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Biomedical subjects

Atsushi Mizota

Publications and source records attributed to Atsushi Mizota.

At least 19 recordsLinked to original sources
PubMed2007

Pattern VEPs before and after idiopathic epiretinal membrane removal.

Pattern visual evoked potentials (pVEPs) were used to assess the visual function before, and 1 and 6 months after removal of an idiopathic epiretinal membrane (ERM) from eight eyes. All patients underwent a standard three-port pars plana vitrectomy to remove the ERM removal and cataract surgery. pVEPs were elicited by check sizes of 15', 30', 60', and 120' with a reversal rate of 2 reversals/s. One hundred responses were averaged with an analysis time of 300 ms. The amplitude ratio (affected eye/fellow eye) of the P100 component were significantly larger at 6 months with smaller check sizes, and the increase was accompanied by an improvement of the VA. The mean peak latency of P100 did not change significantly for all check sizes. We conclude that the improvement of the P100 amplitude with smaller check sizes resulted from the recovery of visual function after the ERM removal.

Aged↗
PubMed2006

Up-regulation of genes for oxidative phosphorylation and protein turnover in diabetic mouse retina.

Diabetic retinopathy is one of the most frequent complications of diabetes and is a leading cause of vision loss in adulthood. To better understand the molecular pathophysiology of diabetic retinopathy, we performed comprehensive gene expression analysis of the mouse retina under diabetic conditions with an in-house cDNA microarray system that was designed to be suitable for the small amount of RNA available from a single mouse retina. Diabetes was induced in male C57BL/6 mice by an intraperitoneal injection of streptozotocin, and the changes in retinal mRNA levels were examined in three pairs of diabetic and age-matched control mice at 1 and 3 months after the injection of streptozotocin. Northern blot analysis with amplified total cRNA confirmed the increase in mRNA levels of several selected genes. Most of the significantly up-regulated genes could be classified into two functional categories: oxidative phosphorylation and protein turnover. All mitochondrial DNA-encoded and most of the nuclear DNA-encoded genes for oxidative phosphorylation were up-regulated in the diabetic retina. This was in sharp contrast with a previous report of a down-regulation of these genes in skeletal muscles of streptozotocin-induced diabetic mice and type 2 diabetic humans. Genes for protein synthesis and ubiquitin were also up-regulated in the diabetic retina, suggesting the increase in turnover rates for at least a part of the protein population. Taken together, the diabetic retina appears to be in a state activated for intermediary metabolism, presumably because of an increase in insulin-independent glucose influx. These results provide insights into possible preventive and therapeutic intervention of diabetic retinopathy.

Animals↗
PubMed2006

Complement factor H polymorphisms in Japanese population with age-related macular degeneration.

PURPOSE: To study the frequency of five haplotypes previously reported in the complement factor H (CFH) gene for Japanese patients with age-related macular degeneration (AMD). METHODS: Genomic DNA was isolated from peripheral blood samples taken from 96 Japanese AMD patients and 89 age-matched controls. All patients were diagnosed as having exudative (wet-type) AMD. The amplified polymerase chain reaction (PCR) products of CFH exons 2, 9, and 13, and intron 6 were analyzed by temperature gradient capillary electrophoresis (TGCE) and by direct sequencing. The haplotypes were identified, and their frequencies were calculated and compared with reported results. RESULTS: Five haplotypes were identified in the Japanese population including four already reported in the American population. The frequencies of these haplotypes were significantly different between Japanese and American in both control and case groups. The haplotype containing Y402H, which was previously reported to be associated with AMD, was only 4% in the control and case population, with a p value of 0.802. However, two other haplotypes were found as risk factors, which gave an increased likelihood of AMD of 1.9 and 2.5 fold (95% CI 1.12-3.69 and 1.42-6.38). One protective haplotype that decreased the likelihood of AMD by 1.6 fold (95% CI 0.26-0.67) was identified. CONCLUSIONS: The frequencies for five haplotypes previously identified were analyzed in a Japanese population with AMD. Four previously found haplotypes were identified and one additional haplotype was found. The frequencies of each haplotype were significantly different from that in found Americans affected with AMD. Two of the haplotypes were identified as risk factors and one was considered protective.

Aged↗
PubMed2006

Arpc1b gene is a candidate prediction marker for choroidal malignant melanomas sensitive to radiotherapy.

PURPOSE: Choroidal malignant melanomas (CMMs) are the most common primary intraocular tumors in adult humans. Although radiotherapy is commonly used to treat the melanomas, the therapeutic effects are unpredictable. The purpose of this study was to search for a gene(s) that can predict the success of radiotherapy for CMMs. METHODS: The cell lines 92-1, OCM-1, and OMM-1 were established from patients with CMM, and radiation sensitivity was determined using the colony-formation assay. RNA was extracted from nonirradiated cells, and gene expression analysis was performed using a microarray containing 10,800 genes. The up- or downregulated genes were verified by real-time PCR using other cancerous cell lines in which radiation sensitivity had been documented. RESULTS: Analysis of radiation survival curves showed that cell line 92-1 was radiation sensitive and OCM-1 and OMM-1 lines were radiation resistant. The results of microarray analyses showed that 34 genes were differentially expressed in the OCM-1 and OMM-1 cell lines compared with the 92-1 cell line. The validity of the expression level of 13 of the 34 genes that were identified by microarray was confirmed by PCR. From the analysis of the different radio-sensitivity cancer cell lines, the Arpc1b gene was selected as a prediction marker gene for sensitivity of CMM to radiotherapy. CONCLUSIONS: Gene expression analysis of CMM cell lines can be used to search for radiation sensitivity prediction markers. Comprehensive gene expression profiles of radiation-sensitive and/or resistant cell lines may provide new insights into the mechanisms of resistance or sensitivity to radiation therapy.

Actin-Related Protein 2-3 Complex↗
PubMed2006

Histopathological study of a case with branch retinal vein occlusion.

A retinal specimen from a 68-year-old patient with glaucoma and branch retinal vein occlusion was examined by light and electron microscopy. The venous and arterial lumina were filled with erythrocytes, and many erythrocytes extravasated into the venous wall. We suggest that constant rubbing of endothelial cells of the occluded vein results in damage and erythrocyte extravasation was caused by diapedesis.

Aged↗
PubMed2005

Relation between stage of endogenous fungal endophthalmitis and prognosis.

BACKGROUND: Although many studies have been published on the risk factors and therapies for endogenous fungal endophthalmitis (EFE), only a few have been published on the relationship between the stage of EFE at the initial examination and the prognosis. Thus, the purpose of this study was to determine the relation between the stage of EFE at the initial examination and the prognosis. METHODS: A total of 103 eyes of 58 patients (40 men, 18 women) with EFE, examined over a 20-year period (1984-2004), were studied. The severity of the EFE at the initial examination was classified into four stages. In addition, the type of fungus, general status, initial and final visual acuity, findings of the anterior and posterior segments, latent fungal infection, duration from initial symptoms to initial visit, history of intravenous hyperalimentation (IVH), results of the Candida Detection System, and beta-D-glucan levels were analyzed. RESULTS: More than 95% of the patients had some type of underlying disorder. Candida albicans was detected initially in the blood in 40 patients. The stage of the EFE advanced as the time from the initial symptoms to the beginning of therapy increased. The final visual acuity was significantly correlated with the stage of EFE at the initial examination. In 20 of 21 patients, blood beta-D-glucan was positive, and 42 patients (90%) were receiving IVH. CONCLUSIONS: Because the stage of EFE advanced with the time between the initial symptoms and the beginning of therapy, and because of the high correlation between the stage of EFE and the final visual acuity, it is very important that treatment be begun as soon as possible. Thus, in patients with visual symptoms and susceptible to opportunistic infections, an early consultation with an ophthalmologist is highly recommended.

Adolescent↗
PubMed2005

Outcomes of visual acuity in carbon ion radiotherapy: analysis of dose-volume histograms and prognostic factors.

PURPOSE: To analyze the tolerance dose for retention of visual acuity in patients with head-and-neck tumors treated with carbon ion radiotherapy. METHODS AND MATERIALS: From June 1994 to March 2000, 163 patients with tumors in the head and neck or skull base region were treated with carbon ion radiotherapy. Analysis was performed on 54 optic nerves (ONs) corresponding to 30 patients whose ONs had been included in the irradiated volume. These patients showed no evidence of visual impairment due to other factors and had a follow-up period of >4 years. All patients had been informed of the possibility of visual impairment before treatment. We evaluated the dose-complication probability and the prognostic factors for the retention of visual acuity in carbon ion radiotherapy, using dose-volume histograms and multivariate analysis. RESULTS: The median age of 30 patients (14 men, 16 women) was 57.2 years. Median prescribed total dose was 56.0 gray equivalents (GyE) at 3.0-4.0 GyE per fraction per day (range, 48-64 GyE; 16-18 fractions; 4-6 weeks). Of 54 ONs that were analyzed, 35 had been irradiated with <57 GyE (maximum dose [Dmax]) resulting in no visual loss. Conversely, 11 of the 19 ONs (58%) irradiated with >57 GyE (Dmax) suffered a decrease of visual acuity. In all of these cases, the ONs had been involved in the tumor before carbon ion radiotherapy. In the multivariate analysis, a dose of 20% of the volume of the ON (D20) was significantly associated with visual loss. CONCLUSIONS: The occurrence of visual loss seems to be correlated with a delivery of >60 GyE to 20% of the volume of the ON.

Adult↗
PubMed2005

Molecular composition of drusen and possible involvement of anti-retinal autoimmunity in two different forms of macular degeneration in cynomolgus monkey (Macaca fascicularis).

We have previously reported a cynomolgus monkey (Macaca fascicularis) pedigree with early onset macular degeneration that develops drusen at 2 yr after birth. In this study, the molecular composition of drusen in monkeys affected with late onset and early onset macular degeneration was both characterized. Involvement of anti-retinalautoimmunity in the deposition of drusen and the pathogenesis of the disease was also evaluated. Funduscopic and histological examinations were performed on 278 adult monkeys (mean age=16.94 yr) for late onset macular degeneration. The molecular composition of drusen was analyzed by immunohistochemistry and/or direct proteome analysis using liquid chromatography tandem mass spectroscopy (LC-MS/MS). Anti-retinal autoantibodies in sera were screened in 20 affected and 10 age-matched control monkeys by Western blot techniques. Immunogenic molecules were identified by 2D electrophoresis and LC-MS/MS. Relative antibody titer against each antigen was determined by ELISA in sera from 42 affected (late onset) and 41 normal monkeys. Yellowish-white spots in the macular region were observed in 90 (32%) of the late onset monkeys that were examined. Histological examination demonstrated that drusen or degenerative retinal pigment epithelium (RPE) cells were associated with the pigmentary abnormalities. Drusen in both late and early onset monkeys showed immunoreactivities for apolipoprotein E, amyloid P component, complement component C5, the terminal C5b-9 complement complex, vitronectin, and membrane cofactor protein. LC-MS/MS analyses identified 60 proteins as constituents of drusen, including a number of common components in drusen of human age-related macular degeneration (AMD), such as annexins, crystallins, immunoglobulins, and complement components. Half of the affected monkeys had single or multiple autoantibodies against 38, 40, 50, and 60 kDa retinal proteins. The reacting antigens of 38 and 40 kDa were identified as annexin II and mu-crystallin, respectively. Relative antibody titer against annexin II in affected monkeys was significantly higher than control animals (P<0.01). Significant difference was not observed in antibody titer against mu-crystallin; however, several affected monkeys showed considerably elevated titer (360-610%) compared with the mean for unaffected animals. Monkey drusen both in late and early onset forms of macular degeneration had common components with drusen in human AMD patients, indicating that chronic inflammation mediated by complement activation might also be involved in the formation of drusen in these affected monkeys. The high prevalence of anti-retinalautoantibodies in sera from affected monkeys demonstrated an autoimmune aspect of the pathogenesis of the disease. Although further analyses are required to determine whether and how autoantibodies against annexin II or mu-crystallin relate to the pathogenesis of the disease, it could be hypothesized that immune responses directed against these antigens might trigger chronic activation of the complement cascade at the site of drusen formation.

Aging↗
PubMed2005

Two cases of orbital adenocarcinoma treated with heavy charged carbon particle irradiation.

BACKGROUND: Orbital adenocarcinoma is a relatively rare, primary orbital malignant epithelial tumor, and shares the poor prognosis of orbital adenoid cystic carcinoma. We report the cases of two patients with orbital adenocarcinoma who were treated with heavy charged carbon particle irradiation and followed up for more 6 years. METHOD: Two patients with orbital adenocarcinoma, 62 and 74 years old, received 57.6 GyE of heavy charged particle irradiation therapy. RESULTS: In both cases, the size of the tumor gradually decreased after carbon ion irradiation therapy. No recurrences or metastasis of the tumor were found for more than 6 years. CONCLUSION: Orbital adenocarcinoma has a poor prognosis in general. Two patients with orbital adenocarcinoma were treated with heavy charged carbon particle irradiation therapy and had a relatively good outcome and good prognosis. We believe that heavy charged carbon particle irradiation therapy is a promising therapy for orbital adenoid cystic carcinoma and adenocarcinoma.

Adenocarcinoma↗
PubMed2005

Deterioration of visual function as examined by electroretinograms in Toxoplasma gondii-infected IFN-gamma-knockout mice.

PURPOSE: To investigate by ERG the effects of Toxoplasma gondii infection on the visual function of interferon gamma knockout (GKO) mice, as a model of immunocompromised hosts. METHODS: Susceptible wild-type (WT) C57BL/6 and GKO C57BL/6 mice were infected with five cysts of the avirulent T. gondii perorally. ERGs were recorded before and after the infection. The eyes of WT and GKO mice were enucleated and prepared for histologic studies 4 weeks and 12 days after infection, respectively. RESULTS: The a- and b-waves of ERGs did not change significantly up to 1 month after infection in WT mice, but those of GKO mice were significantly reduced 11 days after infection. Histopathology revealed focal retinitis and vasculitis in WT mice 4 weeks after infection. Mild inflammation and sludging of blood in the retina and choroid were found in GKO mice 12 days after infection, just before death. Cysts were found in the inner nuclear layer, with little disturbance of the surrounding retinal architecture in both WT and GKO mice. CONCLUSIONS: ERG clearly showed deterioration of visual function in GKO but not in WT mice after T. gondii infection. ERG is a sensitive and reliable method for observing activity in mice severely affected with experimental toxoplasmic retinochoroiditis.

Animals↗
PubMed2005

Early-onset macular degeneration with drusen in a cynomolgus monkey (Macaca fascicularis) pedigree: exclusion of 13 candidate genes and loci.

PURPOSE: To describe hereditary macular degeneration observed in the cynomolgus monkey (Macaca fascicularis), which shares phenotypic features with age-related macular degeneration in humans, and to test the involvement of candidate gene loci by mutation screening and linkage analysis. METHODS: Ophthalmic examinations with fundus photography, fluorescein angiography (FA), indocyanine green angiography (IA), electroretinography (ERG), and histologic studies were performed on both affected and unaffected monkeys in the pedigree. The monkey orthologues of the human ABCA4, VMD2, EFEMP1, TIMP3, and ELOVL4 genes were cloned and screened for mutations by single-strand conformation polymorphism (SSCP) analysis or denaturing high-performance liquid chromatography (DHPLC) and direct sequencing in six affected and five unaffected monkeys from the pedigree and in six unrelated, unaffected monkeys. Subsequently, 13 human macular degeneration loci including these five genes were analyzed to test for linkage with the disease. Nineteen affected and seven unaffected monkeys in the pedigree were analyzed by using human microsatellite markers linked to the 13 loci. RESULTS: Yellowish white spots were observed in the macula and fovea centralis, and in some cases the spots scattered to the peripheral retina along the blood vessels. FA showed hyperfluorescence corresponding to the dots except in the foveola. No anomalies were found by IA and ERG. Histologic studies demonstrated that the spots were drusen. Mutation analysis of the ABCA4, VMD2, EFEMP1, TIMP3, and ELOVL4 genes identified a few sequence variants, but none of them segregated with the disease. Linkage analysis with markers linked to these five genes and an additional eight human macular degeneration loci failed to establish linkage. Haplotype analysis excluded the involvement of the 13 candidate loci for harboring the gene associated with macular degeneration in the monkeys. CONCLUSIONS: Significant homology was identified between monkey and human orthologues of the five macular degeneration genes. Thirteen loci associated with macular degeneration in humans or harboring macular degeneration genes were excluded as causal of early-onset macular degeneration in the monkeys. It is likely that none of these loci, but rather a novel gene, is involved in causing the observed phenotype in this monkey pedigree.

ATP-Binding Cassette Transporters↗
PubMed2005

Safety of in vivo pharmacologic vitreolysis with recombinant microplasmin in rabbit eyes.

PURPOSE: To investigate the safety of intravitreal microplasmin in rabbits and to confirm previous findings of posterior vitreous detachment (PVD). METHODS: Different doses of microplasmin, from 12.5 microg to 250 microg, in 0.1 mL balanced salt solution (BSS) were injected into the vitreous cavity of rabbit eyes to induce PVD. Fellow eyes were injected with the same volume of BSS. Slit-lamp biomicroscopy, ophthalmoscopic fundus examinations, A- and B-mode ultrasonography, and electroretinography were performed to assess the retina. Electroretinograms (ERGs) were recorded up to 90 days after injection. Morphologic alterations were assessed by light microscopy, scanning electron microscopy (SEM), and transmission (TEM) electron microscopy. RESULTS: A slight aqueous flare and cells were observed in the anterior chamber after microplasmin and BSS injection. A slight inflammatory reaction was also observed transiently in the vitreous cavity. In control eyes, B-mode ultrasonography and SEM examination demonstrated that PVD did not develop after BSS injection. Intravitreal injections of 125 microg or greater of microplasmin induced complete PVD with an internal limiting membrane (ILM) devoid of vitreous collagen fibrils. Eyes injected with 12.5 microg microplasmin had partial PVD, and SEM showed residual fibrils covering the ILM. In all eyes, there was a transient reduction in the a- and b-waves of the ERG on days 2 through 7. The ERGs showed less effect with < 250 microg microplasmin. CONCLUSIONS: Intravitreal injection of recombinant microplasmin in the rabbit induces no ERG or retinal ultrastructural abnormalities. Pharmacologic vitreolysis with this agent may be a useful adjunct to vitreous surgery and could be used to induce PVD without vitreous surgery.

Animals↗
PubMed2004

Binocular summation in visual evoked cortical potential in patients who have significantly different P100 peak latencies in their two eyes.

PURPOSE: To determine whether binocular summation in visual evoked cortical potential (VEP) is present in patients who have significantly different P100 peak latencies in their two eyes. METHODS: Twelve patients with unilateral optic neuritis (ON) and 11 normal controls were studied. All of them had visual acuity of > or = 20/20 in both two eyes and good stereoacuity. Transient and steady-state VEPs were recorded with monocular and binocular pattern-reversal stimulation. RESULTS: In normal controls, the binocular summation ratio was 1.05 with transient stimulation and 1.21 with steady-state stimulation, and in ON patients it was 1.19 and 1.30, respectively. In ON patients, the peak latency of P100 components was delayed significantly when the affected eye was stimulated, but with binocular stimulation the waveform was very similar to that when the fellow eye was stimulated. CONCLUSION: Binocular summation of VECP is not present in ON cases with large differences in the peak latency between the two eyes even if they have good stereoacuity. Binocular summation may not be correlated with stereopsis in adults whose binocular function has already matured.

Adolescent↗
PubMed2004

Clinical characteristics of Japanese children with optic neuritis.

The clinical characteristics of children with optic neuritis have been reported to be different from that of adults and to vary among different races. To determine the clinical characteristics of Japanese children with optic neuritis, we examined the medical records of 41 children who were diagnosed with optic neuritis at the Department of Ophthalmology of Chiba University Hospital between January 1979 and December 2001. Information on the sex, age of onset, laterality, initial visual acuity, final visual acuity, recent infections and immunizations, and presence of systemic neurologic diseases, such as multiple sclerosis or acute disseminated encephalomyelitis, was obtained. These findings revealed that the clinical features of optic neuritis in children were similar to those reported earlier. The percentage of optic neuritis cases that developed multiple sclerosis in children was similar to that for children in Europe and North America, and this percentage was not lower than that in adults in our clinic. These findings can be taken as the characteristics of optic neuritis of children in Japan.

Adolescent↗
PubMed2004

A homozygosity-based search for mutations in patients with autosomal recessive retinitis pigmentosa, using microsatellite markers.

PURPOSE: To identify possible mutations in known candidate genes in patients with autosomal recessive (ar) and simplex retinitis pigmentosa (RP), by using an established strategy of flexible, multiplexed, microsatellite-based homozygosity mapping. METHODS: A total of 78 microsatellite markers corresponding to 16 genes known to be responsible for arRP were selected and used in 18 multiplex amplifications, followed by genotyping. Twelve consanguineous probands and 47 nonconsanguineous probands (59 patients with arRP or simplex RP) agreed to the screening. RESULTS: Of the 59 probands examined, 24 had a mean of 1.4 genes showing homozygosity for all markers within the corresponding gene region. Subsequent direct sequencing revealed three homozygous mutations. Two of them were novel mutations in the genes TULP1 (c.1145T-->C, F382S) and CNGB1 (c.3444 + 1G-->A). The other was a mutation in RPE65 (c.1543C-->T, R515W), which is known to cause Leber's congenital amaurosis. The clinical features of each patient, together with the cosegregation analysis, strongly support the pathogenicity of these mutations. CONCLUSIONS: This systematic approach facilitated the identification of genes that cause arRP, and the results provide a widened spectrum of the mutation severity associated with a broader range of phenotypic manifestations of arRP.

Adult↗
PubMed2003

Effect of MCI-9042, a 5-HT2 receptor antagonist, on retinal ganglion cell death and retinal ischemia.

The neuroprotective effect of MCI-9042 (Mitsubishi Pharma Corporation) was investigated on glutamate-induced retinal ganglion cell (RGC) death in vitro and on rat retinal ischemia in vivo. RGCs were purified from retinal cells isolated from 6-day-old Wistar rats and cultured in serum-free media. After application of 25 microM glutamate, the viability of RGCs treated with or without several serotonin 2 (5-HT(2)) receptor antagonists: MCI-9042, M-1 (a major metabolite of MCI-9042), ketanserin, and LY-53857; was evaluated by calcein-acetoxymethyl ester staining. Retinal ischemia was induced by intraocular pressure (IOP) elevation (130 mmHg, 50 min). Rats were intraperitoneally injected with MCI-9042 at a dose of 3, 30 mg/kg or base at 30 min before and just after ischemia-reperfusion. Retinal damages were evaluated by histology, morphometric analysis and electroretinograms (ERGs) recordings at 7 days after ischemia-reperfusion. 25 microM glutamate decreased the number of viable RGCs to about 60 to 65% of untreated RGCs. MCI-9042, M-1, ketanserin, and LY-53857 significantly reduced glutamate-induced RGC death at concentrations of more than 100 nM, 1 nM, 1 microM and 100 nM, respectively. Ischemia-reperfusion caused thinning of the thickness between the inner plexiform layer and the outer plexiform layer and attenuation of a-and b-waves in ERG recordings. The intraperitoneal injection of MCI-9042 significantly reduced morphological and functional damages in retinal ischemia. Our data demonstrate that 5-HT(2) receptor antagonists including MCI-9042 and M-1 have the neuroprotective effects in cultured RGCs and that MCI-9042 protects against ischemic retinal diseases.

Animals↗
PubMed2003

Diagnosis of autosomal dominant retinitis pigmentosa by linkage-based exclusion screening with multiple locus-specific microsatellite markers.

PURPOSE: To describe a hierarchical approach for efficient genetic diagnosis of autosomal dominant retinitis pigmentosa (adRP). METHODS: Forty di-, tri-, or tetra-nucleotide repeats tightly linked to 10 genes known to be responsible for adRP were identified from the human genome sequence and used as markers in multiplex amplification and genotyping, followed by linkage analysis. Discordance of cosegregation of markers and the disease excluded the majority of the examined genes as candidates, and mutation screening for the remaining genes was performed. RESULTS: With this strategy, examination of an adRP-affected family indicated that 3 of 10 candidate genes segregated concordantly with the disease. Further searches for mutations revealed a novel insertion and deletion in the last exon of a splicing factor gene, PRPF8. CONCLUSIONS: This systematic approach facilitates the molecular diagnosis of adRP, which is known to have a highly heterogeneous genetic background.

Carrier Proteins↗