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Find video protocols related to scientific articles indexed in Pubmed.
Efficacy of Intravitreal Injection of Aflibercept in Neovascular Age-Related Macular Degeneration with or without Choroidal Vascular Hyperpermeability.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 11-15-2014
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PURPOSE. To compare therapeutic responses to intravitreal aflibercept and ranibizumab in neovascular age-related macular degeneration (AMD)-affected eyes with and without choroidal vascular hyperpermeability (CVH). METHODS. Medical records of 216 consecutive patients (216 eyes) with treatment-naïve exudative AMD who had received 3 monthly intravitreal injections of aflibercept (2 mg) and ranibizumab (0.5 mg) at a single institution were analyzed. The associations of CVH with functional and morphologic changes were compared between the treatment groups. RESULTS. Although foveal thickness (P = 0.85) and visual acuity (P = 0.13) changes were not significantly different between the treatment groups, subfoveal choroidal thickness (CT) (P = 0.001) and pigment epithelial detachment (PED) height (P = 0.043) decreased more profoundly in the aflibercept-treated group. The incidence of dry macula after treatments was lower in the ranibizumab-treated eyes with CVH than in those without CVH (P = 0.043), but it showed no significant difference between the aflibercept-treated eyes with and without CVH (P = 0.74). The aflibercept-treated eyes with CVH showed a higher incidence of dry macula (P = 0.04) and greater decrease in subfoveal CT (P = 0.002) than the ranibizumab-treated eyes with CVH. CONCLUSIONS. Intravitreal aflibercept can achieve remission of exudative retinal changes in eyes with AMD even in the presence of CVH. In addition, it showed greater effects on the choroid and PED than intravitreal ranibizumab, which may contribute to additional therapeutic effect on eyes with CVH in the long term. The possible relationship between CVH suppression and decrease in CT warrants further study.
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miRNA-629 Targets TRIM33 to Promote TGF-beta/Smad Signaling and Metastatic Phenotypes in ccRCC.
Mol. Cancer Res.
PUBLISHED: 11-09-2014
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Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney, and clear cell RCC (ccRCC) represents its most common histological subtype. To identify a therapeutic target for ccRCC, microRNA (miRNA) expression signatures from ccRCC clinical specimens were analyzed. miRNA microarray and real-time PCR analyses revealed that miR-629 expression was significantly upregulated in human ccRCC compared to adjacent non-cancerous renal tissue. Functional inhibition of miR-629 by a hairpin miRNA inhibitor suppressed ccRCC cell motility and invasion. Mechanistically, miR-629 directly targeted tripartite motif-containing 33 (TRIM33), which inhibits the TGF-beta/Smad signaling pathway. In clinical ccRCC specimens, downregulation of TRIM33 was observed with the association of both pathological stages and grades. The miR-629 inhibitor significantly suppressed TGF-beta-induced Smad activation by upregulating TRIM33 expression and subsequently inhibited the association of Smad2/3 and Smad4. Moreover, a miR-629 mimic enhanced the effect of TGF-beta on the expression of epithelial-mesenchymal transition (EMT)-related factors as well as on the motility and invasion in ccRCC cells. These findings identify miR-629 as a potent regulator of the TGF-beta/Smad signaling pathway via TRIM33 in ccRCC. Implications: This study suggests that miR-629 has biomarker potential through its ability to regulate TGF-beta/Smad signaling and accelerate ccRCC cell motility and invasion.
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Central blood pressure relates more strongly to retinal arteriolar narrowing than brachial blood pressure: the Nagahama Study.
J. Hypertens.
PUBLISHED: 11-08-2014
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Although central blood pressure (BP) is considered to be more closely associated with large arterial remodeling and cardiovascular outcomes than brachial BP, few studies have investigated these associations with changes in small arteries. As morphological changes in retinal vessels might be associated with cardiovascular outcomes, we conducted a cross-sectional study to investigate the association of central BP with retinal vessel caliber.
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Brain imaging for oxidative stress and mitochondrial dysfunction in neurodegenerative diseases.
Q J Nucl Med Mol Imaging
PUBLISHED: 11-05-2014
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Oxidative stress, one of the most probable molecular mechanisms for neuronal impairment, is reported to occur in the affected brain regions of various neurodegenerative diseases. Recently, many studies showed evidence of a link between oxidative stress or mitochondrial damage and neuronal degeneration. Basic in vitro experiments and postmortem studies demonstrated that biomarkers for oxidative damage can be observed in the pathogenic regions of the brain and the affected neurons. Model animal studies also showed oxidative damage associated with neuronal degeneration. The molecular imaging method with positron emission tomography (PET) is expected to delineate oxidatively stressed microenvironments to elucidate pathophysiological changes of the in vivo brain; however, only a few studies have successfully demonstrated enhanced stress in patients. Radioisotope copper labeled diacetyl--bis(N4--methylthiosemicarbazone) (Cu--ATSM) may be the most promising candidate for this oxidative stress imaging. The tracer is usually known as a hypoxic tissue imaging PET probe, but the accumulation mechanism is based on the electron rich environment induced by mitochondrial impairment and/or microsomal over--reduction, and thus it is considered to represent the oxidative stress state correlated with the degree of disease severity. In this review, Cu--ATSM PET is introduced in detail from the basics to practical methods in clinical studies, as well as recent clinical studies on cerebrovascular diseases and neurodegenerative diseases. Several other PET probes are also introduced from the point of view of neuronal oxidative stress imaging. These molecular imaging methods should be promising tools to reveal oxidative injuries in various brain diseases.
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PLC-based LP11 mode rotator for mode-division multiplexing transmission.
Opt Express
PUBLISHED: 10-17-2014
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A PLC-based LP11 mode rotator is proposed. The proposed mode rotator is composed of a waveguide with a trench that provides asymmetry of the waveguide. Numerical simulations show that converting LP11a (LP11b) mode to LP11b (LP11a) mode can be achieved with high conversion efficiency (more than 90%) and little polarization dependence over a wide wavelength range from 1450 nm to 1650 nm. In addition, we fabricate the proposed LP11 mode rotator using silica-based PLC. It is confirmed that the fabricated mode rotator can convert LP11a mode to LP11b mode over a wide wavelength range.
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Ocular forward light scattering and corneal backward light scattering in patients with dry eye.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 09-20-2014
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To evaluate ocular forward light scattering and corneal backward light scattering in patients with dry eye.
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Expression of ABCB6 is related to resistance to 5-FU, SN-38 and vincristine.
Anticancer Res.
PUBLISHED: 09-10-2014
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A previously established arsenite-resistant cell line, KAS, is also resistant to a variety of anticancer drugs. In order to understand responsible molecules for the multidrug resistance phenotype of KAS cells, we examined the expressions of ATP-binding cassette (ABC) transporters and found that the ABCB6 and ABCC1/ multidrug resistance protein 1 (ABCC1/MRP1) were increased. ABCC1/MRP1 was not completely responsible for the drug resistance spectrum of KAS cells and several reports have suggested that ABCB6 is related to anticancer drug and metal resistance. We, therefore, established and examined ABCB6-expressing KB cells and ABCB6-knockdown KAS cells. ABCB6 expression enhanced resistance to 5-fluorouracil (5-FU), SN-38 and vincristine (Vcr) but not to arsenite. Conversely, down-regulation of ABCB6 in KAS cells increased the sensitivity of KAS cells to 5-FU, SN-38 and Vcr, but not to arsenite. Our findings suggest that ABCB6 is involved in 5-FU, SN-38 and Vcr resistance.
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Association of focal choroidal excavation with age-related macular degeneration.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 09-04-2014
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To study the prevalence, tomographic features, and clinical characteristics of focal choroidal excavation (FCE) in eyes with exudative age-related macular degeneration (AMD).
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LOXL2 Status Correlates with Tumor Stage and Regulates Integrin Levels to Promote Tumor Progression in ccRCC.
Mol. Cancer Res.
PUBLISHED: 08-06-2014
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Clear cell renal cell carcinoma (ccRCC) is the most common histologically-defined subtype of renal cell carcinoma (RCC). To define the molecular mechanism in the progression of ccRCC, we focused on LOX-like protein 2 (LOXL2), which is critical for the first-step in collagen and elastin crosslinking. Using exon array analysis and quantitative validation, LOXL2 was shown to be significantly upregulated in clinical specimens of human ccRCC tumor tissues, compared to adjacent non-cancerous renal tissues, and this elevated expression correlated with the pathological stages of ccRCC. RNAi-mediated knockdown of LOXL2 resulted in marked suppression of stress-fiber and focal adhesion formation in ccRCC cells. Moreover, LOXL2 siRNA knockdown significantly inhibited cell growth, migration, and invasion. Mechanistically, LOXL2 regulated the degradation of both integrins alpha5 (ITGAV5) and beta1 (ITGB1) via protease- and proteasome-dependent systems. In clinical ccRCC specimens, the expression levels of LOXL2 and integrin alpha5 correlated with the pathological tumor grades. In conclusion, LOXL2 is a potent regulator of integrin alpha5 and integrin beta1 protein levels and functions in a tumor-promoting capacity in ccRCC. Implications: This is the first report demonstrating that LOXL2 is highly expressed and involved in ccRCC progression by regulating the levels of integrins alpha5 and beta1.
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Quantitative regional differences in corneal endothelial abnormalities in the central and peripheral zones in Fuchs' endothelial corneal dystrophy.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 07-26-2014
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To quantitate the regional corneal differences in endothelial abnormalities in Fuchs' endothelial corneal dystrophy at multiple sites, including the peripheral zone.
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Use of the structure-function relationship in detecting glaucoma progression in early glaucoma.
BMC Ophthalmol
PUBLISHED: 06-03-2014
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To evaluate the use of optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness and visual field (VF) measurements in detecting disease progression in patients with early glaucoma.
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Two-year visual outcome of polypoidal choroidal vasculopathy treated with photodynamic therapy combined with intravitreal injections of ranibizumab.
Graefes Arch. Clin. Exp. Ophthalmol.
PUBLISHED: 05-14-2014
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To investigate the 2-year outcomes of photodynamic therapy (PDT) combined with intravitreal injections of ranibizumab for polypoidal choroidal vasculopathy (PCV).
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Effects of aflibercept for ranibizumab-resistant neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.
Graefes Arch. Clin. Exp. Ophthalmol.
PUBLISHED: 05-10-2014
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To evaluate visual and anatomic outcomes in response to the conversion of treatment in patients with neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) refractory to previous treatment. We also investigated the effect of genetic factors.
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Choroidal neovascularization in eyes with choroidal vascular hyperpermeability.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 05-01-2014
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We describe the clinical and genetic characteristics of choroidal neovascularization (CNV) in eyes with choroidal vascular hyperpermeability (CVH).
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Identification and potential application of human corneal endothelial progenitor cells.
Stem Cells Dev.
PUBLISHED: 04-10-2014
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The corneal endothelium is believed to be developmentally originated from the periocular mesenchyme via the neural crest. Human corneal endothelial progenitor cells (HCEPs) have been investigated because of their potential availability for the tissue regenerative medicine. However, the existence and the properties of HCEPs have not been elucidated yet. We first established a novel serum-free culture system for HCEPs. The HCEPs highly expressed p75 neurotrophin receptor, SOX9, and FOXC2, and partially retained the properties of neural crest and periocular mesenchyme. Further, we demonstrated that HCEPs had a high proliferative potency, and the differentiated HCEP sheets had corneal endothelial function by using the Ussing chamber system and transplantation to the rabbit cornea. These findings suggest that the HCEPs can be selectively expanded from the corneal endothelium using a specific culture system and will provide cell sheets for corneal regenerative medicine.
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Comparison of the Growth of Lactobacillus delbrueckii, L. paracasei and L. plantarum on Inulin in Co-culture Systems.
Biosci Microbiota Food Health
PUBLISHED: 04-07-2014
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Lactobacillus delbrueckii TU-1, which apparently takes intact inulin into its cells and then degrades it intracellularly, was co-cultured in vitro with L. paracasei KTN-5, an extracellular inulin degrader; or L. plantarum 22A-3, a strain that is able to utilize fructose but not inulin; or both in order to prequalify inulin as a prebiotic agent in vivo. When L. delbrueckii TU-1 was co-cultured with L. paracasei KTN-5 on fructose or inulin, the growth of L. delbrueckii TU-1 on inulin was markedly higher than that of L. paracasei KTN-5, whereas the growth of L. delbrueckii TU-1 on fructose was much lower than that of L. paracasei KTN-5. These results suggest that L. delbrueckii TU-1 and L. paracasei KTN-5 were efficient at utilizing inulin and fructose, respectively. When L. plantarum 22A-3 was co-cultured with L. delbrueckii TU-1 on inulin, the growth of L. plantarum 22A-3 was enhanced by L. paracasei KTN-5 but not by L. delbrueckii TU-1, suggesting that the fructose moiety that L. paracasei KTN-5 released temporarily into the medium was "scavenged" by L. plantarum 22A-3. Thus, L. delbrueckii TU-1, L. paracasei KTN-5, and L. plantarum 22A-3 were then cultured altogether on inulin. The growth of L. delbrueckii TU-1 was unaffected but that of L. paracasei KTN-5 was markedly suppressed. This evidence suggests that prebiotic use of inulin supported the selective growth of intracellular inulin degraders such as L. delbrueckii rather than extracellular inulin degraders such as L. paracasei in the host microbiota.
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Comparison of exudative age-related macular degeneration subtypes in Japanese and French Patients: multicenter diagnosis with multimodal imaging.
Am. J. Ophthalmol.
PUBLISHED: 03-01-2014
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To compare and analyze differences and similarities between Japanese and French patients in subtype diagnosis of exudative age-related macular degeneration (AMD) as determined by fundus photography (FP) and fluorescein angiography (FA), and a multimodal imaging involving FP, FA, indocyanine green angiography (ICGA), and optical coherence tomography (OCT).
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Three-dimensional optical coherence tomography evaluation of vascular changes at arteriovenous crossings.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 03-01-2014
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To study the three-dimensional morphologic features of retinal arteriovenous crossings with optical coherence tomography (OCT) and elucidate the vascular changes associated with crossing phenomena as seen on fundus photographs.
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Two-year visual outcome of ranibizumab in typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.
Graefes Arch. Clin. Exp. Ophthalmol.
PUBLISHED: 02-26-2014
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To investigate the 2-year outcomes of intravitreal injections of ranibizumab in typical neovascular age-related macular degeneration (tAMD) and polypoidal choroidal vasculopathy (PCV). Factors associated with visual outcomes are examined.
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Effect of diquafosol ophthalmic solution on the optical quality of the eyes in patients with aqueous-deficient dry eye.
Acta Ophthalmol
PUBLISHED: 02-12-2014
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To investigate the short- and long-term effects of diquafosol ophthalmic solution on the optical quality of the eyes in patients with aqueous-deficient dry eye.
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Retinal microstructural changes in eyes with resolved branch retinal vein occlusion: an adaptive optics scanning laser ophthalmoscopy study.
Am. J. Ophthalmol.
PUBLISHED: 02-10-2014
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To assess macular photoreceptor abnormalities in eyes with resolved branch retinal vein occlusion (BRVO) using adaptive optics scanning laser ophthalmoscopy (AO-SLO).
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Rigid gas-permeable contact lens-assisted cataract surgery in patients with severe keratoconus.
J Cataract Refract Surg
PUBLISHED: 01-31-2014
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We describe rigid gas-permeable (RGP) contact lens-assisted cataract surgery in patients with severe keratoconus. During cataract surgery in cases with severe keratoconus, the intraocular images are distorted and visual perspective is lost because of irregular corneal astigmatism. Poor visibility can lead to complications, including posterior capsule rupture and corneal endothelial cell damage. To overcome these problems, an RGP contact lens was placed on the cornea in 2 cases. The image distortion decreased markedly, and the visual perspective improved. Intraocular manipulations such as irrigation/aspiration were performed safely. Improvement in transillumination led to good visualization of the anterior and posterior capsules. No intraoperative or postoperative complications developed in either case. This technique provided excellent visualization during cataract surgery in patients with severe keratoconus.
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Characterization of gut microbiota profiles by disease activity in patients with Crohn's disease using data mining analysis of terminal restriction fragment length polymorphisms.
Biomed Rep
PUBLISHED: 01-23-2014
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The gut microbiota plays a significant role in the pathogenesis of Crohn's disease (CD). In this study, we analyzed the disease activity and associated fecal microbiota profiles in 160 CD patients and 121 healthy individuals. Fecal samples from the CD patients were collected during three different clinical phases, the active (n=66), remission-achieved (n=51) and remission-maintained (n=43) phases. Terminal restriction fragment length polymorphism (T-RFLP) and data mining analysis using the Classification and Regression Tree (C&RT) approach were performed. Data mining provided a decision tree that clearly identified the various subject groups (nodes). The majority of the healthy individuals were divided into Node-5 and Node-8. Healthy subjects comprised 99% of Node-5 (91 of 92) and 84% of Node-8 (21 of 25 subjects). Node-3 was characterized by CD (136 of 160 CD subjects) and was divided into Node-6 and Node-7. Node-6 (n=103) was characterized by subjects in the active phase (n=48; 46%) and remission-achieved phase (n=39; 38%) and Node-7 was characterized by the remission-maintained phase (21 of 37 subjects; 57%). Finally, Node-6 was divided into Node-9 and Node-10. Node-9 (n=78) was characterized by subjects in the active phase (n=43; 55%) and Node-10 (n=25) was characterized by subjects in the remission-maintained phase (n=16; 64%). Differences in the gut microbiota associated with disease activity of CD patients were identified. Thus, data mining analysis appears to be an ideal tool for the characterization of the gut microbiota in inflammatory bowel disease.
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Macular choroidal thickness and volume of eyes with reticular pseudodrusen using swept-source optical coherence tomography.
Am. J. Ophthalmol.
PUBLISHED: 01-21-2014
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To investigate the choroidal thickness/volume of eyes with reticular pseudodrusen using high-penetration swept-source optical coherence tomography (SS-OCT) and to evaluate the choroidal vasculature changes using en face images.
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Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-02-2014
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A series of 1-aryl-3,4-substituted-1H-pyrazol-5-ol derivatives was synthesized and evaluated as prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors to obtain a novel anti-prostate cancer drug. After modifying 1-(1H-benzimidazol-2-yl)-3,4-dimethyl-1H-pyrazol-5-ol (1), a hit compound found during random screening using a recombinant PCA-1/ALKBH3, 1-(1H-5-methylbenzimidazol-2-yl)-4-benzyl-3-methyl-1H-pyrazol-5-ol (35, HUHS015), was obtained as a potent PCA-1/ALKBH3 inhibitor both in vitro and in vivo. The bioavailability (BA) of 35 was 7.2% in rats after oral administration. As expected, continuously administering 35 significantly suppressed the growth of DU145 cells, which are human hormone-independent prostate cancer cells, in a mouse xenograft model without untoward effects.
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Maintenance and distribution of epithelial stem/progenitor cells after corneal reconstruction using oral mucosal epithelial cell sheets.
PLoS ONE
PUBLISHED: 01-01-2014
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We assessed the maintenance and distribution of epithelial stem/progenitor cells after corneal reconstruction using tissue-engineered oral mucosal cell sheets in a rat model. Oral mucosal biopsy specimens were excised from green fluorescent protein (GFP) rats and enzymatically treated with Dispase II. These cells were cultured on inserts with mitomycin C-treated NIH/3T3 cells, and the resulting cell sheets were harvested. These tissue-engineered cell sheets from GFP rats were transplanted onto the eyes of a nude rat limbal stem cell deficiency model. Eight weeks after surgery, ocular surfaces were completely covered by the epithelium with GFP-positive cells. Transplanted corneas expressed p63 in the basal layers and K14 in all epithelial layers. Epithelial cells harvested from the central and peripheral areas of reconstructed corneas were isolated for a colony-forming assay, which showed that the colony-forming efficiency of the peripheral epithelial cells was significantly higher than that of the central epithelial cells 8 weeks after corneal reconstruction. Thus, in this rat model, the peripheral cornea could maintain more stem/progenitor cells than the central cornea after corneal reconstruction using oral mucosal epithelial cell sheets.
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Analysis of fundus shape in highly myopic eyes by using curvature maps constructed from optical coherence tomography.
PLoS ONE
PUBLISHED: 01-01-2014
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To evaluate fundus shape in highly myopic eyes using color maps created through optical coherence tomography (OCT) image analysis.
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Calcitonin gene-related peptide regulates type IV hypersensitivity through dendritic cell functions.
PLoS ONE
PUBLISHED: 01-01-2014
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Dendritic cells (DCs) play essential roles in both innate and adaptive immune responses. In addition, mutual regulation of the nervous system and immune system is well studied. One of neuropeptides, calcitonin gene-related peptide (CGRP), is a potent regulator in immune responses; in particular, it has anti-inflammatory effects in innate immunity. For instance, a deficiency of the CGRP receptor component RAMP 1 (receptor activity-modifying protein 1) results in higher cytokine production in response to LPS (lipopolysaccharide). On the other hand, how CGRP affects DCs in adaptive immunity is largely unknown. In this study, we show that CGRP suppressed Th1 cell differentiation via inhibition of IL-12 production in DCs using an in vitro co-culture system and an in vivo ovalbumin-induced delayed-type hypersensitivity (DTH) model. CGRP also down-regulated the expressions of chemokine receptor CCR2 and its ligands CCL2 and CCL12 in DCs. Intriguingly, the frequency of migrating CCR2(+) DCs in draining lymph nodes of RAMP1-deficient mice was higher after DTH immunization. Moreover, these CCR2(+) DCs highly expressed IL-12 and CD80, resulting in more effective induction of Th1 differentiation compared with CCR2(-) DCs. These results indicate that CGRP regulates Th1 type reactions by regulating expression of cytokines, chemokines, and chemokine receptors in DCs.
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Roles of receptor activity-modifying protein 1 in angiogenesis and lymphangiogenesis during skin wound healing in mice.
FASEB J.
PUBLISHED: 12-05-2013
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Receptor activity-modifying protein 1 (RAMP1) forms a complex with calcitonin receptor-like receptor (CLR) to produce the receptor for calcitonin gene-related peptide (CGRP). CGRP, a 37-aa neuropeptide, is widely distributed in neuronal tissues and exerts its biological effects via CLR/RAMP1; however, the pathophysiological roles of CLR/RAMP1 remain to be clarified. To study the functions of CLR/RAMP1, we generated RAMP1-knockout (RAMP1(-/-)) mice. Compared with those of wild-type (WT) mice, wound healing and wound-induced angiogenesis were significantly suppressed in RAMP1(-/-) mice, with reduced expression of vascular endothelial growth factor (VEGF)-A. Formation of the lymphatic vessels that drain interstitial fluids was also suppressed in RAMP1(-/-) mice, with reduced expression of VEGF-C and VEGFR-3 in wound granulation tissues. RAMP1 was expressed in endothelial cells (ECs) in the preexisting skin blood vessels, but was not observed in ECs in newly formed blood or lymphatic vessels. Macrophages in the wound granulation tissues expressed RAMP1 and produced substantial amounts of VEGF-C in response to CGRP in vitro. RAMP1(-/-) bone marrow chimeric mice showed delayed wound healing with reduced angiogenesis/lymphangiogenesis in wound granulation tissues. These findings suggest that RAMP1 plays a crucial role in wound healing and wound-induced angiogenesis and lymphangiogenesis and that it is a promising target for controlling angiogenesis and lymphangiogenesis.-Kurashige, C., Hosono, K., Matsuda, H., Tsujikawa, K., Okamoto, H., Majima, M. Roles of receptor activity-modifying protein 1 in angiogenesis and lymphangiogenesis during skin wound healing in mice.
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Development of a Cell Sheet Transportation Technique for Regenerative Medicine.
Tissue Eng Part C Methods
PUBLISHED: 11-26-2013
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Purpose: A transportation technique for cell sheets is necessary to standardize regenerative medicine. The aim of this article is to develop and evaluate a new transportation technique for cell sheets. Material and Methods: We developed a transportation container with three basic functions: the maintenance of interior temperature, air pressure, and sterility. The interior temperature and air pressure were monitored by a recorder. Human oral mucosal epithelial cells obtained from two healthy volunteers were cultured on temperature-responsive culture dishes. The epithelial cell sheets were transported via an airplane between the Osaka University and Tohoku University using the developed cell transportation container. Histological and immunohistochemical analyses and flow cytometric analyses for cell viability and cell purity were performed for the cell sheets before and 12?h after transportation to assess the influence of transportation on the cell sheets. Sterility tests and screening for endotoxin and mycoplasma in the cell sheets were performed before and after transportation. Results: During transportation via an airplane, the temperature inside the container was maintained above 32°C, and the changes in air pressure remained within 10?hPa. The cell sheets were well stratified and successfully harvested before and after transportation. The expression patterns of keratin 3/76, p63, and MUC16 were equivalent before and after transportation. However, the expression of ZO-1 in the cell sheet after transportation was slightly weaker than that before transportation. The cell viability was 72.0% before transportation and 77.3% after transportation. The epithelial purity was 94.6% before transportation and 87.9% after transportation. Sterility tests and screening for endotoxin and mycoplasma were negative for all cell sheets. Conclusion: The newly developed transportation technique for air travel is essential technology for regenerative medicine and promotes the standardization and spread of regenerative therapies.
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Two-mode PLC-based mode multi/demultiplexer for mode and wavelength division multiplexed transmission.
Opt Express
PUBLISHED: 11-13-2013
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We proposed a PLC-based mode multi/demultiplexer (MUX/DEMUX) with an asymmetric parallel waveguide for mode division multiplexed (MDM) transmission. The mode MUX/DEMUX including a mode conversion function with an asymmetric parallel waveguide can be realized by matching the effective indices of the LP(01) and LP(11) modes of two waveguides. We report the design of a mode MUX/DEMUX that can support C-band WDM-MDM transmission. The fabricated mode MUX/DEMUX realized a low insertion loss of less than 1.3 dB and high a mode extinction ratio that exceeded 15 dB. We used the fabricated mode MUX/DEMUX to achieve a successful 2 mode x 4 wavelength x 10 Gbps transmission over a 9 km two-mode fiber with a penalty of less than 1 dB.
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The time course changes of choroidal neovascularization in angioid streaks.
Retina (Philadelphia, Pa.)
PUBLISHED: 10-26-2013
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To assess the clinical course of choroidal neovascularization (CNV) in patients with angioid streaks using optical coherence tomography and fluorescein angiography/indocyanine green angiography.
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Association between ZIC2, RASGRF1, and SHISA6 genes and high myopia in Japanese subjects.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 10-24-2013
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We investigated the association of genetic variations, which were identified recently in a large-scale genome-wide association study (GWAS) to confer risk of refractive error and common myopia in Caucasians, with high myopia in Japanese subjects.
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Association between the cholesteryl ester transfer protein gene and polypoidal choroidal vasculopathy.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 08-17-2013
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To determine whether genetic variants in the lipid-associated genes are related to the risk of developing polypoidal choroidal vasculopathy (PCV) in a Japanese population.
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Effect of instillation of eyedrops for dry eye on optical quality.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 07-02-2013
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To investigate the effects of viscosity and suspensibility of eyedrops for dry eye by evaluating an eyedrop with one of the solutions or no solution (0.3% sodium hyaluronate ophthalmic solution, 3% diquafosol ophthalmic solution, and 2% rebamipide ophthalmic suspension) on ocular higher-order aberrations (HOAs) and forward light scatter.
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Multimodal evaluation of macular function in age-related macular degeneration.
Jpn. J. Ophthalmol.
PUBLISHED: 06-20-2013
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To evaluate macular function using multimodality in eyes with age-related macular degeneration (AMD) at various stages.
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Vascular Endothelial Growth Factor Gene and the Response to Anti-Vascular Endothelial Growth Factor Treatment for Choroidal Neovascularization in High Myopia.
Ophthalmology
PUBLISHED: 06-20-2013
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To investigate the association between the vascular endothelial growth factor (VEGF) gene polymorphism and the response to anti-VEGF treatment for choroidal neovascularization (CNV) in highly myopic eyes.
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Evaluation of pigment epithelium-derived factor and complement factor I polymorphisms as a cause of choroidal neovascularization in highly myopic eyes.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 06-01-2013
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A case-control study in a relatively large cohort of highly myopic patients was conducted to explore the genetic background of the occurrence of choroidal neovascularization (CNV) secondary to high myopia.
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Validation of Na,K-ATPase Pump Function of Corneal Endothelial Cells for Corneal Regenerative Medicine.
Tissue Eng Part C Methods
PUBLISHED: 05-14-2013
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Tissue-engineering approaches to cultivate corneal endothelial cells (CECs) or induce CECs from stem cells are under investigation for the treatment of endothelial dysfunction. Before clinical application, a validation method to determine the quality of these cells is required. In this study, we quantified the endothelial pump function required for maintaining the corneal thickness using rabbit CECs (RCECs) and a human CEC line (B4G12). The potential difference of RCECs cultured on a permeable polyester membrane (Snapwell), B4G12 cells on Snapwell, or B4G12 cells on a collagen membrane (CM6) was measured by an Ussing chamber system, and the effect of different concentrations of ouabain (Na,K-ATPase specific inhibitor) was obtained. A mathematical equation derived from the concentration curve revealed that 2?mM ouabain decreases pump function of RCECs to 1.0?mV, and 0.6?mM ouabain decreases pump function of B4G12 on CM6 to 1.0?mV. Ouabain injection into the anterior chamber of rabbit eyes at a concentration of <2?mM maintained the corneal thickness, while those over 3?mM significantly increased the corneal thickness. B4G12 cell sheets transplanted into rabbit eyes treated with 0.6?mM ouabain maintained the corneal thickness, while 3.5?mM ouabain significantly increased the corneal thickness. Taken together, pump function >1.0?mV is required to maintain the corneal thickness. These results can be used for standardization of CEC pump function and validation of tissue-engineered CEC sheets for clinical use.
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Intravitreal injection of ranibizumab for recovery of macular function in eyes with subfoveal polypoidal choroidal vasculopathy.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 05-11-2013
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To evaluate changes in macular function in eyes with polypoidal choroidal vasculopathy (PCV) after intravitreal ranibizumab (IVR) treatment.
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Choroidal thickness in central serous chorioretinopathy.
Retina (Philadelphia, Pa.)
PUBLISHED: 05-10-2013
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To study the choroidal thickness profile using high-penetration optical coherence tomography in central serous chorioretinopathy (CSC).
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Regulation of eotaxin-3/CC chemokine ligand 26 expression by T helper type 2 cytokines in human colonic myofibroblasts.
Clin. Exp. Immunol.
PUBLISHED: 04-03-2013
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Eotaxins induce the trafficking of eosinophils to the sites of inflammation via CC chemokine receptor 3 (CCR3). In this study, we investigated eotaxin-3/CC chemokine ligand 26 (CCL26) expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD), and characterized the molecular mechanisms responsible for eotaxin-3 expression in human colonic myofibroblasts. Eotaxin-3?mRNA and protein expression was evaluated by real time-polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Eotaxin-3?mRNA expression was elevated significantly in the active lesions of ulcerative colitis (UC) patients. Significant elevations were also observed in the active lesions of Crohns disease (CD) patients, but this was significantly lower than that detected in the active UC lesions. There were no significant increases in the inactive lesions of UC or CD patients. Colonic myofibroblasts were identified as a major source of eotaxin-3 in the colonic mucosa, and interleukin (IL)-4 and IL-13 enhanced eotaxin-3?mRNA and protein expression significantly in these cells. There was a significant positive correlation between mucosal eotaxin-3 and IL-4?mRNA expression in the active lesions of IBD patients. The IL-4- and IL-13-induced eotaxin-3?mRNA expression was regulated by the signal transducer and activator of transcription-6 (STAT-6) and suppressor of cytokine signalling (SOCS)1-mediated pathways. Interferon (IFN)-? acts as a negative regulator on the IL-4- and IL-13-induced eotaxin-3 expression via STAT-1 activation. Eotaxin-3 expression was elevated specifically in the active lesions of IBD, in particular UC. Eotaxin-3 derived from colonic myofibroblasts may play an important role in the pathophysiology of UC.
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Reduction of retinal sensitivity in eyes with reticular pseudodrusen.
Am. J. Ophthalmol.
PUBLISHED: 03-29-2013
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To evaluate the effect of macular reticular pseudodrusen on retinal function using multiple imaging methods.
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Age- and hypertension-dependent changes in retinal vessel diameter and wall thickness: an optical coherence tomography study.
Am. J. Ophthalmol.
PUBLISHED: 03-23-2013
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To validate and evaluate the reliability of retinal vessel diameter measurements by optical coherence tomography (OCT). The effects of age and hypertension on vessel diameter were also examined.
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Prevalence and characteristics of age-related macular degeneration in the Japanese population: the Nagahama study.
Am. J. Ophthalmol.
PUBLISHED: 03-21-2013
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To estimate the age- and sex-specific prevalence of early age-related macular degeneration (AMD; drusen and retinal pigment abnormalities) and late AMD (exudative AMD and geographic atrophy) in the Japanese population.
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Relationship between serum infliximab trough levels and endoscopic activities in patients with Crohns disease under scheduled maintenance treatment.
J. Gastroenterol.
PUBLISHED: 03-19-2013
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BACKGROUND AND AIMS: Few data are available to support the clinical relevance of infliximab (IFX) trough levels for prediction of endoscopic disease activity in Crohns disease (CD). This study evaluated the endoscopic disease activities in relation to clinical outcome using several laboratory markers including serum IFX trough levels in patients with CD undergoing scheduled IFX maintenance treatment. MATERIALS AND METHODS: A total of 78 sessions of endoscopy were performed on 45 patients with CD. Endoscopic activity was assessed using the modified Rutgeerts scoring system. IFX trough levels and anti-IFX antibodies (ATIs) were determined by immunoassays. RESULTS: Endoscopic activity negatively correlated with serum IFX trough levels (Spearmans rank correlation coefficient (?) = -0.54, P < 0.0001) and serum albumin levels (? = -0.46, P < 0.0001), and positively correlated with CRP (C-reactive protein) levels (? = 0.55, P < 0.0001), ESR (erythrocyte sedimentation rate) (? = 0.47, P < 0.0001) and fecal calprotectin levels. IFX trough levels and serum albumin levels were significantly elevated in the mucosal healing (MH) group, but ATIs, CRP, ESR and fecal calprotectin levels were significantly elevated in the nonmucosal healing group. Receiver operation curve revealed that the optimal cutoff value of IFX trough levels for identifying normal laboratory markers was 0.6 ?g/ml for CRP, 1.0 ?g/ml for serum albumin and 1.1 ?g/ml for fecal calprotectin. Identification of mucosal healing needed a higher cutoff value of 4.0 ?g/ml. Thiopurine treatment did not affect IFX trough and ATI levels. CONCLUSION: Mucosal healing requires higher IFX trough levels, compared to those to achieve normalization of routine clinical markers.
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Calcitonin gene-related peptide and cyclic adenosine 5-monophosphate/protein kinase A pathway promote IL-9 production in Th9 differentiation process.
J. Immunol.
PUBLISHED: 03-15-2013
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Th9 cells are a novel Th cell subset that produces IL-9 and is involved in type I hypersensitivity such as airway inflammation. Although its critical roles in asthma have attracted interest, the physiological regulatory mechanisms of Th9 cell differentiation and function are largely unknown. Asthma is easily affected by psychological factors. Therefore, we investigated one of the physiological mediators derived from the nervous system, calcitonin gene-related peptide (CGRP), in asthma and Th9 cells because CGRP and activation of the cAMP/protein kinase A (PKA) pathway by CGRP are known to be important regulators in several immune responses and allergic diseases. In this study, we demonstrated that the CGRP/cAMP/PKA pathway promotes IL-9 production via NFATc2 activation by PKA-dependent glycogen synthase kinase-3? inactivation. Moreover, CGRP also induces the expression of PU.1, a critical transcriptional factor in Th9 cells, which depends on PKA, but not NFATc2. Additionally, we demonstrated the physiological importance of CGRP in IL-9 production and Th9 differentiation using an OVA-induced airway inflammation model and T cell-specific CGRP receptor-deficient mice. The present study revealed a novel regulatory mechanism comprising G protein-coupled receptor ligands and nervous system-derived substances in Th9 cell differentiation and type I hypersensitivity.
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Focal choroidal excavation in eyes with central serous chorioretinopathy.
Am. J. Ophthalmol.
PUBLISHED: 03-07-2013
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To study the prevalence and 3-dimensional (3-D) tomographic features of focal choroidal excavations in eyes with central serous chorioretinopathy (CSC) using swept-source optical coherence tomography (OCT).
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The role of the Nrf2-mediated defense system in corneal epithelial wound healing.
Free Radic. Biol. Med.
PUBLISHED: 03-05-2013
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The corneal epithelium exists at the surface of cornea and is easily damaged by external stresses such as UV radiation or physical injury. The Nrf2-mediated defense system plays a central role in protecting cells by activating genes against these types of stress. In this study, we investigated the role of the Nrf2-mediated defense system in corneal epithelial wound healing by using Nrf2-knockout (KO) mice. Nrf2 was expressed in the corneal epithelium of wild-type (WT) mice, but not in KO mice. Observation of wounds after 24h of healing revealed that healing of the corneal epithelium was significantly delayed in the Nrf2 KO mice, whereas Nrf2 was activated in the corneal epithelium of WT mice. Ki-67 staining revealed that the number of Ki-67-positive proliferating cells was significantly lower in the Nrf2 KO mice than in the WT mice at 24-36h after injury; however, these numbers were approximately equivalent by 48h. To clarify the role of Nrf2 during wound healing, we performed in vitro experiments with siRNA for Nrf2 and its suppressor Keap1. Nrf2 knockdown significantly delayed corneal epithelial cell migration, but did not affect cell proliferation. Conversely, Keap1 knockdown significantly accelerated cell migration. These results suggest that Nrf2 contributed to the corneal epithelial wound-healing process by accelerating cell migration, and Nrf2 would therefore be a good target for the treatment of corneal epithelial diseases such as dry eye or chronic corneal epithelial defect.
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Clinical utility of newly developed immunoassays for serum concentrations of adalimumab and anti-adalimumab antibodies in patients with Crohns disease.
J. Gastroenterol.
PUBLISHED: 02-19-2013
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BACKGROUND/AIM: The appearance of anti-adalimumab antibodies (AAAs) is associated with low serum adalimumab (ADA) trough levels and a decrease of clinical response. The goal of this study was to assess the accuracy and clinical utility of new immunoassays for serum ADA and AAA levels. PATIENTS AND METHODS: Serum ADA trough levels and AAA levels were measured using new immunoassays in 40 patients with Crohns disease (CD) receiving ADA maintenance therapy. RESULTS: Serum ADA trough levels were 12.3 ± 9.6 ?g/ml (n = 40) in CD patients, and 14 of 40 patients (35 %) were positive for AAAs. A negative correlation was observed between serum AAA levels and ADA trough levels (y = -6.02x + 18.7, r = -0.54, P < 0.001, n = 40). The ROC (receiver-operator curve) analyses indicated that an ADA trough of 5.9 ?g/ml was optimal to maintain negative CRP (C-reactive protein) levels (?0.3 mg/dl). The ADA trough levels were significantly lower in patients positive for AAAs (5.5 ± 5.4 ?g/ml, n = 14) than in patients negative for AAAs (16.0 ± 9.5 ?g/ml, n = 26). The CRP and ESR levels were significantly higher in AAA-positive patients than in AAA-negative patients. Serum albumin levels were significantly lower in AAA-positive patients. The positive rate for AAAs in patients who lost a response to infliximab (50 %) was significantly higher than that of anti-TNF-? drug naïve patients (12.5 %). CONCLUSIONS: These new assays for serum AAA trough and AAA levels are useful for routine clinical use and may help guide selection of optimal management strategies for IBD patients with a loss of response to ADA.
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Sensitivity and specificity of detecting reticular pseudodrusen in multimodal imaging in Japanese patients.
Retina (Philadelphia, Pa.)
PUBLISHED: 02-14-2013
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To identify reticular pseudodrusen (RPD) in age-related macular degeneration using multiple imaging modalities, including the blue channel image of fundus photography, infrared reflectance (IR), fundus autofluorescence, near-infrared fundus autofluorescence, confocal blue reflectance, indocyanine green angiography, and spectral-domain optical coherence tomography (SD-OCT), and to compare the sensitivities and specificities of these modalities for detecting RPD.
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Branch retinal vein occlusion-associated subretinal hemorrhage.
Jpn. J. Ophthalmol.
PUBLISHED: 02-06-2013
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To study the pathomorphology of subretinal hemorrhage (SRH) seen in eyes with branch retinal vein occlusion (BRVO) and its association with visual prognosis.
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Subfoveal serous retinal detachment associated with extramacular branch retinal vein occlusion.
Clin Ophthalmol
PUBLISHED: 01-30-2013
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To study the pathophysiology of subfoveal serous retinal detachment (SRD) observed in eyes with extramacular branch retinal vein occlusion (BRVO).
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Imatinib attenuates severe mouse dystrophy and inhibits proliferation and fibrosis-marker expression in muscle mesenchymal progenitors.
Neuromuscul. Disord.
PUBLISHED: 01-10-2013
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Imatinib mesylate inhibits signaling of tyrosine kinase receptors, including PDGFR?, and has been used for human cancer therapy. Recent studies have indicated that imatinib is also effective in treatment of some chronic diseases with fibrosis. Fibrosis is the feature of Duchenne muscular dystrophy. It has been reported that imatinib attenuates fibrosis in mdx mice. Recently we revealed that PDGFR? is specifically expressed in muscle mesenchymal progenitors, which are the origin of muscle fibrosis. Here, we show that imatinib ameliorates the muscular pathology of DBA/2-mdx, a more severe mouse muscular dystrophy. In addition, imatinib inhibits both the proliferation and fibrosis marker expression induced by PDGF-AA in muscle mesenchymal progenitors in vitro. Importantly, the effective dose of imatinib on muscle mesenchymal progenitors did not inhibit myoblast proliferation. These results suggest that imatinib targets mesenchymal progenitors, and that a therapeutic strategy targeting mesenchymal progenitors could be a potential treatment for muscular dystrophies.
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Comparison of cone pathologic changes in idiopathic macular telangiectasia types 1 and 2 using adaptive optics scanning laser ophthalmoscopy.
Am. J. Ophthalmol.
PUBLISHED: 01-03-2013
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To compare pathologic changes in the photoreceptors of eyes with idiopathic macular telangiectasia types 1 and 2 using adaptive optics scanning laser ophthalmoscopy (AO-SLO).
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Insulin-like growth factor 1 is not associated with high myopia in a large Japanese cohort.
Mol. Vis.
PUBLISHED: 01-01-2013
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To investigate whether genetic variations in the insulin-like growth factor 1 (IGF-1) gene are associated with high myopia in Japanese.
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Fibrosis and adipogenesis originate from a common mesenchymal progenitor in skeletal muscle.
J. Cell. Sci.
PUBLISHED: 11-01-2011
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Accumulation of adipocytes and collagen type-I-producing cells (fibrosis) is observed in muscular dystrophies. The origin of these cells had been largely unknown, but recently we identified mesenchymal progenitors positive for platelet-derived growth factor receptor alpha (PDGFR?) as the origin of adipocytes in skeletal muscle. However, the origin of muscle fibrosis remains largely unknown. In this study, clonal analyses show that PDGFR?(+) cells also differentiate into collagen type-I-producing cells. In fact, PDGFR?(+) cells accumulated in fibrotic areas of the diaphragm in the mdx mouse, a model of Duchenne muscular dystrophy. Furthermore, mRNA of fibrosis markers was expressed exclusively in the PDGFR?(+) cell fraction in the mdx diaphragm. Importantly, TGF-? isoforms, known as potent profibrotic cytokines, induced expression of markers of fibrosis in PDGFR?(+) cells but not in myogenic cells. Transplantation studies revealed that fibrogenic PDGFR?(+) cells mainly derived from pre-existing PDGFR?(+) cells and that the contribution of PDGFR?(-) cells and circulating cells was limited. These results indicate that mesenchymal progenitors are the main origin of not only fat accumulation but also fibrosis in skeletal muscle.
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Hesr1 and Hesr3 are essential to generate undifferentiated quiescent satellite cells and to maintain satellite cell numbers.
Development
PUBLISHED: 10-13-2011
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Satellite cells, which are skeletal muscle stem cells, divide to provide new myonuclei to growing muscle fibers during postnatal development, and then are maintained in an undifferentiated quiescent state in adult skeletal muscle. This state is considered to be essential for the maintenance of satellite cells, but their molecular regulation is unknown. We show that Hesr1 (Hey1) and Hesr3 (Heyl) (which are known Notch target genes) are expressed simultaneously in skeletal muscle only in satellite cells. In Hesr1 and Hesr3 single-knockout mice, no obvious abnormalities of satellite cells or muscle regenerative potentials are observed. However, the generation of undifferentiated quiescent satellite cells is impaired during postnatal development in Hesr1/3 double-knockout mice. As a result, myogenic (MyoD and myogenin) and proliferative (Ki67) proteins are expressed in adult satellite cells. Consistent with the in vivo results, Hesr1/3-null myoblasts generate very few Pax7(+) MyoD(-) undifferentiated cells in vitro. Furthermore, the satellite cell number gradually decreases in Hesr1/3 double-knockout mice even after it has stabilized in control mice, and an age-dependent regeneration defect is observed. In vivo results suggest that premature differentiation, but not cell death, is the reason for the reduced number of satellite cells in Hesr1/3 double-knockout mice. These results indicate that Hesr1 and Hesr3 are essential for the generation of adult satellite cells and for the maintenance of skeletal muscle homeostasis.
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Transmission over large-core few-mode photonic crystal fiber using distance-independent modal dispersion compensation technique.
Opt Express
PUBLISHED: 09-02-2011
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We propose a transmission distance-independent technique for modal dispersion compensation over few-mode fiber that uses a single-input multiple-output configuration and adaptive equalization. Our technique can compensate for the modal dispersion of a signal with 1-tap FIR filters regardless of the amount of modal delay difference, and enables us to utilize fiber with a large core and few modes as a long-haul transmission line. We also show numerically the advantage of few-mode photonic crystal fiber (PCF) for realizing a larger effective area (A(eff)), and finally we report a transmission over a large-core two-mode PCF with A(eff)>280 ?m(2).
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Grid photocoagulation combined with intravitreal bevacizumab for recurrent macular edema associated with retinal vein occlusion.
Clin Ophthalmol
PUBLISHED: 07-25-2011
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To report the efficacy of grid photocoagulation combined with intravitreal bevacizumab (IVB) for macular edema recurring after previous IVBs associated with retinal vein occlusion (RVO).
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Intravitreal bevacizumab for exudative branching vascular networks in polypoidal choroidal vasculopathy.
Br J Ophthalmol
PUBLISHED: 06-30-2011
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To assess the long-term efficacy of intravitreal bevacizumab for recurrent leakage owing to the residual branching vascular networks in polypoidal choroidal vasculopathy after photodynamic therapy.
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[Regenerative medicine in cornea].
Nippon Rinsho
PUBLISHED: 06-28-2011
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Cornea is unique organ in its transparency. It consists of three different layers epithelium, stroma, and endothelium. Defect of each layers decrease the transparency resulting in blindness. Corneal transplant from donors is performed for these conditions. However it sometimes does not work because of immuno-rejection and shortage of donors is still problem. Regenerative medicine resolves these problems. According to epithelium, we had succeeded in making epithelial sheet from oral mucosa epithelium. The sheet is clear and very resembles normal corneal epithelium in histology. We have auto transplantation of this epithelial sheet to severe corneal deficiency patients and obtained good clinical results. According to endothelium, we are trying to make the sheet from various stem sells including iPS cells.
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Hole-assisted dual concentric core fiber with ultralarge negative dispersion coefficient of -13,200 ps/nm/km.
Appl Opt
PUBLISHED: 06-22-2011
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We propose a dual concentric core fiber (DCCF) with six homogeneous air holes, designed to realize a large negative dispersion coefficient. We clarify numerically that the dispersion property of the proposed DCCF can be controlled flexibly by adjusting the air-hole structure, and we realize the largest reported negative dispersion of -13,200 ps/nm/km experimentally.
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Non-Epstein-Barr virus associated lymphoepithelioma-like carcinoma of the inferior common bile duct.
World J Gastrointest Oncol
PUBLISHED: 06-21-2011
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A carcinoma displaying undifferentiated features with dense lymphoplasmacytic infiltration is defined as a lymphoepithelioma-like carcinoma (LEC), and some of LEC is associated with Epstein-Barr virus (EBV). All of the 13 previously reported cases of LEC of the biliary system were intrahepatic in location. Herein, we describe the first case of LEC of the inferior common bile duct. A 68-year-old Japanese man, who had been previously treated for hepatocellular carcinoma using microwave coagulation therapy, was found to have tumors of the common bile duct and pancreas head. Histopathological study of the resected tumor showed solid or cohesive nests of large undifferentiated cells with irregular large vesicular nuclei and nucleoli. Around the tumor cell nests, dense lymphoplasmacytic infiltration was observed. Focal glandular differentiation (approximately 5%) was also present. These histopathological features corresponded morphologically to LEC. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 7, CK 19 and CA19-9, but negative for CK 20 and Hep Par 1. In situ hybridization for Epstein Barr virus early small RNAs disclosed no nuclear signal in tumor cells. Therefore, a diagnosis of non-EBV-associated LEC of the inferior common bile duct was made. Although the prognosis of the biliary LEC is thought to be better than that of conventional cholangiocarcinoma, the differences in prognosis between EBV-positive and -negative cases have not yet been established. Therefore, additional case studies will be needed to clarify the clinicopathological features of LEC of the biliary tract.
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Combination of endoscopic submucosal dissection and chemoradiation therapy for superficial esophageal squamous cell carcinoma with submucosal invasion.
Exp Ther Med
PUBLISHED: 06-07-2011
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The efficacy, safety and clinical outcomes of a combination of endoscopic submucosal dissection (ESD) with subsequent chemoradiation therapy (CRT) for superficial esophageal squamous cell carcinomas (superficial ESCC) remain unclear. We assessed the outcome of the combination of ESD plus CRT for superficial ESCC. Fourteen patients with superficial ESCC invading into the muscularis mucosa or submucosa were treated with ESD plus CRT from 2004 to 2010. En bloc resection of the lesion was successfully performed in all patients. The mean diameter of the lesions was 25 mm (range 10-55). The distribution of the depth of tumor invasion was to the muscularis mucosa in 8 patients, to the upper submucosal third (sm1) in 4 patients and to the middle submucosal third (sm2) in 2 patients. The laterally resected margins and vascular invasion were cancer-negative in all patients, but lymph node involvement was detected in 2 patients. The mean follow-up period after CRT was 45 months (range 19-70). No patients died of esophageal cancer. Recurrence or metastasis of the esophageal cancer was not observed in any of the patients. The combination of ESD plus CRT is effective for superficial ESCC.
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Suppression of ovalbumin-induced allergic diarrhea by diminished intestinal peristalsis in RAMP1-deficient mice.
Biochem. Biophys. Res. Commun.
PUBLISHED: 05-26-2011
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Recent studies have revealed that various neurotransmitters regulate the immune system via their receptors expressed on the immune cells. Calcitonin gene-related peptide (CGRP), a sensory nerve C-fiber neuropeptide, is also known to have the ability to modulate the functions of immune cells in vitro. However, the contribution of CGRP to the immune regulation in vivo remains to be fully elucidated. Here we report that mice deficient in receptor activity-modifying protein 1 (RAMP1), which is a subunit of the CGRP receptor, showed a significantly lower incidence of diarrhea compared with wild-type (WT) mice in the ovalbumin (OVA)-induced food allergic model. Serum OVA-specific IgE levels and the differentiation of T helper cells was comparable in WT mice and RAMP1-deficient mice. Moreover, there were no significant differences between recruitment and degranulation of mast cells in the small intestine of these mice. In contrast, significantly diminished intestinal peristalsis was observed by the allergy induction in RAMP1-deficient mice compared with WT mice. These results suggest that this suppression of allergic diarrhea is due to the diminished intestinal peristalsis in RAMP1-deficient mice.
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Retinal microstructural abnormalities in central serous chorioretinopathy and polypoidal choroidal vasculopathy.
Retina (Philadelphia, Pa.)
PUBLISHED: 05-13-2011
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To compare retinal morphologic alterations in eyes with polypoidal choroidal vasculopathy (PCV) and central serous chorioretinopathy (CSC) using speckle noise-reduced spectral-domain optical coherence tomography.
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Calcitonin gene-related peptide is an important regulator of cutaneous immunity: effect on dendritic cell and T cell functions.
J. Immunol.
PUBLISHED: 05-06-2011
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Some cutaneous inflammations are induced by percutaneous exposure to foreign Ags, and many chemical mediators regulate this inflammation process. One of these mediators, calcitonin gene-related peptide (CGRP), is a neuropeptide released from nerve endings in the skin. CGRP binds to its receptors composed of receptor activity-modifying protein 1 and calcitonin receptor-like receptor to modulate immune cell function. We show that CGRP regulates skin inflammation under physiological conditions, using contact hypersensitivity (CHS) models of receptor activity-modifying protein 1-deficient mice. CGRP has different functions in CHS responses mediated by Th1 or Th2 cells; it inhibits Th1-type CHS, such as 2,4,6-trinitrochlorobenzene-induced CHS, but promotes Th2-type CHS, such as FITC-induced CHS. CGRP inhibits the migration of Langerin(+) dermal dendritic cells to the lymph nodes in 2,4,6-trinitrochlorobenzene-induced CHS, and upregulates IL-4 production of T cells in the draining lymph nodes in FITC-CHS. These findings suggest that CGRP regulates several types of CHS reactions under physiological conditions and plays an important role in cutaneous immunity.
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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.