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Biomedical subjects

R Koide

Publications and source records attributed to R Koide.

At least 37 records · Page 2Linked to original sources

In vitro testing of antioxidants and biochemical end-points in bovine retinal tissue.

Lipid peroxidation in aliquots of bovine retina (without rod outer segments, ROS), purified ROS and retinal pigment epithelium (RPE) was initiated with 5 mM ferric iron and 80 mM ADP. After 30 min of oxidation at 37 degrees C, the concentration of thiobarbituric-acid-reacting substances (TBARS) which approximates lipid hydroperoxide (LHP), increased in the ROS from 2.0 +/- 3.6 to 90.2 +/- 34.5 nmol malondialdehyde (MDA)/mg protein and in the RPE from 0.54 +/- 0.2 to 51.5 +/- 15.8 nmol MDA/mg protein. Sixteen lipid and aqueous antioxidants (AOX) from natural or synthetic sources, including five flavonoids, were evaluated for their ability to inhibit the oxidative reaction. Palm-oil-derived vitamin E showed significant protection in retina, ROS and RPE (64, 68 and 74%), respectively. Of the flavonoids tested, good protection in the retina was found at 10(-5) M for epigallocatechin gallate (50%) and at 50 ng/ml for pycnogenol (61%) and catechin (52%). When catechin and palm oil vitamin E, catechin and coenzyme Q(10) or coenzyme Q(10) and pycnogenol were combined, the individual effect was enhanced. TBARS as an indirect measure of LHP level and hemoglobin-methylene blue determination for direct LHP were used as alternative end-point determinations of lipid peroxidation. These measure different aspects of AOX reactions. The results demonstrate the usefulness of an in vitro model system that can rapidly and accurately determine the capacity of a single AOX against lipid peroxidation or be used to show synergistic efficacy.

Animals↗

[Accuracy of intraocular power calculation formulas].

PURPOSE: We examined the accuracy of intraocular lens power calculation formulas, with special emphasis on the prediction of refraction in different axial lengths. MATERIAL AND METHODS: 786 cases were subdivided into four groups based on the axial length (short axial length < 22.0 mm, normal axial length = 22-24.4 mm, mid-range axial length = 24.5-26.9 mm and long axial length > 27 mm). Seven different formulas (Holladay, SRK, SRK II, SRK/T, S-SRK, M-SRK, L-SRK) were tested for their accuracy in predicting post-operative refraction. RESULT: The best results were obtained using the S-SRK formula in the short axial length group (n = 114), The SRK and Holladay formulas in the normal axial length group (n = 278). The Holladay and SRK/T formulas in the mid-range axial length group (n = 135), and the SRK/T and L-SRK in the long axial length group (n = 259). CONCLUSION: Our results emphasize the importance of using an intraocular lens formula specific for each range of axial length when calculating the predicted refraction.

Aged↗

Glutamate-stimulated proliferation of rat retinal pigment epithelial cells.

We investigated the effects of glutamate on cell proliferation and the expression of basic fibroblast growth factor (bFGF) and its receptor (FGF-R1) mRNA in cultured rat retinal pigment epithelial (RPE) cells. The number of primary RPE cells was significantly higher after treatment with 0.2 to 1.0 mM glutamate (maximum at 1.0 mM) for 7 days than in controls. Glutamate-stimulated cell proliferation was abolished by (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), but not by 6,7-dinitroquinoxaline-2,3-dione or L(+)-2-amino-3-phosphonopropionic acid. Proliferation was increased to a similar extent by N-methyl-D-aspartate (NMDA), but not by kainate, alpha-amino-3-hydroxy-3-methyl-4-isoxazolepropionic acid or trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid. NMDA-receptor-like immunoreactivity was detected in most cells cultured. Treatment of cells with glutamate increased the level of bFGF mRNA and, to a lesser extent, that of FGF-R1 mRNA, which peaked 2 and 4 days, respectively, after glutamate was added. The increase in bFGF mRNA induced by glutamate was inhibited by MK-801. These findings suggest that glutamate might stimulate proliferation of RPE cells through activation of NMDA receptors and expression of bFGF and further suggest that glutamate may be involved in the proliferative changes of RPE cells in retinal wound healing.

Animals↗

Pharmacokinetics of topical beta-adrenergic antagonists in rabbit aqueous humor evaluated with the microdialysis method.

The microdialysis method was used to evaluate the pharmacokinetics of the beta-adrenergic antagonists carteolol and timolol and the new ophthalmic solution WP-934 in rabbit aqueous humor, following instillation. A probe with a microdialysis membrane (length, 5 mm; diameter, 0.2 mm) was implanted in the anterior chamber of the pigmented rabbit and perfused with Ringer's solution. Twenty microliters of 0.5% timolol maleate (0.5% Timoptol(R)), 2% carteolol hydrochloride (2% Mikelan(R)), or a novel preparation of 0.5% timolol maleate (WP-934) that gels after instillation were then instilled. The concentrations of these drugs in dialysates were measured using high-performance liquid chromatography and an electrochemical detection system. In vitro relative recovery of the membrane with timolol and carteolol was approximately 17.5% and 21. 6%, respectively. Timolol and carteolol levels in aqueous humor increased rapidly after instillation of Timoptol and Mikelan and reached maximal levels (Cmax) within 60 minutes. The Cmax of carteolol (4.25 microg ml-1) was lower than that of timolol (5.52 microg ml-1), suggesting that the corneal permeability of timolol is higher than that of carteolol. After instillation of WP-934, the Cmax of timolol (12.32 microg ml-1) was 2.2-fold higher than that after instillation of Timoptol. However, t1/2 values of beta-adrenergic antagonists after instillation of the three preparations were not significantly different. These data suggest that the microdialysis technique is useful for continuous monitoring of aqueous levels of beta-blockers and for analysis of their pharmacokinetic parameters while requiring much fewer animals than conventional sampling with paracentesis.

Administration, Topical↗

Hereditary dentatorubral-pallidoluysian atrophy: detection of widespread ubiquitinated neuronal and glial intranuclear inclusions in the brain.

We examined the brains and spinal cords of seven patients with clinicopathologically and genetically confirmed hereditary dentatorubral-pallidoluysian atrophy (DRPLA) using an antibody against ubiquitin, and found small, round immunoreactive intranuclear inclusions in both neurons and glial cells in various brain regions. Ubiquitinated neuronal intranuclear inclusions (uNIIs) were consistently found in the striatum, the pontine nuclei, the inferior olivary complex, the cerebellar cortex and the dentate nucleus. Ubiquitinated glial intranuclear inclusions (uGIIs) were found less frequently than uNIIs. Most of the inclusion-bearing nuclei were of an astrocytic nature. Immunostaining with an antibody against DRPLA protein revealed similar immunoreactive neuronal and glial intranuclear inclusions, but in much smaller in numbers compared with uNIIs and uGIIs. Electron microscopy showed that such inclusions were composed of granular and filamentous structures. These findings strongly suggest that, in DRPLA, the occurrence of uNIIs and uGIIs is directly related to the causative gene abnormality (an expanded CAG repeat encoding polyglutamine), that neurons are affected much more widely than previously recognized and that glial cells are also involved in the disease process.

Adult↗

Analysis of preoperative factors predictive of visual acuity in axial myopia.

PURPOSE: To identify the factors predicting visual acuity after cataract surgery in patients with high myopia. SETTING: Departments of Ophthalmology, Showa University School of Medicine and Showa University Fujigaoka Hospital, Kanagawa, Japan. METHODS: Stepwise regression analysis was used to identify the factors determining the visual acuity in 940 eyes with an axial length of 27.0 mm or longer having cataract surgery. Using a formula derived from the stepwise regression analysis, the predicted postoperative visual acuity was compared with the actual value measured in another group of 104 eyes. RESULTS: Five factors were identified to significantly determine postoperative visual acuity: axial length, age, corneal opacity, refractive power of the cornea, and history of retinal detachment surgery. There was a significant relationship between predicted and actual postoperative visual acuities (r = .51, P < .001). Postoperative visual acuity was similar in 63% of cases. CONCLUSION: The results showed that at least five factors determine visual acuity after cataract surgery in patients with high myopia.

Adolescent↗

Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch.

To elucidate the molecular mechanisms whereby expanded polyglutamine stretches elicit a gain of toxic function, we expressed full-length and truncated DRPLA (dentatorubral-pallidoluysian atrophy) cDNAs with or without expanded CAG repeats in COS-7 cells. We found that truncated DRPLA proteins containing an expanded polyglutamine stretch form filamentous peri- and intranuclear aggregates and undergo apoptosis. The apoptotic cell death was partially suppressed by the transglutaminase inhibitors cystamine and monodansyl cadaverine (but not putrescine), suggesting involvement of a transglutaminase reaction and providing a potential basis for the development of therapeutic measures for CAG-repeat expansion diseases.

Animals↗

Close associations between prevalences of dominantly inherited spinocerebellar ataxias with CAG-repeat expansions and frequencies of large normal CAG alleles in Japanese and Caucasian populations.

To test the hypothesis that the frequencies of normal alleles (ANs) with a relatively large number of CAG repeats (large ANs) are related to the prevalences of the dominant spinocerebellar ataxias (SCAs)-SCA types 1, 2, 3 (Machado-Joseph disease), 6, and dentatorubral-pallidoluysian atrophy (DRPLA)-we investigated the relative prevalences of these diseases in 202 Japanese and 177 Caucasian families and distributions of the number of CAG repeats of ANs at these disease loci in normal individuals in each population. The relative prevalences of SCA1 and SCA2 were significantly higher in Caucasian pedigrees (15% and 14%, respectively) than in Japanese pedigrees (3% and 5%, respectively), corresponding to the observation that the frequencies of large ANs of SCA1 (alleles >30 repeats) and of SCA2 (alleles >22 repeats) were significantly higher in Caucasians than in Japanese. The relative prevalences of MJD/SCA3, SCA6, and DRPLA were significantly higher in Japanese pedigrees (43%, 11%, and 20%, respectively) than in Caucasian pedigrees (30%, 5%, and 0%, respectively), corresponding to the observation that the frequencies of large ANs of MJD/SCA3 (>27 repeats), SCA6 (>13 repeats), and DRPLA (>17 repeats) were significantly higher in Japanese than in Caucasians. The close correlations of the relative prevalences of the dominant SCAs with the distributions of large ANs strongly support the assumption that large ANs contribute to generation of expanded alleles (AEs) and the relative prevalences of the dominant SCAs.

Asian People↗

[Change in intraocular pressure after intraocular lens implant during a follow-up period of over 10 years].

Changes in intraocular pressure were studied in 141 eyes following intraocular lens implant. The average observational time was twelve years. We tried to fix both loops of the implant in the ciliary sulcus. The intraocular pressure increased over the ten year interval at 0.19 mmHg per year. Twenty-seven of the 141 eyes developed glaucoma. We studied the intraocular pressure of the cases with or without complications. Thirty-eight eyes had complications, fifteen eyes (39%) developed secondary glaucoma, and three eyes (8%) developed glaucomatous visual field defect. In twenty-three cases without secondary glaucoma, the intraocular pressure increased over a three-year interval after surgery and remained constant thereafter. 103 eyes had no complications to influence the intraocular pressure, twelve eyes (12%) developed secondary glaucoma, and four eyes (4%) developed glaucomatous visual field defect. In 91 cases without secondary glaucoma, the intraocular pressure increased over a five-year interval after surgery at 0.28 mmHg per year and remained constant thereafter. We recommend regular examination, especially during the initial five-year period when the intraocular pressure is apt to increase even if complications are not evident.

Adult↗

Distribution and ultrastructural localization of a receptor for pituitary adenylate cyclase activating polypeptide and its mRNA in the rat retina.

Localization and gene expression of pituitary adenylate cyclase activating polypeptide receptor (PACAPR) in the rat retina were studied by immunocytochemistry and in situ hybridization, respectively. Antisera were raised against a synthetic peptide that corresponds to the carboxy-terminal cytoplasmic domain which is found in all subtypes of PACAPR. Strong PACAPR mRNA expression and PACAPR-like immunoreactivity (PACAPR-LI) were detected in ganglion cells, amacrine cells, and in the inner plexiform layer. PACAPR-LI appeared to be concentrated predominantly in the neuronal perikarya and processes. At the ultrastructural level, strong immunostaining for PACAPR was visible in the plasma membranes, rough endoplasmic reticulum and cytoplasmic matrix in neurons. This study provides the basis for a better understanding of the functions of PACAP in the rat retina.

Animals↗

Spinocerebellar ataxia type 6: CAG repeat expansion in alpha1A voltage-dependent calcium channel gene and clinical variations in Japanese population.

Autosomal dominant spinocerebellar ataxias (SCAs) are clinically and genetically a heterogeneous group of neurodegenerative disorders. Recently, mild CAG repeat expansion in the alpha1A voltage-dependent calcium channel gene has been found to be associated with a type of autosomal dominant SCA (SCA6). We analyzed 98 Japanese families with autosomal dominant SCAs, for whom CAG repeat expansions of the SCA1, SCA2, Machado-Joseph disease/SCA3, and dentatorubral-pallidoluysian atrophy genes were excluded, and 5 apparently sporadic cases of cortical cerebellar atrophy. The diagnosis of SCA6 was confirmed in 30 families (31%) comprising 47 affected individuals and 1 sporadic case. The size of expanded CAG repeats ranged from 21 to 26 repeat units and was found to be correlated inversely with age at onset. We identified 2 SCA6 patients homozygous for expanded CAG repeats, whose ages at onset were earlier than the 95% lower confidence level, suggesting the presence of a gene dosage effect of expanded CAG repeat. Ataxia is the most common initial symptom found in 45 of the 48 patients. Patients with a prolonged disease course showed other accompanying clinical features including dystonic postures, involuntary movements, and abnormalities in tendon reflexes.

Adult↗

Intraocular lens power calculation for microphthalmos.

PURPOSE: To evaluate the refractive results and accuracy of intraocular lens (IOL) power calculation formulas in eyes with microphthalmos. SETTING: Department of Ophthalmology, Showa University Hospital, Tokyo, Japan. METHODS: The accuracy of IOL power calculated using the SRK, SRK II, S-SRK, SRK/T, Holladay, and Hoffer Q formulas was evaluated in six eyes with axial lengths less than 19.0 mm. RESULTS: Postoperative measurement of refraction showed a tendency toward hypermetropia compared with the refraction predicted by each formula. The best predicted refraction was calculated using the SRK/T formula. The tendency for hyperopic estimation was related to the axial length, particularly in eyes with a shorter axial length. However, there was no relationship between the refractive power of the cornea and the error in the predicted refraction by the SRK/T formula. Two eyes with an IOL power of 30.0 diopters (D) had severe hypermetropia. CONCLUSION: Theoretical formulas were more accurate than empirical ones in eyes with microphthalmos. The severe hypermetropia in the two eyes with a 30.0 D IOL indicates that such patients require a higher IOL power.

Aged↗

Atrophy of the cerebellum and brainstem in dentatorubral pallidoluysian atrophy. Influence of CAG repeat size on MRI findings.

To elucidate how the size of the expanded CAG repeat of the gene for dentatorubral pallidoluysian atrophy (DRPLA) and other factors affect the atrophy of the brainstem and cerebellum, and the appearance of high-intensity signals on T2-weighted MRI of the cerebral white matter of patients with DRPLA, we quantitatively analyzed the MRI findings of 26 patients with DRPLA, the diagnosis of which was confirmed by molecular analysis of the DRPLA gene. When we classified the patients into two groups based on the size of the expanded CAG repeat of the DRPLA gene (group 1, number of CAG repeat units > or = 66; group 2, number of CAG repeat units < or = 65), we found strong inverse correlations between the age at MRI and the areas of midsagittal structures of the cerebellum and brainstem in group 1 but not in group 2. Multiple regression analysis, however, revealed that both the patient's age at MRI and the size of the expanded CAG repeat correlated with the areas of midsagittal structures. Involvement of the cerebral white matter as detected on T2-weighted images was observed more frequently in patients belonging to group 2 than in group 1 patients. Furthermore it was demonstrated that high-intensity signals can be detected on T2-weighted images of the cerebral white matter of patients with a largely expanded CAG repeat (group 1) in their thirties. These results suggest that patient age as well as the size of the expanded CAG repeat are related to the degree of atrophy of the brainstem and cerebellum, and the white matter changes in patients with DRPLA.

Adolescent↗

[Accumulation of 14C-cystine in inherited cataractous rat lens].

This study was designed to investigate the formation of mixed disulfides of protein and glutathione (GSH) in the cataractous lens. We compared the changes in accumulation of 14C-cystine in cultured inherited cataractous rat lens (ICR/f) during cataractogensis with those in Wistar strain rats. The accumulation of 14C-cystine in water insoluble protein (WIP) of the lens was increased, especially in lens recognized cataract. The radioactivity accumulated in the WIP was released by incubation with 2-mercaptoethanol (2-ME), dithiothereitol (DTT) and GSH. The accumulation of 14C-cystine in WIP was inhibited by pretreatment with DTT. The existence of some materials in the lens-which combined with S-S compounds became clear. A large part of the materials is present in WIP which is increased along with the lens opacification. We surmised that the accumulation of 14C-cystine was related to the reaction of protein-glutathione disulfide (PSSG).

Aging↗

Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant, neurodegenerative disorder that affects the cerebellum and other areas of the central nervous system. We have devised a novel strategy, the direct identification of repeat expansion and cloning technique (DIRECT), which allows selective detection of expanded CAG repeats and cloning of the genes involved. By applying DIRECT, we identified an expanded CAG repeat of the gene for SCA2. CAG repeats of normal alleles range in size from 15 to 24 repeat units, while those of SCA2 chromosomes are expanded to 35 to 59 repeat units. The SCA2 cDNA is predicted to code for 1,313 amino acids-with the CAG repeats coding for a polyglutamine tract. DIRECT is a robust strategy for identification of pathologically expanded trinucleotide repeats and will dramatically accelerate the search for causative genes of neuropsychiatric diseases caused by trinucleotide repeat expansions.

Amino Acid Sequence↗

Non-Mendelian transmission in dentatorubral-pallidoluysian atrophy and Machado-Joseph disease: the mutant allele is preferentially transmitted in male meiosis.

Autosomal dominant dentatorubral-pallidoluysian atrophy (DRPLA) and Machado-Joseph disease (MJD) are neurodegenerative disorders caused by CAG trinucleotide repeat expansions. An inverse correlation of age at onset with the length of the expanded CAG trinucleotide repeats has been demonstrated, and the intergenerational instability of the length of the CAG trinucleotide repeats, which is more prominent in paternal than in maternal transmissions, has been shown to underlie the basic mechanisms of anticipation in DRPLA and MJD. Our previous observations on DRPLA and MJD pedigrees, as well as a review of the literature, have suggested that the numbers of affected offspring exceed those of unaffected offspring, which is difficult to explain by the Mendelian principle of random segregation of alleles. In the present study, we analyzed the segregation patterns in 211 transmissions in 24 DRPLA pedigrees and 80 transmissions in 7 MJD pedigrees, with the diagnoses confirmed by molecular testing. Significant distortions in favor of transmission of the mutant alleles were found in male meiosis, where the mutant alleles were transmitted to 62% of all offspring in DRPLA (chi2 = 7.69; P<.01) and 73% in MJD (chi2 = 6.82; P<.01). The results were consistent with meiotic drive in DRPLA and MJD. Since more prominent meiotic instability of the length of the CAG trinucleotide repeats is observed in male meiosis than in female meiosis and meiotic drive is observed only in male meiosis, these results raise the possibility that a common molecular mechanism underlies the meiotic drive and the meiotic instability in male meiosis.

Adolescent↗