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Find video protocols related to scientific articles indexed in Pubmed.
Atypical retinopathy in patients with NPHP type 1: an uncommon ophthalmologic finding.
Clin. Experiment. Ophthalmol.
PUBLISHED: 11-01-2014
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Progressive retinal degeneration without retinal pigmentation has been repeatedly observed in Korean nephronophthisis (NPHP) type 1 patients with a total homozygous deletion of NPHP1.
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A normative study of the disability assessment for dementia in community-dwelling elderly koreans.
Psychiatry Investig
PUBLISHED: 10-20-2014
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We investigated demographic influences on Korean version of Disability Assessment for Dementia (DAD-K) performance and developed normative data for DAD-K.
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Preparation and pharmaceutical evaluation of new tacrolimus-loaded solid self-emulsifying drug delivery system.
Arch. Pharm. Res.
PUBLISHED: 08-20-2014
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The purpose of this study was to develop a novel tacrolimus-loaded solid self-emulsifying drug delivery system (SEDDS) using Labrafac as an oil phase. The ternary phase diagram was plotted with Labrafac, Labrasol and Lauroglycol used as an oil, surfactant and co-surfactant, respectively. The liquid SEDDS formulated with Labrasol, Lauroglycol and Labrafac (70:15:15, volume ratio) furnished the smallest emulsion globule size. The solid SEDDS was obtained by spray-drying the liquid mixture containing the liquid SEDDS with 5 % tacrolimus and silicon dioxide. Furthermore, dissolution of tacrolimus from the solid SEDDS and pharmacokinetics in rats was studied compared to the commercial product. The solid SEDDS produced relatively larger emulsion globule size than that exhibited by the corresponding liquid SEDDS. However, this size variation was not significantly different. The solid SEDDS with approximately 280 nm emulsion droplet size improved the dissolution of the drug compared to drug power and the commercial product. It resulted in significantly higher plasma concentration, AUC and Cmax, and shorter Tmax values than did the commercial product (p < 0.05). The enormously enhanced oral bioavailability of tacrolimus in rats was attributed to relatively faster absorption due to accelerated dissolution of the drug from the solid SEDDS. Therefore, this novel solid SEDDS prepared with Labrafac as an oil phase is an excellent way to achieve better bioavailability of tacrolimus given via the oral route.
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The prognostic significance of Smad3, Smad4, Smad3 phosphoisoform expression in esophageal squamous cell carcinoma.
Med. Oncol.
PUBLISHED: 08-15-2014
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Smad3 functions as an integrator of diverse signaling, including transforming growth factor ? signaling and the function of Smad3 is complexly regulated by differential phosphorylation at various sites of Smad3. Despite the importance of Smad3 and its various phosphoisoforms, their prognostic significance has rarely been studied. In this study, we demonstrated the prognostic significance of Smad3, its phosphoisoforms, and Smad4 expression by immunohistochemistry in 126 esophageal squamous cell carcinomas. The phosphoisoforms of Smad3 studied in this article included phosphorylation at C-terminal (pSmad3C)(Ser(423/425)) and phosphorylation at the linker region (pSmad3L)(Ser(213)). High expression of Smad3 was associated with shorter overall survival. Co-existence of high expression of pSmad3L(S213) and low expression of pSmad3C(S423/425) were associated with advanced N stage and an independent prognostic factor for overall [hazard ratio (HR) 2.03, 95 % confidence interval (CI) (1.10-3.75), p = 0.023] and disease-free survival [HR 2.41, 95 % CI (1.32-4.39), p = 0.004]. In conclusion, co-existence of high pSmad3L(Ser(213)) expression and low pSmad3C(Ser(423/425)) expression can be considered as immunohistochemical biomarkers for predicting prognosis as well as future therapeutic targets. In addition, our results of combinatory effect of differential phosphorylation of Smad3 on prognosis suggest the mode of action of Smad3 might be logically determined by its phosphorylation pattern.
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Incidence of and Risk Factors for Alzheimer's Disease and Mild Cognitive Impairment in Korean Elderly.
Dement Geriatr Cogn Disord
PUBLISHED: 08-08-2014
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Background/Aims: Knowledge of incidence rates and risk factors is essential for the development of strategies to treat patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Methods: A subpopulation of the Nationwide Survey on Dementia Epidemiology (460 Korean subjects aged ?65 years from 2 rural and 2 urban districts) was followed up for 3.5 years. The age-specific incidence was estimated and risk factors were identified. Results: The age-standardized incidence of AD and MCI was 7.9 and 28.1 cases per 1,000 person-years, respectively. MCI was associated with a 6-fold increased risk of AD. Depression was a risk factor for AD with MCI. Age, lack of formal education, illiteracy, rural residence, and marital status were associated with the risk of AD. Conclusion: Strategies to control modifiable risk factors should be implemented to decrease the incidence of AD. © 2014 S. Karger AG, Basel.
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Correlation between HER2 Overexpression and Clinicopathological Characteristics in Gastric Cancer Patients Who Have Undergone Curative Resection.
J Gastric Cancer
PUBLISHED: 07-17-2014
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At present, a human epidermal growth factor receptor 2 (HER2)-based concept of tumor biology has been established, and trastuzumab (Herceptin®; Genentech/Roche, San Francisco, CA, USA), a monoclonal humanized antibody directed against HER2, is a pivotal agent for the management of HER2 positive (HER2+) metastatic breast cancer. It is also known that HER2 has a predictive value in gastric cancer; however, its association with the prognosis of this disease remains uncertain. The purpose of this study was to evaluate both the relationship between HER2 overexpression in the tumors of gastric cancer patients, and the prognosis of these patients who have had curative resection.
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Repetitive cleavage of elastomeric membrane via controlled interfacial fracture.
ACS Appl Mater Interfaces
PUBLISHED: 07-14-2014
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Here, we report a method of fabricating thin layer of polydimethylsiloxane (PDMS), with a thickness in the range of 60-80 nm, which can be repeatedly generated (more than 10 times) from the same block of PDMS via controlled interfacial fracture. The thin layers can be transferred to various substrates by peeling off from the bulk PDMS. The cleavage is attributed to the built-in stress at the fracture interface due to plasma treatment, resulting in the repetitive formation of the thin membranes, with no residue from processing, and with a surface roughness of ?5 nm. We were able to demonstrate transferred patterns with controlled thickness by varying the oxygen plasma treatment conditions and the composition of bulk PDMS stamp. Using the method, we achieved residual-free patterns with submicrometer resolution for applications in biomolecule array templates.
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STAT3 inhibition suppresses proliferation of retinoblastoma through down-regulation of positive feedback loop of STAT3/miR-17-92 clusters.
Oncotarget
PUBLISHED: 07-12-2014
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Retinoblastoma, the most common intraocular malignant tumor in children, is characterized by the loss of both functional alleles of RB1 gene, which however alone cannot maintain malignant characteristics of retinoblastoma cells. Nevertheless, the investigation of other molecular aberrations such as matrix metalloproteinases (MMPs) and miRNAs is still lacking. In this study, we demonstrate that STAT3 is activated in retinoblastoma cells, Ki67-positive areas of in vivo orthotopic tumors in BALB/c nude mice, and human retinoblastoma tissues of the advanced stage. Furthermore, target genes of STAT3 including BCL2, BCL2L1, BIRC5, and MMP9 are up-regulated in retinoblastoma cells compared to other retinal constituent cells. Interestingly, STAT3 inhibition by targeted siRNA suppresses the proliferation of retinoblastoma cells and the formation of in vivo orthotopic tumors. In line with these results, STAT3 siRNA effectively induces down-regulation of target genes of STAT3. In addition, miRNA microarray analysis and further real-time PCR experiments with STAT3 siRNA treatment show that STAT3 activation is related to the up-regulation of miR-17-92 clusters in retinoblastoma cells via positive feedback loop between them. In conclusion, we suggest that STAT3 inhibition could be a potential therapeutic approach in retinoblastoma through the suppression of tumor proliferation.
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Another option of perforator flap in the lateral thoracic area: lateral thoracic perforator flap.
J Reconstr Microsurg
PUBLISHED: 07-10-2014
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The lateral thoracic donor site provides two types of perforator flap; the latissimus dorsi perforator flap based on the musculocutaneous perforator, and the thoracodorsal perforator flap based on the septocutaneous perforators from the thoracodorsal artery. In this article, we introduce a direct cutaneous perforator derived from the lateral thoracic artery, which provides another option for harvesting a perforator flap from the lateral thoracic region.
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Effects of social supports on burden in caregivers of people with dementia.
Int Psychogeriatr
PUBLISHED: 07-09-2014
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Social support programs for dementia caregivers were widely used in order to reduce care burden. We investigated which types of social supports can reduce psychological and non-psychological burdens of dementia caregivers, and explored the mechanism of those social supports.
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Impact of aerobic exercise training on endothelial function in acute coronary syndrome.
Ann Rehabil Med
PUBLISHED: 06-26-2014
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To confirm the improvement in arterial endothelial function by aerobic exercise training, flow-mediated dilation (FMD) was tested by ultrasonography.
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Micro-to-nano-scale deformation mechanisms of a bimodal ultrafine eutectic composite.
Sci Rep
PUBLISHED: 06-03-2014
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The outstading mechanical properties of bimodal ultrafine eutectic composites (BUECs) containing length scale hierarchy in eutectic structure were demonstrated by using AFM observation of surface topography with quantitative height measurements and were interpreted in light of the details of the deformation mechanisms by three different interface modes. It is possible to develop a novel strain accommodated eutectic structure for triggering three different interface-controlled deformation modes; (I) rotational boundary mode, (II) accumulated interface mode and (III) individual interface mode. A strain accommodated microstructure characterized by the surface topology gives a hint to design a novel ultrafine eutectic alloys with excellent mechanical properties.
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Which Combination of MR Imaging Modalities Is Best for Predicting Recurrent Glioblastoma? Study of Diagnostic Accuracy and Reproducibility.
Radiology
PUBLISHED: 05-30-2014
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Purpose To compare the added value of dynamic contrast material-enhanced (CE) (DCE) magnetic resonance (MR) imaging with that of dynamic susceptibility CE (DSC) MR imaging with the combination of CE T1-weighted imaging and diffusion-weighted (DW) imaging for predicting recurrent glioblastoma. Materials and Methods This retrospective study was approved by the institutional review board, with the requirement for informed patient consent waived. CE T1-weighted images, DW images, DSC MR images, and DCE MR images in 169 patients with pathologically or clinicoradiologically diagnosed recurrent glioblastoma (n = 87) or radiation necrosis (n = 82) were retrospectively reviewed. Histogram cutoffs of quantitative parametric values were calculated from DW images, DSC MR images, and DCE MR images. Area under the receiver operating characteristic curve (Az) and interreader agreement were assessed. Results For predicting recurrent glioblastoma, adding DCE MR imaging to the combination of CE T1-weighted imaging and DW imaging significantly improved Az from 0.84 to 0.96 for reader 1 and from 0.81 to 0.97 for reader 2, respectively. Adding DSC MR imaging also significantly improved Az (0.95 for reader 1 and 0.93 for reader 2). However, there was no significant difference in Az between the combination of CE T1-weighted imaging, DW imaging, and DSC MR imaging and the combination of CE T1-weighted imaging, DW imaging, and DCE MR imaging for both readers. The interreader agreement was highest for the combination of CE T1-weighted imaging, DW imaging, and DCE MR imaging (? = 0.78) and lowest for CE T1-weighted imaging and DW imaging (? = 0.65). Conclusion Adding perfusion MR imaging to the combination of CE T1-weighted imaging and DW imaging significantly improves the prediction of recurrent glioblastoma; however, selection of perfusion MR method does not affect the diagnostic performance. © RSNA, 2014.
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Treatment and Outcomes for Gangliogliomas: A Single-Center Review of 16 Patients.
Brain Tumor Res Treat
PUBLISHED: 05-29-2014
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Ganglioglioma is a rare and slowly growing benign tumor. We investigated the outcomes of patients who underwent different combination treatments.
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CD10 expression is enhanced by Twist1 and associated with poor prognosis in esophageal squamous cell carcinoma with facilitating tumorigenicity in vitro and in vivo.
Int. J. Cancer
PUBLISHED: 05-16-2014
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CD10 expression was identified as a contributor to cancer progression in several cancers; however, the exact biological significance and mechanism of CD10 expression remains unclear. In addition, CD10 expression in esophageal squamous cell carcinoma (ESCC) has not been studied. We investigated the relationship between CD10 and Twist1. Furthermore, we examined the effect of CD10 on tumorigenicity using in vivo and in vitro systems as well as establishing the clinical significance of CD10 expression in ESCC using large clinical samples. CD10 expression was upregulated by Twist1 and there was a strong correlation between mRNA and protein expression. Twist1 can specifically upregulate CD10 at the transcriptional level via an interaction with the promoter region of CD10 and the proximal E-box CAGGTG in the CD10 promoter was identified as a binding site for Twist1. CD10 is frequently expressed in ESCC cell lines and silencing CD10 suppresses migration/invasion and anchorage-independent tumor growth of ESCC cells. Knockdown of CD10 inhibits the growth of ESCC xenograft in nude mice, suggesting that CD10 plays a role in enhancing the tumorigenesis of ESCC. From among 153 ESCC samples, 46 (30.0%) showed varying degrees of CD10 expression in cancer cells. In addition, stromal fibroblasts also showed varying amounts of CD10 expression in 92 (60.9%) tumor samples. CD10 overexpression in cancer cells as well as in stromal fibroblasts was an independent poor prognostic factor in both overall survival and disease-free survival. CD10 could be a promising target for the treatment of ESCC.
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ZNF282 (Zinc finger protein 282), a novel E2F1 co-activator, promotes esophageal squamous cell carcinoma.
Oncotarget
PUBLISHED: 05-14-2014
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Zinc finger protein 282 (ZNF282) is a newly identified transcription factor and little is known about its expression and function. Originally, ZNF282 is known to bind U5RE (U5 repressive element) of HLTV-1 (human T cell leukemia virus type 1) with a repressive effect. Recently we reported that ZNF282 functions as an estrogen receptor co-activator and plays an essential role in breast tumorigenesis. Although these results suggest the possible role of ZNF282 in cancers, clinical significance and function of ZNF282 are completely unknown in most of cancers. Here we found that ZNF282 was frequently overexpressed in esophageal squamous cell carcinoma (ESCC) (n=165) compared with normal esophageal epithelium and its overexpression was correlated with adverse clinical outcome. Multivariate survival analysis indicated that ZNF282 expression was an independent prognostic predictor for poor survival in ESCC (HR: 2.56 (95% CI 1.54-4.26), p<0.001). In addition, depletion of ZNF282 inhibited the cell cycle progression, migration, and invasion of ESCC cells and reduced the tumorigenicity of ESCC xenograft in nude mouse. We further showed that ZNF282 is required for E2F1-mediated gene expression in ESCC cells. Thus, ZNF282 is E2F1 co-activator involved in ESCC and elevated expression of ZNF282 is an independent adverse prognostic factor in ESCC.
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Treatment outcome of osteosarcoma after bilateral retinoblastoma: a retrospective study of eight cases.
Br J Ophthalmol
PUBLISHED: 05-02-2014
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To analyse clinical characteristics and treatment outcomes of osteosarcoma that developed in survivors of bilateral retinoblastoma.
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Hypoxia-mediated retinal neovascularization and vascular leakage in diabetic retina is suppressed by HIF-1? destabilization by SH-1242 and SH-1280, novel hsp90 inhibitors.
J. Mol. Med.
PUBLISHED: 04-25-2014
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In diabetic retinopathy (DR), visual deterioration is related with retinal neovascularization and vascular hyperpermeability. Anti-vascular endothelial growth factor (VEGF) agents are currently utilized to suppress retinal neovascularization and macular edema (ME); however, there are still concerns on the widespread use of them because VEGF is a trophic factor for neuronal and endothelial cells in the retina. As an alternative treatment strategy for DR, it is logical to address hypoxia-related molecules to treat DR because the retina is in relative hypoxia as DR progresses. In this study, we demonstrate that destabilization of hypoxia-inducible factor-1? (HIF-1?) by SH-1242 and SH-1280, novel heat shock protein 90 (hsp90) inhibitors, leads to suppression of hypoxia-mediated retinal neovascularization and vascular leakage in diabetic retina. In vitro experiments showed that these inhibitors inhibited hypoxia-induced upregulation of target genes of HIF-1? and further secretion of VEGF. Furthermore, these inhibitors effectively suppressed expression of target genes of HIF-1? including vegfa in the retina of oxygen-induced retinopathy (OIR) mice. Interestingly, despite hsp90 inhibition, these inhibitors do not induce definite toxicity at the level of gene expression, cellular viability, and histologic integrity. We suggest that SH-1242 and SH-1280 can be utilized in the treatment of DR, as an alternative treatment of direct VEGF inhibition.
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A Suggestion of Modified Classification of Trigeminal Schwannomas According to Location, Shape, and Extension.
Brain Tumor Res Treat
PUBLISHED: 04-21-2014
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Comprehensive knowledge of the anatomical features of trigeminal schwannomas (TSs) is essential in planning surgery to achieve complete tumor resection. In the current report, we propose a modified classification of TSs according to their location of origin, shape, and extension into the adjacent compartment, and discuss appropriate surgical strategies with this classification.
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Angiopoietin 2 induces pericyte apoptosis via ?3?1 integrin signaling in diabetic retinopathy.
Diabetes
PUBLISHED: 04-10-2014
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Pericyte loss is an early characteristic change in diabetic retinopathy (DR). Despite accumulating evidence that hyperglycemia-induced angiopoietin 2 (Ang2) has a central role in pericyte loss, the precise molecular mechanism has not been elucidated. This study investigated the role of Ang2 in pericyte loss in DR. We demonstrated that pericyte loss occurred with Ang2 increase in the diabetic mouse retina and that the source of Ang2 could be the endothelial cell. Ang2 induced pericyte apoptosis via the p53 pathway under high glucose, whereas Ang2 alone did not induce apoptosis. Integrin, not Tie-2 receptor, was involved for Ang2-induced pericyte apoptosis under high glucose as an Ang2 receptor. High glucose changed the integrin expression pattern, which increased integrin ?3 and ?1 in the pericyte. Furthermore, Ang2-induced pericyte apoptosis in vitro was effectively attenuated via p53 suppression by blocking integrin ?3 and ?1. Although intravitreal injection of Ang2 induced pericyte loss in C57BL/6J mice retina in vivo, intravitreal injection of anti-integrin ?3 and ?1 antibodies attenuated Ang2-induced pericyte loss. Taken together, Ang2 induced pericyte apoptosis under high glucose via ?3?1 integrin. Glycemic control or blocking Ang2/integrin signaling could be a potential therapeutic target to prevent pericyte loss in early DR.
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Nuclear expression of p53 in mature tumor endothelium of retinoblastoma.
Oncol. Rep.
PUBLISHED: 04-07-2014
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The present study aimed to investigate the p53 expression pattern in tumor cells and in mature tumor vascular endothelium of retinoblastoma. Nuclear p53 accumulation was observed in most of the tumor cells in both the human and orthotopic retinoblastoma animal models using SNUOT-Rb1 and Y79 cells. In the orthotopic animal model, some of the tumor vascular endothelium also demonstrated nuclear p53 immunoreactivity, and the ratio of p53 positivity among the total mature tumor vascular endothelium was slightly higher in the Y79 cell model when compared with the SNUOT-Rb1 cell model. In addition, in the human retinoblastoma specimens, 32.9% of the tumor vascular endothelium showed p53 nuclear staining. In conclusion, some of the mature tumor vascular endothelium in both the human and orthotopic models of retinoblastoma share the same cytogenetic abnormality (an abnormal nuclear accumulation of p53) with retinoblastoma cells.
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Overexpression of integrin ?v correlates with poor prognosis in colorectal cancer.
J. Clin. Pathol.
PUBLISHED: 04-02-2014
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Integrin ?v subunits are involved in tumour angiogenesis and tumour progression in various types of cancers. Clinical trials evaluating agents targeting integrin ?v are ongoing. Integrin ?v expression has been reported in several cancers in association with tumour progression or poor survival. However, no study has addressed the prognostic influence of integrin ?v expression on survival of patients with colorectal cancer (CRC).
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Delayed hypersensitivity reaction resulting in maculopapular-type eruption due to entecavir in the treatment of chronic hepatitis B.
World J. Gastroenterol.
PUBLISHED: 02-23-2014
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Several clinical trials have demonstrated the potent antiviral efficacy of entecavir (ETV), and this relatively new nucleoside analogue drug has rapidly become a frequently prescribed therapy for chronic hepatitis B (CHB) worldwide. While the studies have also shown a good overall safety profile for ETV, adverse drug reactions (ADRs) in patients with advanced cirrhosis have been reported and represent a broad spectrum of drug-induced injuries, including lactic acidosis, myalgia, neuropathy, azotemia, hypophosphatemia, muscular weakness, and pancreatitis, as well as immune-mediated responses (i.e., allergic reactions). Cutaneous ADRs associated with ETV are very rare, with only two case reports in the publicly available literature; both of these cases were classified as unspecified hypersensitivity allergic (type I) ADR, but neither were reported as pathologically proven or as evaluated by cytokine release analysis. Here, we report the case of a 45-year-old woman who presented with a generalized maculopapular rash after one week of ETV treatment for lamivudine-resistant CHB. The patient reported having experienced a similar skin eruption during a previous three-month regimen of ETV, for which she had self-discontinued the medication. Histopathological analysis of a skin biopsy showed acanthotic epidermis with focal parakeratosis and a perivascular lymphocytic infiltrate admixed with interstitial eosinophils in the papillary and reticular dermis, consistent with a diagnosis of drug sensitivity. A lymphocyte stimulation test showed significantly enhanced IL-4, indicating a classification of type IVb delayed hypersensitivity. The patient was switched to an adefovir-lamivudine combination regimen and the skin eruption resolved two weeks after the ETV withdrawal. This case represents the first pathologically and immunologically evidenced ETV-induced delayed type hypersensitivity skin reaction reported to date. Physicians should be aware of the potential, although rare, for cutaneous ADRs associated with ETV treatment.
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Beta-lapachone inhibits pathological retinal neovascularization in oxygen-induced retinopathy via regulation of HIF-1?.
J. Cell. Mol. Med.
PUBLISHED: 02-18-2014
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Retinal neovascularization in retinopathy of prematurity (ROP) is the most common cause of blindness for children. Despite evidence that hypoxia inducible factor (HIF)-1? -VEGF axis is associated with the pathogenesis of ROP, the inhibitors of HIF-1? have not been established as a therapeutic target in the control of ROP pathophysiology. We investigated the hypothesis that degradation of HIF-1? as a master regulator of angiogenesis in hypoxic condition, using ?-lapachone, would confer protection against hypoxia-induced retinopathy without affecting physiological vascular development in mice with oxygen-induced retinopathy (OIR), an animal model of ROP. The effects of ?-lapachone were examined after intraocular injection in mice with OIR. Intraocular administration of ?-lapachone resulted in significant reduction in hypoxia-induced retinal neovascularization without retinal toxicity or perturbation of developmental retinal angiogenesis. Our results demonstrate that HIF-1?-mediated VEGF expression in OIR is associated with pathological neovascularization, not physiological angiogenesis. Thus, strategies blocking HIF-1? in the developing eye in the pathological hypoxia could serve as a novel therapeutic target for ROP.
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Surgical dose-effect relationship in single muscle advancement in the treatment of consecutive strabismus.
J Pediatr Ophthalmol Strabismus
PUBLISHED: 02-12-2014
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To evaluate the dose-effect relationship for single muscle advancement in consecutive esotropia and consecutive exotropia.
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A new scoring method of the mini-mental status examination to screen for dementia.
Dement Geriatr Cogn Disord
PUBLISHED: 02-06-2014
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Although the Mini-Mental Status Examination (MMSE) is the most widely used screening instrument for dementia, it has several limitations.
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The association of socioeconomic status with three-year clinical outcomes in patients with acute myocardial infarction who underwent percutaneous coronary intervention.
J. Korean Med. Sci.
PUBLISHED: 02-03-2014
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The aim of this study was to evaluate whether the clinical outcomes were associated with socioeconomic status (SES) in patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI). The author analyzed 2,358 patients (64.9 ± 12.3 yr old, 71.5% male) hospitalized with AMI between November 2005 and June 2010. SES was measured by the self-reported education (years of schooling), the residential address (social deprivation index), and the national health insurance status (medical aid beneficiaries). Sequential multivariable modeling assessed the relationship of SES factors with 3-yr major adverse cardiovascular events (MACEs) and mortality after the adjustment for demographic and clinical factors. During the 3-yr follow-up, 630 (26.7%) MACEs and 322 (13.7%) all-cause deaths occurred in 2,358 patients. In multivariate Cox proportional hazards regression modeling, the only lower education of SES variables was associated with MACEs (hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.04-1.91) and mortality (HR, 1.93; 95% CI, 1.16-3.20) in the patients with AMI who underwent PCI. The study results indicate that the lower education is a significant associated factor to increased poor clinical outcomes in patients with AMI who underwent PCI.
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Anti-angiogenic effect of bare titanium dioxide nanoparticles on pathologic neovascularization without unbearable toxicity.
Nanomedicine
PUBLISHED: 01-28-2014
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Local application requires fewer nanoparticles than systemic delivery to achieve effective concentration. In this study, we investigated the potential toxicity and efficacy of bare titanium dioxide (TiO2) nanoparticles by local administration into the eye. Mono-disperse, 20nm-size TiO2 nanoparticles did not affect the viability of retinal constituent cells within certain range of concentrations (~1.30?g/mL). Furthermore, local delivery of TiO2 nanoparticles did not induce any significant toxicity at the level of gene expression and histologic integrity in the retina of C57BL/6 mice. Interestingly, at the low concentration (130ng/mL) without definite toxicity, these nanoparticles suppressed in vitro angiogenesis processes and in vivo retinal neovascularization in oxygen-induced retinopathy mice when they are administered intravitreally. Taken together, our results demonstrate that even TiO2 nanoparticles can be safely utilized for the treatment of retinal diseases at the adequate concentration levels, especially through local administration.
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Analysis on bilateral hindlimb mapping in motor cortex of the rat by an intracortical microstimulation method.
J. Korean Med. Sci.
PUBLISHED: 01-27-2014
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Intracortical microstimulation (ICMS) is a technique that was developed to derive movement representation of the motor cortex. Although rats are now commonly used in motor mapping studies, the precise characteristics of rat motor map, including symmetry and consistency across animals, and the possibility of repeated stimulation have not yet been established. We performed bilateral hindlimb mapping of motor cortex in six Sprague-Dawley rats using ICMS. ICMS was applied to the left and the right cerebral hemisphere at 0.3 mm intervals vertically and horizontally from the bregma, and any movement of the hindlimbs was noted. The majority (80%± 11%) of responses were not restricted to a single joint, which occurred simultaneously at two or three hindlimb joints. The size and shape of hindlimb motor cortex was variable among rats, but existed on the convex side of the cerebral hemisphere in all rats. The results did not show symmetry according to specific joints in each rats. Conclusively, the hindlimb representation in the rat motor cortex was conveniently mapped using ICMS, but the characteristics and inter-individual variability suggest that precise individual mapping is needed to clarify motor distribution in rats.
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Intracellular amyloid beta alters the tight junction of retinal pigment epithelium in 5XFAD mice.
Neurobiol. Aging
PUBLISHED: 01-21-2014
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Extracellular deposit of amyloid beta (A?) is a common pathologic feature in both age-related macular degeneration (AMD) and Alzheimer's disease, but the role of intracellular A? on the tight junction of the retinal pigment epithelium (RPE) is unknown. In this study, we investigated the intracellular A? expression and its role on the outer blood retinal barrier in the retina of 5XFAD mice, a mouse model of Alzheimer's disease. The retina of 5XFAD mice showed the pathologic features of AMD with intracellular A? in the RPE. As intracellular A? accumulated, zonular occludens-1 and occludin were markedly attenuated and lost their integrity as tight junctions in the RPE of 5XFAD mice. Also, A?42 uptake by ARPE-19 cells induced the tight junction breakdown of zonular occludens-1 and occludin without cell death. These results implicate that intracellular A?42 could play a role in the breakdown of the outer blood retinal barrier in 5XFAD mice. Thus, we suggested that 5XFAD mice could be a mouse model of dry AMD with regard to the A?42 related pathology.
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Mechanical properties, skin permeation and in vivo evaluations of dexibuprofen-loaded emulsion gel for topical delivery.
Arch. Pharm. Res.
PUBLISHED: 01-16-2014
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The aim of this research was to evaluate the gel properties, skin permeation and in vivo drug efficacy of a novel dexibuprofen-loaded emulsion gel for topical delivery. In this study, the dexibuprofen-loaded emulsion gel and ibuprofen-loaded emulsion gel were prepared with isopropanol, Tween 80, propylene glycol, isopropyl myristate and carbopol. Their mechanical properties such as hardness and adhesiveness were assessed. Moreover, their skin permeation, anti-inflammatory and anti-nociceptive efficacy were evaluated using Franz diffusion cell with the hairless mouse skin, the carrageenan-induced paw oedema test and paw pressure test in rat's hind paws compared with the commercial hydrogel, respectively. The dexibuprofen emulsion gel and ibuprofen emulsion gel provided significantly higher hardness and adhesiveness than the commercial hydrogel. The dexibuprofen emulsion gel enhanced skin permeability by about twofold and 3.5-fold without lag time compared to the ibuprofen emulsion gel and the commercial hydrogel, respectively, suggesting its faster skin permeation. Moreover, the anti-inflammatory efficacy and alleviation in carrageenan-induced inflammation was in the order of dexibuprofen emulsion gel > commercial hydrogel > ibuprofen emulsion gel. The dexibuprofen emulsion gel furnished significantly higher nociceptive thresholds than the ibuprofen emulsion gel and the commercial hydrogel, leading to the most improved anti-nociceptive efficacy. Thus, this dexibuprofen-loaded emulsion gel with good mechanical property, rapid skin permeation and excellent anti-inflammatory and anti-nociceptive efficacy would be a strong candidate for the topical delivery of anti-inflammatory dexibuprofen.
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Suppression of protein kinase C-? attenuates vascular leakage via prevention of tight junction protein decrease in diabetic retinopathy.
Biochem. Biophys. Res. Commun.
PUBLISHED: 01-07-2014
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To investigate the effect of protein kinase C (PKC)-? inhibition on vascular leakage in diabetic retinopathy, streptozotocin-induced diabetic mice were intravitreously injected with siPKC-?. According to the fluorescein angiography of the retinal vessels, suppression of PKC-? effectively attenuated vascular leakage in diabetic retina. Further evaluation on the retina with western blot analysis and immunohistochemistry revealed accompanying restoration of tight junction proteins on retinal vessels. As two major contributors to vascular leakage in diabetic retinopathy, vascular endothelial growth factor (VEGF) and advanced glycation end products (AGEs) were investigated on the tight junction protein expression in endothelial cells. Inhibition of PKC-? attenuated VEGF-induced decrease of tight junction proteins and accompanying hyperpermeability in human retinal microvascular endothelial cells (HRMECs). PKC-? inhibition also attenuated AGE-induced decrease of tight junction proteins in HRMECs. Our findings suggest that inhibition of PKC-? could be an alternative treatment option for compromised blood-retinal barrier in diabetic retinopathy.
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Allosteric regulation of pathologic angiogenesis: potential application for angiogenesis-related blindness.
Arch. Pharm. Res.
PUBLISHED: 01-07-2014
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Angiogenesis-related blindness (ARB) includes age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity, all of which are based on pathologic angiogenesis. Current treatment options such as surgery, laser photocoagulation, and steroid have shown limitations because they do not directly resolve the pathologic events in the retina. Furthermore, recently approved and developed therapeutic drugs only focus on direct inhibition of growth factors and suppression of downstream signaling molecules of activated receptor proteins by orthosteric ligands. In this regard, allosteric regulation of receptors and ligands can be a valuable mechanism in the development of novel drugs for ARB. In this review, we briefly address the clinical significance of ARB for further discussion on allosteric regulation of pathologic angiogenesis for ARB. Interestingly, key molecules in the pathogenesis of ARB can be targets for allosteric regulation, sharing characteristics as allosteric proteins. With investigation of allostery by introducing well-established models for allosteric proteins and currently published novel allosteric modulators, we discuss the potential of allosteric regulation for ARB. In conclusion, we hope that allosteric regulation of pathologic angiogenesis in ARB can open new opportunities for drug development.
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VEGF-binding aptides and the inhibition of choroidal and retinal neovascularization.
Biomaterials
PUBLISHED: 01-02-2014
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Age-related macular degeneration and diabetic retinopathy are leading causes of blindness. Vascular endothelial growth factor (VEGF) is known to be the main factor that induces pathological angiogenesis in these diseases. In this study, we investigate the therapeutic potential and safety profiles of high-affinity peptides targeting VEGF which are identified using an 'aptide' technology. We show that two VEGF-binding aptides, APTVEGF1 and APTVEGF2, demonstrate high binding affinity and specificity to VEGF. Furthermore, they suppress VEGF-induced activation of VEGF receptor-2, in vitro angiogenesis, and in vivo pathological choroidal and retinal neovascularization. Despite potent anti-angiogenic effects, both VEGF-binding aptides do not induce any definite toxicity at the level of cellular viability, histological integrity, and gene expression. Our data show the therapeutic potential of VEGF-binding peptides for the treatment of choroidal and retinal neovascularization.
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Frontal white matter alterations in short-term medicated panic disorder patients without comorbid conditions: a diffusion tensor imaging study.
PLoS ONE
PUBLISHED: 01-01-2014
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The frontal cortex might play an important role in the fear network, and white matter (WM) integrity could be related to the pathophysiology of panic disorder (PD). A few studies have investigated alterations of WM integrity in PD. The aim of this study was to determine frontal WM integrity differences between patients with PD without comorbid conditions and healthy control (HC) subjects by using diffusion tensor imaging. Thirty-six patients with PD who had used medication within 1 week and 27 age- and sex-matched HC subjects participated in this study. Structural brain magnetic resonance imaging was performed on all participants. Panic Disorder Severity Scale and Beck Anxiety Inventory (BAI) scores were assessed. Tract-based spatial statistics (TBSS) was used for image analysis. TBSS analysis showed decreased fractional anisotropy (FA) in frontal WM and WM around the frontal lobe, including the corpus callosum of both hemispheres, in patients with PD compared to HC subjects. Moreover, voxel-wise correlation analysis revealed that the BAI scores for patients with PD were positively correlated with their FA values for regions showing group differences in the FA of frontal WM of both hemispheres. Altered integrity in frontal WM of patients with PD without comorbid conditions might represent the structural pathophysiology in these patients, and these changes could be related to clinical symptoms of PD.
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Development of a screening algorithm for Alzheimer's disease using categorical verbal fluency.
PLoS ONE
PUBLISHED: 01-01-2014
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We developed a weighted composite score of the categorical verbal fluency test (CVFT) that can more easily and widely screen Alzheimer's disease (AD) than the mini-mental status examination (MMSE). We administered the CVFT using animal category and MMSE to 423 community-dwelling mild probable AD patients and their age- and gender-matched cognitively normal controls. To enhance the diagnostic accuracy for AD of the CVFT, we obtained a weighted composite score from subindex scores of the CVFT using a logistic regression model: logit (case) ?=?1.160+0.474× gender +0.003× age +0.226× education level - 0.089× first-half score - 0.516× switching score -0.303× clustering score +0.534× perseveration score. The area under the receiver operating curve (AUC) for AD of this composite score AD was 0.903 (95% CI?=?0.883 - 0.923), and was larger than that of the age-, gender- and education-adjusted total score of the CVFT (p<0.001). In 100 bootstrapped re-samples, the composite score consistently showed better diagnostic accuracy, sensitivity and specificity for AD than the total score. Although AUC for AD of the CVFT composite score was slightly smaller than that of the MMSE (0.930, p?=?0.006), the CVFT composite score may be a good alternative to the MMSE for screening AD since it is much briefer, cheaper, and more easily applicable over phone or internet than the MMSE.
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Ninjurin1 deficiency attenuates susceptibility of experimental autoimmune encephalomyelitis in mice.
J. Biol. Chem.
PUBLISHED: 12-17-2013
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Ninjurin1 is a homotypic adhesion molecule that contributes to leukocyte trafficking in experimental autoimmune encephalomyelitis (EAE), an animal model of Multiple sclerosis (MS). However, in vivo gene-deficiency animal studies have not yet been done. Here, we constructed Ninjurin1 knockout (KO) mice and investigated the role of Ninjurin1 on leukocyte trafficking under inflammation conditions such as EAE and endotoxin-induced uveitis (EIU). Ninjurin1 KO mice attenuated EAE susceptibility by reducing leukocyte recruitment into the injury regions of the spinal cord and showed less adhesion of leukocytes on inflamed retinal vessels in EIU mice. Moreover, the administration of a custom-made antibody (Ab26-37) targeting the Ninjurin1 binding domain ameliorated the EAE symptoms, showing the contribution of its adhesion activity to leukocyte trafficking. In addition, we addressed the transendothelial migration (TEM) activity of bone-marrow derived macrophages (BMDMs) and Raw264.7 cells according to the expression level of Ninjurin1. TEM activity was decreased in Ninjurin1 KO BMDMs and siNinj1 Raw264.7 cells. Consistent with this, GFP-tagged mNinj1 overexpressing Raw264.7 cells increased their TEM activity. Taken together, we have clarified the contribution of Ninjurin1 to leukocyte trafficking in vivo and delineated its direct functions to TEM, emphasizing Ninjurin1 as a beneficial therapeutic target against inflammatory diseases such as MS.
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Hypofractionated intensity-modulated radiotherapy using simultaneous integrated boost technique with concurrent and adjuvant temozolomide for glioblastoma.
Tumori
PUBLISHED: 12-12-2013
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Aims and background. We assessed the therapeutic efficacy of combined hypofractionated intensity-modulated radiotherapy with temozolomide in patients with primary glioblastoma. Methods and study design. Thirty-nine patients with histologically confirmed glioblastoma were accrued. Using the simultaneous integrated boost technique, a dose of 50 Gy in 5-Gy fractions was applied to the gross tumor volume, together with 40 Gy in 4-Gy fractions and 30 Gy in 3-Gy fractions to the 1- and 2-cm margins from the gross tumor volume, respectively. Patients were also treated with concurrent temozolomide during intensity-modulated radiotherapy, followed by six cycles of adjuvant temozolomide. Results. Median follow-up was 16.8 months (range, 4.3-54.3). Tumor progression was observed in 28 patients (71.8%), and the median time to progression was 6.8 months. Median survival was 16.8 months, and it was affected significantly by the extent of surgery. During adjuvant temozolomide treatment, 3 patients (9.7%) developed grade 3-4 hematologic or hepatic toxicity. Radiation necrosis developed in 7 patients (17.9%) and massive necrosis, requiring emergency surgery, in 1 patient (2.6%). Conclusions. The regimen of hypofractionated intensity-modulated radiotherapy with temozolomide showed a relatively good outcome in patients with glioblastoma. Further studies are required to define the optimal fraction size for glioblastoma using this highly sophisticated radiation technique.
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A basosquamous cell carcinoma of the periorbital region arising from a chronic wound created by laser ablation of a basal cell carcinoma.
J Craniofac Surg
PUBLISHED: 11-14-2013
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Basosquamous cell carcinomas (BSCs) are very rare and behave aggressively, with features of both basal cell carcinoma and squamous cell carcinoma. The diagnosis of BSC includes a spectrum of histologic definitions, ranging from coexistence of basal cell carcinoma and squamous cell carcinoma with or without a transition zone, to any basal cell carcinoma with evidence of keratinization.A 63-year-old man presented with a BSC within a chronic periorbital wound, which was confirmed through a postoperative histologic examination. The wound was created from a previous laser ablation of a diagnosed basal cell carcinoma. The BSC was excised without causing any deformity, and coverage of the defect was obtained using a local perforator-based flap. No recurrence was observed during a 5-month follow-up.
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Multidisciplinary approach to lethal bleeding from an arteriovenous malformation in the external auditory canal.
J Craniofac Surg
PUBLISHED: 11-14-2013
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Arteriovenous malformations (AVMs) are composed of abnormally connecting feeding arteries as well as draining veins and lack a regulatory system. Frequent recurrences and unpredictable behavior are their main problems. Potential mortality and morbidity associated with therapeutic procedures must be considered with these patients. Improper treatment often aggravates the condition, potentially rendering therapy more complex. A multidisciplinary approach, including an endovascular approach, surgical excision, and flap reconstruction, is considered to completely eradicate an AVM. This study introduces a complicated case of AVM with massive bleeding through the external auditory canal that was treated with a multidisciplinary approach.
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A bioengineered array of 3D microvessels for vascular permeability assay.
Microvasc. Res.
PUBLISHED: 09-14-2013
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Blood vessels exhibit highly regulated barrier function allowing selective passage of macromolecules. Abnormal vascular permeability caused by disorder in barrier function is often associated with various pathological states such as tumor progression or pulmonary fibrosis. There are no realistic in vitro models for measuring vascular permeability as most models are limited to mimicking anatomical structural properties of in vivo vessel barriers. This paper presents a reliable microfluidic-based chip for measuring permeability by engineering tubular perfusable microvessels. This platform is compatible with high resolution, live-cell time-lapse imaging and high throughput permeability measurements. The microvessels were formed by natural angiogenic process and thus exhibit reliable barrier properties with permeability coefficient of 1.55×10(-6)cm/s (for 70kDa FITC-dextran). The bioengineered microvessels showed properties similar to in vivo vessels in terms of cell-cell junction expression (ZO-1, Claudin-5 and VE-cadherin) and response to agonists such as histamine and TNF-?. We showed that hyperpermeability of the tumor microvessel could be normalized with anti-VEGF (bevacizumab) treatment, consistent with the mechanism of action for bevacizumab. The method developed here provides a relatively simple, robust technique for assessing drug effects on permeability of microvessels with a number of potential applications in fundamental vascular biology as well as drug screening.
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A chimaeric-pattern flap design for implantable Doppler surrogate monitoring: A novel placement technique.
J Plast Reconstr Aesthet Surg
PUBLISHED: 09-11-2013
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Postoperative flap monitoring is a vital aspect of free tissue transfer in order to detect early vascular compromise and to enable early flap salvage. The implantable Doppler monitoring system is one of many monitoring devices used to ensure accuracy and reduce unnecessary flap explorations. However, there are a number of concerns with its use, namely tension on the anastomosis, possible vessel constriction and false-negative detection. This study aimed to alleviate these concerns, by introducing a new method of placing the implantable Doppler probe on the adjacent vessel limb of a chimaeric flap. This is illustrated by a case series of chimaeric free tissue flaps that allow this surrogate placement of the Doppler probe.
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Interaction between pericytes and endothelial cells leads to formation of tight junction in hyaloid vessels.
Mol. Cells
PUBLISHED: 08-16-2013
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The hyaloid vessel is a transient vascular network that nourishes the lens and the primary vitreous in the early developmental periods. In hyaloid vessels devoid of the support of astrocytes, we demonstrate that tight junction proteins, zonula occludens-1 and occludin, are regularly expressed at the junction of endothelial cells. To figure out the factor influencing the formation of tight junctions in hyaloid vessels, we further progress to investigate the interactions between endothelial cells and pericytes, two representative constituent cells in hyaloid vessels. Interestingly, endothelial cells interact with pericytes in the early postnatal periods and the interaction between two cell types provokes the up-regulation of transforming growth factor ?1. Further in vitro experiments demonstrate that transforming growth factor ?1 induces the activation of Smad2 and Smad3 and the formation of tight junction proteins. Taken together, in hyaloid vessels, pericytes seem to regulate the formation of tight junctions by the interaction with endothelial cells even without the support of astrocytes. Additionally, we suggest that the hyaloid vessel is a valuable system that can be utilized for the investigation of cell-cell interaction in the formation of tight junctions in developing vasculatures.
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Lessons Learned from the Development of Health Applications in a Tertiary Hospital.
Telemed J E Health
PUBLISHED: 08-02-2013
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Abstract Background: Adoption of smart devices for hospital use has been increasing with the development of health applications (apps) for patient point-of-care and hospital management. To promote the use of health apps, we describe the lessons learned from developing 12 health apps in the largest tertiary hospital in Korea. Materials and Methods: We reviewed and analyzed 12 routinely used apps in three categories-Smart Clinic, Smart Patient, and Smart Hospital-based on target users and functions. The log data for each app were collected from the date of release up until December 2012. Results: Medical personnel accessed a mobile electronic medical record app classified as Smart Clinic an average of 452 times per day. Smart Hospital apps are actively used to communicate with each other. Patients logged on to a mobile personal health record app categorized as Smart Patient an average of 222 times per day. As the mobile trend, the choice of supporting operating system (OS) is more difficult. By developing these apps, a monitoring system is needed for evaluation. Conclusions: We described the lessons learned regarding OS support, device choice, and developmental strategy. The OS can be chosen according to market share or hospital strategic plan. Smartphones were favored compared with tablets. Alliance with an information technology company can be the best way to develop apps. Health apps designed for smart devices can be used to improve healthcare. However, to develop health apps, hospitals must define their future goals and carefully consider all the aspects.
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CCAR1 promotes chromatin loading of androgen receptor (AR) transcription complex by stabilizing the association between AR and GATA2.
Nucleic Acids Res.
PUBLISHED: 07-25-2013
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Androgen receptor (AR), a ligand-dependent transcription factor, plays a critical role in prostate cancer onset and progression, and its transcriptional function is mediated largely by distinct nuclear receptor co-regulators. Here, we show that cell cycle and apoptosis regulator 1 (CCAR1) functions as an AR co-activator. CCAR1 interacted with and enhanced the transcriptional activity of AR. Depletion of CCAR1 caused reduction in androgen-dependent expression of a subset of AR target genes. We further showed that CCAR1 is required for recruitment of AR, MED1 and RNA polymerase II to the enhancers of AR target genes and for androgen-induced long-range prostate specific antigen enhancer-promoter interaction. The molecular mechanism underlying CCAR1 function in AR-mediated transcription involves CCAR1-mediated enhanced recruitment of GATA2, a pioneer factor for AR, to AR-binding sites. CCAR1 stabilized the interaction between AR and GATA2 by interacting directly with both proteins, thereby facilitating AR and GATA2 occupancy on the enhancers. Furthermore, CCAR1 depletion inhibited the growth, migration, invasion of prostate cancer cells and reduced the tumorigenicity of prostate cancer cells in vivo. Our results firmly established CCAR1 as an AR co-activator that plays a key role in AR transcription complex assembly and has an important physiological role in androgen signaling and prostate tumorigenesis.
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Anti-apoptotic effect of clusterin on cisplatin-induced cell death of retinoblastoma cells.
Oncol. Rep.
PUBLISHED: 07-18-2013
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Clusterin is a cytoprotective chaperone protein that is known to protect various retinal cells. It was also reported to be overexpressed in several types of malignant tumors, whose chemoresistance correlates with the expression of clusterin. Herein, we investigated the effect of clusterin on cisplatin-induced cell death of retinoblastoma cells. Firstly, evaluation of clusterin expression demonstrated that it was highly expressed in human retinoblastoma tissues and cell lines (SNUOT-Rb1 and Y79) particularly in the area between viable cells around vessels and necrotic zones in the relatively avascular area in human retinoblastoma tissues. Furthermore, the effects of cisplatin on retinoblastoma cells were evaluated. Cisplatin (1 µg/ml) significantly affected cell viability of SNUOT-Rb1 cells by inducing caspase-3-dependent apoptosis. Notably, the cell death due to cisplatin was prevented by 5 µg/ml of clusterin administered 4 h prior to cisplatin treatment by inhibiting cisplatin-induced apoptosis. Furthermore, overexpression of clusterin exerted its anti-apoptotic effect on cisplatin-induced apoptosis, and effectively prevented cisplatin-induced cell death. These data suggest that clusterin, found to be expressed in human retinoblastoma, may exert anti-apoptotic effects on cisplatin-induced apoptosis and prevent cell death. Therefore, clusterin can contribute to cisplatin resistance of retinoblastoma.
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Surgical outcomes after intraocular lens implantation for posterior lenticonus-related cataract according to preoperative lens status.
J Cataract Refract Surg
PUBLISHED: 07-17-2013
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To address the surgical outcomes of pediatric patients with cataracts associated with posterior lenticonus who required cataract extraction and intraocular lens (IOL) implantation according to preoperative lens status.
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Development of novel DNA vaccine for VEGF in murine cancer model.
Sci Rep
PUBLISHED: 06-26-2013
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We developed DNA vaccine for vascular endothelial growth factor (VEGF), which may provide the therapeutic option instead of anti-VEGF antibody, bevacizumab. Plasmid containing VEGF mini-gene was constructed in the insertion of B-cell epitope of Hepatitis B core protein [HBc-VEGF], which was an epitope carrier. High titer of anti-VEGF antibody was observed in BALB/c mice which were intramuscularly immunized with HBc-VEGF by electropolator. In mice inoculated with colon 26 cells, tumor volume and microvessel density was decreased in HBc-VEGF with a significant prolonged survival. Co-treatment of purified IgG from immunized mice with HBc-VEGF showed in vitro neutralizing activity for VEGF-induced ERK phosphorylation and tube formation in cultured endothelial cells. Furthermore, intravitreally injection of this purified IgG reduced the neovessel formation in the mouse oxygen-induced retinopathy and laser-induced choroidal neovascularization models. These results first provided that DNA vaccine against VEGF possessed the anti-angiogenic effect, leading to prolonged survival in mouse cancer model.
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A practical scoring system to determine whether to proceed with surgical resection in recurrent glioblastoma.
Neuro-oncology
PUBLISHED: 06-25-2013
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To determine the benefit of surgical management in recurrent glioblastoma, we analyzed a series of patients with recurrent glioblastoma who had undergone surgery, and we devised a new scale to predict their survival.
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An electroplating-free and minimal noise polyimide microelectrode for recording auditory evoked potentials from the epicranius.
IEEE Trans Biomed Eng
PUBLISHED: 06-07-2013
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In this paper, we introduce an electrode for measuring auditory evoked potentials by employing the advantages of polyimide (PI), which is a well-known substrate material for producing flexible electrodes using MEMS technology. The PI multimicro-electrode array has four fingers that include 16 electrodes in order to achieve sufficient adhesion to the curved surface of the animal skull. For high-quality signal acquisition, we optimized the device to decrease crosstalk and improve contact impedance by adding ground channels and fabricating a raised electrode structure. In addition, implantation of the device was facilitated by the addition of an alignment site to ensure optimal positioning and enable signal measurement from the specific part of the cerebral cortex in charge of auditory sensing. After the implantation of the PI electrode on the skull surface, electrical signals were measured following stimulation at different stimulus frequencies (5 or 10 kHz). Unlike other techniques, administration of this PI electrode is less invasive, reducing patient recovery time dramatically in comparison with other electrocorticographic operations. Furthermore, as the exterior of the brain would not be exposed at any point, the chance of infection is minimized.
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Neurotoxic amyloid beta oligomeric assemblies recreated in microfluidic platform with interstitial level of slow flow.
Sci Rep
PUBLISHED: 05-07-2013
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Alzheimers disease is accompanied by progressive, time-dependent changes of three moieties of amyloid beta. In vitro models therefore should provide same conditions for more physiologic studies. Here we observed changes in the number of fibrils over time and studied the correlation between amyloid beta moieties and neurotoxicity. Although the number of fibrils increased dramatically, the change in neurotoxicity with time was small, suggesting that fibrils make little contribution to neurotoxicity. To study the neurotoxicity of diffusible moieties by regulating microenvironments, we created a bio-mimetic microfluidic system generating spatial gradients of diffusible oligomeric assemblies and assessed their effects on cultured neurons. We found amyloid beta exposure produced an atrophy effect and observed neurite extension during the differentiation of neural progenitor cells increased when cells were cultured with continuous flow. The results demonstrate the potential neurotoxicity of oligomeric assemblies and establish a prospective microfluidic platform for studying the neurotoxicity of amyloid beta.
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Multiple-digit resurfacing using a thin latissimus dorsi perforator flap.
J Plast Reconstr Aesthet Surg
PUBLISHED: 05-03-2013
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Traumatic digit defects of high complexity and with inadequate local tissue represent challenging surgical problems. Recently, perforator flaps have been proposed for reconstructing large defects of the hand because of their thinness and pliability and minimal donor site morbidity. Here, we illustrate the use of thin latissimus dorsi perforator flaps for resurfacing multiple defects of distal digits. We describe the cases of seven patients with large defects, including digits, circumferential defects and multiple-digit defects, who underwent reconstruction with thin latissimus dorsi perforator flaps between January 2008 and March 2012. Single-digit resurfacing procedures were excluded. The mean age was 56.3 years and the mean flap size was 160.4 cm(2). All the flaps survived completely. Two patients had minor complications including partial flap loss and scar contracture. The mean follow-up period was 11.7 months. The ideal flap for digit resurfacing should be thin and amenable to moulding, have a long pedicle for microanastomosis and have minimal donor site morbidity. Thin flaps can be harvested by excluding the deep adipose layer, and their high pliability enables resurfacing without multiple debulking procedures. The latissimus dorsi perforator flap may be the best flap for reconstructing complex defects of the digits, such as large, multiple-digit or circumferential defects, which require complete wrapping of volar and dorsal surfaces.
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Animal models of diabetic retinopathy: doors to investigate pathogenesis and potential therapeutics.
J. Biomed. Sci.
PUBLISHED: 04-13-2013
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Effective and validated animal models are valuable to investigate the pathogenesis and potential therapeutics for human diseases. There is much concern for diabetic retinopathy (DR) in that it affects substantial number of working population all around the world, resulting in visual deterioration and social deprivation. In this review, we discuss animal models of DR based on different species of animals from zebrafish to monkeys and prerequisites for animal models. Despite criticisms on imprudent use of laboratory animals, we hope that animal models of DR will be appropriately utilized to deepen our understanding on the pathogenesis of DR and to support our struggle to find novel therapeutics against catastrophic visual loss from DR.
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A capacitive, biocompatible and adhesive electrode for long-term and cap-free monitoring of EEG signals.
J Neural Eng
PUBLISHED: 04-10-2013
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Long-term electroencephalogram (EEG) monitoring broadens EEG applications to various areas, but it requires cap-free recording of EEG signals. Our objective here is to develop a capacitive, small-sized, adhesive and biocompatible electrode for the cap-free and long-term EEG monitoring.
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Systemic steroid-induced cataracts in children: long-term changes in morphology and visual acuity.
J AAPOS
PUBLISHED: 04-02-2013
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To report the long-term visual prognosis and surgical rates of steroid-induced cataracts in children.
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Foot reconstruction using a serratus anterior muscle flap from the same donor site after failure of a thoracodorsal artery perforator flap.
Microsurgery
PUBLISHED: 03-31-2013
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The free flap failure rate for the lower extremities is high, which adversely affects limb salvage efforts. In this article, we report a case of failure of a thoracodorsal artery perforator flap, which was simultaneously reconstructed with a serratus anterior muscle flap from the same donor site. A 56-year-old male patient had infected wound for 3 months due to Achilles tendon rupture. We reconstructed the defect using a thoracodorsal artery perforator flap. However, 2 days after the operation, we found the congested flap. We were obliged to discard the whole flap and harvested a serratus anterior muscle flap from the same donor site. The patients foot healed uneventfully. After flap failure, the use of a second free flap from the same donor site may be an effective and safe procedure in specific cases. © 2013 Wiley Periodicals, Inc. Microsurgery, 2013.
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Orthotopic transplantation of retinoblastoma cells into vitreous cavity of zebrafish for screening of anticancer drugs.
Mol. Cancer
PUBLISHED: 03-30-2013
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With high throughput screening, novel therapeutic agents can be efficiently identified. Unfortunately, researchers only resort to in vitro cell viability assays for screening of anticancer drugs for retinoblastoma, the most common intraocular cancer in the childhood. Current available animal models of retinoblastoma require more than 2 weeks for tumour formation and the investigation of the efficacy of therapeutic agents. In this study, we established a novel orthotopic transplantation model of retinoblastoma in zebrafish as an in vivo animal model for screening of anticancer drugs.
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Non-invasively measured aortic wave reflection and pulse pressure amplification are related to the severity of coronary artery disease.
J Cardiol
PUBLISHED: 03-12-2013
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Augmentation index (AIx) and pulse pressure amplification (PPA, here the aortic/brachial pulse pressure ratio) are an age-related emerging risk factor for cardiovascular disease. However, it has not been clearly shown that AIx and PPA predict a high risk of coronary artery disease (CAD).
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Vertebral Distraction during Anterior Cervical Discectomy and Fusion Causes Postoperative Neck Pain.
J Korean Neurosurg Soc
PUBLISHED: 03-10-2013
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Vertebral distraction is routinely performed during anterior cervical discectomy and fusion (ACDF). Overdistraction can injure the facet joints and may cause postoperative neck pain consequently. The purpose of this study was to investigate the clinical relevance of distraction force during ACDF.
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Prognostic factors and therapeutic outcomes in 22 patients with pleomorphic xanthoastrocytoma.
J Korean Neurosurg Soc
PUBLISHED: 03-10-2013
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Pleomorphic xanthoastrocytoma (PXA) is a rare primary low-grade astrocytic tumor classified as WHO II. It is generally benign, but disease progression and malignant transformation have been reported. Prognostic factors for PXA and optimal therapies are not well known.
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Capillary-free vascularized retina in patients with aggressive posterior retinopathy of prematurity and late retinal capillary formation.
Korean J Ophthalmol
PUBLISHED: 03-07-2013
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To report the clinical features, clinical course, and treatment outcomes after laser photocoagulation in infants with aggressive posterior retinopathy of prematurity (APROP) and capillary-free zones in vascularized retina.
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Localization of primary cilia in mouse retina.
Acta Histochem.
PUBLISHED: 03-04-2013
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The primary cilia are considered as "cellular antennae" that sense and interchange information with the extracellular environment. Nearly all mammalian cells have a single primary cilium. In the retina, the outer segment of the photoreceptor is known to be a specialized form of primary cilium, but studies on cilia in other layers of the retina are scarce. In this study, we investigated the expression of primary cilia in the whole thickness of the mouse retina using immunofluorescence with three different ciliary markers: Arl13b, acetylated ?-tubulin and adenylyl cyclase III. Our results show positive reactions in the photoreceptor layer, outer plexiform layer and ganglion cell layer, which might suggest the possible presence of primary cilia in these areas, but we could not directly prove the strand-like shape of cilia in those areas. In the outer plexiform layer, all three markers showed intense staining along the neuronal synapses, which suggests that the neuronal processes themselves might share the features of cilia.
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Pathogenic mutations in two families with congenital cataract identified with whole-exome sequencing.
Mol. Vis.
PUBLISHED: 02-15-2013
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Congenital cataract is one of the most frequent causes of visual impairment and childhood blindness. Approximately one quarter to one third of congenital cataract cases may have a genetic cause. However, phenotypic variability and genetic heterogeneity hamper correct genetic diagnosis. In this study, we used whole-exome sequencing (WES) to identify pathogenic mutations in two Korean families with congenital cataract.
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Validation of the Korean version of the European Organization for Research and Treatment of Cancer brain cancer module (EORTC QLQ-BN20) in patients with brain tumors.
Health Qual Life Outcomes
PUBLISHED: 02-14-2013
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The European Organization for Research and Treatment of Cancer Quality of Life Brain Cancer Module has been translated into Korean, but to date, its reliability and validity have been evaluated in a pilot study alone. The European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire is, overall, a valid instrument to assess the health-related quality of life in Korean cancer patients, although its reliability and validity have not yet been evaluated in patients with brain tumors. This study aimed at evaluating the psychometric properties of these instruments in patients with brain tumors.
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A Case of Kommerells Diverticulum Initially Detected by Transesophageal Echocardiography.
J Cardiovasc Ultrasound
PUBLISHED: 02-13-2013
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Kommerells diverticulum is a rare congenital disorder characterized by typical right sided aortic arch and aberrant left subclavian artery which are usually detected by accident in asymptomatic patients. However, some of patients complain of severe symptoms caused by compression of the adjacent organs or complicated aortic dissection by the diverticulum. Early detection of the disease can lead to elective surgical correction. In this article, we report a Kommerells diverticulum case initially detected by transesophageal echocardiography.
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Mitochondrial UQCRB regulates VEGFR2 signaling in endothelial cells.
J. Mol. Med.
PUBLISHED: 01-22-2013
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Vascular endothelial growth factor (VEGF) signal transduction is involved in tumor angiogenesis, and the inhibition of this pathway is considered to be a powerful strategy for cancer therapy. We previously showed that small molecules targeting the ubiquinol-cytochrome c reductase binding protein (UQCRB), a subunit of mitochondrial complex III, in tumor cells suppress hypoxia-induced tumor angiogenesis. However, the mechanism by which UQCRB functioned remained unknown. In the present study, we demonstrate in endothelial cells (ECs) that UQCRB enhances VEGF receptor type 2 (VEGFR2) signaling by increasing the levels of mitochondrial reactive oxygen species (ROS). By contrast, terpestacin, a UQCRB targeting small molecule, blocked mitochondrial ROS-mediated VEGFR2 signaling pathways in ECs, thereby suppressing VEGF-dependent angiogenesis in vitro and in vivo. Furthermore, treatment with both terpestacin and bevacizumab, a VEGF signaling inhibitor, resulted in additive inhibition of tumor-induced angiogenesis both in vitro and in vivo. These data demonstrate that mitochondrial UQCRB positively regulates VEGFR2 signaling in ECs and the UQCRB targeting agent could be applied in new therapeutic approaches for human cancer.
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Candidate target genes for the Saccharomyces cerevisiae transcription factor, Yap2.
Folia Microbiol. (Praha)
PUBLISHED: 01-09-2013
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In Saccharomyces cerevisiae, the Yap family of basic leucine zipper (bZip) proteins contains eight members. The Yap family proteins are implicated in a variety of stress responses; among these proteins, Yap1 acts as a major regulator of oxidative stress responses. However, the functional roles of the remaining Yap family members are poorly understood. To elucidate the function of Yap2, we mined candidate target genes of Yap2 by proteomic analysis. Among the identified genes, FRM2 was previously identified as a target gene of Yap2, which confirmed the validity of our screening method. YNL134C and YDL124W were also identified as candidate Yap2 target genes. These genes were upregulated in strains overexpressing Yap2 and possess Yap2 target sequences in their promoter regions. Furthermore, chromatin immunoprecipitation assays showed that YNL134C and YDL124W have Yap2 binding motif. These data will help to elucidate the functional role of Yap2.
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A Case of medullary thyroid carcinoma with de novo V804M RET germline mutation.
J. Korean Med. Sci.
PUBLISHED: 01-08-2013
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Many cases of RET proto-oncogene mutations of hereditary medullary thyroid carcinoma (MTC) have been reported in Korea. However, MTC with V804M RET proto-oncogene germline mutations have not been reported in Korea. A 33-yr-old man was diagnosed with a 0.7-cm sized thyroid nodule. Laboratory testing revealed serum calcitonin was elevated. The patient underwent total thyroidectomy with central compartment neck dissection for the thyroid tumor. RET gene analysis was performed in both the index patient and his family. There were no V804M RET mutation and abnormal laboratory findings within his family except the index patient. Therefore, this patient was a de novo V804M RET germline mutation.
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Nerve growth factor-mediated vascular endothelial growth factor expression of astrocyte in retinal vascular development.
Biochem. Biophys. Res. Commun.
PUBLISHED: 01-03-2013
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The angiogenic aspect of neurotrophins and their receptors rather than the neuroscientific aspect has been focused. However, their role in retinal vascular development is underdiscovered. The purpose of this study is to understand the role of neurotrophin receptors in retinal vascular development and the mechanisms of their action. To identify the expression of tropomyosin receptor kinase receptor (Trk) in developing retina, tissues of 4, 8, 12, 16 and 26 day-old mice were prepared for experiments. Immunohistochemistry and immunofluorescence double staining against glial fibrillary acidic protein and type IV collagen were performed. TrkA was expressed mainly along the vessel structure in inner part of retina, especially in retinal astrocyte. In cultured primary astrocyte, recombinant nerve growth factor (NGF) was used to activate TrkA. NGF induced the phosphorylation of TrkA, and it also enhanced the level of activated Akt and vascular endothelial growth factor (VEGF) mRNA. Inhibition of phosphoinositide 3-kinase (PI3K) reversed the NGF-induced activation of these two molecules. This study demonstrated that TrkA activation on NGF leads to VEGF elevation by PI3K-Akt pathway and therefore suggested that TrkA could be a stimulator of retinal vascular development.
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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.