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Biomedical subjects

T Tokoro

Publications and source records attributed to T Tokoro.

At least 109 records · Page 6Linked to original sources

Molecular characteristics in Japanese patients with lipidosis: novel mutations in metachromatic leukodystrophy and Gaucher disease.

The characterization of mutations in Japanese patients with lipidosis, particularly in metachromatic leukodystrophy (MLD) and Gaucher disease has been studied in detail. Metachromatic leukodystrophy is characterized by an accumulation of sulfatide in nervous tissues and kidney due to a deficiency of arylsulfatase A (ASA). We analyzed the presence of three known mutant arylsulfatase A alleles in Japanese patients with MLD. Among 10 patients of Japanese patients with MLD, we found that allele 445A mutation has moderately high incidence and also homozygosity of this mutation results in the late infantile form. Allele 2381T was not found in Japanese patients. Furthermore, we found novel mutation which is G- to A mutation at the 1070 nucleotide of the ASA gene (designated 1070 A) in Japanese patients with juvenile onset. This mutation results in a amino acid substitution of Gly245 by Arg and found in heterozygote form. Our studies of molecular analysis in 10 Japanese patients with MLD indicate that Japanese MLD patients have unique characteristics of ASA mutations compared with those of Caucasian patients. On the other hand, Gaucher disease is the most prevalent sphingolipidosis, characterized by an accumulation of glucocerebroside in macrophage derived cells due to a deficiency of lysosomal hydrolase glucocerebrosidase. To study the molecular basis of Gaucher disease in Japanese patients, we analyzed the presence of the two known mutations (6433C and 3548A) in the glucocerebrosidase gene of 15 patients with Gaucher disease. We found that the 6433C and 3548A mutations occur in all subtypes of Japanese patients with Gaucher disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Accommodative hysteresis of refractive errors in light and dark fields.

We investigated the accommodative hysteresis of the refractive error in the light and also in the dark in 19 healthy young women. We measured refractive error under light and dark conditions using the Nidek Autorefractometer AR 1600 with its target light on or off. Then we measured refractive error in the light and in the dark again after they performed nearwork. Post-task refractive error was measured after reading a magazine for 15 min wearing glasses -3.0 D over their distance correction. Nearwork produced a myopic shift of 0.21 D in the refractive error in the light but no shift in the refractive error in the dark. Refractive error in the dark increased significantly by the near task in eyes with more than 2.0 D of myopia, but it did not increase in eyes with less than 2.0 D of myopia. These apparent differences in the accommodative hysteresis are due to the different pre-task baseline values. If the post-task refractive error is evaluated with the same pre-task baseline value, the accommodative hysteresis does not differ among different refractive errors whether measured in the light or in the dark.

Accommodation, Ocular↗

Relation between the dark focus of accommodation and refractive error--a cycloplegic study.

We measured distance refractive error (Dist R), dark refractive error (Dark R), and cycloplegic refractive error (Cyclo R) in 196 subjects whose ages ranged from 4 to 17 years, using the Canon Autoref R-1. We defined the values of (Dark R--Dist R) as DFcus (Dist R) and those of (Dark R--Cyclo R) as DFcus (Cyclo R) in this study. Although DFcus (Dist R) was larger in less myopic and more hyperopic eyes similar to DFcus (Cyclo R), it was zero or plus in high hyperopic eyes, unlike DFcus (Cyclo R). We found Dist R was more strongly influenced by Cyclo R than was Dark R. It is not adequate to use Dist R as the far point for precise evaluation of the dark focus. We should use the difference between Dark R vs. Cyclo R as the true value of the dark focus of accommodation.

Accommodation, Ocular↗

Dark focus of accommodation and uncorrected visual acuity.

We compared the dark focus of accommodation in 33 healthy children, 19 eyes with good uncorrected visual acuity (1.0 or more) vs. 14 with poor uncorrected visual acuity (below 1.0). The two groups were matched for age and cycloplegic refractive error. Cycloplegic refractive error ranged from +0.15 to +1.75 D in the good visual acuity group and from +0.25 to +1.87 D in the poor visual acuity group. The dark focus was defined as the difference between the refractive error in the dark and the refractive error under cycloplegia. Initially, visual acuity was measured subjectively. Next, refractive error in the dark was measured using the Nidek Autorefractometer AR1600 with its optical target light off. Refractive error under cycloplegia was measured 40 min after the instillation of cyclopentolate hydrochloride using the same autorefractometer. There was a significant correlation between the dark focus and the cycloplegic refractive error (r = -0.53, p < 0.01). Despite an equal refractive error under cycloplegia the dark focus was significantly larger in the eyes with good uncorrected visual acuity than in those with poor uncorrected visual acuity (p < 0.01). Tonic accommodation may influence uncorrected visual acuity.

Accommodation, Ocular↗

Dark focus of accommodation in children with accommodative esotropia and hyperopic anisometropia.

We evaluated the dark focus of accommodation, referred to as tonic accommodation, in 60 young hyperopic subjects, 20 with and 20 without accommodative esotropia, and 20 with hyperopic anisometropia. We measured the distance, dark, and cycloplegic refractive errors by the Nidek Autorefractometer AR1600. The difference between dark and cycloplegic refractive errors was defined as the dark focus. The dark focus was significantly larger in esotropic eyes than in non-esotropic eyes, despite similar cycloplegic refractive errors in both types of eyes, suggesting that tonic accommodation may be associated with ocular position. The dark focus was similar in eyes of the same subjects with hyperopic anisometropia and also in normal and amblyopic eyes, suggesting that tonic accommodation is similar in both eyes in subjects with anisometropia and amblyopia.

Accommodation, Ocular↗

A multicenter study of typical retinitis pigmentosa in Japan.

A nationwide, multicenter study of typical retinitis pigmentosa was carried out in collaboration with 13 university hospitals throughout Japan. A total of 253 patients, 122 males and 131 females, with a wide range of ages (mean 48 years), were registered during a two-month period in 1989. Determination of inheritance pattern revealed 30.2% autosomal recessive cases, 15.4% autosomal dominant, 0.5% X-linked, and 48.9% simplex, indicating a relative decrease in autosomal recessive cases and a relative increase in simplex cases in recent decades. The age at onset, initial symptom, and visual functions including visual acuity, visual field and electroretinogram showed a marked interindividual variability, but statistical analysis demonstrated that visual defects progressed with increasing age and disease duration. A correlation between the phenotypic variation and the genetic type was observed. This survey of retinitis pigmentosa in Japan provides information for counseling and rehabilitation of patients and encourages basic and clinical research of this genetic disease.

Adolescent↗

[Aging changes in accommodation--comparison of subjective method with objective method].

We investigated age-related changes in accommodation of the human eye by measuring the subjective amplitude of accommodation with a Visual Display Terminals Accommodometer (Tokyo-Medical NP-200) and the objective amplitude with an Auto Refkeratometer (Canon, RK-1). The accommodative responses of 5 normal eyes of 5 subjects ranging from 29 to 32 years of age were measured with 6 different sizes of targets. A distinct tendency for the subjective amplitude of accommodation to increase was observed with the targets of larger sizes, but no definite tendency was found in the objective amplitude. The accommodative responses of 92 normal eyes of 92 subjects ranging from 15 to 58 years of age were measured. Both the subjective and objective amplitude of accommodation decreased with aging. In subjects under 44 years of age, the objective amplitude was 2.2-2.5D less than the subjective amplitude, but over 45 the difference between the subjective and objective amplitude was 1.2-1.4D.

Accommodation, Ocular↗

Novel procedure for measuring psychosine derivatives by an HPLC method.

We developed a sensitive and simple method to determine galactosylsphingosine and glucosylsphingosine as a 4-fluoro-7-nitrobenzofurazan autofluorescent compound, using HPLC equipped with a Showdex sugar column. Amounts of galactosylsphingosine were successfully measured in the picomole range. This novel procedure is more stable and simpler than the previous method using o-phthalaldehyde. It was applied to tissues from the twitcher mouse, an animal model of human globoid cell leukodystrophy. The amount of galactosylsphingosine was 34-102 micrograms/kg of wet tissues in control cerebrum and cerebellum, whereas in twitcher mice the range was 2,251-4,228 micrograms/kg of wet tissues. The psychosine concentration was also increased in the liver and kidney of twitcher mice, respectively, 1,513 micrograms and 1,106 micrograms/kg of wet tissue (normal liver, 125 micrograms; normal kidney, 74 micrograms/kg of wet tissue). This novel procedure is useful for the pathochemical evaluation of lysosphingolipids in various sphingolipidoses as well as in other neuropathological and cellular conditions.

4-Chloro-7-nitrobenzofurazan↗

[Effects of timolol and carteolol on ocular pulsatile blood flow].

Effects of timolol (0.5%) and carteolol (2%) on ocular pulsatile blood flow (PBF) were studied in healthy adult volunteers. PBF was measured with the BFA system, analyzing the ocular pressure waves. Each drug was instilled in one eye and PBF was measured in both eyes before and fifteen minutes after the instillation. In each drug, the PBF change between the two measurements was evaluated with a control study, which was performed in the same manner with physiological saline solution. In the non-instilled eyes, both timolol (n = 6) and carteolol (n = 9) had no significant change on PBF. In the instilled eyes, timolol (n = 6) caused no significant change, whereas carteolol (n = 9) increased PBF significantly. The range of the BFA system measurement error was within 4.7 +/- 2.4 microliters/min (P = 95%). Taking the error into account in each instilled eye, timolol (n = 6) increased PBF in 3 eyes and decreased it in 3 eyes, while carteolol (n = 9) increased PBF in 7 eyes, did not change it in one eye and decreased it in one eye. It is thought the effect of carteolol to increase PBF may be explained by endothelium-dependent relaxing factor (EDRF).

Adult↗

[An epidemiogenetic study of typical retinitis pigmentosa in Japan--a preliminary report of nationwide, multicenter study].

We performed a nationwide, multicenter study of typical retinitis pigmentosa with reference to the inheritance patterns of the disease. A total of 253 probands were registered during two months of 1989, and an analysis of the parental consanguinity of 182 probands with the method of inbreeding coefficient enabled us to estimate the relative prevalence of genetic types; autosomal recessive trait: 47.6%; autosomal dominant trait: 17.3%; sporadic cases: 34.6%. A comparison of the results with previous studies has indicated a decrease in the prevalence of the autosomal recessive trait and an increase in the sporadic cases, as would be expected from the decrease in consanguineous marriages and offsprings in the past few decades in Japan. X-linked retinitis pigmentosa was rarely identified, but precise evaluation of its frequency needs further investigation.

Adolescent↗

Galactosylceramide and galactosylsphingosine loading studies in cultured skin fibroblasts in human and murine globoid cell leukodystrophy.

Cell level studies of 3H-galactosylceramide(GalCer) and 3H-galactosyl sphingosine (GalSph) have been carried out in cultured skin fibroblasts from human and murine globoid cell leukodystrophy (GLD). GalCer loading studies disclosed that the hydrolysis rates of GalCer in human control and GLD were 72% and 45%, respectively, and those from the murine control and GLD cells were 77% and 21%, respectively, on the 5th day of culture. On the other hand, GalSph loading studies showed that the hydrolysis rate of GalSph in the human control and GLD were 40% and 10%, respectively, and those from murine control and GLD cells were 38% and 10% on the 12th day of culture. These data suggest that both GalCer and GalSph degradations were impaired in cell level in human and murine GLD. Furthermore, when radioactive 3H-GalSph was loaded into cultured fibroblasts from murine and human GLD, 3H-GalCer band was formed via GalSph. These data strongly suggest that GalCer could be synthesized through the GalSph route as a minor pathway at least in cultured skin fibroblasts, although the major pathway to synthesize GalCer should be via ceramide.

Animals↗

Scleral change in experimentally myopic monkeys.

To elucidate changes in the sclera of myopic eyes free of other obvious pathological features, morphometric and ultrastructural studies on the posterior sclera at the foveola of the three lid-fused monkeys that had developed high myopia were performed. The myopic eyes showed increased axial length, and their scleral thickness was about half that of the control eyes. Furthermore, a gradual increase in the size of collagen bundles and fibrils from the inner to the outer layer of the sclera was observed in the control eyes, but was not evident in the myopic eyes. From the present study, it can be speculated that an alteration of fibrillogenesis in the sclera is a key feature of scleral thinning in lid-suture myopia, and that axial elongation of the eyeball results from a combination of altered fibrillogenesis and mechanical expansion.

Animals↗

Influence of intraocular pressure on axial elongation.

The role of intraocular pressure (IOP) on axial elongation was studied by the following three experiments. 1) Thickness of the sclera in the lid-sutured-myopia of three monkeys was examined by light microscopy. The sclera of the experimental eye in the posterior pole was thinner than that of the control eye, but no differences were found in the equatorial and limbal parts of the sclera. 2) By increasing IOP, the scleral wall extensibility in 8 normal, enucleated rabbit eyes was measured by placing the foil strain gauges on the sclera. Extensibility of the sclera in the posterior pole showed a different response from that at the equator and in the limbus. 3) IOPs of the 184 human myopic eyes were measured by a Mackay-Marg tonometer in various postures. IOP elevations in high myopia and postural variations of IOP were obtained. From these experiments, it was suggested that IOP seemed to be one of the main factors in increasing the axis to the posterior pole.

Adolescent↗

Eye-tracking infra-red optometer.

An eye-tracking infra-red optometer has been developed to measure dynamic refractive power during slow horizontal eye movement. It consists of two instruments: an optometer to measure the refractive power of the human eye, and an eye tracker. When measuring refractive power, the eye tracker is used to maintain automatically the optical axis of the optometer coincident with the visual axis of the human eye. The measurement range of the optometer is approximately -10 to +10 D; refractive power is measured with an accuracy of about 0.4 D and with a precision of 0.05 D over an eye movement range of 60 degrees. The maximum trackable eye movement velocity is over 100 deg s-1, with a time delay of about 0.13 s. Furthermore it was confirmed that eye refraction measurement during vergence is possible using this eye-tracking infra-red optometer.

Accommodation, Ocular↗

[Accommodation in ametropia and the effect of targets on astigmatism].

Measurements of accommodative responses in 28 astigmatic eyes (22 patients, 19-32 years of age) were made with an objective Auto Refkeratometer (Canon, RK-1). We constructed an actual target representative instrument with a star burst chart and a fine line chart, and attached this instrument to the Auto Refkeratometer. The fine line chart was turned around the sight line of the eye at a fixed distance. The amount of mean accommodative responses decreased in the following order; the fine line chart parallel to the first principal meridian of subjects, the star burst chart, the fine line chart parallel to the second principal one. This tendency was also shown in cases of subjects with astigmatism less than 1.25 diopters. The slopes of mean accommodative response curves reduced in the similar order as above, significantly in the cases of astigmatism over 1.25 diopters. These results suggest that target charts for accommodation and the degree of astigmatism have influence on the amount of accommodative response and the slope of its curve.

Accommodation, Ocular↗