology
PUBLISHED: 03-06-2013
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To retrospectively investigate the differentiating computed tomographic (CT) features between invasive pulmonary adenocarcinoma (IPA) and preinvasive lesions appearing as ground-glass nodules (GGNs) in 253 patients.
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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.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.