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Biomedical subjects

M Kiyosawa

Publications and source records attributed to M Kiyosawa.

At least 19 recordsLinked to original sources

Development of myopia as a hazard for workers in pneumatic caissons.

BACKGROUND/AIM: Pneumatic caisson engineering has been developed for large civil engineering constructions. Because of complaints of blurred vision by personnel working in pneumatic caissons, the development of myopia was suspected. The aim of this study was to determine the cause of the blurred vision and the mechanism underlying the changes. METHODS: 12 caisson workers underwent a complete ophthalmological examination after completing up to 11 weeks of work (4 days/week) in a pneumatic caisson. Six months later, nine of the workers were examined again. RESULTS: Nine subjects were myopic at the initial examination, and seven of these were considered to have developed the myopia after starting to work in the pneumatic caisson. Six months after completion of the work, the mean refractive change was significantly towards hyperopia. CONCLUSIONS: The blurred vision in pneumatic caisson workers was in all likelihood due to the development of myopia. The refractive shift towards hyperopia after completion of work in the pneumatic caisson supports this and demonstrates that the changes were temporary. The myopia is similar to the myopia seen in patients treated by hyperbaric oxygen. Careful monitoring of the refraction of caisson workers should be performed for industrial health control.

Adult↗

Auditory triggered mental imagery of shape involves visual association areas in early blind humans.

Previous neuroimaging studies identified a large network of cortical areas involved in visual imagery in the human brain, which includes occipitotemporal and visual associative areas. Here we test whether the same processes can be elicited by tactile and auditory experiences in subjects who became blind early in life. Using positron emission tomography, regional cerebral blood flow was assessed in six right-handed early blind and six age-matched control volunteers during three conditions: resting state, passive listening to noise sounds, and mental imagery task (imagery of object shape) triggered by the sound of familiar objects. Activation foci were found in occipitotemporal and visual association areas, particularly in the left fusiform gyrus (Brodmann areas 19-37), during mental imagery of shape by both groups. Since shape imagery by early blind subjects does involve similar visual structures as controls at an adult age, it indicates their developmental crossmodal reorganization to allow perceptual representation in the absence of vision.

Adult↗

Application of visual evoked potentials for preoperative estimation of visual function in eyes with dense cataract.

PURPOSE: To determine whether the temporal frequency characteristics of the visual system as determined by visually evoked potentials (VEP) can be used for a preoperative estimation of the visual function in eyes with cataracts. METHODS: Light stimuli driven by a pseudorandom binary sequence (PRBS) of 40950 ms duration were presented and EEG recordings were made from 13 control and 20 patients with cataracts preoperatively and 1 week after cataract operation. The first kernel of the PRBS-VEP was obtained as the first-order cross-correlation function between PRBS and PRBS-VEP. The Fourier transform of this function was used as the temporal frequency characteristic (TFC). RESULTS: The mean +/- standard deviation of the latency and amplitude of the VEP in normal controls were 110.8+/-4.3 ms and 2.01+/-0.67 microV, respectively. A high correlation (r>0.7) between the pre-and postoperative VEP waveform was obtained in 13 eyes (65%), and 14 eyes (70%) in the VEP-TFC curves. The sensitivity of the examination was 73%, 27%, and 91% for the latency, amplitude and TFC of the VEP, respectively. The specificity of the examination was 67%, 100%, and 89% for the same measures. Eleven of 12 eyes with abnormal TFC preoperatively showed retinal or optic nerve lesions postoperatively. False-negative results were seen in cases with delayed corneal edema. CONCLUSION: Postoperative visual function of patients with cataracts can be predicted by preoperative measurement of the TFC obtained by PRBS-VEP.

Adult↗

[Visual evoked potentials elicited by pseudorandom stimulation in macular degeneration].

PURPOSE: To investigate the effect of a central scotoma on the amplitude, latency, and temporal frequency characteristics(TFCs) of the visual evoked potentials(VEPs) elicited by a pseudorandom binary stimulus(PRBS). METHOD: Patients with age-related macular degeneration(AMD) were selected, and VEPs were recorded from 26 eyes with AMD(17 eyes with visual acuity of less than 0.2, and 9 eyes with visual acuity between 0.3 and 0.9). Nine eyes of age-matched normal volunteers served as controls. To acquire the PRBS-VEPs, one eye was stimulated with a PRBS stimulus. The first order kernel was calculated from a cross correlation between PRBS and VEPs. The Fourier transformed first-order kernel was used as the TFC of the VEPs. RESULTS: The P2 latency of the first order kernels was delayed(p < 0.05), and the P2-N2 amplitude was reduced(p < 0.01) in AMD. A depression of the TFC values in the 6-18 Hz band was prominent in the patients with AMD(p < 0.01). CONCLUSION: The TFC, were strongly correlated with the visual acuity of patients with macular degeneration.

Aged↗

Evaluation of iodinated and brominated [11C]styrylxanthine derivatives as in vivo radioligands mapping adenosine A2A receptor in the central nervous system.

In vivo assessment of the adenosine A2A receptors localized in the striatum by PET or SPECT offers us a new diagnostic tool for neurological disorders. In the present study, we evaluated the potential of iodinated and brominated styrylxanthine derivatives labeled with 11C as an in vivo probe. [7-Methyl-11C]-(E)-3,7-dimethyl-8-(3-iodostyryl)-1-propargylxan thine ([11C]IS-DMPX) and [7-methyl-11C]-(E)-8-(3-bromostyryl)-3,7-dimethyl-1-propargylxa nthine ([11C]BS-DMPX) were prepared by the 11C-methylation of corresponding 7-demethyl derivatives. An in vitro membrane binding study showed a high affinity (Ki values) of the two ligands for A2A receptor: 8.9 nM for IS-DMPX and 7.7 nM for BS-DMPX, and a high A2A/A1 selectivity: > 1100 for IS-DMPX and 300 for BS-DMPX. In mice, [11C]IS-DMPX and [11C]BS-DMPX were taken up slightly more in the striatum than in the reference regions such as the cortex and cerebellum. The uptake ratios of striatum to cortex and striatum to cerebellum gradually increased but were very small: 1.6-1.7 for the striatum-to-cortex ratio and 1.2 for the striatum-to-cerebellum ratio at 60 min postinjection. The uptake by these three regions was reduced by co-injection of an excess amount of carrier or an A2A antagonist KF17837, but not by an A1 antagonist KF15372. The blocking effects in the three regions were greater for [11C]BS-DMPX (32-57%) than for [11C]IS-DMPX (6-29%). Ex vivo autoradiography confirmed that the two ligands were slightly concentrated in the striatum. [11C]BS-DMPX showed more selective affinity for adenosine A2A receptors than [11C]IS-DMPX, but these results have shown that the two tracers were not suitable as in vivo ligands because of low selectivity for the striatal A2A receptors and a high nonspecific binding.

Animals↗

Carbon-11-labeled KF21213: a highly selective ligand for mapping CNS adenosine A(2A) receptors with positron emission tomography.

In vivo assessment of the adenosine A(2A) receptors localized in the striatum with positron emission tomography (PET) may offers us a new diagnostic tool for neurological disorders. We evaluated the potential of [7-methyl-(11)C](E)-8-(2,3-dimethyl-4-methoxystyryl)-1, 3,7-trimethylxanthine ([(11)C]KF21213) as a PET ligand for mapping adenosine A(2A) receptors in the central nervous system. KF21213 showed a high affinity for the adenosine A(2A) receptors in vitro (Ki = 3.0 nM) and a very low affinity for the A(1) receptors (Ki > 10,000 nM). In mice, the striatal uptake of [(11)C]KF21213 increased for the first 15 min and then gradually decreased, whereas the uptake in the reference regions such as the cortex and cerebellum rapidly decreased. The uptake ratio of striatum to cortex and striatum to cerebellum increased to 8.6 and 10.5, respectively, at 60 min postinjection. The striatal uptake was significantly blocked by co-injection of carrier KF21213 or each of three other A(2A) antagonists, but not by co-injection of A(1) antagonist. The specific uptake was not detected in the cortex or in the cerebellum. Ex vivo autoradiography and PET clearly visualized adenosine A(2A) receptors in the rat striatum. [(11)C]KF21213 was the most selective tracer for mapping adenosine A(2A) in the central nervous system by PET among the tracers proposed to date.

Animals↗

Postmortem study of ataxia with retinitis pigmentosa by mutation of the alpha-tocopherol transfer protein gene.

A new syndrome of ataxia and retinitis pigmentosa with vitamin E deficiency caused by the missense mutation of alpha-tocopherol transfer protein (alpha-TTP) gene was recently proposed. After studying the first postmortem case with this mutation pathologically and biochemically, whether the symptoms can be treated by supplementation of vitamin E or not is discussed. The major pathological findings were retinal atrophy; severe dying back-type degeneration of the posterior column; and massive accumulation of lipofuscin in neurons including dorsal root ganglion (DRG) cells, which were almost identical to those in vitamin E deficient animals and patients with fat malabsorption. Also, mild loss of Purkinje cells was noted. Because robust expression of alpha-TTP was detected in the cerebellum as well as in the liver and the tissue concentration of vitamin E in the cerebellum was still low even after oral supplementation, the mild Purkinje cell loss might be related to the mutant alpha-TTP in the cerebellum. By contrast, in the DRG, thought to be mainly responsible for ataxia, no expression of alpha-TTP was detected, and the tissue concentration of vitamin E increased to normal after supplementation. It is therefore considered that oral supplementation of vitamin E should effectively counteract the progression of ataxia.

Aged↗

Bilateral serous retinal detachment associated with Alport's syndrome.

We report a 14-year-old girl with Alport's syndrome who developed bilateral exudative retinal detachment in the macula. With the development of chronic renal failure, bilateral serous retinal detachment appeared which had the retinal flecks characteristic of Alport's syndrome. The serous detachment was resolved and vision recovered following intensive hemodialysis. As far as we know this is the first case with documentation of the onset and resolution of serous retinal detachment in Alport's syndrome.

Adolescent↗

Benzodiazepine receptor distribution and cerebral blood flow in early blindness--a PET study.

We studied benzodiazepine receptor (BZR) distribution, which is thought to be affected by neuronal density in the cerebral cortex, and CBF using [11C]flumazenil and [15O]water PET in early blind (EB) and in blindfold sighted control (SC) subjects. PET images were co-registered to the subject's MRI. Using SPM96, MRI images were normalized in the Talairach and Tournoux coordinate system, and accordingly MRI-registered PET images were spatially normalized. Statistical parametric maps were computed on a voxel-by-voxel basis, using the general linear model. CBF for EB was significantly larger in the Brodmann area 17 and 18, especially anterior area, than that for SC, while there was no significant difference in BZR distribution. Our BZR data suggest that the amount of neurons do not change due to early visual deprivation in the visual cortex, in spite of high CBF in visual cortex of EB subjects.

Adult↗

Cataract and retinal detachment in patients with severe atopic dermatitis who were withdrawn from the use of topical corticosteroid.

Many patients with severe atopic dermatitis (AD) in Japan are afflicted with persistent erythema of the face (atopic red face) that is not only resistant to topical corticosteroid, but often becomes worse with its use. During a three-year period (1991-1993), we treated 79 inpatients with severe AD by a combination of careful daily skin care, use of emollients, and exclusion of exacerbating factors. Occular complications before and after treatment were examined in these cases. After withdrawal of topical corticosteroid, almost all of the patients showed a temporary worsening of their skin condition. Immediately thereafter, their occular symptoms did not change. Cataract was found in 20 cases (25.3%), and retinal detachment in 9 (11.4%). After 2 months, 11 cases of cataract and 5 cases of retinal detachment in the peripheral retina were observed. However, these incidences were similar to the numbers reported in Japan during conventional treatment with topical corticosteroid. The development of cataract or retinal detachment had no relationship to serum IgE levels, personal history of respiratory atopy, the duration of topical corticosteroid use on the face, or treatment with systemic corticosteroid. Our observations suggest that patients who habitually tap or rub their faces strongly tend to develop cataract or retinal detachment at a statistically significant higher frequency. Patients with AD should have ophthalmologic examinations every one to two months for at least one year after a facial oozing attack or withdrawal of corticosteroid.

Administration, Topical↗

Visual temporal frequency characteristics determined by pseudorandom stimuli.

PURPOSE: To investigate whether a rapid and practical determination of the temporal frequency characteristic (TFC) of the visual system can be obtained by using the visually evoked potentials (VEPs) elicited by pseudorandom binary sequence (PRBS) stimulation. METHODS: VEPs were recorded from eight volunteers. For the conventional steady state VEPs (S-VEP), the eye was stimulated with five stimulus frequencies. To acquire the PRBS-VEPs, the eye was stimulated with a PRBS stimulus for 40 seconds. The TFC for the S-VEP was calculated from the root mean squared amplitude for each frequency using Fourier transform. For the PRBS stimulus, a cross-correlation function between PRBS (x[t]) and PRBS-VEP (y[t]) was calculated to obtain the TFC. RESULTS: The TFCs obtained by the PRBS and S-VEP methods were highly correlated (P < 0.05), and the TFC curves resembled those in the literature. Most important, the data necessary to determine the TFCs using the PRBS stimulus could be obtained in 4 minutes, whereas that for the S-VEP required 60 minutes for the two eyes. CONCLUSIONS: The high correlation between the TFCs obtained by the two methods indicated that the PRBS technique gives a good measure of the TFC of the human visual system. The significantly shorter time required for this method demonstrated that it is a practical method for determining the linear (and nonlinear) property of the visual system and that it may be useful in clinical applications.

Adult↗

Ophthalmological findings in patients with Takayasu disease.

We examined 65 (61 female and 4 male) Takayasu patients. Patient age ranged from 17 to 78 years old (mean 50.2); age of onset was from 11 to 60 years old (mean 32.8); and duration from onset to referral ranged from 1 month to 43 years (mean 16.8 years). Routine ophthalmological examinations were performed. Fluorescein angiography, kinetic perimetry by Goldmann perimetry, static perimetry by Octopus 1-2-3, electroretinography (ERG), and measurements of central retinal arterial pressure were also performed, as appropriate. Major causes of impaired visual acuity (less than 16/20) were cataract. A few patients had low visual acuity caused by Takayasu disease itself. On the other hand, although not many complained of visual disturbance, about 35% of patients had subnormal visual functions. Because the visual deterioration may be based on ocular hypoperfusion, which may subsequently lead to more serious changes, regular ophthalmological examination for every Takayasu disease patient is recommended.

Adolescent↗

A family with Leber's hereditary optic neuropathy with mitochondrial DNA heteroplasmy related to disease expression.

A Japanese family has members with Leber's hereditary optic neuropathy resulting from the heteroplasmic 11778 mutation and the homoplasmic 4216 mutation. Quantitative determination of heteroplasmy was performed by a combination of polymerase chain reaction and single-strand conformation polymorphism analysis. The association between heteroplasmy and clinical features was determined. Eleven people from the maternal side of the family, including four affected and seven unaffected members, showed heteroplasmy of the mtDNA mutation ranging from 5% to more than 95%. Four possibly affected patients had more than 90% of the mutant mtDNA. Seven unaffected people had mutant mtDNA ranging from 5% to 77%. A recovery episode of visual acuity was noted in the history of three of the four patients. Heteroplasmy is likely to be a factor in the expression of disease in this family.

Adult↗

Friedreich-like ataxia with retinitis pigmentosa caused by the His101Gln mutation of the alpha-tocopherol transfer protein gene.

The alpha-tocopherol transfer protein (alpha-TTP) is a cytosolic liver protein that is presumed to function in the intracellular transport of alpha-tocopherol, the most biologically active form of vitamin E. We studied 4 unrelated patients with autosomal recessive Friedreich-like ataxia who had isolated vitamin E deficiency. A point mutation was identified in all of them at position 101 of the gene for alpha-TTP, where histidine (CAT) was replaced with glutamine (CAG). Three of the 4 patients developed retinitis pigmentosa subsequent to the onset of ataxia. Neurological symptoms included ataxia, dysarthria, hyporeflexia, and decreased proprioceptive and vibratory sensations. Electrophysiological and pathological examinations showed that the cardinal sites affected were the central axons of dorsal root ganglion cells and the retina, with minor involvement of the peripheral sensory nerve, optic nerve, and pyramidal tract. The vitamin E tolerance test performed showed that the absorption of vitamin E was normal but that its decrease from the serum was accelerated. Oral administration of vitamin E appeared to halt the progression of visual and neurological symptoms. We propose a new treatable syndrome of Friedreich-like ataxia and retinitis pigmentosa caused by a defect in the alpha-TTP gene.

Aged↗

Evaluation of carbon-11 labeled KF15372 and its ethyl and methyl derivatives as a potential CNS adenosine A1 receptor ligand.

We prepared [11C]KF15372 ([1-propyl-11C]8-dicyclopropylmethyl-1,3-dipropylxanthine, refs 10, 13) as well as its 11C-ethyl and 11C-methyl derivatives ([11C]EPDX and [11C]MPDX), and examined the potential of the three compounds as PET ligands for CNS adenosine A1 receptors. The three compounds had high affinity for the A1 receptors in vitro in the following order; [11C]EPDX > [11C]KF15372 > [11C]MPDX. In mice, the highest initial brain uptake was found in [11C]MPDX followed by [11C]EPDX and [11C]KF15372, but the level of [11C]MPDX decreased faster than those of the other two compounds. The uptake of each compound was decreased by carrier KF15372, but not by an A2A antagonist, indicating the selective affinity for the A1 receptors. Autoradiography with [11C]MPDX ex vivo demonstrated decreased A1 receptor binding in the superior colliculus of rats deprived of retino-collicular fibers by contralateral eye enucleation. These results show that three compounds have potential as PET ligands for CNS adenosine A1 receptors.

Animals↗

Mapping visual field with positron emission tomography by mathematical modeling of the retinotopic organization in the calcarine cortex.

We developed an objective and quantitative method of mapping the human visual field with positron emission tomography (PET) and magnetic resonance image (MRI). The regional cerebral blood flow (rCBF) images were acquired with H2(15)O-PET under visual fixation as well as under visual stimulation with flickering diodes arranged along the ring at 0 degree, 3 degrees, 7 degrees, 14 degrees, 21 degrees, or 29 degrees from the fixation point. After coregistration of PET and MR images, we extracted the surface of the calcarine cortex from the MR images and unfolded it to a two-dimensional (2-D) elliptic plane, on which the activated PET images were superimposed. Then we transformed the unfolded calcarine cortex into the visual field coordinates using the complex logarithmic function proposed by Schwartz. A large individual variation was observed in the retinotopical organization as well as in the morphology of the calcarine cortex. The formula was valid only within 15 degrees from the center of the visual field. The constant parameter in the formula was estimated to be 1.5. The cortical linear magnification factor was 12.1, 2.8, and 1.6 at 0, 5, and 10 degrees, respectively. The areas of the central 10 degrees and 40 degrees in the visual field correspond to 50% and 81% of the calcarine surface, respectively.

Adult↗

Bilateral horizontal gaze palsy with pontine cavernous hemangioma: a case report.

A 31-year-old man demonstrating acquired bilateral gaze palsy as an isolated symptom of a paramedian pontine reticular formation (PPRF) lesion due to a ruptured cryptic cavernous hemangioma is herein reported. MRI revealed a flow void surrounded by a hemorrhagic lesion, which was located in the lower dorsal part of the pons. This lesion corresponded to the PPRF. His eye movement almost completely recovered and MRI revealed the absorption of the hematoma 2 months later, with only conservative observation. This is a rare case presenting most likely with a minimal lesion for bilateral gaze palsy. Based on the above findings it is thus concluded that surgical removal of such a cryptic cavernous hemangioma should therefore not be the only choice.

Adult↗