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H Shinotoh

Publications and source records attributed to H Shinotoh.

At least 55 records · Page 3Linked to original sources
PubMed1995

MRI and PET studies of manganese-intoxicated monkeys.

Using MRI and PET, we investigated the consequences of manganese intoxication in a primate model of parkinsonism and dystonia. Three rhesus monkeys were injected intravenously with doses of 10 to 14 mg/kg of MnCl2 on seven occasions, each a week apart. Two animals became hypoactive with abnormal extended posturing in the hind limbs. These motor disturbances did not improve with administration of levodopa. In all three monkeys, T1-weighted MRI demonstrated high signal intensities in the regions of the striatum, globus pallidus, and substantia nigra. No significant changes were found on [18F]6-fluoro-L-dopa, [11C]raclopride, or [18F]fluorodeoxyglucose PET. These results are consistent with the pathologic findings, which were primarily confined to the globus pallidus, and indicate that manganese intoxication is associated with preservation of the nigrostriatal dopaminergic pathway, despite clinical evidence of parkinsonian deficits. Chronic manganese intoxication may cause parkinsonism by damaging output pathways downstream to the nigrostriatal dopaminergic pathway. This is consistent with the demonstrated lack of therapeutic response to levodopa.

Animals↗
PubMed1995

[Frontal type adrenoleukodystrophy: the progress of the white matter lesion--a neuroradiological and pathological study].

We studied the correlation between neuroradiological findings and pathological observations of white matter lesions in a patient with frontal type adrenoleukodystrophy. A 41-year-old man developed schizophrenic symptoms and generalized convulsions at the age of 40. Examination revealed baldness, loss of the axillary hair, stereotypical behavior, mutism, dysphagia echographia, right hemiparesis, and brisk reflexes in all four limbs with bilateral extensor plantar responses. Blood examination revealed a high concentration of very-long-chain fatty acids in plasma; the patient was diagnosed as having adrenoleukodystrophy. His condition continued to worsen, and gradually he became akinetic. He died of pneumonia at the age of 43. T1- and T2-weighted MR images distinguished three abnormal zones in the cerebral white matter in this case. In the first zone (Z1), the signal intensity was moderately high on T2-weighted images and slightly low on T1-weighted images; this zone was not enhanced with Gd-DTPA. In the second zone (Z2), the signal intensity was slightly high on T2-weighted images, while moderately low on T1-weighted images; Z2 was enhanced with Gd-DTPA. In the third zone (Z3), the signal intensity was markedly high on T2-weighted images and low on T1-weighted images; Z3 was not enhanced with Gd-DTPA. Z3 was located in the frontal pole; Z2 and Z1 were consecutively located in rostro-caudal fashion in the brain. The subsequent pathological study of the brain of this patient revealed the following findings: Z1 showed destruction of myelin with axonal sparing, Z2 showed numerous lipid-laden macrophages, demyelinated axons, and a vigorous perivascular mononuclear cell response, Z3 consisted of a dense mesh of glial fibrils and scattered astrocytes without any evidence of an active process. In this study, the correlation between MR images and pathological findings in adrenoleukodystrophy was clearly established. Single photon emission tomography with 99mTc-hexamethylpropyleneamine oxime, and positron emission tomography with 15O2 continuous inhalation technique showed a reduction in the regional cerebral blood flow (rCBF) and in the regional cerebral metabolic rate of oxygen (rCMRO2) in the cerebral cortex near the Z1 and Z3. A normal or slight increase of rCBF and a reduction of r CMRO2 was found in the cerebral cortex near the Z2. Coronal MR images showed that Z3 was located in the deep white matter, while Z2 and Z1 were consecutively located in an inner-outward fashion, suggesting that the demyelination process started in the cingulum and spread in an inner-outward fashion and progressed in rostro-caudal manner.

Adrenoleukodystrophy↗
PubMed1994

Parkinsonism induced by solvent abuse.

We report the first description of a patient with parkinsonism induced by solvent abuse. Our patient developed parkinsonism acutely, following heavy abuse of lacquer thinner. Her clinical deficits were indistinguishable from idiopathic parkinsonism (Parkinson's disease) and she responded to levodopa. Parkinsonism has persisted for more than 3 months. Brain computed tomography was normal. Positron emission tomographic studies showed normal fluorodopa uptake and reduced raclopride binding, indicating an unusual disturbance of striatal dopaminergic function. This patient suggests that organic solvents may cause parkinsonism in susceptible individuals.

Administration, Inhalation↗
PubMed1994

Effects of trihexyphenidyl and L-dopa on brain muscarinic cholinergic receptor binding measured by positron emission tomography.

The effects of pharmacological intervention on brain muscarinic cholinergic receptor (mAChR) binding were assessed in seven patients with Parkinson's disease by positron emission tomography and carbon-11 labelled N-methyl-4-piperidyl benzilate ([11C]NMPB). [11C]NMPB was injected twice, approximately 2 hours apart, in each patient, to assess the effect of single doses of 4 mg of trihexyphenidyl (n = 5) or 400 mg of L-dopa with 57 mg of benserazide (n = 2) on the binding parameter of mAChRs (K3). There was a mean 28% inhibition of K3 values in the brain in the presence of trihexyphenidyl, which was assumed to reflect mAChR occupancy. No significant change in K3 was observed in the presence of L-dopa. This study demonstrates the feasibility of measuring mAChR occupancy by an anticholinergic medication with PET.

Aged↗
PubMed1994

Normal CAG repeat length in the Huntington's disease gene in senile chorea.

There is a widely held belief that most patients presenting with senile chorea have late-onset Huntington's disease (HD) with an unknown family history. We measured CAG trinucleotide repeat expansion in the HD gene in four patients with a clinical presentation of senile chorea and found that CAG repetition lengths were normal. These findings support senile chorea as being a distinct clinical entity that is nosologically separate from late-onset HD.

Aged↗
PubMed1993

Dopamine D1 receptors in Parkinson's disease and striatonigral degeneration: a positron emission tomography study.

Striatal dopamine D1 receptors were investigated in 11 patients with Parkinson's disease (PD), five patients with striatonigral degeneration (SND) and six age-matched controls by positron emission tomography and carbon-11 labelled SCH23390. The SND patients showed mean 12%, 21%, and 31% declines in the ratios of radioactivity in the caudate, anterior putamen, and posterior putamen compared with that in the occipital cortex. These ratios were not significantly altered in the PD patients. The results may explain the different therapeutic responses to levadopa between SND and PD patients, and this technique might prove useful for their differentiation.

Adult↗
PubMed1993

[Paramedian dorsal syndrome of mesencephalic tegmentum].

Two cases of brainstem infarction involving a unilateral side of the midbrain tegmentum showed a peculiar ocular symptom complex. The ocular syndrome consisted of (1) oculomotor palsy ipsilateral to the lesion, (2) monocular eyelid retraction and upward gaze palsy contralateral to the lesion, and (3) conjugate downward gaze and convergence palsy. By computed tomography and cerebral angiography, the lesion shared by the two cases was identified in the territory of median mesencephalic rami originating from the posterior cerebral artery. The lesion involved oculomotor nucleus on a side. Contralateral monocular symptoms and conjugate palsies could be attributed to a damage in their supranuclear tracts. Considering with two similar cases in the literature, it is strongly suggested that a unilateral ischemic lesion of the paramedian dorsal part of the midbrain tegmentum is responsible for this syndrome. Bilateral or unilateral eyelid retraction (Collier's sign) was considered to locate a lesion in the posterior commisure by Collier himself. The posterior commisure is, however, not involved in our two cases, and a paramedian lesion of the midbrain tegmentum deviated to a side may cause contralateral eyelid retraction. A combination of ophthalmoplegia ipsilateral to the lesion, upward or lateral (in the opposite direction to the lesion) gaze palsy, and hemiataxia on the contralateral side resembling our second case is sometimes erroneously called Nothnagel's syndrome. Nothnagel mentioned symptomatology of the quadrigeminal bodies for local diagnosis in his text in which he did not describe this combination of signs.

Cerebral Infarction↗
PubMed1992

[Magnetic resonance imaging in multiple system atrophy].

We studied 18 patients with multiple system atrophy (MSA) by high field strength MRI: 6 striatonigral degeneration (SND), 4 Shy-Drager syndrome (SDS), and 8 olivo-ponto-cerebellar atrophy (OPCA). We also studied 30 Parkinson's disease (PD) and 10 age-matched controls. The diagnoses of SND, SDS, and OPCA were based on criteria after Hirayama et al (1985). Bradykinesia, rigidity, and tremor were assessed with the summed scores of the signs used as the extrapyramidal scores. The mean extrapyramidal scores were not significantly different in patients with SND, SDS, OPCA, and PD. MRI studies were performed on 1.5 tesla MRI unit, using a T2 weighted spin echo pulse sequence (TR2500 ms/TE40 ms). The width of the pars compacta signal in all subjects was measured by the method of Duguid et al (1986). Intensity profiles were made on a straight line perpendicular to the pars compacta through the center of the red nucleus on an image of the midbrain. We measured the width of the valley at half-height between the peaks of intensity representing the red nucleus and the crus cerebri-pars reticulata complex and used this measurement as an index of the width of the pars compacta signal. The mean widths of the pars compacta signal were: 2.8 +/- 0.4 mm (SND), 2.8 +/- 0.7 mm (SDS), 3.6 +/- 0.6 mm (OPCA), 2.7 +/- 0.3 mm (PD), and 4.3 +/- 0.6 mm (control). The mean widths of the pars compacta signal in PD, SND, and SDS were significantly narrower than that in the control group (p < 0.05), while the OPCA group was not significantly narrower.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Quantitative in vivo analysis of benzodiazepine binding sites in the human brain using positron emission tomography.

Central-type benzodiazepine binding sites were characterized in a single normal human subject, using positron emission tomography (PET) and the radiolabelled benzodiazepine antagonist, carbon-11 labelled flumazenil ([11C] Ro 15-1788). The subject was scanned using tracer alone and tracer plus 4 different concentrations of unlabelled Ro 15-1788, including one concentration of unlabelled Ro 15-1788, chosen to produce maximum displacement of [11C] Ro 15-1788 from specific binding sites. Concentrations of free, unmetabolized [11C] Ro 15-1788 in plasma were estimated using a simple extraction and ultrafiltration method. Radioactivity in the regional exchangeable pool in brain was estimated under non-saturation conditions from the ratio of radioactivity in brain to plasma, under saturation conditions and the kinetics of free ligand in plasma. The specific binding was, then, estimated by the difference between the total radioactivity in brain and exchangeable pool radioactivity. Scatchard analyses were performed to yield Bmax and Kd values under pseudo-equilibrium conditions, which was observed as an increase of specific binding/free with reduction in specific binding. In cerebral cortex and cerebellum, the Bmax values were about 62-73 nmol/l and the Kd values were 3.6-6 nM in the estimation of free ligand in plasma and 12-15 nM in the estimation of exchangeable pool in brain, as free in brain.

Adult↗
PubMed1991

[Effect of aging on in vivo binding of 11C-N-methylspiperone in living human frontal cortex].

Reduced in vivo binding of 11C-N-methylspiperone (NMSP) with age in the living human frontal cortex was demonstrated, with positron emission tomography (PET). Eleven normal male volunteers (22 to 72 years old) were assessed. The uptake of 11C-NMSP in the frontal cortex peaked 7-15 min after intravenous injection, and then gradually decreased until the end of this study. On the other hand in the cerebellum, the uptake of 11C-NMSP peaked 10 min and rapidly declined. We analyzed the data using a three compartment model and determined rate constants k3 and k4. And the binding potential of receptors was estimated as the ratio of k3 (association rate constant) to k4 (dissociation rate constant) value. The k3 and k4 values were calculated from nonlinear regression, given by the set of parameter values that minimized the deviation between the measured kinetics and model prediction. As an input function, we used the radioactivity in the cerebellum. A significant reduction in BP with age was observed. Though both k3 and k4 values were decreased with age, this decrease of BP was found to be mainly due to the reduced k3 values. These results indicated that numbers of binding sites (Bmax) of serotonin S2 receptors in frontal cortex might be decreased with age.

Adult↗
PubMed1991

[MRI in Parkinson's disease and vascular parkinsonism--study on the lesion of substantia nigra].

We examined the magnetic resonance (MR) image of midbrain and striatum in 30 patients with Parkinson's disease (PD), 10 patients with vascular parkinsonism (VP) and 10 age-matched control subjects. Studies were performed on a high field strength (1.5 tesla) MRI unit. T2 weighted spin echo pulse sequence (TR2500ms/TE40ms) was used. We measured the width of the pars compacta signal in patients and controls on the basis of the method described by Duguid et al. Intensity profiles of a straight line perpendicular to the pars compacta through the center of the red nucleus were made on an image of the midbrain. We measured the width of the valley at half-height between the peaks of intensity representing the red nucleus and the crus cerebri-pars reticulata complex and used this as an index of the width of the pars compacta signal. The results were as follows: 1. The mean width of the pars compacta signal was 2.7 mm (SD = 0.3) in the PD group and 4.3 mm (SD = 0.6) in controls. The difference between the means was highly significant (p less than 0.01). While not significant statistically, there was a trend toward narrowing of the width of pars compacta signal of substantia nigra in the PD group as the Yahr's grade or disease duration progressed. In hemiparkinsonism, MRI revealed significant narrowing of the pars compacta signal on the contra-lateral side to the clinical predominant side compared with the ipsi-lateral side. 2. The mean width of the pars compacta signal was 3.9 mm (SD = 0.4) in the VP group, but the decrease was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Detection of benzodiazepine receptor occupancy in the human brain by positron emission tomography.

Benzodiazepine receptor occupancy in the brain following oral administration of clonazepam (CZP) with a dose of 30 micrograms/kg in six healthy young men and a further dose of 50 micrograms/kg in one of the subjects was estimated by carbon-11 labeled Ro15-1788 and positron emission tomography (PET). The effects of CZP on the latency of auditory event-related potentials (P300) were also studied. Overall brain 11C uptake was depressed and the % inhibition of 11C uptake in the gray matter of the brain at 30 min after [11C]Ro15-1788 injection was 15.3-23.5% (mean, n = 6) following 30 micrograms/kg CZP when compared with that in the control experiment without any previous treatment. The 11C uptake in the cerebral cortex in the subject who received both doses decreased in a dose-related manner after 30 micrograms/kg and 50 micrograms/kg CZP. The P300 latency was prolonged significantly by 30 micrograms/kg CZP [31.6 +/- 16.3 ms (mean +/- SD, n = 6), P less than 0.05]. The P300 latency in the same subject was prolonged in a dose-related manner by 30 micrograms/kg and 50 micrograms/kg CZP. The technique using [11C]Ro15-1788 and PET permits comparison of the pharmacological effects with the percentage of receptor sites which benzodiazepines occupy in the human brain. P300 also seems to be useful to investigate the pharmacological effects of benzodiazepines.

Adult↗
PubMed1989

[Age-related decrease of 11C-N-methylspiperone in vivo binding to human striatum detected by PET].

The effect of aging on 11C-N-methylspiperone binding to living human striatum was demonstrated using positron emission tomography. The 11 normal volunteers (22 to 72 years old) participated in this study. The uptake of 11C-N-methylspiperone in the brain following intravenous injection was highest in the striatum in individual subject. And the uptake in the striatum only gradually increased until the end of the study. The uptake of 11C-N-methylspiperone in cerebellum peaked within 10 minutes following injection and then rapidly dropped. The association rate constant "k3" was calculated from the slope of the radioactivity-ratio of striatum to cerebellum versus the equivalent time. The equivalent time was calculated from the radioactivity of cerebellum as an input function. The exponential decrease of the k3 value with aging was observed. The k3 value of the youngest subject (22 years old, male) was 0.035/min, while that of the oldest one (72 years old, male) was found to be 0.020/min. These data suggested that the dopaminergic activity through D2 dopamine receptors reduces with aging in human striatum.

Adult↗