Biomedical subjects

T Tokoro

Publications and source records attributed to T Tokoro.

At least 73 records · Page 4Linked to original sources

PubMed1996

Functional neuroanatomy of visual object naming: a PET study.

BACKGROUND: The ability to name objects depends partly on visual perception. We used positron emission tomography (PET) to measure activity-related changes in regional cerebral blood flow (r-CBF) in order to identify regions of the brain activated during visual object naming. METHODS: Four right-handed volunteers were recruited. Following an intravenous injection of 15O-labeled water, r-CBF was measured during visual object naming, counting numbers, and resting. PET and MRI images were coregistered, the size of the brain was proportionally adjusted in each axis to Talairach's and Tournoux's atlas, and the comparison of stimulated versus resting blood flow images revealed activated brain regions. RESULTS: In the subtraction of resting from naming, activation was observed in the bilateral primary visual cortex, bilateral fusiform gyrus, left lingual gyrus, bilateral inferotemporal cortex, bilateral inferior frontal gyrus, bilateral precentral gyrus, anterior cingulate gyrus, left parietal operculum, and left putamen. In the subtraction of counting from naming, most of the those areas were activated, but no significant activity was observed in the left lingual gyrus, left parietal operculum, or bilateral precentral gyrus (motor cortex). The areas activated with the paradigm included those dedicated to visual perception (primary and associate visual cortex), visual recognition (inferior temporal cortex), and phonological output (Broca's area). CONCLUSION: Our results indicated that the major neural network from occipital lobe to frontal cortex, which is mainly involved in the ventral visual pathway, demonstrated activation in these tasks. Result of this study will serve as base line data for analyzing the findings in patients with impaired visual perception.

Adult↗

PubMed1996

Unilateral eyeball enucleation differentially alters AMPA-, NMDA- and kainate glutamate receptor binding in the newborn rat brain.

The aim of the present work was to evaluate the neurochemical effects of early unilateral visual deprivation as a model of impaired visual maturation. For this purpose, binding to the different ionotropic glutamate receptor subtypes was quantified in vision-related and vision-unrelated brain structures of control and unilaterally deprived newborn rats. At post-natal (PN) day 10, male Sprague-Dawley rats underwent either unilateral eyeball enucleation (enucleation group, n = 12) or sham operation (control group, n = 12). In each group, brains were obtained either at post-natal day 20 (n = 6) or post-natal day 30 (n = 6) and processed for quantitative in vitro autoradiography selective for NMDA, kainate, and AMPA glutamate-binding sites, as well as for the presynaptic adenosine A1 receptor as a control of the deafferentation efficacy. In control animals, quantitative autoradiography revealed an increase in NMDA (e.g. +45% in superior colliculus) and kainate receptor binding (e.g. +55% in visual cortex, layer IV) from post-natal day 20 to post-natal day 30, associated with stable levels of AMPA receptor binding, in the vision-related structures. In the deafferented visual structures, monocular enucleation induced a marked decrease in A1 site density (e.g. -38 to -52%, in the superficial layer of superior colliculi, at PN day 20 and PN day 30, respectively) in parallel with a mild increase in both NMDA (e.g. +8 to 9%, in superior colliculi and visual cortex, layer IV at PN day 30, respectively) and AMPA (e.g. +16%, in layer IV of the visual cortex at PN day 30). Superimposed on marked bilateral decreases at PN day 30 in the enucleated rats, kainate receptor binding also revealed a slight but significant decrease (-5%) in the deafferented superior colliculus as compared to the non-deafferented side. The present findings (different time-courses of, and differential effects of deafferentation on, the NMDA, kainate and AMPA glutamate receptor subtypes throughout the visual brain structures) further support the involvement of these receptors in distinctive roles during maturation of the visual system.

Animals↗

PubMed1996

Studies of retroorbital tissue xenografts from patients with Graves' ophthalmopathy in severe combined immunodeficient (SCID) mice: detection of thyroid-stimulating antibody.

The pathogenesis of Graves' ophthalmopathy (GO) is still unclear and the possible role of TSH receptor antibody in the development of GO is controversial. However, the recent availability of severe combined immunodeficient (SCID) mice has provided a means to study of human autoimmune thyroid disease in an in vivo environment. In the present study, we xenografted human retroorbital (RO) tissues from 9 patients with GO into 9 SCID mice and the autologous peripheral blood mononuclear cells (PBMC) from 5 of 9 GO patients were engrafted into 5 separate SCID mice to reconstitute the immunological environment of human GO. Mice blood samples were taken every 2 weeks for the measurements of human IgG, thyroglobulin antibody (Tg-Ab), thyroperoxidase (TPO)-Ab, thyroid-stimulating antibody (TSAb), and interferon-gamma (IFN-gamma). Eight weeks after xenografting, mice were killed; RO tissues were analyzed histologically, SCID mice with RO tissues from 2 of 9 GO patients produced human IgG peaking at 6-8 weeks after xenografting. TPO-Abs and TG-Abs were detectable in low titer in mice with RO tissue xenografts from 3/9 and 4/9 GO patients, respectively. The mean level of IFN-gamma in SCID mice with GO RO xenografts was higher than that of a control subject (RO tissue from a non-GO patient). TSAbs were actually produced from 7 of 9 mice xenografted with GO RO tissues, and reached their peaks at 2-8 weeks after xenografting; autologous PBMC (alone, without RO tissues)-engrafted SCID mice did not produce any detectable level of TSAb. The control mouse did not produce any detectable levels of human IgG, TPO-Ab, Tg-Ab, or TSAb. Immunohistochemical analysis of orbital mononuclear cell infiltrates revealed a predominance of T lymphocytes, with a small percentage of B lymphocytes in GO RO tissue graft. In conclusion, we have successfully reconstituted the SCID mice with human lymphocytes of RO tissues from patients with GO. Autoreactive B cell clones responsible for secreting TSAb exist in GO RO tissue and may be a key factor in the initiation and/or the progression of GO.

Adult↗

PubMed1996

IFN-gamma has a protective role against thyroid-specific autoantibody production in severe combined immunodeficient (SCID) mice xenografted with Graves' thyroid tissue.

We studied the effects of exogenous human IFN-gamma or neutralizing monoclonal antibody (mAb) to IFN-gamma on xenografted human Graves' thyroid tissue in severe combined immunodeficient (SCID) mice to investigate a possible role of IFN-gamma in the pathogenesis of human Graves' disease. Human thyroid tissues from four patients with Graves' disease were xenografted into SCID mice. Two weeks after xenografting, mice were divided into three groups with human IgG levels similar to each other. Mice in the first group were treated with human IFN-gamma daily for 6 weeks; mice in the second (similar) group were treated with an mAb to IFN-gamma; mice in the third group were given mouse IgG only (control group). Blood samples were taken every 2 weeks for human IgG and thyroid-specific autoantibodies (Tg-Ab, TPO-Ab, and thyroid-stimulating antibody). After 6 weeks' treatment, mice were killed, and the thyroid xenograft was examined for thyrocyte HLA-DR expression. Human IgGs were produced equally in all three groups; mice treated with IFN-gamma showed significantly lower amounts of thyroid autoantibodies than those in the control group. Thyrocyte HLA-DR expression was markedly increased in xenografts from mice with IFN-gamma administration. On the other hand, anti-IFN-gamma mAb injection caused only slight suppression of HLA-DR expression on xenografted thyroid cells. In conclusion, IFN-gamma may down-regulate the production of thyroid-specific autoantibodies but not human IgG, at least under these circumstances; there thus may be specific inhibitory effects of IFN-gamma against thyroid-specific autoantibody production of intrathyroidal plasma cells, and this animal model may help to elucidate the possible role of cytokines in the pathogenesis of Graves' disease.

Animals↗

PubMed1996

The progression of lacquer cracks in pathologic myopia.

PURPOSE: Lacquer cracks are found in the posterior fundus of 4.3% of highly myopic eyes. They represent healed and mechanical breaks of the retinal pigment epithelium, Bruch's membrane, and choriocapillaris complex. This prospective study examined the progressive course and angiographic characteristics of transitional changes in highly myopic eyes with lacquer cracks. METHODS: The authors studied 66 eyes (53 patients with lacquer cracks, using general ocular examinations and fluorescein angiography once every 3 to 12 months. Follow-up ranged from 7 to 243 months (average, 72.8 months). RESULTS: The lacquer cracks progressed in 37 eyes (56.1%). Of these 37 eyes, the number of lacquer cracks increased in 14 eyes and turned into other myopic fundus changes in 25 eyes. These changes included patchy atrophy, diffuse atrophy, and choroidal hemorrhage with neovascular membrane (Fuchs' spot). Fluorescein angiography showed patchy atrophy beginning with a small hypofluorescent area at the peripheral end of the lacquer cracks. CONCLUSION: A high incidence of lacquer cracks progressed into advanced fundus changes during a mean follow-up period of 6 years. Even faint lacquer cracks may characterize an unfavorable prognostic course, leading to macular pathology in patients with pathologic myopia.

Adolescent↗

PubMed1996

Subretinal bleeding without choroidal neovascularization in pathologic myopia. A sign of new lacquer crack formation.

PURPOSE: The clinical significance of subretinal bleeding without choroidal neovascularization in pathologic myopia is unclear. Only two reports in the ophthalmic literature have demonstrated the clinical course of subretinal bleeding and have indicated that it might be a precursor of lacquer cracks. In this study, the authors observed the clinical course of subretinal bleeding in highly myopic eyes and studied this condition in relation to new lacquer crack formation. METHODS: The authors examined consecutively and prospectively 22 highly myopic eyes (19 patients) with subretinal bleeding. Indirect ophthalmoscopy and fluorescein fundus angiography were performed in all patients. Indocyanine green (ICG) angiography could be performed in three patients. The follow-up period ranged from 6 to 198 months (mean, 61.3 months). RESULTS: In 17 of 22 eyes, lacquer cracks appeared at the site of previous subretinal bleeding. The period for the formation of new lacquer cracks after the onset of the bleeding ranged from 2 to 6 months (mean, 4.0 months). In one patient, ICG angiography revealed linear hypofluorescence, indicating a ruptured Bruch's membrane at the onset of subretinal bleeding. CONCLUSION: A rupture of Bruch's membrane and choriocapillaris complex results in subretinal bleeding, which is the first process of new lacquer crack formation. Atrophy of the overlying pigment epithelium and further scar formation results in the development of a lacquer crack.

Adolescent↗

PubMed1996

Posterior routes of choroidal blood outflow in high myopia.

PURPOSE: A few reports in the ophthalmic literature have described choroidal blood outflow through posterior routes. Most of the patients reported were highly myopic; therefore, a correlation between such posterior routes and high myopia has been suspected. The authors examined highly myopic eyes using indocyanine green (ICG) videoangiography and investigated the prevalence and clinical significance of posterior routes in them. METHODS: The authors examined 255 highly myopic eyes (146 patients) using ICG videoangiography. All had refractive errors greater than--8.25 diopters (D). They also examined a control group consisting of 42 eyes (26 patients) that had refractive errors within +/- 3D. RESULTS: Of 255 highly myopic eyes, 61 (23.9%) had choroidal blood outflow through posterior routes. These routes were classified by type of vein according to its penetration site. One drained into the margin of the optic nerve head, and the other penetrated the sclera near the macula. However, only 1 of the 42 eyes (2.4%) in the control group showed choroidal outflow by a posterior route. The prevalence of posterior routes was significantly higher in the highly myopic eyes than in the control group (P < 0.05). CONCLUSION: Posterior routes of choroidal blood outflow were observed in nearly 25% of highly myopic eyes. These vessels appear to be one of the major routes of posterior choroidal outflow in highly myopic eyes.

Adolescent↗

PubMed1996

A new drug delivery system utilizing piggyback contact lenses.

We designed and evaluated a new drug delivery system (DDS) in which a drug plate containing levofloxacin was placed between a hydrophilic soft contact lens (SCL) and a non-hydrophilic SCL. The drug plate (diameter 8.0 mm, thickness 0.2 mm) was prepared by coating and freeze-drying a poly(vinyl alcohol) (PVA) disc containing 20, 30 or 40 wt% levofloxacin with a block styrene-(ethylene/butene)-styrene (SEBS) polymer solution. The release rate of the levofloxacin in vitro reduced with an increase in the concentration of SEBS polymer in solution used for coating. The release rate was well controlled and in zero-order kinetics was observed. The drug release from the drug plate consisting of a PVA disc loaded with 30 wt% levofloxacin and coated with 7.5 wt% SEBS polymer solution was 3.07 +/- 0.39 mg during 8 h. This drug plate was placed on an albino rabbit's eye wearing a hydrophilic soft contact lens (SCL), and then covered with a non-hydrophilic SCL. The drug concentrations in the anterior chamber were 156.0 +/- 133.6 micrograms/ml and 193.2 +/- 136.1 micrograms/ml after 4 and 8 h, respectively. The values obtained with frequent instillation of 0.5% levofloxacin every 30 min were 9.9 +/- 4.3 micrograms/ml and 12.5 +/- 10.0 micrograms/ml after 4 and 8 h, respectively. Therefore a significantly higher drug level was achieved with DDS compared to frequent instillation.

Administration, Topical↗

PubMed1996

Thyroid cell proliferation-inhibiting activity in serum of patients with chronic renal failure on hemodialysis.

To investigate the possible humoral factor(s) influencing thyroid cell activity in chronic renal failure, we measured serum activity which stimulates or inhibits the [3H]thymidine incorporation by using a cultured functioning rat thyroid cell line (FRTL-5 cells) in 17 patients on hemodialysis and 19 healthy controls. Polyethylene glycol-treated serum was centrifuged and FRTL-5 cells were cultured with the supernatant. Thyroid stimulating activity was determined by [3H]thymidine incorporation after incubation for 72 h. There was no significant difference in [3H]thymidine incorporation between cultures incubated with patient and normal serum, suggesting the absence of the stimulating activity. But when patient serum was added to cultures together with 20 or 50 microU/ml of TSH, the TSH-stimulated increase in [3H]thymidine incorporation was significantly decreased, indicating the presence of thyroid inhibiting activity, which possibly inhibits the thyroid cell growth. This activity was not significantly altered by hemodialysis. No significant correlation was observed between this activity and serum levels of thyroid hormones or the iodine concentration. Patients on hemodialysis therefore have serum thyroid inhibiting activity which is nondialysable, differs from iodine, and could influence the thyroid cell growth.

Adult↗

PubMed1996

Alterations in mitochondrial DNA and enzyme activities in hypertrophied myocardium of stroke-prone SHRS.

To clarify the pathophysiological alteration of mitochondria in SHRSP hypertrophied heart, mitochondria-related enzyme changes were examined and compared to those in WKY. Furthermore, the structure alteration in mitochondrial DNA (mtDNA) was examined by restriction fragment length polymorphisms (RFLPs). Both isocitrate dehydrogenase (ICDH) and cytochrome c oxidase (COX), which are related to energy production or the respiratory chain in mitochondria, were significantly lower in SHRSP myocardium than in WKY. Furthermore, superoxide dismutase (SOD), a potent radical scavenger, was also lower in SHRSP myocardium. RFLPs analysis by Rsa I revealed two deletions in the electrophoretic band in the SHRSP myocardium, but not in the liver. These findings suggest that mitochondrial dysfunction, especially lower energy production, could be an important factor for the pathogenesis of further myocardial degeneration. The results also suggest that mitochondrial alterations, in the membrane system as well as mtDNA, may be caused by oxidative stress in mitochondria because of decreased scavenging activity.

Animals↗

PubMed1996

Effects of tinted intraocular lens on contrast sensitivity.

We evaluated contrast sensitivity and glare in 64 pseudophakic eyes. An ultraviolet-absorbing intraocular lens (IOL) was implanted in 32 eyes and a noncyanopsia yellow-tinted IOL was implanted in 32 eyes. The latter lens was designed to effectively absorb light below a wave-length of 500 nm. Contrast sensitivity was measured at a pupil diameter of 3 mm using an artificial pupil. The implanted yellow-tinted IOL showed improved contrast sensitivity in the middle spatial frequencies of 6 and 12 c/deg in photopic and mesopic vision. In addition, the yellow-tinted IOL decreased the effect of central glare on the contrast sensitivity.

Aged↗

PubMed1996

[Simultaneous measurement of the tension, elongation, and refractive power of the bovine lens zonule].

We developed a device to measure simultaneously the tension and elongation of the lens zonules, and the refractive power of the lens in 12 bovine eyes. Each sample, which consisted of the lens-zonuleciliary body was fixed to the device at the position of the ciliary process from four directions, and was stretched radially in a container filled with saline solution. The tension was measured by a force transducer, the elongation by a laser-displacement-meter, and the refractive power by a Campbell type refractometer. The refractive power of the lens in the relaxed condition was 24.6 +/- 3.4 D (n = 12, mean +/- standard deviation). When samples were stretched 1 mm from the relaxed condition, the increased change in tension was 2.8 +/- 1.5 g, and the decreased change in refractive power was 1.8 +/- 1.2 D.

Animals↗

PubMed1995

The effects of endothelin-1 on isolated bovine ciliary muscles.

The effects of endothelin-1 on bovine ciliary muscle were investigated in vitro using muscle strips prepared in two different directions (longitudinal and circular). Fifty-two bovine ciliary muscle strips (4 x 6 mm) were prepared. Chemicals were added to both types of strips suspended in an organ chamber, and their changes in isometric tension were recorded. The concentration-response relationship of endothelin-1 (n = 20), the magnitudes of contractions caused by endothelin-1 and carbachol (n = 12), and the effects of an endothelin receptor subtype A antagonist BQ123 (n = 4) and an endothelin receptor subtype B agonist IRL1620 (n = 4) were studied. The cumulative addition of endothelin-1 caused relaxation at low concentrations (10(-11) and 10(-10) M), while it caused contraction of the ciliary muscles at high concentrations (10(-9), 10(-8) and 3 x 10(-8) M). The magnitude of the contraction caused by 10(-8) M endothelin-1 was about 30% in the longitudinal muscle strips and 29% in the circular muscle strips, relative to the contraction caused by 10(-5) M carbachol, a muscarinic agonist. The contractile response caused by 10(-8) M endothelin-1 was abolished and converted to relaxation by pretreatment with BQ123, a selective endothelin receptor subtype A antagonist. Single addition of IRL1620, a selective endothelin receptor subtype B agonist, caused only relaxation. These results suggest that, endothelin-1 causes not only contraction at high concentrations, but also relaxation at low concentrations in bovine ciliary muscle. Also, it suggested that the relaxation is mediated by endothelin receptor subtype B, whereas the contraction is mediated by endothelin receptor subtype A.

Animals↗

PubMed1995

Retinal correspondence under dynamic background.

We examined the binocular vision of 14 patients with esotropia under a dynamic background. The objective and subjective angles of the patients were measured using a phase difference haploscope under three conditions: no background (A), a static background produced by an image slide (B), and a dynamic background produced by 8-mm movies (C). The objective angle remained the same under different backgrounds. On the other hand, the subjective angle tended to become 0 degree under condition C; that is, more harmonious abnormal retinal correspondence (HARC) was obtained under C. Therefore, it was concluded that HARC was more easily detected under the dynamic background than under the static or no background conditions.

Adolescent↗

PubMed1995

A clinical study of the development of posterior vitreous detachment in high myopia.

PURPOSE: The correlation of age, axial length, and myopic chorioretinal atrophy with vitreous changes in high myopia were analyzed to investigate the development of posterior vitreous detachment (PVD) in high myopia. METHODS: The vitreous condition of 329 consecutive eyes with high myopia (more than -8.25 diopters (D) and more than 26.0 mm of axial length) was examined biomicroscopically with a +90-D preset lens and a Goldmann three-mirror contact lens. RESULTS: The prevalence of PVD in high myopia was 12.5% in patients between 20 and 29 years of age, and it increased with age. The incidence of PVD in eyes with axial length of more than 30.0 mm was 60.7% and was statistically higher than the prevalence in eyes with an axial length of less than 29.9 mm (P < 0.01). Multiple logistic regression analysis showed that age and axial length were statistically significant factors in the development of PVD and lacuna formation in high myopia (P < 0.01), but the influence of chorioretinal atrophy was not significant. CONCLUSION: The results of this study suggest that liquefaction of the vitreous begins at a relatively young age in patients with high myopia and progresses with age and axial elongation, thus resulting in a frequent occurrence of PVD.

Adult↗

PubMed1995

Mitochondrial abnormalities in hypertrophied myocardium of stroke-prone spontaneously hypertensive rats.

1. To clarify the pathogenesis of cardiac disorders in SHRSP which showed severe cardiac hypertrophy and myocardial degeneration in the hypertensive stage, restriction fragment length polymorphisms (RFLP) of mitochondrial DNA (mtDNA), and morphological and functional changes of mitochondria were examined. 2. Morphologically, the mitochondrial size showed a wider range of distribution in SHRSP both at prehypertensive and hypertensive stage compared to those in age-matched WKY. 3. Isocitrate dehydrogenase (ICDH) activity, but not superoxide dismutase (SOD) activity, was higher in the young SHRSP, whereas both enzyme activities were lower in the mature SHRSP than in the age-matched WKY. 4. RFLP analysis by electrophoresis revealed that the loss of two restriction sites for Rsa I in the myocardial mtDNA from the SHRSP, but not in that from the WKY. 5. These findings suggest that the structural changes of mtDNA could be related, at least partly, to morphological and functional changes of mitochondria in the SHRSP myocardium.

Animals↗

PubMed1995

Influence of bFGF as a potent growth stimulator and TGF-beta as a growth regulator on scleral chondrocytes and scleral fibroblasts in vitro.

We investigated the proliferation of scleral cells in response to several growth factors in vitro to elucidate the mechanism of scleral growth in visual deprivation myopia. Scleral chondrocytes and scleral fibroblasts were cultured separately in 24-well culture dishes. The number of plated cells was counted after the addition of basic fibroblast growth factor (bFGF), transforming growth factor alpha (TGF-alpha), TGF-beta, insulin-like growth factor I (IGF-I), IGF-II, platelet-derived growth factor AA (PDGF-AA), PDGF-AB and PDGF-BB. All the growth factors studied, except for PDGF-AA, stimulated the proliferation of both scleral chondrocytes and scleral fibroblasts. bFGF showed the highest effect. TGF-beta caused morphologic changes in both scleral chondrocytes and scleral fibroblasts. Various growth factors stimulated the proliferation of scleral chondrocytes and scleral fibroblasts in a similar manner. bFGF was a potent growth stimulator and TGF-beta was suggested to be a growth regulator on scleral chondrocytes and scleral fibroblasts.

Animals↗

PubMed1995

[Relationship between kinetic visual acuity and visual acuity with limited exposure].

Using a kinetic vision tester which we developed, kinetic visual acuity (KVA) at target velocity of 0-100 km/h was measured at background luminance of 0.1-200 cd/m2 in 19 eyes of 10 normal volunteers ranging in age from 20 to 31 years. The decrease in KVA was slow at a target velocity of 30 km/h or more as reported before. KVA was best at background luminance of 100 cd/m2. In 3 eyes of 2 normal subjects, 3 eyes of 2 patients with tonic accommodation and 1 eye of 1 patient with central serous chorioretinopathy, visual acuity at limited exposure times was also measured. In patients with tonic accommodation, visual acuity at limited exposure times was good, but KVA was poor as compared to normal eyes. In the eyes of patients with central serous chorioretinopathy, results were poor for both. The quantity of light required to obtain the same visual acuity was similar for both normal eyes and eyes with central serous chorioretinopathy in terms of both KVA and visual acuity at limited exposure times. In eyes with tonic accommodation, difference was seen in the required quantity of light. We conclude that functions of accommodation are involved in kinetic vision and that higher visual functions are required than those for visual acuity at limited exposure times.

Adult↗