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Biomedical subjects

T Tokoro

Publications and source records attributed to T Tokoro.

At least 127 records · Page 7Linked to original sources

[Electron microscopic study of the choroidal melanocytes and elastic fibers].

The relationship between choroidal melanocytes and elastic fibers as well as collagen fibers was studied by electron microscopy. In pigmented rabbits (Dutch rabbits), the choroidal melanocytes were distributed mainly at the suprachoroidea and formed layers alternating with fibroblasts. The elastic fibers and oxytaran fibers were in close proximity to the melanocytes and their cytoplasmic processes aligned along the long axis of the elastic fibers. Furthermore, the bundles of the collagen fibers were engulfed by the melanocytes. The present findings suggest that the choroidal melanocytes have a close relationship with the elastic fibers, as has been reported with dermal melanocytes and elastic fibers.

Animals↗

Comparison of the chromosomal localization of murine and human glucocerebrosidase genes and of the deduced amino acid sequences.

To study structure-function relationships and molecular evolution, we determined the nucleotide sequence and chromosomal location of the gene encoding murine glucocerebrosidase (glucosylceramidase; D-glucosyl-N-acylsphingosine glucohydrolase, EC 3.2.1.45). In the protein coding region of the murine cDNA, the nucleotide sequence and the corresponding deduced amino acid sequences were 82% and 86% identical to the respective human sequences. All five amino acids presently known to be essential for normal enzymatic activity were conserved between mouse and man. The murine enzyme had a single deletion relative to the human enzyme at amino acid number 273. One ATG translation initiation signal was present in the mouse sequence in contrast to the human sequence, where two start codons have been reported. Nucleotide sequencing of a clone derived from murine genomic DNA revealed that the murine signal for translation initiation was located in exon 2. The locations of all 10 introns were conserved among mouse and man. We mapped the genetic locus for glucocerebrosidase to mouse chromosome 3, at a position 7.6 +/- 3.2 centimorgans from the locus for the beta subunit of nerve growth factor. Comparison of linkage relationships in the human and murine genome indicates that these closely linked mouse genes are also syntenic on human chromosome 1 but in positions that span the centromere.

Amino Acid Sequence↗

[The relation between resting point of accommodation and refractive state].

The refractive state in darkness (dark focus of accommodation) was measured in 224 eyes of 112 young subjects with a Canon Autoref R1 and differences of the refractive state in dark and bright rooms were studied. The dark focus of accommodation was also compared with refractive error after instillation of 1% cyclopentlate hydrochloride. Accommodation was almost entirely responsible for myopic shift in the dark focus of accommodation. Myopic shift was larger in hyperopic eyes than in myopic eyes, but hyperopic shift occurred in markedly hyperopic eyes. In emmetropic and myopic eyes, the degree of hyperopic shift by cycloplegia had no parallel relationship with that of myopic shift in the dark focus of accommodation.

Accommodation, Ocular↗

Niemann-pick variant disorders: comparison of errors of cellular cholesterol homeostasis in group D and group C fibroblasts.

Fluorescence microscopic examination of filipin-stained cultured skin fibroblasts derived from two brothers with group D Niemann-Pick disease revealed abnormal storage of low density lipoprotein (LDL)-derived cholesterol. LDL stimulation of intracellular cholesteryl ester synthesis was severely compromised in the Niemann-Pick D fibroblasts, as it also was in fibroblasts obtained from Niemann-Pick C patients. Cholesteryl ester synthesis was intermediately deficient in cells derived from an obligate group-D heterozygous carrier. Activity of acyl-CoA:cholesterol acyltransferase was within the normal range in cell-free extracts of both LDL-depleted and LDL-supplemented cultures of Niemann-Pick C and D fibroblasts. Incubation of Niemann-Pick D fibroblasts with LDL did not lead to as high a level of intracellular cholesterol accumulation as the excessive storage observed with Niemann-Pick C fibroblasts. These findings suggest that the Niemann-Pick variant disorders may represent a family of specific and possibly individual mutations that disrupt cellular cholesterol homeostasis.

Adult↗

Group C Niemann-Pick disease: faulty regulation of low-density lipoprotein uptake and cholesterol storage in cultured fibroblasts.

Incubation of mutant Niemann-Pick C fibroblasts with low-density lipoprotein (LDL) resulted in excessive internalization of lipoprotein and extensive cellular over-accumulation of unesterified cholesterol. The uptake of LDL by the mutant cells appeared to occur through the classic LDL receptor pathway and internalized lipoprotein was processed in lysosomes. Lipoprotein uptake into mutant cells was associated with delays in the initiation of established cellular cholesterol homeostatic responses. Subcellular fractionation of mutant Niemann-Pick C fibroblasts accumulating LDL-cholesterol showed excess unesterified sterol to be localized in the light lysosome-light membrane region of a Percoll gradient, and revealed that cholesterol storage was associated with a specific alteration in the normal profiles of lysosomal marker enzymes.

Cells, Cultured↗

Studies of the pathogenesis of Gaucher's disease: tissue distribution and biliary excretion of [14C]L-glucosylceramide in rats.

The time course of the clearance from the blood and the tissue localization of [14C]L-glucosylceramide, a nonmetabolizable enantiomorph of D-glucosylceramide that accumulates in Gaucher's disease, has been determined. 14C-labeled L-glucosylceramide injected intravenously in the form of micelles or liposomes is rapidly removed from the circulation. Most of this lipid is taken up by the liver where it is found in both hepatocytes and nonparenchymal cells. This sphingolipid analog is promptly cleared from hepatocytes and a significant portion is recovered in the bile. The clearance of [14C]L-glucosylceramide from Kupffer cells is greatly prolonged in comparison with its brief residence in hepatocytes. These findings have significant implications regarding the pathogenesis and treatment of Gaucher's disease.

Animals↗

Animal and cellular models of sphingolipid storage disorders of humans.

The synthesis of L-galactosylceramide is described. Data are presented indicating that this enantiomorph of D-galactocerebroside is not cleaved by galactocerebroside-beta-galactosidase obtained from mammalian tissues. The synthesis of L-glucosylceramide and beta-D-glucothiocerebroside are outlined. These compounds are also refractory to catabolism by glycosidases in mammalian tissues that catalyze the hydrolysis of naturally occurring cerebrosides. L-Hexosyl- and thioanalogs of cerebrosides and perhaps psychosines as well may be helpful for investigating the pathogenesis of Krabbe's disease and Gaucher's disease.

Animals↗

Indocyanine green angiography of central serous chorioretinopathy.

Indocyanine green angiograms of central serous chorioretinopathy in 30 eyes were evaluated in order to demonstrate the pathologic features of the retinal pigment epithelium. In 5 of the cases, the dye leakage or the pigment epithelial degeneration was seen to be associated with areas of choroidal circulatory insufficiency. This implies that local choroidal ischemia is one of the causes of the pigment epithelial disturbance.

Adult↗

Enzyme replacement with liposomes containing beta-galactosidase from Charonia lumpas in murine globoid cell leukodystrophy (twitcher).

Enzyme replacement with liposomes containing beta-galactosidase obtained from charonia lumpas was carried out in murine globoid cell leukodystrophy (GLD). Charonia lumpas beta-galactosidase was able to hydrolyze galactocerebroside trapped into liposomes prepared from lecithin, cholesterol and sulfatide (molar ratio; 7:2:1). Liposomes containing charonia lumpas beta-galactosidase were successfully incorporated into the mouse tissues. 3H-galactocerebroside labeled liposomes were also incorporated into mouse liver, spleen and other tissues. The accumulation rate of 3H-galactocerebroside into twithcer mice liver and spleen was almost 40 to 100 times higher than those of controls and degraded to 70 to 80% of accumulated radioactivity of 3H-galactocerebroside by single injection of liposomes containing charonia lumpas beta-galactosidase. Results suggest that exogeneous enzyme trapped in liposomes can be useful for the correction of accumulated compound.

Animals↗