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Biomedical subjects

M Kiyosawa

Publications and source records attributed to M Kiyosawa.

At least 55 records · Page 3Linked to original sources

Partially deficient glutamate dehydrogenase activity and attenuated oscillatory potentials in patients with spinocerebellar degeneration.

Glutamate dehydrogenase (GDH, EC 1.4.1.2) catalyzes the synthesis and degradation of glutamate, an excitatory neurotransmitter in the retina. Recently, two forms of GDH, a soluble heat-stable form and a particulate heat-labile form, have been demonstrated to be deficient in some types of spinocerebellar degeneration (SCD). We measured these forms of GDH activity in leukocyte homogenate from patients with SCD (n = 22) and normal subjects (n = 20) who were examined ophthalmoscopically and electrophysiologically. Seven patients with SCD showed attenuated oscillatory potentials (OPs) on electroretinography. The heat-labile GDH activity in these seven patients (78 +/- 51 nmol/mg protein/h) was significantly lower than that of 15 patients with normal OPs (367 +/- 189) and the normal subjects (397 +/- 1720 (P less than 0.001). Our results indicated that patients with SCD could be separated into two groups electrophysiologically, one with normal OPs and one with attenuated OPs. Also indicated was that a deficiency of heat-labile GDH might affect some functions of neural elements in the retina that are responsible for the generation of OPs.

Aged↗

Neuro-imaging and positron emission tomography of congenital homonymous hemianopsia.

Congenital homonymous hemianopsia is an uncommon asymptomatic visual field defect discovered typically in young adult life that is caused by a diverse group of insults to the retrochiasmal afferent visual system occurring prenatally, at birth, or during early childhood. We treated eight patients with congenital homonymous hemianopsia; seven with damage involving the optic radiations and one with an abnormality of the optic tract. We performed positron emission tomography using 18F-fluoro-2-deoxyglucose on two patients with dense homonymous hemianopsias, lesions of the contralateral optic radiations, and largely intact occipital cortex. These studies showed minimal abnormalities in resting visual cortex glucose metabolism of the affected visual cortex.

Adolescent↗

Middle cerebral artery strokes causing homonymous hemianopia: positron emission tomography.

Eight patients were evaluated with 18F-fluorodeoxyglucose positron emission tomography between 3 and 30 days after isolated stroke involving the middle cerebral artery territory that caused homonymous hemianopia. Diffuse hypometabolism was present throughout the damaged cerebral hemisphere, even in cortical areas not obviously ischemic by clinical examination or neuro-imaging. Glucose metabolism in primary and association visual cortex of the damaged hemisphere was decreased by more than 47% (p less than 0.01). Metabolism in the undamaged hemisphere was less profoundly affected, but significant decrements were found in calcarine (40%; p less than 0.01) and lateral occipital cortex (35%; p less than 0.05).

Brain Ischemia↗

Positron emission tomography to study the effect of eye closure and optic nerve damage on human cerebral glucose metabolism.

We used 18F-2-fluoro-2-deoxyglucose and positron emission tomography to evaluate the effect of visual deprivation on brain glucose metabolism. In experiment 1, we compared local cerebral metabolic rates for glucose in seven normal volunteers studied with eyes closed to 11 age- and sex-matched normal volunteers studied with eyes open. Whole brain metabolism was similar in the two groups, and region/whole brain analysis of metabolic data showed that metabolism in the calcarine posterior cortex was decreased by 14% (P less than .05) with eye closure. Glucose metabolism in other regions was not different between the two groups. In experiment 2, we compared glucose metabolism in six patients with severe bilateral optic neuropathies to 12 age- and sex-matched normal controls. Whole brain glucose metabolism was unchanged in the optic neuropathy group compared to controls. However, statistically significant reductions in glucose metabolism in the optic neuropathy group were found in anterior calcarine cortex (17%), posterior calcarine cortex (27%), peristriate cortex (27%), and lateral occipital cortex (15%). The metabolic effects of damage to the pregeniculate visual system went well beyond those of simple eye closure.

Adolescent↗

Alzheimer's disease with prominent visual symptoms. Clinical and metabolic evaluation.

The authors examined eight patients with dementia of the Alzheimer's type (DAT), five with prominent visual symptoms early in the illness (VS) and three with no visual symptoms (NVS). Results of neuro-ophthalmologic examinations on VS patients showed relatively consistent abnormalities in figure copying, color vision tested by isochromatic plates, and stereopsis. Cerebral glucose metabolism determined by 18F-fluoro-2-deoxyglucose positron emission tomography (PET) was unchanged in primary visual cortex of VS and NVS patients compared with 12 normal volunteers of similar age and sex. Glucose metabolism in VS patients was decreased by 45 and 34% in left and right visual association cortex (P less than 0.01 and P less than 0.05, respectively) and 34 and 37% in left and right inferior parietal cortex (P less than 0.05) compared with controls; NVS patients had no significant metabolic alteration in these areas. Symptoms, physical examination, and metabolic imaging imply that these patients are a heterogenous but distinct clinical subgroup of DAT often with mild dementia who have visual symptoms due primarily to visual agnosia.

Aged↗

Time course of effects of unilateral lesions of the nucleus basalis of Meynert on glucose utilization by the cerebral cortex. Positron tomography in baboons.

In order to investigate the effects of a partial cholinergic deafferentation on the functional activity of the cortex, the cerebral metabolic rate of glucose (CMRGlu) was measured with positron emission tomography and 18F-2-fluoro-2-deoxy-D-glucose in 5 baboons (Papio anubis) both before and serially following stereotaxic electrocoagulation of the left nucleus basalis of Meynert (NbM). Four days postlesion, significant metabolic depression was present in the entire ipsilateral cerebral cortex, most marked in the frontotemporal region, and which slowly recovered close to normal within 6-13 weeks. Postmortem studies showed that the lesions were located largely in the NbM, and that a significant decrease in choline-acetyltransferase (ChAT) activity was present in the ipsilateral frontal, temporal and parietal cortices. The animal with the most limited histological lesion showed the least decrease in both ChAT activity and CMRGlu. There was a highly significant linear correlation between the regional cortical decreases in CMRGlu (early postlesion data) and in ChAT activity. These results indicate that cholinergic deafferentation induces a proportional metabolic depression in the cortex. However, compensatory mechanisms operate to restore the cortical metabolic activity gradually despite sustained cholinergic denervation, pointing to pre- and/or postsynaptic adaptation (plasticity). Moreover, unilateral NbM lesions also induced a significant reduction in contralateral CMRGlu, which also demonstrated recovery. Several mechanisms are discussed to explain this contralateral effect, but the most likely implicates a transcallosal depression of function as a result of ipsilateral effects of the NbM lesion. These metabolic effects of cholinergic deafferentation in the primate provide new insight into the mechanisms of cortical dysfunction, and the recovery thereof, following subcortical lesions. In addition, our findings have some relevance to the cortical consequences of cholinergic deafferentation observed in dementia of Alzheimer type.

Animals↗

[18F]setoperone: a new high-affinity ligand for positron emission tomography study of the serotonin-2 receptors in baboon brain in vivo.

The potential usefulness of 18F-labelled setoperone, a high-affinity antagonist of the serotonin-2 (S2) receptors, to study the S2 receptors in vivo with positron emission tomography (PET) was investigated in four baboons. In the control state, there was a rapid wash-out of intravenously injected tracer from the cerebellum, a structure essentially devoid of S2, receptors, and marked retention in both the cerebral cortex and the striatum (region/cerebellum ratios up to 3 and 3.5 after 60 min in cortex and striatum, respectively). The retention of radioligand in the cerebral cortex was abolished after pretreatment with spiperone or ketanserin at saturating doses. In striatum, however, radioligand retention was fully prevented by spiperone but only partly by ketanserin. These results demonstrate that [18F]setoperone was bound to the S2 receptors in the cerebral cortex, whereas the radioligand was bound to both the S2 and the dopamine D2 receptors in the striatum. The high cortex/cerebellum ratio achieved indicates that [18F]setoperone should be a useful radiotracer for PET studies of the S2 receptors.

Animals↗

Positron emission tomography in a patient with progressive multifocal leukoencephalopathy.

A 56-year-old man with chronic lymphocytic leukemia, progressive multifocal leukoencephalopathy, and a dense left homonymous hemianopia had 18F-fluorodeoxyglucose positron emission tomography. Cortical glucose metabolism was decreased in the right cerebral hemisphere and the left cerebellar hemisphere. To our knowledge, this is the first demonstration of cerebral and cerebellar hypometabolism due solely to white matter disease.

Aged↗

Cortical hypometabolism and its recovery following nucleus basalis lesions in baboons: a PET study.

The cerebral metabolic rate for glucose was measured serially with positron emission tomography and [18F]fluorodeoxyglucose in five baboons with stereotactic electrocoagulation of the left nucleus basalis of Meynert (NbM). Four days after lesion, a significant metabolic depression was present in the ipsilateral cerebral cortex, most marked in the frontotemporal region, and which recovered progressively within 6-13 weeks. These data demonstrate that adaptive mechanisms efficiently compensate for the cortical metabolic effects of NbM-lesion-induced cholinergic deafferentation. Moreover, unilateral NbM lesions also induced a transient reduction in contralateral cortical metabolic rate, the mechanisms of which are discussed. Explanation of these effects of cholinergic deafferentation in the primate could further our understanding of the metabolic deficits observed in dementia of the Alzheimer's type.

Animals↗

Cerebral metabolism in chronic ocular ischemia.

Two patients with neovascular glaucoma presented an obstruction in the internal carotid artery and reverse flow of blood through the ophthalmic artery, a so-called ophthalmic artery steal phenomenon, on digital subtraction angiography. To study the cerebral metabolic state maintained by this mechanism, the same patients underwent positron emission tomography. Both displayed decreased regional cerebral blood flow, reduced regional cerebral metabolic rate for oxygen and for glucose and increased regional oxygen and glucose extraction ratios. In our patients with chronic ocular ischemia, the cerebral perfusion maintained by the ophthalmic artery steal phenomenon was in the critical state called misery perfusion.

Brain↗

Positron tomography for ophthalmology.

Positron emission tomography (PET) has been applied so far to estimate the viability of malignant tumors or to assess cerebral higher function in living animals and in man. Our preliminary results suggested possibilities of nontraumatic imaging diagnosis of orbital tumors; the rate of incorporation of glucose analogue, 18F-2-fluorodeoxyglucose, seemed to reflect the malignant nature of the tissue. PET also gives information concerning regional blood flow, glucose metabolism and oxygen consumption in the brain. We demonstrated chronic cerebral ischemia in cases with rubeosis iridis. PET was more sensitive in detecting lesions responsible for cortical hemianopsia than X-ray computed tomography (CT) and magnetic resonance CT.

Aged↗

Nuclear magnetic resonance imaging of subretinal fluid.

We ascertained the relationship between the relaxation time of magnetic resonance imaging and the protein concentration of subretinal fluid, by examining rhegmatogenous and nonrhegmatogenous retinal detachments with a 0.15 tesla nuclear magnetic resonance system, and we calculated T1 and T2 relaxation times of subretinal fluid. The protein concentration of subretinal fluid obtained at the time of surgery was determined by a biochemical method. The subretinal fluid in a fresh rhegmatogenous retinal detachment had a low protein concentration and relaxation times equal to those of vitreous. Conversely, increased protein concentrations and shortened relaxation times were noted in subretinal fluid from long-standing rhegmatogenous retinal detachments. Subretinal fluid in a nonrhegmatogenous retinal detachment with a high concentration of protein showed much shorter relaxation times. The relaxation times and protein concentration of the subretinal fluid correlated closely. It may be possible to measure the protein concentration of subretinal fluid in vivo with nuclear magnetic resonance imaging.

Adult↗

Metabolic imaging in hemianopsia using positron emission tomography with 18F-deoxyfluoroglucose.

To evaluate the usefulness of metabolic mapping by positron emission tomography using 18F-deoxyfluoroglucose as a tracer in the diagnosis of hemianopsia, we examined eight patients who had had cerebrovascular accident, and four controls. Neuro-ophthalmologic examination disclosed hemianopsia in five and incomplete hemianopsia in three patients; computed tomography showed low-density areas in four patients; and nuclear magnetic resonance imaging demonstrated a prolonged T2 area in five patients. The cerebral metabolic rate for glucose without visual stimulation in the visual cortex was 7.4 +/- 1.0 mg/min/100 g of brain without interhemispheric asymmetry. Light stimulation increased cerebral metabolic rate for glucose in the visual cortex of the nonaffected hemisphere and decreased it in the affected hemisphere. Asymmetry in the metabolic rate in the posterior medial occipital cortex in complete hemianopsia was 22% 12% (P less than .01).

Adult↗

Homograft of preserved sclera for post-traumatic scleral staphyloma in Ehlers-Danlos syndrome.

Homotransplantation of preserved sclera was successfully performed for post-traumatic scleral staphyloma in a 38-year-old woman with Ehlers-Danlos syndrome type VI. The transplanted tissue was preserved by glycerol dehydration. For 1 year postoperatively, no sign of graft failure or recurrence of scleral staphyloma has been found. To our knowledge, this is the first report of the use of a preserved scleral homograft to treat this ocular complication in a patient with Ehlers-Danlos syndrome.

Adult↗

Orbital tumor diagnosis by positron emission tomography using 18F-fluorodeoxyuridine.

The distribution of 18F-labeled 5-fluoro-2'-deoxyuridine (18F-FdUrd) in orbital tissue, tumor and aseptic inflammation was examined in rats. The distribution in paraorbital structures, other than bone, was low. The tumor-to-organ ratios were sufficient for tumor imaging by positron emission tomography (PET). Positron emission tomography with 18F-FdUrd clearly showed the experimental orbital VX-2 tumor in rabbits. The difference between the experimental orbital tumor and croton oil-induced aseptic inflammation or a normal orbit was apparently established in the PET image with slow and fast clearance of radioactivity, respectively.

Animals↗