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Yoshihiro Noda

Publications and source records attributed to Yoshihiro Noda.

17 recordsLinked to original sources
PubMed2007

Transforming growth factor-beta2 and connective tissue growth factor in proliferative vitreoretinal diseases: possible involvement of hyalocytes and therapeutic potential of Rho kinase inhibitor.

The critical association of connective tissue growth factor (CTGF), which is thought to be one of the downstream mediators of transforming growth factor-beta (TGF-beta), with vitreoretinal diseases remains to be clarified. In the current study, we first demonstrated the correlation between the concentrations of TGF-beta2 as well as CTGF in the vitreous and CTGF gene regulation in cultured hyalocytes. Concentrations of TGF-beta2 and CTGF in the vitreous from patients with proliferative vitreoretinal diseases were significantly higher than in those with nonproliferative diseases, and there was a positive correlation between their concentrations (r = 0.320, P < 0.01). Cultured hyalocytes expressed CTGF mRNA, which was enhanced in the presence of TGF-beta2, associated with nuclear accumulation of Smad4. TGF-beta2-dependent Smad4 translocation and CTGF gene expression were mediated through Rho kinase and at least partially via p38 mitogen-activated protein kinase. Finally, fasudil, a Rho kinase inhibitor already in clinical use, inhibited both Smad4 translocation and CTGF gene expression. In conclusion, combined effects of TGF-beta2 and CTGF appear to be involved in the pathogenesis of proliferative vitreoretinal diseases. Hyalocytes may be a possible source of CTGF and thus might play a role in vitreoretinal interface diseases. Furthermore, Rho kinase inhibitors might have therapeutic potential to control fibrotic disorders in the eye.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2006

A tool for improving the Web accessibility of visually handicapped persons.

Abstract Much has been written concerning the difficulties faced by visually handicapped persons when they access the internet. To solve some of the problems and to make web pages more accessible, we developed a tool we call the "Easy Bar," which works as a toolbar on the web browser. The functions of the Easy Bar are to change the size of web texts and images, to adjust the color, and to clear cached data that is automatically saved by the web browser. These functions are executed with ease by clicking buttons and operating a pull-down list. Since the icons built into Easy Bar are quite large, it is not necessary for the user to deal with delicate operations. The functions of Easy Bar run on any web page without increasing the processing time. For the visually handicapped, Easy Bar would contribute greatly to improved web accessibility to medical information.

Humans↗
PubMed2005

Critical role of the Rho-kinase pathway in TGF-beta2-dependent collagen gel contraction by retinal pigment epithelial cells.

Retinal pigment epithelial cells (RPEs) are thought to be one of the main components of fibrous membrane observed in eyes with proliferative vitreo-retinopathy. We investigated the signalling mechanisms of TGF-beta2-dependent collagen gel contraction by RPEs. An in vitro type I collagen gel contraction assay was performed to evaluate the effect of TGF-beta2 on gel contraction. The expression of alpha-smooth muscle actin (alpha-SMA) and the phosphorylation state of myosin light chain (MLC) were analyzed by Western blotting. The involvement of protein kinases such as p44/42 mitogen-activated protein kinase (MAPK), protein kinase C (PKC), p38 MAPK and phosphatidylinositol-3 kinase was investigated. The contribution of Rho-kinase and/or MLC-kinase was also evaluated using respective kinase inhibitors (Y27632, hydroxyfasudil and ML7). Additionally, RPEs were immunostained to examine whether the expression of alpha-SMA detected in our western blotting correlated to the stress fiber formation within the cells. TGF-beta2 caused time (0-5 days)-and dose (0 10 ng ml(-1))-dependent gel contraction associated with overexpression of alpha-SMA and phosphorylation of MLC (p < 0.01, respectively). PKC inhibitor (GF109203X, 5 microM) and p38 MAPK inhibitor (SB203580, 10 microM) significantly attenuated TGF-beta2-elicited gel contraction via partial downregulation of both alpha-SMA expression and MLC phosphorylation (p < 0.01, respectively). The gel contraction was prominently inhibited in the presence of Y27632 (10 microM) or hydroxyfasudil (10 microM) with strong suppression of MLC phosphorylation but had no significant effect on alpha-SMA expression. Treatment with ML7, in contrast, resulted in a marginal inhibition of MLC phosphorylation and gel contraction. Finally, pretreatment of the cells with Y27632 or hydroxyfasudil prevented the formation of stress fiber within the cells. These results indicate that TGF-beta2-dependent myofibroblastic transdifferentiation and MLC phosphorylation by RPEs involve both PKC and p38 MAPK pathways at least in part. Myofibroblastic transdifferentiation of RPEs appears to be independent of the Rho-kinase pathway, and the presence of alpha-SMA does not necessarily reflect the contractile potential of a cell. While Rho-kinase inhibitors are incapable of preventing myofibroblastic transdifferentiation itself, this pathway could be one of the critical targets of cell-mediated contraction of the tissue containing fibrillar collagens by transdifferentiated RPEs.

Actins↗
PubMed2005

The novel angiotensin II type 1 receptor (AT1R)-associated protein ATRAP downregulates AT1R and ameliorates cardiomyocyte hypertrophy.

Activation of angiotensin II (Ang II) type 1 receptor (AT1R) signaling is reported to play an important role in cardiac hypertrophy. We previously cloned a novel molecule interacting with the AT1R, which we named ATRAP (for Ang II type 1 receptor-associated protein). Here, we report that overexpression of ATRAP significantly decreases the number of AT1R on the surface of cardiomyocytes, and also decreases the degree of p38 mitogen-activated protein kinase phosphorylation, the activity of the c-fos promoter and protein synthesis upon Ang II treatment. These results indicate that ATRAP significantly promotes downregulation of the AT1R and further attenuates certain Ang II-mediated hypertrophic responses in cardiomyocytes.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Rapid genotyping for most common TGFBI mutations with real-time polymerase chain reaction.

Recent studies of the corneal dystrophies (CDs) have shown that most cases of granular CD, Avellino CD, and lattice CD type I are caused by mutations in the human transforming growth factor beta-induced (TGFBI) gene. The aim of this study was to develop a rapid diagnostic assay to detect mutations in the TGFBI gene. Sixty-six patients from 64 families with TGFBI-associated CD were studied. A primer probe set was designed to examine the genome from exons 4 and 12 of the TGFBI gene in order to identify mutant and wild-type alleles. A region spanning the mutations was amplified by the polymerase chain reaction (PCR) in a commercial cycler. Mutations were then identified by melting curve analysis of the hybrid formed between the PCR product and a specific fluorescent probe. Using this system, we clearly distinguished each CD genotype (homozygous and heterozygous 418G-->A, heterozygous 417C-->T, heterozygous 1710C-->T, and wild-type) of all the patients by means of the clearly distinct melting peaks at different temperatures. One thermal cycling took approximately 54 min, and all results were completely in concordance with the genotypes determined by conventional DNA sequencing. Thus, the technique is accurate and can be used for routine clinical diagnosis. We expect that our new method will help in making precise diagnoses of patients with atypical CDs and aid the revision of the clinical classification of inherited corneal diseases based on the genetic pathogenesis.

Adolescent↗
PubMed2004

Fibrinogen stimulates in vitro angiogenesis by choroidal endothelial cells via autocrine VEGF.

BACKGROUND: The purpose of this study is to investigate the effect of fibrinogen on angiogenesis in vitro formed by cultured bovine choroidal endothelial cells (BCECs) and the involvement of vascular endothelial growth factor (VEGF) in this mechanism. METHODS: For in vitro tube formation assay, BCECs were seeded on collagen gel containing fibrinogen (0-1.5 mg/ml). After 3 days of cultivation, the total length of the tubular structure was measured using Macscope Analyzer. Total RNA and conditioned media were collected after fibrinogen treatment and subjected to Northern and Western blot analyses, respectively. Transcription factor HIF-1alpha was also analyzed by Western blot analysis using cytosolic and nuclear fraction of BCECs. Involvement of VEGF in fibrinogen-dependent in vitro tube formation was evaluated using anti-VEGF neutralizing antibody or VEGF receptor 2-selective inhibitor (SU5416). RESULTS: Formation of the tubular structure was enhanced 20 to approximately 50 times in fibrinogen-containing gel in a concentration-dependent manner. The treatment of BCECs with fibrinogen resulted in a significant increase in VEGF gene and protein expression. Accumulation of HIF-1alpha protein in the nuclear fraction was also detected after the treatment with fibrinogen. Finally, fibrinogen-induced tube formation was significantly inhibited in the presence of anti-VEGF-neutralizing antibody (52.0% inhibition at the concentration of 1 microg/ml, P<0.05) or SU5416 (54.8% inhibition at the concentration of 3 microM, P<0.05). CONCLUSIONS: Extravasated fibrinogen might play an important role in the development of choroidal neovascularization associated with age-related macular degeneration, at least in part, through the function of VEGF in an autocrine manner. Transcription factor HIF-1 appears to be involved in fibrinogen-induced VEGF expression.

Angiogenesis Inhibitors↗
PubMed2004

Novel 2336-2337delCT mutation in RP1 gene in a Japanese family with autosomal dominant retinitis pigmentosa.

PURPOSE: To determine the frequency and kinds of mutations in the RP1 gene, and to characterize the clinical features of a Japanese family with autosomal dominant retinitis pigmentosa (ADRP) with a novel 2336 to 2337delCT mutation in the RP1 gene. DESIGN: Case reports and results of DNA analysis. METHODS: Mutational screening by direct sequencing was performed on 96 unrelated patients with ADRP. The clinical features were determined by complete ophthalmologic examinations. RESULTS: A novel 2336 to 2337delCT mutation in the RP1 gene was identified in two patients from a Japanese family with ADRP. In addition, three families with ADRP carried a previously reported nonpathogenic Arg1933X mutation. The ophthalmic findings with a 2336 to 2337delCT mutation were similar to those of typical retinitis pigmentosa with rapid progression after age 40 years. CONCLUSIONS: The most common Arg677X mutation in the white population was not found in the Japanese population; instead a novel mutation was found.

Aged↗
PubMed2004

Novel mutation in FZD4 gene in a Japanese pedigree with familial exudative vitreoretinopathy.

PURPOSE: To identify the genetic defect in the FZD4 gene responsible for familial exudative vitreoretinopathy (FEVR) in a Japanese family. DESIGN: Interventional case report. METHODS: Complete ophthalmologic examinations were performed, and the FZD4 gene was analyzed by direct genomic sequencing. RESULTS: Fundus examination of a 13-year-old Japanese girl who had had esotropia and exudative retinal detachment at 3 years exhibited peripheral avascular areas bilaterally, a dragged disk, and retinal holes unilaterally. In contrast, her asymptomatic father had only bilateral avascular areas in the peripheral retina. Molecular genetic analysis revealed that both the proband and her father had a heterozygous missense mutation of A to G at 1026 bp of the FZD4 gene (Met342Val). CONCLUSIONS: A novel mutation in the FZD4 gene was identified in Japanese patients with FEVR. Our observations support the hypothesis that the FZD4-associated FEVR might represent a milder form than that associated with other genetic origins.

Adolescent↗
PubMed2004

Residual vitreous cortex after surgical posterior vitreous separation visualized by intravitreous triamcinolone acetonide.

OBJECTIVE: To visualize the residual vitreous cortex (VC) on the retinal surface after surgical posterior vitreous separation (PVS) during a pars plana vitrectomy (PPV), especially in patients with diabetic retinopathy. DESIGN: Case-control study. PARTICIPANTS: Patients with proliferative diabetic retinopathy (PDR), diabetic macular edema (DME), branch retinal vein occlusion (BRVO), and rhegmatogenous retinal detachment (RRD). METHODS: A triamcinolone acetonide (TA)-assisted vitrectomy was performed on patients with the following diseases: PDR (40 eyes), DME (26 eyes), BRVO (11 eyes), and RRD (17 eyes). Eyes with no apparent preoperative posterior vitreous detachment were enrolled in this study. After performance of surgical PVS, the residual VC was visualized as a white gel highlighted by TA. Based on this finding, the residual VC pattern was then divided into 3 groups: (1) diffuse type (VC was diffusely present in the temporal vascular arcade), (2) focal type (a small island of VC was left), and (3) no residual VC. A multivariate analysis using analysis of variance was performed regarding the residual VC pattern, disease type, age, and the 3 different surgeons. MAIN OUTCOME MEASURES: Each surgeon determined the type of residual VC during the operation, and the results were confirmed by a postoperative review of the videotape records judged by the other 2 surgeons. RESULTS: Eighty percent of the PDR eyes demonstrated the diffuse type; 10%, the focal type; and 10%, no residual VC. Fifty-eight percent of the eyes with DME demonstrated the diffuse type; 19%, the focal type; and 23%, no residual VC. Eighteen percent of the BRVO eyes showed the diffuse type; 24%, the focal type; and 59%, no residual VC. Thirty percent of the RRD eyes showed the diffuse type; 30%, the focal type; and 40%, no residual VC. A multivariate logistic regression analysis showed that PDR was a predictor of the diffuse type of residual VC in comparison to RRD (odds ratio = 8.42, 95% confidence interval = 2.07-34.3). Neither age nor the surgeon was a significant factor for a specific type of residual VC. CONCLUSIONS: Diabetic eyes more often demonstrated the diffuse type of residual VC, even after surgical PVS. This information may be valuable for surgeons performing a PPV on patients with diabetic retinopathy.

Aged↗
PubMed2004

Functional properties of hyalocytes under PDGF-rich conditions.

PURPOSE: To investigate the functional properties and intracellular signaling of hyalocytes under platelet-derived growth factor (PDGF)-rich conditions. METHODS: The hyalocytes were isolated from bovine eyes and identified by immunocytochemistry and electron microscope. The expression of PDGF receptor alpha/beta and its phosphorylation in response to PDGF-BB was analyzed by Western blot analysis. PDGF-BB-induced proliferation and migration were evaluated by thymidine uptake and Boyden's chemotaxis assay. The expression of the urokinase-type plasminogen activator (uPA) gene and the fibrinolytic activity were assessed by Northern blotting and fibrin zymography. An in vitro type I collagen gel contraction assay was performed to determine the effect of PDGF-BB on cellular contraction. RESULTS: The hyalocytes were immunocytochemically positive for S-100 and negative for glial fibrillary acidic protein (GFAP) and cytokeratin, as previously described. The electron microscope demonstrated that hyalocytes possess lysosome-like granules, mitochondria, and micropinocytotic vesicles in their cytoplasm. The hyalocytes expressed PDGF receptor alpha and beta, both of which were immediately phosphorylated in response to PDGF-BB. PDGF-BB also activated p85 PI3-kinase, p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase. PDGF-BB induced thymidine uptake and migration in a concentration-dependent (0-10 ng/mL) manner. Inhibitors of the respective kinases prohibited PDGF-BB-dependent thymidine uptake and migration with the exception of the p44/p42 MAP kinase inhibitor, which displayed no inhibitory effects on migration. PDGF-BB increased uPA gene expression and fibrinolytic activity. Collagen gel contraction observed under PDGF-BB-rich conditions was not prohibited by the respective inhibitors investigated. CONCLUSIONS: The hyalocytes demonstrated macrophage-like characteristics and may have both physiologic and pathologic roles, such as the maintenance of vitreous transparency through fibrinolytic activity and the pathogenesis of proliferative-vitreoretinal diseases through cellular proliferation and vitreous hyper-contraction.

Animals↗
PubMed2004

The involvement of the rho-kinase pathway and its regulation in cytokine-induced collagen gel contraction by hyalocytes.

PURPOSE: To investigate the involvement of the Rho-kinase pathway in collagen gel contraction by hyalocytes. METHODS: An in vitro type I collagen gel contraction assay using cultured bovine hyalocytes was performed to evaluate the effect of PDGF-BB and TGF-beta2. The effect of both cytokines on the phosphorylation of myosin light chain (MLC) was analyzed by Western blot analysis. To confirm the involvement of the Rho-kinase pathway in the collagen gel contraction, the effects of Y27632, a specific Rho-kinase inhibitor were examined. The effect of hydroxyfasudil, another potent Rho-kinase inhibitor, was also evaluated. The expression of alpha-smooth muscle actin (alphaSMA) was analyzed by Western blot analysis to examine the myofibroblast-like transdifferentiation of the hyalocytes. RESULTS: Maximum collagen gel contraction was observed within 24 hours after treatment with PDGF-BB and much stronger contraction with TGF-beta2, whose effect was time dependent, at least up to 5 days. Although transient and maximum MLC phosphorylation by PDGF-BB was observed at approximately 4 hours after stimulation (180.8%, P <0.01), TGF-beta2-elicited MLC phosphorylation occurred in a time-dependent manner at least up to 24 hours (220.0%, P <0.01) and was maintained up to 5 days. Y27632 demonstrated significant inhibition of collagen gel contraction induced by both cytokines. Hydroxyfasudil dose-dependently (0.03-20.00 microM) prohibited the phosphorylation of MLC, and inhibited collagen gel contraction at a concentration corresponding to that which inhibited MLC phosphorylation. TGF-beta2, but not PDGF-BB, also caused myofibroblast-like transdifferentiation with alphaSMA overexpression, which was downregulated by hydroxyfasudil in part (P <0.01). CONCLUSIONS: The hyalocytes have a contractile property in the presence of PDGF-BB and TGF-beta2. Whereas PDGF-BB initiates collagen gel contraction by transient activation of the Rho-kinase pathway, sustained activation of the Rho-kinase pathway and myofibroblast-like transdifferentiation appears to be involved in the TGF-beta2-dependent contractile properties of hyalocytes.

Actins↗
PubMed2003

Submacular deposition of triamcinolone acetonide after triamcinolone-assisted vitrectomy.

PURPOSE: We describe a case demonstrating a submacular deposition of triamcinolone acetonide (TA) after a TA-assisted vitrectomy for retinal detachment. DESIGN: Interventional case report. METHODS: A 48-year-old Japanese man with rhegmatogenous retinal detachment in his left eye underwent a TA-assisted vitrectomy, endolaser photocoagulation, and sulfur hexafluoride (SF(6)) gas tamponade. RESULTS: At the end of the surgery and the day after undergoing vitrectomy, the deposition of TA was observed between the retinal pigment epithelium and neurosensory retina in the submacular area. These TA granules disappeared after 2 weeks. Two months after the operation, the retina was observed to be successfully attached and no abnormality was observed in the macula. The patient's visual acuity improved to 20/16, and no ophthalmoscopic or functional damage was observed. CONCLUSION: No apparent adverse effect was found in this case demonstrating a submacular deposition of TA.

Fluorescein Angiography↗
PubMedDate not supplied

A case of Vogt-Koyanagi-Harada disease with good visual acuity in spite of subfoveal fold.

BACKGROUND: Vogt-Koyanagi-Harada (VKH) disease patients with the complication of subretinal pigmented proliferative tissue tend to have a poor visual prognosis. CASE: We herein report a case of VKH with good visual acuity despite a prominent subretinal fold. OBSERVATIONS: A 24-year-old woman, who experienced several recurrent episodes of VKH disease, had bilateral serous retinal detachment with poor vision (RE 20/40 and LE 20/25). After the administration of high doses of systemic corticosteroids and D-mannitol, the subretinal fluid disappeared and the sensory retinas gradually became reattached. During the course of therapy, prominent pigmented subretinal strands were formed in both eyes. Optical coherence tomography disclosed that the strands existed at the retinal pigment epithelium level. Amazingly, we observed a change in the location of the fold in the posterior retina during the course of the disease. The patient finally showed the "sunset glow" fundi and a subretinal fold that was located almost directly beneath both fovea. Fortunately, this patient was able to recover and finally achieve a good visual acuity (RE 20/17 and LE 20/17). CONCLUSION: We reported a VKH disease patient with a good visual acuity despite a remarkable subfoveal fold, which changed its location during the course of the disease.

Adrenal Cortex Hormones↗