Tsunehiko Ikeda

Osaka Medical College, Takatuki, Ōsaka, Japan

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Publications (149)343.94 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To study the indications for and effectiveness of Nunchaku-style silicone tube intubation (NSTI) in treating primary acquired lacrimal drainage obstruction (PALDO). In this interventional cohort study, 235 consecutive patients in 1 institution who had complete lacrimal obstruction were investigated. Of those, 212 PALDO patients were enrolled, and 156 of the PALDO patients ultimately satisfied our treatment protocol and were then followed up for 12 months postsurgery. Patients without dacryocystitis underwent NSTI, while those with dacryocystitis underwent NSTI or endonasal dacryocystorhinostomy (EN-DCR) using the NST as a stent. The tubes were left in place for 8 weeks, and all patients received identical postoperative care. Resolution was deemed as patency assessed by irrigation. Logistic regression analyses were performed to compare the success of NSTI for upper (puncta and canaliculus) and lower (lacrimal sac and nasolacrimal duct) obstruction, NSTI for lower obstruction with and without dacryocystitis, and NSTI and EN-DCR for lower obstruction with dacryocystitis. Comparison of the success rates at 12 months postsurgery showed significance as follows: treatment with NSTI was more successful for upper obstruction (94.6 %) than for lower obstruction (71.4 %) [odds ratio (OR) 8.23; P < 0.01]; treatment with NSTI was more successful for lower obstruction without dacryocystitis (82.9 %) than for dacryocystitis (52.4 %) (OR 4.96; P < 0.05); and treatment with EN-DCR (95.5 %) was more successful than NSTI (52.4 %) for treating lower obstruction with dacryocystitis (OR 16.99; P < 0.001). NSTI is effective for treating PALDO; however, EN-DCR is more effective for treating PALDO cases complicated by dacryocystitis.
    Japanese Journal of Ophthalmology 04/2015; DOI:10.1007/s10384-015-0381-5 · 1.80 Impact Factor
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    ABSTRACT: To investigate the effects and toxicities of gelatin hydrogel (GH) loading mitomycin C (MMC) on intraocular pressure (IOP) and conjunctival scarring in a canine model of glaucoma surgery in comparison to conventional MMC application. Glaucoma surgery models were made in six beagles. An MMC-loaded GH was implanted under the conjunctiva of one eye (GH-MMC group) and 0.04% MMC-soaked sponges were placed under the conjunctiva of the other eye (MMC group) for 5 five minutes. IOPs and bleb features were then assessed for 4four-weeks postoperative, followed by histological evaluation. The ratio of conjunctival area to scleral area, the densities of collagen and the numbers of fibroblasts, vessels, and proliferative cell nuclear antigen (PCNA)-positive cells were then quantified. In both groups, IOP reduction and bleb formation were maintained in a similar manner for 4four-weeks postoperative. No significant difference in the ratio of conjunctival area to scleral area was found between the two groups, however, c. Collagen density and the numbers of fibroblasts and vessels were significantly lower in the MMC-treated group than in the GH-MMC-treated group. No significant difference in PCNA-positive cells was found between the two groups. Implantation of MMC-loaded GH ameliorated toxicity to conjunctiva compared with the 5five-minute placement of MMC, howeverwhereas, its effect on IOP reduction and bleb formation was similar. These results suggest that using GH for the application of MMC is a safer method than the conventional application of MMC in glaucoma filtration surgery. Copyright © 2015 by Association for Research in Vision and Ophthalmology.
    Investigative ophthalmology & visual science 03/2015; DOI:10.1167/iovs.15-16486 · 3.66 Impact Factor
  • Masanori Fukumoto, Tsunehiko Ikeda
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    ABSTRACT: Diabetic macular edema(DME) is a major cause of vision loss and has a remarkable impact on the quality of life of diabetic patients. New pharmacological approaches based on the use of intravitreal drugs, such as corticosteroids and anti-vascular endothelial growth factor, have recently been developed for the treatment of DME. Even though laser therapy has been the standard treatment for DME, the results of several clinical trials have shown the superiority of some of these new agents to laser therapy. The purpose of this review is to briefly summarize the currently available new pharmacological treatments for DME in Japan.
    Nippon rinsho. Japanese journal of clinical medicine 03/2015; 73(3):484-8.
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    ABSTRACT: We report a rare case of large cell neuroendocrine carcinoma (LCNEC) of the lung with cancer-associated retinopathy (CAR). To our knowledge, only two cases of LCNEC with CAR have been reported, one in 1995 and another in 2013. CAR, typically associated with small cell lung cancer (SCLC), is one of the paraneoplastic syndromes with deterioration of visual acuity, visual field constriction, and photophobia. CAR is caused by an autoimmune system reaction against the same antigen in the tumor and retinal photoreceptor cells. To diagnose CAR, genetic retinal dystrophies or any other medical causes of retinopathy should be excluded, but there are no standard diagnostic criteria. Anti-retinal antibodies are known to be positive in CAR patients, and anti-recoverin antibodies are thought to be sensitive and specific to CAR. In our case, anti-recoverin antibodies were not detected by serum tests, but CAR could be diagnosed on the basis of ophthalmological findings including clinical symptoms, electroretinographic findings, and visual field tests. CAR with clinical features of rapid visual disorder should be considered in LCNEC patients as well as in SCLC patients.
    Case Reports in Oncology 01/2015; 8(1):153-158. DOI:10.1159/000380943
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    ABSTRACT: Estrogen, a female hormone, activates collagenase and might be associated with the pathogenesis of vitreoretinal collagen fiber disease. The purpose of the present study was to investigate the vitreous levels of estrone (E1) and estradiol (E2) in subjects with an idiopathic macular hole (IMH). Vitreous samples were obtained from ten female patients with an IMH and from nine female patients with other retinal diseases (six with rhegmatogenous retinal detachment and three with age-related macular degeneration) as a control at the time of vitreous surgery. E1 and E2 levels in the vitreous samples were then determined using the Coat-A-Count(®) Estradiol Radioimmunoassay (RIA) Kit and the DSL-70 Estrone RIA Kit, respectively. The mean vitreous levels of E1 and E2 in the subjects with IMH were 1.83±2.00 pg/mL and 7.03±2.97 pg/mL, respectively, whereas in the control subjects they were 2.42±1.25 pg/mL and 4.90±2.90 pg/mL, respectively. Thus, the vitreous E2 levels in the subjects with IMH were significantly higher than in the controls (P<0.05). The findings of this study suggest that E2 might be associated with the pathogenesis of IMH, but further investigation is needed to elucidate that association.
    Clinical ophthalmology (Auckland, N.Z.) 01/2015; 9:549-52. DOI:10.2147/OPTH.S80754
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    ABSTRACT: It was the aim of this study to report a case of a vitreomacular traction-associated macular microhole (MMH) in an eye with focal choroidal excavation (FCE) detected by spectral-domain optical coherence tomography (SD-OCT). A 38-year-old Japanese female presented to our clinic complaining of metamorphopsia in her left eye. The patient then underwent SD-OCT as well as a routine ophthalmological examination. She had a previous history of a macular hole in her right eye that had been successfully treated by pars plana vitrectomy. Upon initial examination, her best-corrected visual acuity was 20/25 in the left eye with a refractive error of -10.25 diopters. Examination by SD-OCT revealed an MMH with an outer retinal defect adjacent to the FCE. SD-OCT also revealed an intraretinal cystoid space in the macula with vitreous attachment around the foveal center. The findings of this report show that variable changes are likely to be associated with FCE. However, the etiology of FCE has yet to be fully elucidated and careful observation is necessary in cases of FCE.
    01/2015; 6(1):71-5. DOI:10.1159/000377667
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    ABSTRACT: Autoimmune mechanisms have been postulated as a cause of diabetic retinopathy (DR), as several autoantibodies have reportedly been detected in the serum of DR patients. In this present study, we measured serum and vitreous levels of anti-type II collagen (anti-II-C) antibodies in DR patients and investigated their association with the mechanism of development of DR. Blood samples were obtained from patients with proliferative DR and from patients with diabetic macular edema who underwent vitrectomy at Osaka Medical College, Takatsuki City, Osaka, Japan. Diabetic patients without DR were also included. The control group consisted of age- and sex-matched patients with noninflammatory eye diseases who underwent eye surgery for retinal detachment or for cataracts. The levels of anti-II-C immunoglobulin (Ig)G antibody in the vitreous and serum were measured using a human/monkey anti-II-C IgG assay kit. The serum levels of anti-II-C IgG antibody were significantly higher in the DR patients than in the patients with noninflammatory eye disease (56.8±33.8 units/mL versus 30.5±13.7 units/mL, respectively; P<0.05, Fisher's exact test). These levels were also significantly higher in the diabetic patients without DR than in the patients with noninflammatory eye disease (76.3±49.7 units/mL versus 30.5±13.7 units/mL, respectively; P<0.01, Fisher's exact test). However, anti-II-C IgG antibody levels were unable to be detected in all of the obtained vitreous fluid samples. The development and progression of DR may be related to a mechanism involving intraocular type II collagen, which normally has immunological tolerance as a sequestered antigen. In DR, the disruption of the blood-retinal barrier leads to contact between the intraocular type II collagen and immunocompetent cells, and to subsequent activation of the autoimmune mechanism.
    Clinical ophthalmology (Auckland, N.Z.) 01/2015; 9:543-7. DOI:10.2147/OPTH.S75422
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    ABSTRACT: The purpose of this study was to determine the temporal and spatial changes in the expression of AQP4 and AQP9 in the optic nerve after it is crushed. The left optic nerves of rats were either crushed (crushed group) or sham operated (sham group), and they were excised before, and at 1, 2, 4, 7, and 14 days later. Four optic nerves were pooled for each time point in both groups. The expression of AQP4 and AQP9 was determined by western blot analyses. Immunohistochemistry was used to determine the spatial expression of AQP4, AQP9, and GFAP in the optic nerve. Optic nerve edema was determined by measuring the water content in the optic nerve. The barrier function of the optic nerve vessels was determined by the extravasated Evans blue dye on days 7 and 14. The results showed that the expression of AQP4 was increased on day 1 but the level was significantly lower than that in the sham group on days 4 and 7 (P<0.05). In contrast, the expression of AQP9 gradually increased, and the level was significantly higher than that in the sham group on days 7 and 14 (P<0.05, Tukey-Kramer). The down-regulation of AQP4 was associated with crush-induced optic nerve edema, and the water content of the nerve was significantly increased by 4.3% in the crushed optic nerve from that of the untouched fellow nerve on day 7. The expression of AQP4 and GFAP was reduced at the crushed site where AQP4-negative and AQP9-positive astrocytes were present. The barrier function was impaired at the crushed site on days 7 and 14, restrictedly where AQP4-negative and AQP9-positive astrocytes were present. The presence of AQP9-positive astrocytes at the crushed site may counteract the metabolic damage but this change did not fully compensate for the barrier function defect.
    PLoS ONE 12/2014; 9(12):e114694. DOI:10.1371/journal.pone.0114694 · 3.53 Impact Factor
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    ABSTRACT: Purpose: To evaluate the correlation between laser speckle flowgraphy measurements of mean blur rate (MBR) and hydrogen gas clearance measurements of capillary blood flow (CBF) in the optic nerve head (ONH) of albino and pigmented rabbits with or without chronic ischemia-induced ONH atrophy. Methods: ONH MBR and ONH CBF were measured at baseline, 30 and 60 minutes after the intravenous administration of endothelin-1 (ET-1) (10-10 mol/kg) in 6 albino and 6 pigmented rabbit eyes. ONH MBR and ONH CBF were also measured in 9 pigmented rabbit eyes that underwent the intravitreal administration of ET-1 (20 pmol) twice per week for 4 weeks to provoke chronic ischemia-induced ONH atrophy. Results: In the group that received intravenous ET-1, average measurements of ONH MBR and ONH CBF at all time points were correlated in both the albino (r =0.88, P <0.001, n=18) and pigmented rabbits (r =0.85, P <0.001, n =18) with no intra-rabbit correlations (P =0.524). ONH MBR and ONH CBF were also correlated in the model of chronic ischemia-induced ONH atrophy (r =0.78, P =0.013, n =9). Pooled ONH MBR and ONH CBF measurements in both the intravenous and intravitreal groups were also highly correlated (r =0.87, P <0.001, n =45), with no significant inter-group differences in the relationship between ONH MBR and ONH CBF (P =0.14). Conclusion: Regardless of the presence of fundus pigmentation or ONH atrophy, ONH MBR and ONH CBF were highly correlated, suggesting that MBR in the ONH tissue is usable for inter-individual and inter-group comparisons.
    Investigative Ophthalmology &amp Visual Science 11/2014; DOI:10.1167/iovs.14-15373 · 3.66 Impact Factor
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    ABSTRACT: Purpose:The incidence of blindness is increasing, in part, because of the abnormal ocular neovascularization. Anti-VEGF therapies have yielded impressive results; however, they are not a cure for blindness. Recently, metallothioneins (MTs) 1 and 2 have been implicated in the process of angiogenesis. Therefore, we investigated whether MT 1 and MT 2 were also involved in ocular neovascularization. Methods:The concentrations of MT 1 and MT 2 (hereafter MT-1/2) were observed by ELISA. We examined the role of MT-1/2 in ocular neovascularization by using both an oxygen-induced retinopathy (OIR) model and a laser-induced choroidal neovascularization (CNV) model. We investigated the localization of MT-1/2 in retina. Furthermore we investigated the expression of hypoxia-inducible factor (HIF)-1α and VEGF in OIR. In vitro, we investigated the degradation of HIF-1α. Results:The MT-1/2 were significantly elevated in proliferative diabetic retinopathy patients. Ocular neovascularization, which was induced in both the OIR model and the CNV model, was decreased in MT-1/2 knockout (KO) mice. We confirmed that although MT-1/2 was expressed throughout the murine retina, its expression levels were highest in the endothelial cells. Further, OIR enhanced MT-1/2 expression in the retina. Interestingly, in the OIR model, both HIF-1α and VEGF levels were significantly decreased in the retina of MT-1/2 KO mice. In addition, we found that knockdown of MT-1/2 accelerated ubiquitination of HIF-1α. Conclusions:These results indicate that MTs 1 and 2 are involved in retinal and choroidal neovascularization, and that MT-1/2 might be a new therapeutic target in diseases in which ocular angiogenesis is implicated.
    Investigative Ophthalmology &amp Visual Science 09/2014; 55(10). DOI:10.1167/iovs.14-14545 · 3.66 Impact Factor
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    ABSTRACT: Neuroinflammation is involved in the death of retinal ganglion cells (RGCs) after optic nerve injury. The purpose of this study was to determine whether systemic simvastatin can suppress neuroinflammation in the optic nerve and rescue RGCs after the optic nerve is crushed. Simvastatin or its vehicle was given through an osmotic minipump beginning one week prior to the crushing. Immunohistochemistry and real-time PCR were used to determine the degree of neuroinflammation on day 3 after the crushing. The density of RGCs was determined in Tuj-1 stained retinal flat mounts on day 7. The effect of simvastain on the TNF-α-induced NF-κB activation was determined in cultured optic nerve astrocytes. On day 3, CD68-positive cells, most likely microglia/macrophages, were accumulated at the crushed site. Phosphorylated NF-κB was detected in some astrocytes at the border of the lesion where the immunoreactivity to MCP-1 was intensified. There was an increase in the mRNA levels of the CD68 (11.4-fold), MCP-1 (22.6-fold), ET-1 (2.3-fold), GFAP (1.6-fold), TNF-α (7.0-fold), and iNOS (14.8-fold) genes on day 3. Systemic simvastatin significantly reduced these changes. The mean ± SD number of RGCs was 1816.3±232.6/mm(2) (n = 6) in the sham controls which was significantly reduced to 831.4±202.5/mm(2) (n = 9) on day 7 after the optic nerve was crushed. This reduction was significantly suppressed to 1169.2±201.3/mm(2) (P = 0.01, Scheffe; n = 9) after systemic simvastatin. Simvastatin (1.0 µM) significantly reduced the TNF-α-induced NF-κB activation in cultured optic nerve astrocytes. We conclude that systemic simvastatin can reduce the death of RGCs induced by crushing the optic nerve possibly by suppressing astroglial NF-κB activation.
    PLoS ONE 01/2014; 9(1):e84387. DOI:10.1371/journal.pone.0084387 · 3.53 Impact Factor
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    ABSTRACT: To assess efficacy of the conservative management of patients with congenital dacryocystocele. This was a retrospective case series involving six sides of five infants with a dacryocystocele treated at Osaka Kaisei Hospital, Osaka, Japan. The conservative management protocol consisted of the application of warm compresses and massage over the mass, with the addition of antibiotics when dacryocystitis developed. Patient age at the time of resolution, presence of retrograde outflow of contents of dacryocystoceles from the puncta, and development of dacryocystitis were recorded. The dacryocystocele was unilateral in four patients and bilateral in one patient. A nasal cyst was present in four patients without respiratory distress. The median patient age at the time of the diagnosis was 7 days (range 2-10 days). Conservative management was selected in all patients, and the dacryocystocele was resolved in all patients at a median patient age of 14.5 days (range 11-105 days). Two sides developed dacryocystitis, which resolved in a few days with antibiotic treatment. In those two sides, rupture of the dacryocystoceles to the common canaliculus with retrograde discharge of the contents from the puncta before the dacryocystitis developed was noted. For the other four treated sides, no such discharge or development of dacryocystitis was observed. The findings of this study show that a dacryocystocele has a good chance of resolving spontaneously with conservative management and careful observation, and that rupture of the dacryocystocele to the common canaliculus might be an important precursor of dacryocystitis.
    Clinical ophthalmology (Auckland, N.Z.) 01/2014; 8:465-9. DOI:10.2147/OPTH.S58342
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    ABSTRACT: We report our findings in three cases of unilateral macular edema associated with retinal vein occlusion (RVO) that improved after successful treatment of systemic hypertension alone.
    Clinical ophthalmology (Auckland, N.Z.) 01/2014; 8:955-8. DOI:10.2147/OPTH.S63368
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    ABSTRACT: Nuclear sclerosis (NS) based on the Emery-Little classification and refractive values after lens-sparing vitrectomy was compared between proliferative diabetic retinopathy (DR) patients and nondiabetic patients.
    Clinical ophthalmology (Auckland, N.Z.) 01/2014; 8:959-63. DOI:10.2147/OPTH.S61372
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    ABSTRACT: To investigate whether the P2X7 receptor is involved in retinal ganglion cell (RGC) death after the intraocular pressure (IOP) is elevated in rats. After the IOP was elevated to 90 mmHg for 1 h, the rats were subsequently administered oxidized adenosine triphosphate (OxATP) and brilliant blue G (BBG) as P2X7 antagonists. The rats were euthanized 7 days after IOP elevation for histologic evaluation and at 1, 3, and 7 days after IOP elevation to immunostain for the P2X7 receptor and neuron-specific class III β-tubulin in the retina. Changes in P2X7 receptor expression were measured in total retina extracts using western blot analysis. Quantitative real-time PCR was also performed using the entire retina to determine whether the P2X7 receptor is involved in upregulating tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 at 1, 2, and 3 days after the IOP was elevated. RGC density and the inner plexiform layer thickness significantly decreased 7 days after IOP elevation, but were dose-dependently preserved when treated with OxATP or BBG. P2X7 immunoreactivity in the RGCs increased after IOP elevation, with the peak occurring from day 1 through day 3. Protein levels of P2X7 receptor were significantly increased 1, 2, and 3 days after IOP elevation. The messenger ribonucleic acid expression of the P2X7 receptor, TNF-α, IL-1β, and IL-6 was significantly upregulated in the retina after IOP elevation, and was suppressed by treatment with OxATP. These results suggest the expression of the P2X7 receptor is upregulated in the retina after IOP elevation, leading to RGC death. Upregulation of TNF-α, IL-1β, and IL-6 might be involved in this mechanism of RGC death. Furthermore, P2X7 antagonists may prevent RGC death after IOP elevation.
    Molecular vision 09/2013; 19:2080-91. · 2.25 Impact Factor
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    ABSTRACT: The purpose of this study was to develop a screening device for the early detection of glaucoma. We evaluated our proposal system by comparing the results obtained by using the proposed system and Humphrey Field Analyzer (HFA), which was commercially available visual field measurement device. Quantitative evaluation of the proposed system and HFA visual field test results, and calculating the correlation coefficient, we were able to obtain a more moderate positive correlation. This study suggested that the proposed system was potentially useful as an alternate screening device for the detection of the early stage of glaucoma.
    Proceedings of the 15th international conference on Human Interface and the Management of Information: information and interaction for health, safety, mobility and complex environments - Volume Part II; 07/2013
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    ABSTRACT: This case report describes a case of Alagille syndrome with developing intraocular lens subluxation and rhegmatogenous retinal detachment 4 years after cataract surgery. A 15-year-old female patient with Alagille syndrome-associated cataracts in both eyes underwent phacoemulsification aspiration and intraocular lens implantation. Four years postoperative, intraocular lens subluxation developed in her left eye. For treatment, extraction of the dislocated intraocular lens, anterior vitrectomy, and intraocular lens fixation was performed. Three weeks later, the patient developed rhegmatogenous retinal detachment, which was well-treated by pars plana vitrectomy. Cataract surgery needs to be performed carefully in patients with Alagille syndrome due to the weakness of the zonule of Zinn. Careful postoperative observation is necessary for patients with Alagille syndrome who have undergone intraocular surgery in order to facilitate early detection of a possible rhegmatogenous retinal detachment.
    Clinical ophthalmology (Auckland, N.Z.) 07/2013; 7:1463-5. DOI:10.2147/OPTH.S43753
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    ABSTRACT: PURPOSE: To report a case of pseudo-unilateral occult macular dystrophy (OMD) with an Arg45Trp mutation in the RP1L1 gene and had unilateral functional changes for about 9 years. CASE REPORT: A 64-year-old woman with a decimal visual acuity of 1.0 in both eyes complained about difficulties with visual tasks because of presbyopia. At the age of 65 years, her visual acuity in the left eye decreased to 0.2, while that in the right eye was 0.7. The fundus of both eyes was normal except for drusen. After 10 years and at the age of 75 years, her visual acuity in the right eye decreased to 0.3. Focal macular electroretinograms (ERGs) at this time were severely attenuated in both eyes, while the full-field ERGs were within normal limits. Ophthalmoscopy showed that the fundus of both eyes was still normal. Genetic analysis revealed a heterozygous mutation, Arg45Trp, in the RP1L1 gene. CONCLUSIONS: These findings indicate that the phenotype in some cases of OMD with an Arg45Trp mutation in the RP1L1 gene can be unilateral for a considerable period.
    Documenta Ophthalmologica 04/2013; 127(2). DOI:10.1007/s10633-013-9384-z · 1.11 Impact Factor
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    ABSTRACT: The diagnosis of amyotrophic lateral sclerosis (ALS) is difficult due to lack of definitive biomarkers. Our aim was to identify characteristic serum protein patterns that could provide candidate biomarkers for ALS. We divided mutant superoxide dismutase-1 (SOD1)(H46R) rats into three groups based on disease progression: pre-symptom (90 days), onset, and end-stage. After separation of serum proteins using two-dimensional electrophoresis, we selected clear protein spots and identified two candidate proteins-inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and glutathione peroxidase 3 (Gpx3). The 120 kDa ITIH4 increased at the onset of the disease and the 85 kDa ITIH4, a cleaved form, at the end-stage in the sera of the SOD1(H46R) rats. Expression of the 85 kDa ITIH4 was substantial in ALS compared with controls or patients with muscular dystrophy, Alzheimer diseases, or Parkinson diseases. The Gpx3 protein levels in the sera of SOD1(H46R) rats were upregulated pre-symptom and gradually decreased as the disease progressed. The Gpx3 protein levels were lower in the sera of the patients with ALS than in other diseases. These results indicate that ITIH4 and Gpx3 are potential biomarkers for ALS.
    Journal of Neurology 02/2013; 260(7). DOI:10.1007/s00415-013-6877-3 · 3.84 Impact Factor

Publication Stats

1k Citations
343.94 Total Impact Points

Institutions

  • 2000–2015
    • Osaka Medical College
      • Department of Ophthalmology
      Takatuki, Ōsaka, Japan
  • 2010
    • Osaka University
      • Division of Ophthalmology
      Suika, Ōsaka, Japan
  • 1997–2009
    • Kyoto Prefectural University of Medicine
      • Department of Ophthalmology
      Kioto, Kyōto, Japan
    • University of Michigan
      Ann Arbor, Michigan, United States
  • 2005
    • Keio University
      • Department of Ophthalmology
      Edo, Tōkyō, Japan
  • 2004
    • Takatsuki Red Cross Hospital
      Takatuki, Ōsaka, Japan