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Biomedical subjects

Hiromu K Mishima

Publications and source records attributed to Hiromu K Mishima.

At least 19 recordsLinked to original sources
PubMed2006

R659S mutation of gammaPKC is susceptible to cell death: implication of this mutation/polymorphism in the pathogenesis of retinitis pigmentosa.

It has been reported that mutations of gammaPKC cause hereditary spinocerebellar atrophy type 14 (SCA14). Our recent study has revealed that the SCA14 mutant gammaPKC is susceptible to aggregation and causes cell death. Among mutations/polymorphisms of gammaPKC, the R659S mutation was firstly segregated from families with hereditary retinitis pigmentosa type 11 (RP11). Although more reliable etiological mutations of RP11 were subsequently discovered in a human homologue of yeast pre-mRNA splicing gene (PRP31), the role of this R659S missense change in the pathogenicity of RP11 is still controversial. In this study, we overexpressed R659S gammaPKC in CHO cells and characterized the properties of this mutant protein. We found that R659S gammaPKC more prominently induced cell death than did wild-type. This mutant gammaPKC had higher basal activity than wild-type, however, no difference was found in the extent of aggregation and insolubility to detergent between R659S mutant and wild-type. These results suggest that the R659S mutation is susceptible to neuronal death and is involved in the pathogenesis of neurodegenerative diseases, including RP11.

Animals↗
PubMed2006

Risk factors for open-angle glaucoma in a Japanese population: the Tajimi Study.

PURPOSE: To identify the risk factors associated with primary open-angle glaucoma (POAG) in the Tajimi Study. DESIGN: Population-based cross-sectional epidemiologic study. PARTICIPANTS: One hundred nineteen POAG patients and 2755 controls. METHODS: Univariate and multivariate comparison of ocular factors and systemic factors between POAG patients and controls. MAIN OUTCOME MEASURES: Difference in factors between POAG patients and controls, factors associated with POAG patients, and their odds ratio (OR). RESULTS: Intraocular pressure (IOP), age, myopia, and history of hypertension differed between POAG patients and controls in univariate analyses. Multivariate analysis with logistic regression with stepwise selection of variables demonstrated that higher IOP (OR, 1.12 [95% confidence interval (CI), 1.04-1.21]), myopia (ORs, 1.85 [95% CI, 1.03-3.31] for low myopia and 2.60 [95% CI, 1.56-4.35] for moderate to high myopia), and older age (OR, 1.06 [95% CI, 1.04-1.08]) were associated with an increased risk of having POAG. CONCLUSIONS: Although the majority (92%) of POAG patients diagnosed in the Tajimi Study had IOP within the normal range, IOP was still identified as a significant risk factor for POAG. Together with IOP, myopia and age were significant risk factors for having POAG.

Age Factors↗
PubMed2006

High glucose concentration induces elevated expression of anti-oxidant and proteolytic enzymes in cultured human retinal pigment epithelial cells.

We investigated the differential protein expression patterns of retinal pigment epithelial (RPE) cells exposed to increased glucose concentrations. Cultured human RPE cells (ARPE-19) were exposed for 4 days with normal blood glucose concentration (5.5 mM D-glucose), followed by exposure to either normal (5.5 mM) or high (33 mM) concentrations of D-glucose for 48h. Protein extracts of glucose-treated RPE cells were then subjected to comparative proteome analysis based on 2-D gel electrophoresis. Protein spots were visualized by silver staining. The differentially expressed proteins were excised and digested in-gel with trypsin, then analysed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The expression levels of cathepsin B, glutathione peroxidase and heat shock protein 27 were increased, and that of protein disulfide isomerase decreased in high glucose treated RPE compared to normal glucose. The isoelectric point of copper/zinc-containing superoxide dismutase (Cu/Zn-SOD) shifted toward acidic region in response to high glucose. Cu/Zn-SOD activity in high glucose group was significantly lower than that in normal glucose group (P<0.05, Mann-Whitney U-test). Systematic survey of protein expression has revealed that RPE cells respond to acute, pathologically high glucose levels by the elevated expression of anti-oxidant and proteolytic enzymes.

Antioxidants↗
PubMed2006

High frequency of open-angle glaucoma in Japanese patients with Alzheimer's disease.

The clinical and genetic relationships between Alzheimer's disease (AD) and glaucoma remain obscure. The aim of this study was to determine the prevalence of open-angle glaucoma (OAG) in patients with AD and whether the apolipoprotein E (APOE) 4 allele is associated with AD, with or without OAG, in Japanese. The groups consisted of 172 patients with the diagnostic criteria of AD and 176 age-matched controls. Ophthalmic examinations were conducted, and genomic analysis was performed by PCR and digestion of products with an enzyme. OAG was found in 41 (23.8%) of the AD patients, which was a significantly (p = 0.0002) higher prevalence than that in the controls (9.9%). Furthermore, there was no significant difference between intraocular pressures (IOPs) in AD patients with OAG and without OAG. The percentage of AD patients who carried an APOE epsilon4 allele (29.5%) was significantly (p = 0.0007) higher than that of the controls (9.1%). However, the percentage of AD patients with OAG who carried an APOE epsilon4 allele (35.7%) was not significantly different than that of AD patients without OAG (27.7%, p = 0.42). In summary, the prevalence of OAG is high in Japanese patients with AD, suggesting that common factors other than APOE may contribute to the two diseases.

Aged↗
PubMed2005

Intravitreal levels of vascular endothelial growth factor and interleukin-6 are correlated with macular edema in branch retinal vein occlusion.

BACKGROUND: To investigate whether vascular endothelial growth factor (VEGF) or interleukin-6 (IL-6) contributes to the pathogenesis of macular edema in eyes with branch retinal vein occlusion (BRVO), the correlations between these factors were investigated. METHODS: We studied 25 patients suffering from macular edema with BRVO and 14 patients with nonischemic ocular disease (control group). The degree of retinal ischemia was evaluated in terms of the area of capillary nonperfusion using Scion Images, and the severity of macular edema was examined using optical coherence tomography. Vitreous fluid samples were obtained at the time of vitreoretinal surgery, and VEGF and IL-6 levels in the vitreous fluid and plasma were determined by means of enzyme-linked immunosorbent assays. RESULTS: Vitreous fluid levels of VEGF and IL-6 were significantly elevated in patients with BRVO compared with control patients (P = 0.0011 and P < 0.0001, respectively). Also, the vitreous level of VEGF was significantly correlated with that of IL-6 (P = 0.0012), and vitreous levels of VEGF and IL-6 were correlated with the size of the BRVO nonperfusion area (P < 0.0001 and P = 0.0033, respectively). Furthermore, vitreous levels of VEGF and IL-6 were correlated with the severity of macular edema (P = 0.0008 and P = 0.0191, respectively) and the severity of macular edema of BRVO was significantly correlated with the size of the BRVO nonperfusion area (P=0.0044). CONCLUSIONS: The levels of VEGF and IL-6 are increased in patients with macular edema with BRVO and are significantly correlated with the size of the nonperfusion area and the severity of macular edema. Therefore, they may play a role in macular edema with BRVO.

Enzyme-Linked Immunosorbent Assay↗
PubMed2005

Neuroprotective effects of erythropoietin on glutamate and nitric oxide toxicity in primary cultured retinal ganglion cells.

Erythropoietin receptor (EpoR) is expressed in the central nervous system (CNS), however, no clear consensus has been obtained whether Epo acts as a prosurvival factor in neurons. Because retinal ganglion cell (RGC) death is a common cause of reduced visual function in several ocular diseases, we explored whether Epo might potentially be beneficial in protecting RGCs from glutamate and nitric oxide (NO)-induced cytotoxicity, using isolated RGCs by a two-step panning method. Brain-derived neurotrophic factor (BDNF) was used as a positive control. EpoR mRNA was expressed in isolated RGCs, and EpoR protein was expressed on the RGCs in the normal and ischemic retinas. Epo had less potential to improve the survival of primary RGCs in serum-free medium than BDNF. In these cells, BDNF, but not Epo, downregulated the expression of Bim, a proapoptotic Bcl-2 family member that plays a key role in cytokine-mediated cell survival, suggesting a possible mechanism for this difference. When RGCs were cultured with glutamate or an NO-generating reagent, the survival of RGCs was compromised, and Bcl-2 expression was decreased in these cells. Both Epo and BDNF significantly reduced RGC death induced by glutamate and NO. In agreement with this, these factors reversed the Bcl-2 expression. These findings suggest that Epo may be a potent neuroprotective therapeutic agent for the treatment of ocular diseases that are characterized by RGC death.

Animals↗
PubMed2005

Pathogenesis of macular edema with branch retinal vein occlusion and intraocular levels of vascular endothelial growth factor and interleukin-6.

PURPOSE: To determine whether correlations between vascular endothelial growth factor (VEGF) or interleukin-6 (IL-6) contribute to the pathogenesis of macular edema in eyes of patients with branch retinal vein occlusion (BRVO). DESIGN: Retrospective case-control study. METHODS: Nineteen patients with macular edema with BRVO and seven patients with non-ischemic ocular disease (control group) were studied. The degree of retinal ischemia was evaluated in terms of the area of capillary non-perfusion, and the severity of macular edema was examined by optical coherence tomography. Aqueous humor samples were obtained at the time of combined vitrectomy and cataract surgery, and VEGF and IL-6 levels in aqueous humor and plasma were determined by enzyme-linked immunosorbent assay. RESULTS: Aqueous levels of VEGF (351 +/- 273 pg/ml) and IL-6 (7.10 +/- 6.51 pg/ml) were significantly elevated in patients with BRVO compared with the control patients (119 +/- 38.7 pg/ml and 2.27 +/- 1.11 pg/ml, respectively) (P = .0017 and P = .0052, respectively). Aqueous level of VEGF was significantly correlated with that of IL-6 (P = .0396), and aqueous levels of VEGF and IL-6 were correlated with the size of the BRVO non-perfused area (P < .0001 and P = .0331, respectively). Aqueous level of VEGF was correlated with the severity of macular edema (P = .0306). CONCLUSIONS: VEGF and IL-6 may be involved in the pathogenesis of macular edema with BRVO. The increase in these cytokines might be used as a unique index of BRVO, through which we can determine the severity of the ischemic condition as being in a quiescent state or an exacerbation of macular edema.

Aged↗
PubMed2005

The Tajimi Study report 2: prevalence of primary angle closure and secondary glaucoma in a Japanese population.

PURPOSE: To determine the prevalence of primary angle-closure glaucoma (PACG), secondary glaucoma (SG), and all glaucoma in a Japanese population as a part of the Tajimi Study. DESIGN: Population-based epidemiological survey. PARTICIPANTS: A random sample of residents 40 years or older from Tajimi, Japan. INTERVENTION: Each subject underwent a screening program comprising an interview and an ophthalmic examination, including Goldmann applanation tonometry, slit-lamp examination, a van Herick test, fundus photography, and a screening visual field (VF) test using frequency-doubling technology. If glaucoma was suspected, the subject was referred for a definitive examination that included slit-lamp examination, gonioscopy, intraocular pressure measurement, a VF test, and optic disc and fundus examination. A diagnosis of PACG or SG was made based on slit-lamp examination, gonioscopy, optic disc appearance, and perimetric results. MAIN OUTCOME MEASURES: Prevalences of PACG, SG, and all cases of glaucoma. RESULTS: Of 3870 eligible people, 3021 (78.1%) participated in the study. Estimated prevalences of PACG and SG in those over 40 years were 0.6% (95% confidence interval [CI], 0.4%-0.9%) and 0.5% (95% CI, 0.2%-0.7%), respectively. Prevalences of all glaucoma and glaucoma/suspected glaucoma were estimated to be 5.0% (95% CI, 4.2%-5.8%) and 7.5% (95% CI, 6.5%-8.4%), respectively. CONCLUSIONS: Prevalences were 0.6%, 0.5%, and 5.0%, respectively, for PACG, SG, and all glaucoma in subjects over 40 years from Tajimi, Japan.

Adult↗
PubMed2005

The efficacy and safety of topical brinzolamide and dorzolamide when added to the combination therapy of latanoprost and a beta-blocker in patients with glaucoma.

PURPOSE: Brinzolamide and dorzolamide are often used as adjunctive therapy to other antiglaucoma agents. The purpose of this study was to compare the efficacy and safety of brinzolamide 1% versus dorzolamide 1% when added to the combination therapy of latanoprost and a beta-blocker in patients with glaucoma. METHODS: An 8-week, randomized, open-label comparative study was performed in 52 patients with glaucoma. Brinzolamide 1% (twice a day) or dorzolamide 1% (3 times a day) was randomly administered to the patients who had been treated with both latanoprost and a betablocker. RESULTS: Intraocular pressure (IOP) were both decreased significantly (P < 0.0001) from 18.6 +/- 2.3 mmHg to 16.7 +/- 2.3 mmHg and from 18.4 +/- 2.6 mmHg to 16.6 +/- 2.5 mmHg, respectively, 8 weeks after the addition of brinzolamide or dorzolamide. However, the difference between the groups was not significant (P = 0.86). The incidence of ocular irritation was significantly higher (P < 0.0001) in the dorzolamide group (74%) than the brinzolamide group (16%), but there was no significant difference in blurred vision between the groups (dorzolamide 37% versus brinzolamide 52%, P = 0.40). CONCLUSIONS: We concluded that the efficacy of brinzolamide 1% was equivalent to dorzolamide 1%; however, the safety of brinzolamide 1% was superior to dorzolamide 1% as adjunctive therapy to the combination with latanoprost and a beta-blocker.

Adrenergic beta-Antagonists↗
PubMed2005

The efficacy and ocular discomfort of substituting brinzolamide for dorzolamide in combination therapy with latanoprost, timolol, and dorzolamide.

PURPOSE: The aim of this study was evaluate the efficacy and ocular discomfort of substituting brinzolamide for dorzolamide in patients with glaucoma treated by latanoprost, timolol, and dorzolamide. METHODS: An 8-week, prospective, randomized, open-label, comparative study was performed in 58 patients with primary open-angle glaucoma treated by latanoprost, timolol, and dorzolamide. These patients were randomly enrolled into two groups: (1) dorzolamide three times daily was substituted with brinzolamide twice-daily (substituting group); and (2) dorzolamide three times daily was continued (control group). Intraocular pressure (IOP) was measured at baseline, 4, and 8 weeks after the enrollment. Subjective ocular discomfort (irritation and blurred vision) at the time of the instillation of the patient was noted with interview. RESULTS: The IOPs at baseline, 4 and 8 weeks after the enrollment were 17.7 +/- 2.7 mmHg, 17.5 +/- 2.6 mmHg, and 17.4 +/- 2.9 mmHg in the substituting group, and 18.0 +/- 2.5 mmHg, 17.8 +/- 2.5 mmHg, and 17.9 +/- 2.6 mmHg in the control group, respectively. There were no significant differences in IOP changes between the two groups (P = 0.74). In the substituting group, ocular irritation was decreased significantly (P = 0.0014) from 63% to 20%. The slight increase of blurred vision from 27% to 37% that occurred in the substituting group was not significant (P = 0.58). In the control group, neither ocular irritation (P = 0.58, from 68% to 57%) nor blurred vision (P = 0.99, from 25% to 21%) was changed. CONCLUSIONS: Substituting brinzolamide for dorzolamide maintained stable IOP with improvement in ocular comfort in patients with glaucoma.

Aged↗
PubMed2005

A five-year review of patients admitted with the diagnosis of bacterial endophthalmitis.

We conducted a retrospective, hospital-based study of patients who were diagnosed with bacterial endophthalmitis on admission to the Department of Ophthalmology, Hiroshima University Hospital, between January 1999 and December 2003. Thirty eyes of 30 patients were identified. Of these patients, 19 eyes had postoperative endophthalmitis, 8 eyes had penetrating trauma and 3 eyes were infected from an endogenous source. All of the patients underwent immediate three-port pars plana vitrectomy. Vitreous specimens of diabetic patients demonstrated a significantly higher incidence of positive bacterial culture. Diabetic vitreous appeared to be a good medium for culture. Visual acuity of hand motion or less at the latest follow-up visit was associated with the presence of diabetes. Prompt treatment with vitrectomy and intra-vitreal antibiotics is crucial for patients with bacterial endophthalmitis, especially if they are diabetic.

Adult↗
PubMed2004

Role of C-terminal region in the functional regulation of rat serotonin transporter (SERT).

Previously, we revealed that the state of the actin cytoskeleton affects the uptake activity of the serotonin transporter (SERT). Recently, it was reported that the C-terminus of SERT interacts with MacMARCKS, a substrate of PKC that can bind to the actin cytoskeleton. To elucidate the importance of the C-terminal region in the regulation of SERT activity and the interaction with the actin cytoskeleton, we examined whether the overexpression of the C-terminus affects the transport activity of SERT. To this end, we overexpressed a GFP-fused 30-amino acid construct of the SERT C-terminus (GFP-SERT-CT) in HEK293 cells stably expressing FLAG-tagged SERT (FL-SERT-HEK293 cells). The SERT uptake activity and transporter current were attenuated in GFP-SERT-CT-expressing FL-SERT-HEK293 cells, as compared with GFP-expressing FL-SERT-HEK293 cells. Eadie-Hofstee analysis revealed that GFP-SERT-CT overexpression attenuated the SERT uptake activity by reducing the Vmax, but not changing the Km, which was consistent with the results of experiments on the cell-surface expression of SET using biotinylation/immunoblot analysis. Immunocytochemical analysis demonstrated that GFP-SERT-CT was co-localized with FLAG-SERT and cortical actin at the plasma membrane. In addition, the SERT C-terminus did not affect dopamine transporter activity. These findings showed the significance of the C-terminal region to the functional regulation of SERT, suggesting that GFP-SERT-CT acts as a molecular decoy to disrupt the interaction between SERT and the actin cytoskeleton.

Animals↗
PubMed2004

Improvement in cognitive impairment after cataract surgery in elderly patients.

PURPOSE: To evaluate whether cognitive impairment improves in elderly patients who have cataract surgery with intraocular lens (IOL) implantation. SETTING: Kouki Hospital, Yamaguchi, Japan. METHODS: A prospective observational study evaluated patients' scores on the Revised Hasegawa Dementia Scale (HDS-R) and the HDS-R minus 1 item regarding immediate regeneration (ie, function of vision and memory). Twenty patients (6 men, 14 women) with cognitive impairment had cataract surgery in 1 eye between March 1996 and July 2001 at Kouki Hospital, Japan. The mean age of the patients was 81.8 years (range 61 to 90 years). Twenty patients (4 men, 16 women) with cognitive impairment who did not have cataract surgery were selected as a control. The mean age in the control group was 84.3 years (range 70 to 93 years). The HDS-R was administered twice between March 1996 and July 2001. RESULTS: The mean HDS-R scores in the cataract surgery group improved from 12.5 points +/- 5.3 (SD) preoperatively to 16.6 +/- 6.2 points postoperatively; the improvement was significant (t = -5.02; P<.0001). After cataract surgery, the grade of cognitive impairment improved in 12 patients (60%), was unchanged in 7 (35%), and was worse in 1 (5%). CONCLUSION: Cataract surgery improved cognitive impairment in elderly Japanese patients.

Aged↗
PubMed2004

The prevalence of primary open-angle glaucoma in Japanese: the Tajimi Study.

PURPOSE: To assess the prevalence of primary open-angle glaucoma (POAG) and its association with intraocular pressure (IOP) in Tajimi City in central Japan. DESIGN: A cross-sectional epidemiologic study in a defined population. PARTICIPANTS: Subjects randomly selected from the population older than 40 years in Tajimi City. INTERVENTION: Each subject underwent a screening examination comprised of an interview and ophthalmic examinations, including measurement of IOP by a Goldmann applanation tonometer, central corneal thickness (CCT), slit-lamp examination, fundus photography, and a screening visual field test using frequency doubling technology. When ocular diseases were suspected, the subjects were referred for definitive examination. During the definitive examination, slit-lamp examination, IOP measurement, a visual field test using Humphrey Field Analyzer 30-2 SITA Standard program (Humphrey Instruments, San Leandro, CA), optic disc and fundus examination, and gonioscopy were performed and stereoscopic disc photographs were obtained. A diagnosis of glaucoma was made based on optic disc appearance, perimetric results, and other ocular findings. MAIN OUTCOME MEASURES: Prevalence of POAG, mean IOP, and mean CCT. RESULTS: Of 3870 eligible people, 3021 (78.1%) participated in the study. The estimated prevalence of POAG in the population older than 40 years was 3.9% (95% confidence interval [CI]), 3.2%-4.6%). The prevalence of cases of POAG with IOP levels of 21 mmHg or less was 3.6% (95% CI, 2.9%-4.3%), whereas the prevalence for those with IOP levels of more than 21 mmHg was 0.3% (95% CI, 0.1%-0.5%). The average IOP for eyes with POAG was 15.4+/-2.8 (standard deviation) in the right eye (n = 115) and 15.2+/-2.8 mmHg in the left eye (n = 115), which was significantly higher than that of nonglaucoma subjects (14.5+/-2.5 in the right eye; n = 2759; P = 0.0004; and 14.4+/-2.6 mmHg in the left eye; n = 2757; P = 0.0026). The mean CCT of POAG eyes with IOP levels of 21 mmHg or less was 518+/-29 (n = 109) in the right eye and 519+/-29 microm (n = 110) in the left eye, levels that were not significantly different from that of nonglaucoma eyes (520+/-32 microm [n = 2690]; and 522+/-32 microm [n = 2692]; P>0.05). CONCLUSIONS: The prevalence of POAG in this population was 3.9%. In 92% patients with POAG, the IOP was 21 mmHg or less.

Adult↗
PubMed2004

Statistical evaluation of the diagnostic accuracy of methods used to determine the progression of visual field defects in glaucoma.

OBJECTIVE: To evaluate trend-type analyses to judge the progression of visual field damage (VFD) of glaucoma in terms of ratios of making judgments of progression and specificity, and to report a new method. DESIGN: Retrospective analysis of visual field (VF) results of actual glaucoma cases and those simulated by computer, and receiver operating characteristic curve analysis of performance of methods to judge the progression of VFD. PARTICIPANTS: One hundred five eyes of 105 open-angle glaucoma (OAG) patients with progressing VFD and 355 eyes of 355 clinically stable OAG patients for VF simulation from 4 university-based referral practices. METHODS: Methods using regression analysis of total deviation (TD), mean deviation (MD), mean TD of a sectored VF, and original scoring used in the Advanced Glaucoma Intervention Study (AGIS) were compared. A VF test was repeated twice in a short period on the 355 stable OAG eyes, and test-retest fluctuation, including variance at each test point and covariance between 2 test points, was calculated to simulate stable glaucomatous VF series by computer. The sensitivity of each method was calculated with 105 progressing VF series, and specificity was calculated with 10,000 simulated stable glaucomatous VF series. MAIN OUTCOME MEASURES: Sensitivity (ratios of making judgments of progression), specificity, and diagnostic power. RESULTS: The methods using the TD slope on one test location showed a sensitivity of 0.848 to 1.000, with a specificity of 0.105 to 0.721, and on 2 adjacent test locations showed a sensitivity of 0.848, with a specificity of 0.722. A significant negative MD slope with P<0.05 showed a sensitivity of 0.524, with a specificity of 0.945. The method using a sectored VF showed a sensitivity of 0.695, with a high specificity of 0.946. The AGIS method showed a sensitivity of 0.305 to 0.467, with a very high specificity of 0.999 to 1.000. The method using previously reported mathematically sectored VFs showed a sensitivity of 0.790, with a specificity of 0.900, and higher diagnostic power (1.69) than the others in this study population. CONCLUSIONS: Most of the methods using the TD slope were characterized by high sensitivity, the AGIS method had a very high specificity, and those using VF sectors had reasonable sensitivity and specificity.

Adolescent↗