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Find video protocols related to scientific articles indexed in Pubmed.
A patient with mosaic neurofibromatosis type 2 presenting with early onset meningioma.
BMJ Case Rep
PUBLISHED: 11-20-2014
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A female patient was found to have meningioma when she was 3?years and 11?months old and subtotal excision was performed. The residual tumour recurred 3?months after the first excision, and again 11?months after the second one. She was also found to have subcutaneous neurofibroma. However, her clinical features did not fulfil the diagnostic criteria for neurofibromatosis type 2 (NF2), and her family history was unremarkable. Considering that primary meningioma is extremely rare in the paediatric population, the diagnosis of NF2 was considered. It was thought that this might have an impact on her subsequent management. Genetic testing on blood DNA for NF2 was arranged, and the results confirmed that she had mosaic deletion of the promoter to exon 16 of NF2. With uncertainty of whether NF2 mutations are also present in other tissues, vigilant follow-up for other NF2-related complications would be required in the future.
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Cytoplasmic HIV-1 RNA is mainly transported by diffusion in the presence or absence of Gag protein.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-19-2014
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Full-length HIV-1 RNA plays a central role in viral replication by serving as the mRNA for essential viral proteins and as the genome packaged into infectious virions. Proper RNA trafficking is required for the functions of RNA and its encoded proteins; however, the mechanism by which HIV-1 RNA is transported within the cytoplasm remains undefined. Full-length HIV-1 RNA transport is further complicated when group-specific antigen (Gag) protein is expressed, because a significant portion of HIV-1 RNA may be transported as Gag-RNA complexes, whose properties could differ greatly from Gag-free RNA. In this report, we visualized HIV-1 RNA and monitored its movement in the cytoplasm by using single-molecule tracking. We observed that most of the HIV-1 RNA molecules move in a nondirectional, random-walk manner, which does not require an intact cytoskeletal structure, and that the mean-squared distance traveled by the RNA increases linearly with time, indicative of diffusive movement. We also observed that a single HIV-1 RNA molecule can move at various speeds when traveling through the cytoplasm, indicating that its movement is strongly affected by the immediate environment. To examine the effect of Gag protein on HIV-1 RNA transport, we analyzed the cytoplasmic HIV-1 RNA movement in the presence of sufficient Gag for virion assembly and found that HIV-1 RNA is still transported by diffusion with mobility similar to the mobility of RNAs unable to express functional Gag. These studies define a major mechanism of HIV-1 gene expression and resolve the long-standing question of how the RNA genome is transported to the assembly site.
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AMACR amplification in myxofibrosarcomas: a mechanism of overexpression that promotes cell proliferation with therapeutic relevance.
Clin. Cancer Res.
PUBLISHED: 11-12-2014
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Purpose: Myxofibrosarcomas frequently display arm-level gains on 5p. We characterized the pathogenetic and therapeutic relevance of the alpha-methylacyl coenzyme A racemase (AMACR) at 5p13.3. Experimental Design: AMACR mRNA expression in myxofibrosarcomas was analyzed using the public transcriptome and laser-microdissected sarcoma cells. We performed FISH and immunohistochemistry in independent samples for clinical correlates. In AMACR-overexpressing myxofibrosarcoma cells and xenografts, we elucidated the biological function of AMACR using RNA interference and explored the therapeutic effect and mechanism of an AMACR inhibitor, ebselen oxide (EO). Results: AMACR protein overexpression and gene amplification were significantly associated with each other (p<0.001), with higher tumor grades (both p?0.002), and univariately with worse metastasis-free survival (MFS, both p<0.0001) and disease-specific survival (DSS, p=0.0002 for overexpression; p=0.0062 for amplification). AMACR protein overexpression also independently portended adverse outcome (DSS, p=0.007; MFS, p=0.001). However, 39% of AMACR-overexpression cases did not show gene amplification, implying alternative regulatory mechanisms. In myxofibrosarcoma cell lines, stable AMACR knockdown suppressed cell proliferation, anchorage-independent growth, and expression of cyclin D1 and cyclin T2. These growth-promoting attributes of AMACR were corroborated in the AMACR-silenced xenograft model and AMACR-underexpressed myxofibrosarcomas, showing decreased labeling for cyclin D1, cyclin T2, and Ki-67. Compared to fibroblasts, AMACR-expressing myxofibrosarcoma cells were more susceptible to EO, which not only decreased viable cells, promoted proteasome-mediated degradation of AMACR protein, and induced cellular apoptosis in vitro but also dose-dependently suppressed xenografted tumor growth in vivo. Conclusions: Overexpressed AMACR in myxofibrosarcomas can be amplification-driven, associated with tumor aggressiveness, and may be relevant as a druggable target.
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Using Second-derivative Filters to Assist in Width Estimations of Size Exclusion Chromatography Signal Peaks with Static Light-scattering Detections to Obtain More Accurate Molecular Weight.
Anal Sci
PUBLISHED: 11-11-2014
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Static light-scattering (LS) detection can determine the molecular weight (MW) of polymers eluted with size-exclusion chromatography (SEC) without using any standards when the differential refraction index (RI) of solutes are obtained. On the other hand, the noisy chromatographic signal peak acquired using a static LS detector often causes difficulty in peak-width recognition. This disadvantage limits the determination accuracy and precision of the MW values. This study developed one second-order derivative filtering procedure by convolving the original LS chromatogram against the second-derivative curve of one artificial Gaussian-shape chromatographic peak to suppress the noises and to correct the baseline of the chromatogram. More accurate estimations of the chromatographic peak widths of pullulan samples were achieved to improve the MW determination accuracy. For noisy original chromatography peaks of pullulan 5 k (SNR of approximately 10), the non-ideal determination accuracy of the MW values (9.3%) is improved to -1.3% with the assistance of the filtering procedures.
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Grouper heat-shock cognate protein 70 (GHSC70) is involved in the cellular entry of nervous necrosis virus (NNV).
J. Virol.
PUBLISHED: 10-17-2014
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Nervous necrosis virus (NNV) is a devastating pathogen of cultured marine fish, and has affected more than 40 fish species. NNV belongs to the betanodavirus of Nodaviridae and is a non-enveloped icosahedral particle with 2 single-stranded positive-sense RNAs. To date, the knowledge regarding NNV entry into the host cell remains limited, and no NNV-specific receptor protein has been published. Using grouper fin cell line GF-1 and purified NNV capsid protein in a virus overlay protein binding assay (VOPBA), grouper heat-shock cognate protein 70 (GHSC70) and grouper voltage-dependent anion selective channel protein 2 (GVDAC2) were presumably to be NNV receptor protein candidates. We cloned, sequenced, and expressed the genes of GHSC70 and GVDAC2 in Escherichia coli for anti-serum preparation. The expression knockdown of GHSC70 and GVDAC2 genes with specific short interfering RNA (siRNA) significantly downregulated viral RNA expression in NNV-infected GF-1 cells. After an immuno-precipitation assay, we confirmed that GHSC70 interacted with NNV capsid protein, while VDAC2 did not. Immunofluorescence staining and flow cytometry analysis revealed the GHSC70 protein on the cell surface. After a blocking assay, we detected the NNV RNA2 level after 1 h of adsorption to GF-1 cells, which was significantly lower in the cells pretreated with the GHSC70 antiserum than in non-treated cells. Therefore, we suggest that GHSC70 participates in the NNV entry of GF-1 cells, likely functions as NNV receptor or co-receptor protein.
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Approach to Pain Management in Chronic Opioid Users Undergoing Orthopaedic Surgery.
J Am Acad Orthop Surg
PUBLISHED: 10-05-2014
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Opioids are commonly used for the management of pain in patients with musculoskeletal disorders; however, national attention has highlighted the potential adverse effects of the use of opioid analgesia in this and other nonmalignant pain settings. Chronic opioid users undergoing orthopaedic surgery represent a particularly challenging patient population in regard to their perioperative pain control and outcomes. Preoperative evaluation provides an opportunity to estimate a patient's preoperative opioid intake, discuss pain-related fears, and identify potential psychiatric comorbidities. Patients using high levels of opioids may also require referral to an addiction specialist. Various regional blockade and pharmaceutical options are available to help control perioperative pain, and a multimodal pain management approach may be of particular benefit in chronic opioid users undergoing orthopaedic surgery.
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APOBEC3D and APOBEC3F potently promote HIV-1 diversification and evolution in humanized mouse model.
PLoS Pathog.
PUBLISHED: 10-01-2014
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Several APOBEC3 proteins, particularly APOBEC3D, APOBEC3F, and APOBEC3G, induce G-to-A hypermutations in HIV-1 genome, and abrogate viral replication in experimental systems, but their relative contributions to controlling viral replication and viral genetic variation in vivo have not been elucidated. On the other hand, an HIV-1-encoded protein, Vif, can degrade these APOBEC3 proteins via a ubiquitin/proteasome pathway. Although APOBEC3 proteins have been widely considered as potent restriction factors against HIV-1, it remains unclear which endogenous APOBEC3 protein(s) affect HIV-1 propagation in vivo. Here we use a humanized mouse model and HIV-1 with mutations in Vif motifs that are responsible for specific APOBEC3 interactions, DRMR/AAAA (4A) or YRHHY/AAAAA (5A), and demonstrate that endogenous APOBEC3D/F and APOBEC3G exert strong anti-HIV-1 activity in vivo. We also show that the growth kinetics of 4A HIV-1 negatively correlated with the expression level of APOBEC3F. Moreover, single genome sequencing analyses of viral RNA in plasma of infected mice reveal that 4A HIV-1 is specifically and significantly diversified. Furthermore, a mutated virus that is capable of using both CCR5 and CXCR4 as entry coreceptor is specifically detected in 4A HIV-1-infected mice. Taken together, our results demonstrate that APOBEC3D/F and APOBEC3G fundamentally work as restriction factors against HIV-1 in vivo, but at the same time, that APOBEC3D and APOBEC3F are capable of promoting viral diversification and evolution in vivo.
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Long-term outcomes after revision neural decompression and fusion for same-level recurrent lumbar stenosis: defining the effectiveness of surgery.
J Spinal Disord Tech
PUBLISHED: 09-24-2014
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Single-cohort study of patients undergoing revision neural decompression and fusion for same-level recurrent lumbar stenosis.
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A baseline measure of tree and gastropod biodiversity in replanted and natural mangrove stands in malaysia: langkawi island and sungai merbok.
Trop Life Sci Res
PUBLISHED: 09-12-2014
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THE DIVERSITIES OF MANGROVE TREES AND OF THEIR ASSOCIATED GASTROPODS WERE ASSESSED FOR TWO MANGROVE REGIONS ON THE WEST COAST OF PENINSULAR MALAYSIA: Langkawi Island and Sungai Merbok. The mangrove area sampled on Langkawi Island was recently logged and replanted, whereas the area sampled in Sungai Merbok was part of a protected nature reserve. Mangrove and gastropod diversity were assessed in four 50 m(2) (10 × 5 m) sites per region. The species richness (S), Shannon Index (H') and Evenness Index (J') were calculated for each site, and the mean S, H' and J' values were calculated for each region. We report low tree and gastropod S, H' and J' values in all sites from both regions. For Langkawi Island, the mean S, H' and J' values for mangrove trees were S = 2.00±0, H' = 0.44±0.17 and J' = 0.44±0.17; the mean S, H' and J' values for gastropods were S = 4.00±1.63, H' = 0.96±0.41 and J' = 0.49±0.06. In Sungai Merbok, the mean S, H' and J' values for mangrove trees were S = 1.33±0.58, H' = 0.22±0.39 and J' = 0.22 ±0.39; the mean S, H' and J' values for gastropods were S = 4.75±2.22, H' = 1.23±0.63 and J' = 0.55±0.12. This study emphasises the need for baseline biodiversity measures to be established in mangrove ecosystems to track the impacts of anthropogenic disturbances and to inform management and restoration efforts.
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Can aspirin reduce the risk of colorectal cancer in people with diabetes? A population-based cohort study.
Diabet. Med.
PUBLISHED: 09-09-2014
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To evaluate whether aspirin can reduce the risk of colorectal cancer in people with diabetes.
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Longitudinal brain white matter alterations in minimal hepatic encephalopathy before and after liver transplantation.
PLoS ONE
PUBLISHED: 08-28-2014
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Cerebral edema is the common pathogenic mechanism for cognitive impairment in minimal hepatic encephalopathy. Whether complete reversibility of brain edema, cognitive deficits, and their associated imaging can be achieved after liver transplantation remains an open question. To characterize white matter integrity before and after liver transplantation in patients with minimal hepatic encephalopathy, multiple diffusivity indices acquired via diffusion tensor imaging was applied. Twenty-eight patients and thirty age- and sex-matched healthy volunteers were included. Multiple diffusivity indices were obtained from diffusion tensor images, including mean diffusivity, fractional anisotropy, axial diffusivity and radial diffusivity. The assessment was repeated 6-12 month after transplantation. Differences in white matter integrity between groups, as well as longitudinal changes, were evaluated using tract-based spatial statistical analysis. Correlation analyses were performed to identify first scan before transplantation and interval changes among the neuropsychiatric tests, clinical laboratory tests, and diffusion tensor imaging indices. After transplantation, decreased water diffusivity without fractional anisotropy change indicating reversible cerebral edema was found in the left anterior cingulate, claustrum, postcentral gyrus, and right corpus callosum. However, a progressive decrease in fractional anisotropy and an increase in radial diffusivity suggesting demyelination were noted in temporal lobe. Improved pre-transplantation albumin levels and interval changes were associated with better recoveries of diffusion tensor imaging indices. Improvements in interval diffusion tensor imaging indices in the right postcentral gyrus were correlated with visuospatial function score correction. In conclusion, longitudinal voxel-wise analysis of multiple diffusion tensor imaging indices demonstrated different white matter changes in minimal hepatic encephalopathy patients. Transplantation improved extracellular cerebral edema and the results of associated cognition tests. However, white matter demyelination may advance in temporal lobe.
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Immune gene expressions in grouper larvae (Epinephelus coioides) induced by bath and oral vaccinations with inactivated betanodavirus.
Fish Shellfish Immunol.
PUBLISHED: 08-15-2014
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Nervous necrosis virus (NNV) has caused mass mortality in many mariculture fish species. Bath vaccination of inactivated NNV and oral immunization of recombinant NNV coat protein are reported to protect grouper larvae against NNV infection. However, the information of immune gene expression in grouper larvae (Epinephelus coioides) after bath and oral immunizations is still limited. In this study, grouper larvae were respectively bath- and orally immunized with binary ethylenimine (BEI)-inactivated NNV, and the expression levels of immune genes were analyzed. Significant gene expressions of IL-1?, Mx, MHC-I, MHC-II, CD8?, IgM and IgT were observed in bath- and orally immunized fish 1-4 weeks post immunization (wpi). Particularly, the up-regulation of IL-1? and Mx gene expression lasted for 4 weeks. The IgT gene expression in gill was only induced by bath immunization, while that in gut was only stimulated by oral immunization. Both immunizations elicited MHC-I and CD8? gene expression relative to cellular immunity. Furthermore, NNV RNA genome, which was detected in inactivated NNV, could induce Mx gene expression in grouper brain (GB) cells, indicating that NNV RNA genome could be recognized by pathogen-recognition receptors (PRRs). In summary, bath and oral vaccinations with BEI-inactivated NNV triggered the gene expression of not only humoral immunity but also cellular immunity.
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Disease-specific T-helper cell polarizing function of lesional dendritic cells in different types of chronic rhinosinusitis with nasal polyps.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 08-14-2014
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Although eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) exhibit distinct T-helper (Th) responses, the underlying mechanisms remain unclear.
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Interplay between brain stem angiotensins and monocyte chemoattractant protein-1 as a novel mechanism for pressor response after ischemic stroke.
Neurobiol. Dis.
PUBLISHED: 08-12-2014
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Pressor response after stroke commonly leads to early death or susceptibility to stroke recurrence, and detailed mechanisms are still lacking. We assessed the hypothesis that the renin-angiotensin system contributes to pressor response after stroke by differential modulation of the pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) in the rostral ventrolateral medulla (RVLM), a key brain stem site that maintains blood pressure. We also investigated the beneficial effects of a novel renin inhibitor, aliskiren, against stroke-elicited pressor response. Experiments were performed in male adult Sprague-Dawley rats. Stroke induced by middle cerebral artery occlusion elicited significant pressor response, accompanied by activation of angiotensin II (Ang II)/type I receptor (AT1R) and AT2R signaling, depression of Ang-(1-7)/MasR and Ang IV/AT4R cascade, alongside augmentation of MCP-1/C-C chemokine receptor 2 (CCR2) signaling and neuroinflammation in the RVLM. Stroke-elicited pressor response was significantly blunted by antagonism of AT1R, AT2R or MCP-1/CCR2 signaling, and eliminated by applying Ang-(1-7) or Ang IV into the RVLM. Furthermore, stroke-activated MCP-1/CCR2 signaling was enhanced by AT1R and AT2R activation, and depressed by Ang-(1-7)/MasR and Ang IV/AT4R cascade. Aliskiren inhibited stroke-elicited pressor response via downregulating MCP-1/CCR2 activity and reduced neuroinflammation in the RVLM; these effects were potentiated by Ang-(1-7) or Ang IV. We conclude that whereas Ang II/AT1R or Ang II/AT2R signaling in the brain stem enhances, Ang-(1-7)/MasR or Ang IV/AT4R antagonizes pressor response after stroke by differential modulations of MCP-1 in the RVLM. Furthermore, combined administration of aliskiren and Ang-(1-7) or Ang IV into the brain stem provides more effective amelioration of stroked-induced pressor response.
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Type 2 diabetes mellitus is associated with increased mortality in Chinese patients receiving curative surgery for colon cancer.
Oncologist
PUBLISHED: 07-24-2014
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We investigated the association between diabetes mellitus (DM) and the prognosis of patients with early colon cancer who had undergone curative surgery.
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Environmental-stress-induced Chromatin Regulation and its Heritability.
J Carcinog Mutagen
PUBLISHED: 07-22-2014
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Chromatin is subject to proofreading and repair mechanisms during the process of DNA replication, as well as repair to maintain genetic and epigenetic information and genome stability. The dynamic structure of chromatin modulates various nuclear processes, including transcription and replication, by altering the accessibility of the DNA to regulatory factors. Structural changes in chromatin are affected by the chemical modification of histone proteins and DNA, remodeling of nucleosomes, incorporation of variant histones, noncoding RNAs, and nonhistone DNA-binding proteins. Phenotypic diversity and fidelity can be balanced by controlling stochastic switching of chromatin structure and dynamics in response to the environmental disruptors and endogenous stresses. The dynamic chromatin remodeling can, therefore, serve as a sensor, through which environmental and/or metabolic agents can alter gene expression, leading to global cellular changes involving multiple interactive networks. Furthermore its recent evidence also suggests that the epigenetic changes are heritable during the development. This review will discuss the environmental sensing system for chromatin regulation and genetic and epigenetic controls from developmental perspectives.
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Utility of Postoperative Radiographs for Pediatric Scoliosis: Association Between History and Physical Examination Findings and Radiographic Findings.
J Bone Joint Surg Am
PUBLISHED: 07-04-2014
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Postoperative radiographs are routinely obtained following surgery for the correction of scoliosis in pediatric patients. The purpose of this study was to comprehensively evaluate the utility of obtaining routine postoperative radiographs in the management of these patients.METHODS: A total of 1969 clinic notes and corresponding radiographs regarding 451 consecutive patients with scoliosis (age range, ten to eighteen years) who had surgical correction over a ten-year period at a single institution were retrospectively reviewed. Curve etiology, preoperative curve characteristics, and surgical procedures performed were recorded. All postoperative clinic notes and radiographs were reviewed for abnormalities and changes in treatment course. It was then determined whether clinical signs and symptoms and/or abnormal radiographic findings led to a change in treatment course, which was defined as a therapeutic intervention or further diagnostic testing.RESULTS: Of the 451 patients in this study (average age [and standard deviation], 14.7 ± 2.4 years), 72.5% had adolescent idiopathic scoliosis, 23.3% had neuromuscular scoliosis, and 4.2% had other underlying causes of scoliosis. A change in treatment course occurred in the cases of forty-two patients, all of whom had symptomatic findings on postoperative history and physical examination and only fifteen of whom had supportive abnormal findings on postoperative radiographs. Curve etiology and surgical procedures performed had no impact on radiographic utility. A significant increase in utility was seen for radiographs obtained at visits one year or more following surgery compared with those obtained at visits less than one year following surgery (1.7% compared with 0.3%, p = 0.001). The overall sensitivity, specificity, positive predictive value, and negative predictive value of routine postoperative radiographs in guiding treatment course were 35.7%, 98.1%, 28.8%, and 98.6%, respectively.CONCLUSIONS: Routine radiographs provide low utility in guiding the course of treatment for asymptomatic pediatric patients following surgery for scoliosis. The results of this study suggest that patient or caregiver complaints, comorbidities, and clinical suspicion should be considered before obtaining radiographs at postoperative visits in order to minimize radiation exposure in pediatric patients and reduce medical costs without compromising care.LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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Prognostic impact of renin-angiotensin system blockade in esophageal squamous cell carcinoma.
J Renin Angiotensin Aldosterone Syst
PUBLISHED: 06-24-2014
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The aim of this study is to evaluate whether the administration of renin-angiotensin system (RAS) inhibitors, angiotensin-I converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), is associated with treatment outcome in patients with esophageal squamous cell carcinoma.
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The open service signal in space navigation data comparison of the Global Positioning System and the BeiDou Navigation Satellite System.
Sensors (Basel)
PUBLISHED: 06-17-2014
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More and more Global Navigation Satellite Systems (GNSSs) have been developed and are in operation. Before integrating information on various GNSSs, the differences between the various systems must be studied first. This research focuses on analyzing the navigation data differences between the Chinese BeiDou Navigation Satellite System (BDS) and the United States' Global Positioning System (GPS). In addition to explaining the impact caused by these two different coordinate and time systems, this research uses an actual open service signal in space (SIS) for both GPS and BDS to analyze their current system performance. Five data quality analysis (DQA) mechanisms are proposed in this research to validate both systems' SIS navigation data. These five DQAs evaluate the differences in ephemeris and almanac messages from both systems for stability and accuracy. After all of the DQAs, the different issues related to GPS and BDS satellite information are presented. Finally, based on these DQA results, this research provides suggested resolutions for the combined use of GPS and BDS for navigation and guidance.
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Sex- and age-specific prevalence and incidence rates of sight-threatening diabetic retinopathy in Taiwan.
JAMA Ophthalmol
PUBLISHED: 05-10-2014
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The prevalence of diabetic retinopathy (DR) is high in individuals with diabetes mellitus. Published estimates for sight-threatening DR (STDR) prevalence range widely. There is a need for precise contemporary estimates of the prevalence and incidence of STDR for providing optimal strategies of clinical management in Taiwan.
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Two-year comprehensive medical management of degenerative lumbar spine disease (lumbar spondylolisthesis, stenosis, or disc herniation): a value analysis of cost, pain, disability, and quality of life: clinical article.
J Neurosurg Spine
PUBLISHED: 05-02-2014
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Current health care reform calls for a reduction of procedures and treatments that are less effective, more costly, and of little value (high cost/low quality). The authors assessed the 2-year cost and effectiveness of comprehensive medical management for lumbar spondylolisthesis, stenosis, and herniation by utilizing a prospective single-center multidisciplinary spine center registry in a real-world practice setting.
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The prognostic significance of early treatment response in pediatric relapsed acute myeloid leukemia: results of the international study Relapsed AML 2001/01.
Haematologica
PUBLISHED: 04-24-2014
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The prognostic significance of early response to treatment has not been reported in relapsed pediatric acute myeloid leukemia. In order to identify an early and easily applicable prognostic factor allowing subsequent treatment modifications, we assessed leukemic blast counts in the bone marrow by morphology on days 15 and 28 after first reinduction in 338 patients of the international Relapsed-AML2001/01 trial. Both day 15 and day 28 status was classified as good (?20% leukemic blasts) in 77% of patients. The correlation between day 15 and 28 blast percentages was significant, but not strong (Spearman correlation coefficient = 0.49, P<0.001). Survival probability decreased in a stepwise fashion along with rising blast counts at day 28. Patients with bone marrow blast counts at this time-point of ?5%, 6-10%, 11-20% and >20% had 4-year probabilities of survival of 52%±3% versus 36%±10% versus 21%±9% versus 14%±4%, respectively, P<0.0001; this trend was not seen for day 15 results. Multivariate analysis showed that early treatment response at day 28 had the strongest prognostic significance, superseding even time to relapse (< or ?12 months). In conclusion, an early response to treatment, measured on day 28, is a strong and independent prognostic factor potentially useful for treatment stratification in pediatric relapsed acute myeloid leukemia. This study was registered with ISRCTN code: 94206677.
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Potential involvement of IL-17F in asthma.
J Immunol Res
PUBLISHED: 04-14-2014
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The expression of IL-17F is seen in the airway of asthmatics and its level is correlated with disease severity. Several studies have demonstrated that IL-17F plays a pivotal role in allergic airway inflammation and induces several asthma-related molecules such as CCL20. IL-17F-induced CCL20 may attract Th17 cells into the airway resulting in the recruitment of additional Th17 cells to enhance allergic airway inflammation. We have recently identified, for the first time, that bronchial epithelial cells are its novel cell source in response to IL-33 via ST2-ERK1/2-MSK1 signaling pathway. The receptor for IL-17F is the heterodimeric complex of IL-17RA and IL-17RC, and IL-17F activates many signaling pathways. In a case-control study of 867 unrelated Japanese subjects, a His161 to Arg161 (H161R) substitution in the third exon of the IL-17F gene was associated with asthma. In atopic patients with asthma, prebronchodilator baseline FEV1/FVC values showed a significant association with the H161R variant. Moreover, this variant is a natural antagonist for the wild-type IL-17F. Moreover, IL-17F is involved in airway remodeling and steroid resistance. Hence, IL-17F may play an orchestrating role in the pathogenesis of asthma and may provide a valuable therapeutic target for development of novel strategies.
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Ploidy and clinical characteristics of childhood acute myeloid leukemia: A NOPHO-AML study.
Genes Chromosomes Cancer
PUBLISHED: 04-04-2014
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We report the first large series (n = 596) of pediatric acute myeloid leukemia (AML) focusing on modal numbers (MN) from the population-based NOPHO-AML trials. Abnormal karyotypes were present in 452 cases (76%) and numerical aberrations were present in 40% (n = 237) of all pediatric AML. Among patients with an abnormal karyotype, the MN 46 was most common (n = 251; 56%) of which 36 (8%) were pseudodiploid with numerical aberrations, followed by MN 47 (n = 80; 18%) and MN 43-45 (n = 48; 8%). No cases had MN less than 43. Hyperdiploid AML with MN 48-65 comprised 11% of all cases and was associated with early onset (median age 2 years), female sex (57%), and a dominance of acute megakaryoblastic leukemia (AMKL) (29%). Hypodiploidy constituted 8% of all AML and was associated with older age (median age 9 years), male predominance (60%), FAB M2 (56%), and t(8;21)(q22;q22) (56%) with loss of sex chromosomes. Inferior outcome was observed for hypodiploid cases (5-year event-free survival 40% and 5-year overall survival 40%) but did not reach statistical significance. Chromosomes were gained in a nonrandom pattern, where chromosomes 8, 21, 19, and 6 were the most commonly gained. In conclusion, based on MNs, two cytogenetic subgroups with characteristic clinical features are described; hypodiploidy found in 8% and associated with high median age, male sex, t(8;21)(q22;q22), and FAB M2 and possibly associated with inferior outcome (P = 0.13), and hyperdiploidy with MN 48-65 in 11% associated with early onset, female sex, and AMKL.
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Intra-arterial chemotherapy with doxorubicin and cisplatin is effective for advanced hepatocellular cell carcinoma.
ScientificWorldJournal
PUBLISHED: 04-01-2014
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Advanced hepatocellular carcinoma (HCC) remains a fatal disease even in the era of targeted therapies. Intra-arterial chemotherapy (IACT) can provide therapeutic benefits for patients with locally advanced HCC who are not eligible for local therapies or are refractory to targeted therapies. The aim of this retrospective study was to analyze the effect of IACT with cisplatin and doxorubicin on advanced HCC.
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A model measuring therapeutic inertia and the associated factors among diabetes patients: A nationwide population-based study in Taiwan.
J Clin Pharmacol
PUBLISHED: 03-13-2014
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This article presents an analysis conducted on the patterns related to therapeutic inertia with the aim of uncovering how variables at the patient level and the healthcare provider level influence the intensification of therapy when it is clinically indicated. A cohort study was conducted on 899,135 HbA1c results from 168,876 adult diabetes patients with poorly controlled HbA1c levels. HbA1c results were used to identify variations in the prescription of hypoglycemic drugs. Logistic regression and hierarchical linear models (HLMs) were used to determine how differences among healthcare providers and patient characteristics influence therapeutic inertia. We estimated that 38.5% of the patients in this study were subject to therapeutic inertia. The odds ratio of cardiologists choosing to intensify therapy was 0.708 times that of endocrinologists. Furthermore, patients in medical centers were shown to be 1.077 times more likely to be prescribed intensified treatment than patients in primary clinics. The HLMs presented results similar to those of the logistic model. Overall, we determined that 88.92% of the variation in the application of intensified treatment was at the within-physician level. Reducing therapeutic inertia will likely require educational initiatives aimed at ensuring adherence to clinical practice guidelines in the care of diabetes patients.
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Central Nervous System Tumors in Chinese Children Under The Age of 3: A Population Study.
J. Pediatr. Hematol. Oncol.
PUBLISHED: 03-11-2014
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The management of central nervous system tumors in children below the age of 3 years represents special challenge to pediatric oncologists with distinctive epidemiology, treatment considerations, and prognosis. Population-based epidemiological data on this particular patient group is lacking in Chinese. We reviewed the population-based pediatric tumor registry in Hong Kong between 1999 and 2011. Eighty-one children with primary central nervous system tumors from 0 to 3 years of age were identified (annual incidence: 4.16 cases per 100,000). Forty-one (50.6%) were male and the mean duration of follow-up was 94 months (±8.1). Primary tumors were infratentorial in 43 (53.1%). The tumor types in decreasing frequency were astrocytoma (n=17), medulloblastoma (n=16), ependymoma (n=13), choroid plexus tumor (n=7), primitive neuroectodermal tumor (n=7), atypical teratoid rhabdoid tumor (n=6), germ cell tumor (GCT, n=5), craniopharyngioma (n=4), and ganglioglioma (n=3). Three patients presented antenatally. Treatment included surgery in 82.7%, chemotherapy in 50.6%, and radiotherapy in 25.9%. There were 29 deaths (35.8%) and 19 relapses (23.5%) during the review period with the 1-year overall survival (OS), 5-year OS, 1-year event-free survival (EFS), and 5-year EFS being 79.4% (±4.6), 63.5% (±5.9), 68.9% (±5.3), and 52.5% (±5.9), respectively. Significantly better OS and EFS were observed in patients who received gross total resection but those with high-grade tumors, antenatal diagnosis, or atypical teratoid rhabdoid tumor/primitive neuroectodermal tumor had worse outcome. Survival did not differ with age. Comparison with statistics from other studies revealed higher rates of embryonal tumor, GCT, and craniopharyngioma in Hong Kong Chinese. Disease outcome appeared to be better in our cohort comparing to previous reports probably due to the higher proportion of GCT locally.
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Dietary supplementation of Pediococcus pentosaceus enhances innate immunity, physiological health and resistance to Vibrio anguillarum in orange-spotted grouper (Epinephelus coioides).
Fish Shellfish Immunol.
PUBLISHED: 02-27-2014
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Groupers (Epinephelus spp.) are economically important fish species in Southeast Asian aquaculture. Vibriosis caused by Vibro spp. is one of the severe bacterial diseases that devastate the grouper aquaculture industry. Probiotics have been reported to show the potential to enhance fish immunity and to antagonize pathogens. In our previous study, a lactic acid bacterium Pediococcus pentosaceus strain 4012 (LAB4012), isolated from cobia intestine, protects cobia from photobacteriosis after a 2-week feeding. In this study, we examined the potential of LAB4012 to be a probiotic for the orange-spotted grouper through feeding, thus to guard against vibriosis. In vitro, LAB4012 culture supernatant with low pH suppressed the growth of Vibrio anguillarum, and lactic acid in the metabolite of LAB4012 appeared to be the major factor to the growth inhibition of V. anguillarum. In vivo, the challenge test showed that the cumulative mortality of the LAB4012-fed groupers was significantly lower than that of the control fish after V. anguillarum infection. Supplementation of LAB4012 in commercial diet not only enhanced the growth rate and erythrocyte numbers of the groupers, but also regulated the gene expression of the pro-/anti-inflammatory cytokines. One day post-infection of V. anguillarum, the leukocyte numbers in the peripheral blood and the phagocytic activity of the head-kidney phagocytes in the LAB4012-fed groupers were found significantly increased, when compared with those without LAB4012-feeding. These results suggested that LAB4012 can be a dietary probiotic for groupers in modulating the immunity and protecting the groupers from V. anguillarum infection.
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Association between peripheral oxidative stress and white matter damage in acute traumatic brain injury.
Biomed Res Int
PUBLISHED: 02-11-2014
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The oxidative stress is believed to be one of the mechanisms involved in the neuronal damage after acute traumatic brain injury (TBI). However, the disease severity correlation between oxidative stress biomarker level and deep brain microstructural changes in acute TBI remains unknown. In present study, twenty-four patients with acute TBI and 24 healthy volunteers underwent DTI. The peripheral blood oxidative biomarkers, like serum thiol and thiobarbituric acid-reactive substances (TBARS) concentrations, were also obtained. The DTI metrics of the deep brain regions, as well as the fractional anisotropy (FA) and apparent diffusion coefficient, were measured and correlated with disease severity, serum thiol, and TBARS levels. We found that patients with TBI displayed lower FAs in deep brain regions with abundant WMs and further correlated with increased serum TBARS level. Our study has shown a level of anatomic detail to the relationship between white matter (WM) damage and increased systemic oxidative stress in TBI which suggests common inflammatory processes that covary in both the peripheral and central reactions after TBI.
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Long-acting insulin analogues and diabetic retinopathy: a retrospective cohort study.
Clin Ther
PUBLISHED: 02-04-2014
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Long-acting insulin analogues were developed to facilitate consistent glycemic control without excessive hypoglycemia. However, structural modifications of the insulin molecule can alter biological responses and binding characteristics with specific receptors. The aim of this study was to estimate the risk of sight-threatening diabetic retinopathy (STDR) associated with treatment using long-acting insulin analogues compared with intermediate-acting insulin in patients with type 2 diabetes mellitus (T2DM).
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Deciphering the role of the Gag-Pol ribosomal frameshift signal in HIV-1 RNA genome packaging.
J. Virol.
PUBLISHED: 01-22-2014
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A key step of retroviral replication is packaging of the viral RNA genome during virus assembly. Specific packaging is mediated by interactions between the viral protein Gag and elements in the viral RNA genome. In HIV-1, similar to most retroviruses, the packaging signal is located within the 5' untranslated region and extends into the gag-coding region. A recent study reported that a region including the Gag-Pol ribosomal frameshift signal plays an important role in HIV-1 RNA packaging; deletions or mutations that affect the RNA structure of this signal lead to drastic decreases (10- to 50-fold) in viral RNA packaging and virus titer. We examined here the role of the ribosomal frameshift signal in HIV-1 RNA packaging by studying the RNA packaging and virus titer in the context of proviruses. Three mutants with altered ribosomal frameshift signal, either through direct deletion of the signal, mutation of the 6U slippery sequence, or alterations of the secondary structure were examined. We found that RNAs from all three mutants were packaged efficiently, and they generate titers similar to that of a virus containing the wild-type ribosomal frameshift signal. We conclude that although the ribosomal frameshift signal plays an important role in regulating the replication cycle, this RNA element is not directly involved in regulating RNA encapsidation.
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Addition of the Akt inhibitor triciribine overcomes antibody resistance in cells from ErbB2/Neu-positive/PTEN-deficient mammary tumors.
Int. J. Oncol.
PUBLISHED: 01-21-2014
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Trastuzumab resistance is a challenging problem in ErbB2/HER2-positive breast cancers. Multiple mechanisms of resistance have been proposed and, thus, may require the development of more personalized therapies. In this study, we report the establishment of a mouse mammary cancer cell line, designated MT104T, obtained from spontaneous tumors in genetically engineered FVB/N-ErbB2/Neu-positive-PTEN-deficient mice. The critical molecular phenotype of MT104T cells was confirmed by genotyping and western blot analysis. This cell line was tumorigenic in immunologically intact syngeneic mice, forming tumors of generally similar histology as its origin. PTEN loss led to hyperactivation of Akt and conferred resistance to anti-ErbB2/Neu antibody treatment in MT104T cells. Addition of the Akt inhibitor triciribine (TCN) inhibited the viability of MT104T cells in a dose- and time-dependent manner as evaluated by MTT assay. ErbB2/Neu antibody and TCN combination treatment greatly induced apoptosis of MT104T cells as indicated by Annexin V-FITC staining. Moreover, this combination treatment also significantly reduced both Akt and Erk activities, which are responsible for the inhibitory effect on MT104T cells. Therefore, MT104T cells could represent an alternative model system to investigate the nature of ErbB2?positive breast cancer and for the experimental therapeutics studies of this disease. Our findings also suggest that combination of TCN may be a potential strategy for the treatment of trastu-zumab-resistant breast cancer mediated by PTEN loss or PI3K hyperactivation, which may facilitate the development of more personalized therapies for breast cancer patients.
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Budget impact analysis-principles of good practice: report of the ISPOR 2012 Budget Impact Analysis Good Practice II Task Force.
Value Health
PUBLISHED: 01-21-2014
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Budget impact analyses (BIAs) are an essential part of a comprehensive economic assessment of a health care intervention and are increasingly required by reimbursement authorities as part of a listing or reimbursement submission.
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Peripheral leukocyte apoptosis in patients with Parkinsonism: correlation with clinical characteristics and neuroimaging findings.
Biomed Res Int
PUBLISHED: 01-17-2014
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Apoptosis of both brain neurons and peripheral blood leukocyte is believed to be an important biomarker for evaluating the functional status of Parkinson's disease (PD). However, their correlation remains unknown. A better understanding of the pathophysiology of neurodegeneration is essential for the treatment and prevention of PD. The present study demonstrated that leukocyte apoptosis is significantly higher in PD patients and is associated with central dopamine neuron loss by using (99m)Tc-TRODAT-1 SPECT. The leukocyte apoptosis and striatal dopamine transporter uptake ratios were further associated with increased severity and longer duration of disease. The interaction between brain and systemic inflammation may be responsible for the neurodegenerative disease progression.
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Left ventricular torsional mechanics and myocardial iron load in beta-thalassaemia major: a potential role of titin degradation.
BMC Cardiovasc Disord
PUBLISHED: 01-15-2014
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Iron may damage sarcomeric proteins through oxidative stress. We explored the left ventricular (LV) torsional mechanics in patients with beta-thalassaemia major and its relationship to myocardial iron load. Using HL-1 cell and B6D2F1 mouse models, we further determined the impact of iron load on proteolysis of the giant sarcomeric protein titin.
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Life of psi: how full-length HIV-1 RNAs become packaged genomes in the viral particles.
Virology
PUBLISHED: 01-03-2014
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As a member of the retrovirus family, HIV-1 packages its RNA genome into particles and replicates through a DNA intermediate that integrates into the host cellular genome. The multiple genes encoded by HIV-1 are expressed from the same promoter and their expression is regulated by splicing and ribosomal frameshift. The full-length HIV-1 RNA plays a central role in viral replication as it serves as the genome in the progeny virus and is used as the template for Gag and GagPol translation. In this review, we summarize findings that contribute to our current understanding of how full-length RNA is expressed and transported, cis- and trans-acting elements important for RNA packaging, the locations and timing of RNA:RNA and RNA:Gag interactions, and the processes required for this RNA to be packaged into viral particles.
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Association of adjuvant antiviral therapy with risk of cancer progression and deaths in patients with hepatitis-B-virus-related hepatocellular carcinoma following curative treatment: a nationwide cohort study.
PLoS ONE
PUBLISHED: 01-01-2014
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Limited information about tumor status and the time at which antiviral therapy was initiated may have influenced effect estimation in previous research. The aim of this study was to investigate the effect of antiviral therapies on HBV-related HCC progression and deaths in patients receiving curative treatment based on clear clinical-pathological cancer status and the association of start time of adjuvant antiviral therapy initiation and outcomes.
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Diffusion tensor imaging study of white matter damage in chronic meningitis.
PLoS ONE
PUBLISHED: 01-01-2014
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Tuberculous meningitis (TBM) and cryptococcal meningitis (CM) are two of the most common types of chronic meningitis. This study aimed to assess whether chronic neuro-psychological sequelae are associated with micro-structure white matter (WM) damage in HIV-negative chronic meningitis. Nineteen HIV-negative TBM patients, 13 HIV-negative CM patients, and 32 sex- and age-matched healthy volunteers were evaluated and compared. The clinical relevance of WM integrity was studied using voxel-based diffusion tensor imaging (DTI) magnetic resonance imaging. All of the participants underwent complete medical and neurologic examinations, and neuro-psychological testing. Differences in DTI indices correlated with the presence of neuro-psychological rating scores and cerebrospinal fluid (CSF) analysis during the initial hospitalization. Patients with CM had more severe cognitive deficits than healthy subjects, especially in TBM. There were changes in WM integrity in several limbic regions, including the para-hippocampal gyrus and cingulate gyrus, and in the WM close to the globus pallidus. A decline in WM integrity close to the globus pallidus and anterior cingulate gyrus was associated with worse CSF analysis profiles. Poorer DTI parameters directly correlated with worse cognitive performance on follow-up. These correlations suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities. Abnormalities in the limbic system and globus pallidus, with their close relationship to the CSF space, may be specific biomarkers for disease evaluation.
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Preoperative narcotic use and its relation to depression and anxiety in patients undergoing spine surgery.
Spine
PUBLISHED: 12-04-2013
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Prospective review of registry data at a single institution from October 2010 to June 2012.
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Nuclear import of APOBEC3F-labeled HIV-1 preintegration complexes.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-18-2013
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Human cytidine deaminases APOBEC3F (A3F) and APOBEC3G (A3G) are host factors that incorporate into virions and restrict virus replication. We labeled HIV-1 particles with yellow fluorescent protein (YFP)-tagged APOBEC3 proteins and examined their association with preintegration complexes (PICs) in infected cells. Labeling of PICs with A3F-YFP, and to a lesser extent A3G-YFP, could be used to visualize PICs in the nuclei, which was dependent on nuclear pore protein Nup153 but not TNPO3. We show that reverse transcription is not required for nuclear import of PICs, indicating that a viral core uncoating event associated with reverse transcription, and the central DNA flap that forms during reverse transcription, are not required for nuclear import. We also quantify association of cytoplasmic PICs with nuclear envelope (NE) and report that capsid mutations that increase or decrease core stability dramatically reduce NE association and nuclear import of PICs. In addition, we find that nuclear PICs remain close to the NE and are not distributed throughout the nuclei. These results provide tools for tracking retroviral PICs in infected cells and reveal insights into HIV-1 replication.
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14-3-3? Orchestrates Mammary Tumor Onset and Progression via miR-221-Mediated Cell Proliferation.
Cancer Res.
PUBLISHED: 11-06-2013
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14-3-3? is overexpressed in more than 40% of breast cancers, but its pathophysiologic relevance to tumorigenesis has not been established. Here, we show that 14-3-3? overexpression is sufficient to induce tumorigenesis in a transgenic mouse model of breast cancer. MMTV-LTR promoter-driven HA-14-3-3? transgenic mice (MMTV-HA-14-3-3?) developed mammary tumors, whereas control mice did not. Whey acidic protein promoter-driven HA-14-3-3? transgenic mice (WAP-HA-14-3-3?) developed hyperplastic lesions and showed increased susceptibility to carcinogen-induced tumorigenesis. When crossed with MMTV-neu transgenic mice, 14-3-3?.neu transgenic mice exhibited accelerated mammary tumorigenesis and metastasis compared with MMTV-neu mice. Mechanistically, 14-3-3? overexpression enhanced MAPK/c-Jun signaling, leading to increased miR-221 transcription, which inhibited p27 CDKI translation and, consequently, promoted cell proliferation. Importantly, this 14-3-3?-miR-221-p27 proliferation axis is also functioning in breast tumors in patients and is associated with high-grade cancers. Taken together, our findings show that overexpression of 14-3-3? has a causal role in mammary tumorigenesis and progression, acting through miR-221 in cooperation with known oncogenic events to drive neoplastic cell proliferation. Cancer Res; 74(1); 1-11. ©2013 AACR.
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Midkine neurite growth-promoting factor 2 expression as a potential prognostic marker of adjuvant therapy in head and neck squamous cell carcinoma.
Biomarkers
PUBLISHED: 10-28-2013
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Abstract Objective: The prognostic function of neurite growth-promoting factor 2 (Midkine (MK)) in adjuvant treatment of head and neck squamous cell carcinoma (HNSCC) is unclear. This study examined whether MK expression may predict treatment response and survival in resectable HNSCC patients. Methods: In this retrospective study, MK expression in 144 HNSCC patients was analyzed by immunohistochemistry. A subset of patients (n?=?10) had MK expression levels analyzed by western blot and semi-quantitative reverse transcription polymerase chain reaction. Data were analyzed using the Log-rank test and ??=?0.05. Results: Expression of MK was associated with poorer five-year progression-free and overall survival rates in HNSCC patients (p?=?0.002). Conclusion: MK might play an important role in the progression of HNSCC and may be a useful prognostic factor.
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Structural and cognitive deficits in chronic carbon monoxide intoxication: a voxel-based morphometry study.
BMC Neurol
PUBLISHED: 09-26-2013
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Patients with carbon monoxide (CO) intoxication may develop ongoing neurological and psychiatric symptoms that ebb and flow, a condition often called delayed encephalopathy (DE). The association between morphologic changes in the brain and neuropsychological deficits in DE is poorly understood.
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Murine Mast Cells Secrete and Respond to Interleukin-33.
J. Interferon Cytokine Res.
PUBLISHED: 09-12-2013
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Interleukin-33 (IL-33) appears to play a crucial role in the expression of allergic diseases, but its cellular source and regulatory mechanisms remain to be fully elucidated. Mast cells, one of the major effecter cell populations in mediating allergy, express high levels of IL-33 receptor, ST2, and have been shown to express IL-33 transcripts. In this study, we aimed to examine the secretion of IL-33 in mast cells and their response to IL-33. We have successfully detected secreted IL-33 from cell supernatants through a modified enzyme-linked immunosorbent assay (ELISA) technique-cell-based ELISA. Activation of bone marrow-derived cultured mast cells (BMMCs) by crosslinkage of an antigen [ovalbumin (OVA)] and OVA-specific IgE mAbs significantly induced the expression of IL-33 transcripts, cytosolic and secreted proteins. In addition, the Toll-like receptor (TLR) 2 and TLR-9 ligands could trigger IL-33 mRNA expression. Exposure of BMMCs to IL-33 significantly increased the levels of IL-13 and IL-6 expression, concomitant with enhanced activation of mitogen-activated protein kinase (MAPKs) (ERK, p38, and JNK) and nuclear factor-kappa B. These results suggest that mouse BMMCs are capable of producing and serving as endogenous sources of IL-33, and that IL-33 plays an important role in regulating mast cell functions.
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Tri-modal microscopy with multiphoton and optical coherence microscopy/tomography for multi-scale and multi-contrast imaging.
Biomed Opt Express
PUBLISHED: 09-01-2013
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Multi-scale multimodal microscopy is a very useful technique by providing multiple imaging contrasts with adjustable field of views and spatial resolutions. Here, we present a tri-modal microscope combining multiphoton microscopy (MPM), optical coherence microscopy (OCM) and optical coherence tomography (OCT) for subsurface visualization of biological tissues. The advantages of the tri-modal system are demonstrated on various biological samples. It enables the visualization of multiple intrinsic contrasts including scattering, two-photon excitation fluorescence (TPEF), and second harmonic generation (SHG). It also enables a rapid scanning over a large tissue area and a high resolution zoom-in for cellular-level structures on regions of interest. The tri-modal microscope can be important for label-free imaging to obtain a sufficient set of parameters for reliable sample analysis.
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Gag-dependent enrichment of HIV-1 RNA near the uropod membrane of polarized T cells.
J. Virol.
PUBLISHED: 08-21-2013
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The enrichment of HIV-1 macromolecules at the uropod of polarized T cells can significantly promote virus assembly and cell-mediated infection. Using live-cell fluorescence microscopy, we demonstrate that full-length HIV-1 RNA is enriched at the uropod membrane; furthermore, the presence of HIV-1 Gag containing a functional nucleocapsid domain is necessary for this HIV-1 RNA enrichment. The results from these studies provide novel insights into the mechanism of HIV-1 replication in polarized T cells.
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Generation of multiple replication-competent retroviruses through recombination between PreXMRV-1 and PreXMRV-2.
J. Virol.
PUBLISHED: 08-21-2013
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We previously identified two novel endogenous murine leukemia virus proviruses, PreXMRV-1 and PreXMRV-2, and showed that they most likely recombined during xenograft passaging of a human prostate tumor in mice to generate xenotropic murine leukemia virus-related virus (XMRV). To determine the recombination potential of PreXMRV-1 and PreXMRV-2, we examined the generation of replication-competent retroviruses (RCRs) over time in a cell culture system. We observed that either virus alone was noninfectious and the RNA transcripts of the viruses were undetectable in the blood and spleen of nude mice that carry them. To determine their potential to generate RCRs through recombination, we transfected PreXMRV-1 and PreXMRV-2 into 293T cells and used the virus produced to infect fresh cells; the presence of reverse transcriptase activity at 10 days postinfection indicated the presence of RCRs. Population sequencing of proviral DNA indicated that all RCRs contained the gag and 5 half of pol from PreXMRV-2 and the long terminal repeat, 3 half of pol (including integrase), and env from PreXMRV-1. All crossovers were within sequences of at least 9 identical nucleotides, and crossovers within each of two selected recombination zones of 415 nucleotides (nt) in the 5 untranslated region and 982 nt in pol were required to generate RCRs. A recombinant with the same genotype as XMRV was not detected, and our analysis indicates that the probability of generating an identical RCR is vanishingly small. In addition, the studies indicate that the process of RCR formation is primarily driven by selection for viable cis and trans elements from the parental proviruses.
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Risk of severe dysglycemia among diabetic patients receiving levofloxacin, ciprofloxacin, or moxifloxacin in Taiwan.
Clin. Infect. Dis.
PUBLISHED: 08-14-2013
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Observational studies and fatal case reports raise concern about the safety of severe dysglycemia associated with fluoroquinolone use. The objective of this study was to assess the risk of severe dysglycemia among diabetic patients who received different fluoroquinolones.
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Mov10 and APOBEC3G localization to processing bodies is not required for virion incorporation and antiviral activity.
J. Virol.
PUBLISHED: 08-07-2013
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Mov10 and APOBEC3G (A3G) localize to cytoplasmic granules called processing bodies (P bodies), incorporate into human immunodeficiency virus type 1 (HIV-1) virions, and inhibit viral replication. The functional relevance of Mov10/A3G P-body localization to virion incorporation and antiviral activity has not been fully explored. We found that a helicase V mutant of Mov10 exhibits significantly reduced localization to P bodies but still efficiently inhibits viral infectivity via virion incorporation. Disruption of the P bodies by DDX6 knockdown also confirmed Mov10 antiviral activity without P-body localization. In addition, overexpression of SRP19, which binds to 7SL RNA, depleted A3G from P bodies but did not affect its virion incorporation. Sucrose gradient sedimentation assays revealed that the majority of Mov10, A3G, HIV-1 RNA, and Gag formed high-molecular-mass (HMM) complexes that are converted to low-molecular-mass (LMM) complexes after RNase A treatment. In contrast, the P-body markers DCP2, LSM1, eIF4e, DDX6, and AGO1 were in LMM complexes, whereas AGO2, an effector protein of the RNA-induced silencing complex that localizes to P bodies, was present in both LMM and HMM complexes. Depletion of AGO2 indicated that RNA-induced silencing function is required for Mov10s ability to reduce Gag expression upon overexpression, but not its virion incorporation or effect on virus infectivity. We conclude that the majority of Mov10 and A3G are in HMM complexes, whereas most of the P-body markers are in LMM complexes, and that virion incorporation and the antiviral activities of Mov10 and A3G do not require their localization to P bodies.
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Pneumonia risk and use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers.
J Epidemiol
PUBLISHED: 08-03-2013
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Recent studies have shown that use of angiotensin-converting enzyme (ACE) inhibitors may decrease pneumonia risk in various populations. We investigated the effect of ACE inhibitors and angiotensin II receptor blockers (ARBs) on pneumonia hospitalization in the general population of Taiwan.
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Comprehensive assessment of 1-year outcomes and determination of minimum clinically important difference in pain, disability, and quality of life after suboccipital decompression for Chiari malformation I in adults.
Neurosurgery
PUBLISHED: 06-22-2013
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To date, there has been no study to comprehensively assess the effectiveness of suboccipital craniectomy (SOC) for Chiari malformation I (CMI) using validated patient-reported outcome measures.
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Statin use and cataract surgery: a nationwide retrospective cohort study in elderly ethnic Chinese patients.
Drug Saf
PUBLISHED: 06-18-2013
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Since a report of lenticular opacities in dogs treated with high dosages of statins, the debate on the relationship between statin therapy and cataracts has not reached a conclusion.
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Quantification of tumor necrosis factor-? and matrix metalloproteinases-3 in synovial fluid by a fiber-optic particle plasmon resonance sensor.
Analyst
PUBLISHED: 06-12-2013
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The availability of techniques for sensitive detection of early stage osteoarthritis is critical for improving patient health. This study illustrates the feasibility of a fiber-optic particle plasmon resonance (FOPPR) sensor with gold nanoparticles on the unclad region of optical fiber probes for analysis of osteoarthritis biomarkers, tumor necrosis factor-? (TNF-?) and matrix metalloproteinases-3 (MMP-3). Results show that the sensor can achieve a refractive index resolution of 5.18 × 10?? RIU and limits of detection for TNF-? and MMP-3 as low as 8.22 pg ml?¹ (0.48 pM) and 34.3 pg ml?¹ (1.56 pM), respectively. Additionally, the FOPPR sensor shows a good correlation in determining TNF-? and MMP-3 in synovial fluid with the clinically accepted enzyme-linked immunosorbent assay (ELISA) method. Finally, given the FOPPR sensors nature of being low-cost, label-free, highly sensitive, real-time, simple-to-operate, the FOPPR sensor could offer potential to monitor biomarkers of various diseases, and provide an ideal technical tool for point-of-care diagnostics.
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Timing of adjuvant radiotherapy and treatment outcome in childhood ependymoma.
Pediatr Blood Cancer
PUBLISHED: 06-05-2013
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Several trials incorporating adjuvant focal RT for treatment of young children with ependymoma have demonstrated improved survival with acceptable adverse effects. The optimal timing of RT administration is, however, unknown.
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The CC16 A38G polymorphism is associated with asymptomatic airway hyper-responsiveness and development of late-onset asthma.
Ann. Allergy Asthma Immunol.
PUBLISHED: 05-28-2013
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Clara cell secretory protein (CC16) is expressed primarily in the respiratory tract and is a potent anti-inflammatory agent that protects the airway from inflammation. The associations of the A38G polymorphism in this gene with asymptomatic airway hyper-responsiveness (AHR), which is considered a risk factor for future asthma in adults, and the development of adult-onset asthma are unclear.
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Treatment of patients with dual hepatitis C and B by peginterferon ? and ribavirin reduced risk of hepatocellular carcinoma and mortality.
Gut
PUBLISHED: 05-15-2013
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OBJECTIVE: Whether peginterferon ? and ribavirin combination therapy reduces risk of hepatocellular carcinoma (HCC) or improves survival in patients dual-infected with hepatitis C virus (HCV) and hepatitis B virus (HBV) is unknown. Since it is ethically impossible to conduct a randomised trial to learn the long-term efficacy, we rely upon the large database to explore the effectiveness of combination therapy among dual-infected patients. DESIGN: Data for this population-based retrospective cohort study were obtained from the treatment programme, Cancer Registry, National Health Insurance and death certification. We examined the risk of HCC, mortality and adverse events in 1096 treated and 18 988 untreated HCV-HBV dually-infected patients. Outcomes were analysed using the bias corrected inverse probability weighting (IPW) by propensity scores. Outcomes of HCV-HBV dually-infected and HCV mono-infected patients receiving the same treatment were compared using new user design with IPW estimators to adjust for confounding. RESULTS: After adjustment, combination therapy significantly reduced the risk of HCC (HR 0.76, 95% CI 0.59 to 0.97), liver-related mortality (HR 0.47, 95% CI 0.37 to 0.6) and all-cause mortality (HR 0.42, 95% CI 0.34 to 0.52). Nevertheless, the underlying HBV infection was still a risk factor for HCC and mortality after treatment. Treatment was associated with an increase in the incidence of thyroid dysfunction (HR 1.9, p<0.001) and mood disorders (HR 1.81, p=0.005). CONCLUSIONS: This is the first evidence showing that combination therapy decreased the risk of HCC and improved survival in HCV-HBV dually-infected patients despite a slight increase in the incidence of thyroid and mood disorders.
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Quantifying the backscattering of second harmonic generation in tissues with confocal multiphoton microscopy.
J Biomed Opt
PUBLISHED: 05-04-2013
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The backward second harmonic generation (SHG) in mouse tissues is studied with a confocal multiphoton microscopy system. The total backward collected SHG (B-SHG) consists of the backward generated SHG and the backward-scattered forward-generated SHG (BS-SHG), which can be modeled by a Gaussian and a uniform distribution, respectively, at the confocal pinhole plane. By varying the pinhole size with a series of collection fibers, the proportion of the BS-SHG to the B-SHG and the proportion of BS-SHG to the forward generated SHG can be obtained. The approach is first validated by Monte Carlo simulation. It is then applied to two types of mouse tissues: mouse tail tendon and Achilles tendon. It is found that the BS-SHG contributes less to the B-SHG for the tail tendon than Achilles tendon with thicknesses of ~300 ?m. With the thickness of the Achilles tendon tissue increased to 1000 ?m but the focal plane kept at the same depth, as high as ~10% of the total forward SHG is backscattered and collected. The results indicate that BS-SHG may not be the major source of B-SHG in the tail tendon, but it may be the major source in the Achilles tendon. These methods and results provide a noninvasive method and supporting information for investigating the generation mechanism of SHG and help with optimizing backward SHG microscopy and spectroscopy measurements.
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Using induced electroosmotic micromixer to enhance the reproducibility of chemiluminescence intensity.
Electrophoresis
PUBLISHED: 04-19-2013
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In this study, induced electroosmotic vortex flows were generated using an AC electric field by one pair of external electrodes to rapidly mix luminescence reagents in a 30 ?L micromixer and enhance the reproducibility of chemiluminescence (CL) assays. A solution containing the catalyst reagent ferricyanide ions (4 ?L) was pipetted into a reservoir containing luminol to produce CL in the presence of hydrogen peroxide. When the added ferricyanide aliquot contacted the reservoir solution, the CL began flashing, but rapidly diminished as the ferricyanide was consumed. In such a short illumination period, the solutes could not mix homogeneously. Therefore, the reproducibility of CL intensities collected using a CCD and multiple aliquot additions was determined to be inadequate. By contrast, when the solutes were efficiently mixed after adding a ferricyanide aliquot to a micromixer, the intensity reproducibility was significantly improved. When the CL temporal profile was analyzed using a PMT, a consistent improvement in reproducibility was observed between the CL intensity and estimated CL reaction rate. Replicating the proposed device would create a multiple well plate that contains a micromixer in each reservoir; this system is compatible with conventional CL instrumentation and requires no CL enhancer to slow a reaction.
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Diet supplementation of Pediococcus pentosaceus in cobia (Rachycentron canadum) enhances growth rate, respiratory burst and resistance against photobacteriosis.
Fish Shellfish Immunol.
PUBLISHED: 04-13-2013
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Cobia (Rachycentron canadum) is an economically important fish species for aquaculture in tropical and sub-tropical areas. Cobia aquaculture industry has severely damaged due to photobacteriosis caused by Photobacterium damselae subsp. piscicida (Pdp), especially in Taiwan. Antibiotics and vaccines have been applied to control Pdp infection, but the efficacy has been inconsistent. One species of lactic acid bacteria, Pediococcus pentosaceus strain 4012 (LAB 4012), was isolated from the intestine of adult cobia, and its culture supernatant can effectively inhibit Pdp growth in vitro. The acidic pH derived from metabolic acids in LAB culture supernatant was demonstrated to be an important factor for the suppression. After a 2-week feeding of LAB 4012, the growth rate of the fed cobia was 12% higher than that of the non-fed group, and the relative percentage of survival (RPS) of the fed cobia was found to be 74.4 in Pdp immersion challenge. In addition, the respiratory burst (RB) of peripheral blood leukocytes (PBL) in the LAB 4012-fed group was significantly higher than that of the non-fed group. Although feeding LAB 4012 did not improve specific antibody response in cobia after immunization with Pdp vaccine, it still significantly raised the survival rate by 22% over that of the non-fed group after Pdp immersion challenge. Judging by the quick induction of high protection against Pdp infection and promotion of growth in larvae, LAB 4012 was considered to be a viable probiotic for cobia aquaculture.
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Central diabetes insipidus: an unusual complication in a child with juvenile myelomonocytic leukemia and monosomy 7.
J. Pediatr. Hematol. Oncol.
PUBLISHED: 04-12-2013
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Central diabetes insipidus (DI) is well-documented as a presenting feature of myelodysplastic syndrome and acute myeloid leukemia in adults. However, DI is unusual in pediatric patients with myeloid malignancies. We report here this rare complication in a child with neurofibromatosis type 1 who developed juvenile myelomonocytic leukemia and monosomy 7. Our case and previously reported cases of DI arising as a complication in myeloid malignancies demonstrate a close association with deletion of chromosome 7. The clinical characteristics and outcomes of these uncommon cases in children are reviewed and discussed.
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Persistently betanodavirus-infected barramundi (Lates calcarifer) exhibit resistances to red sea bream iridovirus infection.
Dev. Comp. Immunol.
PUBLISHED: 04-07-2013
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Nervous necrosis virus (NNV) and red sea bream iridovirus (RSIV) are two important pathogens that have caused acute, highly contagious, and widespread diseases among wild and cultured fish, especially at larval and juvenile stages. We discovered that the pathogenicity of NNV to the 80 days post-hatch (dph) barramundi is lower than that to the 14 dph barramundi. Following NNV challenge, no mortality occurred in the 80 dph barramundi, but NNV RNA2 and barramundi Mx (BMx) gene expression was detected in the brain and liver. The 80 dph barramundi pre-challenged with NNV became more resistant to the following RSIV challenge (mortality: 62%) compared to the NNV-free barramundi challenged with RSIV (mortality: 100%). A similar phenomenon was revealed in the cell culture system that RSIV proliferated less progeny in the barramundi brain (BB) cell line which exhibit persistent NNV infection than in NNV-free cured BB (cBB) cell line. The potential factors involved in the resistance of the persistently NNV-infected barramundi and BB cells to the secondary RSIV infection were examined in this study. We prove that barramundi anti-NNV polyclonal antibodies do not cross-neutralize RSIV, and NNV infection does not interfere with RSIV replication. However, the interferon (IFN) response and BMx gene expression in cBB cells suppresses the RSIV proliferation. Our study suggests that the NNV-induced IFN response and BMx expression are responsible for the resistance of barramundi to RSIV infection.
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Radar tracking with an interacting multiple model and probabilistic data association filter for civil aviation applications.
Sensors (Basel)
PUBLISHED: 03-22-2013
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The current trend of the civil aviation technology is to modernize the legacy air traffic control (ATC) system that is mainly supported by many ground based navigation aids to be the new air traffic management (ATM) system that is enabled by global positioning system (GPS) technology. Due to the low receiving power of GPS signal, it is a major concern to aviation authorities that the operation of the ATM system might experience service interruption when the GPS signal is jammed by either intentional or unintentional radio-frequency interference. To maintain the normal operation of the ATM system during the period of GPS outage, the use of the current radar system is proposed in this paper. However, the tracking performance of the current radar system could not meet the required performance of the ATM system, and an enhanced tracking algorithm, the interacting multiple model and probabilistic data association filter (IMMPDAF), is therefore developed to support the navigation and surveillance services of the ATM system. The conventional radar tracking algorithm, the nearest neighbor Kalman filter (NNKF), is used as the baseline to evaluate the proposed radar tracking algorithm, and the real flight data is used to validate the IMMPDAF algorithm. As shown in the results, the proposed IMMPDAF algorithm could enhance the tracking performance of the current aviation radar system and meets the required performance of the new ATM system. Thus, the current radar system with the IMMPDAF algorithm could be used as an alternative system to continue aviation navigation and surveillance services of the ATM system during GPS outage periods.
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HuR cytoplasmic expression is associated with increased cyclin A expression and inferior disease-free survival in patients with gastrointestinal stromal tumours (GISTs).
Histopathology
PUBLISHED: 03-21-2013
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HuR is an RNA-binding protein that post-transcriptionally modulates the expression of various target genes involved in carcinogenesis, such as CCNA2, which encodes cyclin A. The aim of this study was to evaluate the significance of HuR expression and subcellular localization in a large cohort of gastrointestinal stromal tumours (GISTs).
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A comparative study of isolated and metachronous oesophageal squamous cell carcinoma with antecedent upper aerodigestive tract cancer.
Eur J Cardiothorac Surg
PUBLISHED: 03-07-2013
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Metachronous oesophageal squamous cell carcinoma (OSCC) has been increasing in long-term survivors of upper aerodigestive tract (UADT) cancers in recent years, but the treatment of such cases is not well established. The aim of this study was to compare the prognosis between patients with metachronous OSCC who had antecedent UADT cancers and patients with isolated OSCC.
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Persistence of antidepressant treatment for depressive disorder in Taiwan.
Gen Hosp Psychiatry
PUBLISHED: 02-12-2013
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We sought to explore factors associated with persistence of antidepressant treatment in Taiwan and to compare persistence rates across various antidepressants.
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Development and validation of a pharmacy-based comorbidity measure in a population-based automated health care database.
Pharmacotherapy
PUBLISHED: 02-07-2013
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To develop the Pharmacy-Based Disease Indicator (PBDI), and to evaluate its performance versus the diagnosis-based Deyo version of the Charlson Index in predicting subsequent-year hospitalization in adults.
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Dimeric RNA recognition regulates HIV-1 genome packaging.
PLoS Pathog.
PUBLISHED: 01-30-2013
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How retroviruses regulate the amount of RNA genome packaged into each virion has remained a long-standing question. Our previous study showed that most HIV-1 particles contain two copies of viral RNA, indicating that the number of genomes packaged is tightly regulated. In this report, we examine the mechanism that controls the number of RNA genomes encapsidated into HIV-1 particles. We hypothesize that HIV-1 regulates genome packaging by either the mass or copy number of the viral RNA. These two distinct mechanisms predict different outcomes when the genome size deviates significantly from that of wild type. Regulation by RNA mass would result in multiple copies of a small genome or one copy of a large genome being packaged, whereas regulation by copy number would result in two copies of a genome being packaged independent of size. To distinguish between these two hypotheses, we examined the packaging of viral RNA that was larger (?17 kb) or smaller (?3 kb) than that of wild-type HIV-1 (?9 kb) and found that most particles packaged two copies of the viral genome regardless of whether they were 17 kb or 3 kb. Therefore, HIV-1 regulates RNA genome encapsidation not by the mass of RNA but by packaging two copies of RNA. To further explore the mechanism that governs this regulation, we examined the packaging of viral RNAs containing two packaging signals that can form intermolecular dimers or intramolecular dimers (self-dimers) and found that one self-dimer is packaged. Therefore, HIV-1 recognizes one dimeric RNA instead of two copies of RNA. Our findings reveal that dimeric RNA recognition is the key mechanism that regulates HIV-1 genome encapsidation and provide insights into a critical step in the generation of infectious viruses.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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

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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.