Amplitude difference between pattern-evoked potentials after left and right hemifield stimulation in normal subjects.

The amplitude of visual evoked potentials (VEPs) to pattern hemifield stimulation was measured in 14 normal right-handed subjects. The paired t test was used to determine if the values differed between right and left hemifield stimulation. The amplitude of transient VEPs from a midoccipital electrode and a lateral occipital electrode ipsilateral to the hemifield stimulated was significantly greater with right hemifield stimulation. This result is compatible with neuroanatomic asymmetries of human striate cortex. Amplitude distribution over the scalp was markedly different between transient and steady-state VEPs that probably reflect activities of different populations of cortical neurons.

Development of large platelet aggregates from small aggregates as determined by laser-light scattering: effects of aggregant concentration and antiplatelet medication.

Particle-counting methods that employ light scattering (LS) quantify changes in the number of platelet aggregates of different sizes after the application of an aggregating stimulus. Using the LS method, we studied the effects of aggregant concentration, aspirin administration, and ticlopidine administration on aggregate formation and compared the results with those obtained using the conventional optical density (OD) method. Subjects were 47 controls, 31 patients treated with aspirin (330 mg/day), and 37 patients treated with ticlopidine (200 mg/day). Platelet aggregation after stimulation by 0.5, 1.0 or 5.0 muM ADP, or 0.5, 1.0 or 2.0 micrograms/ml collagen was determined using both methods. Using the LS method, small (9-25 micrograms), medium (25-50 micrograms), and large (50-70 micrograms) aggregates were counted. In patients untreated with antiplatelet medication, greater concentrations of ADP or collagen generated larger aggregates. Generation of small and medium-sized aggregates showed a significant positive correlation with OD levels after stimulation with 0.5 or 1.0 muM ADP, or 0.5 or 1.0 micrograms/ml collagen. In patients treated with aspirin, the development of small aggregates into large aggregates was inhibited. Thus, the number of small aggregates increased. Inhibition induced by aspirin was more effective against aggregation after stimulation with collagen than with ADP. In patients treated with ticlopidine, small and medium-sized aggregate formation was inhibited after stimulation with low concentrations of ADP or collagen, but was promoted after stimulation with high aggregant concentrations. The capability of the LS method to quantify different sizes of aggregates after stimulation with low concentration agonists may facilitate investigation of the aggregation process, and of how this process is affected by antiplatelet agents.

Decrease with age in methylcytosines in the promoter region of receptor for advanced glycated end products (RAGE) gene in autopsy human cortex.

Changes with age in the methylation status of cytosines in the promoter region of the receptor for advanced glycated end products (RAGE) in autopsy human cortex were investigated, using the bisulfite method, polymerase chain reaction (PCR), and direct sequencing of PCR products. The total number of methylcytosines significantly decreased with age. While the number of methylated cytosines at CpG dinucleotides was stable throughout adult life, that at sites other than CpG dinucleotides significantly decreased with age in cases >/=70 years old. Of 13 transcription factor binding sites, cytosines in CpG doublets in NF-IL6 and SP-1 binding sites were methylated in all cases, suggesting that these sites are repressed throughout adulthood. In contrast, the number of methylcytosines in AP-2 or SP-1 binding sites located at CpC, CpA, or CTG was significantly lower or at least tended to be lower in cases >/=70 years than <70 years old. These reductions in the number of methylcytosines at transcription factor binding sites may increase expression of RAGE, which may in turn play a role in aging of the brain.

Reduction with age in methylcytosine in the promoter region -224 approximately -101 of the amyloid precursor protein gene in autopsy human cortex.

Methylation status of cytosines and its changes with age in the promoter region (-226 approximately -101) of the amyloid precursor protein (APP) was analyzed using bisulfite genomic sequencing in the cerebral cortex of human autopsy brain. Cytosines at 13 locations were methylated in at least one of the cases studied. Methylcytosines at these locations was more frequent in cases 70 years old (8%) (p<0.05). Cytosines at -207, -204, -200, and -182 are frequently methylated, and the frequency of methylcytosine in these locations was significantly higher in cases 70 years old (5%) (p<0.01). These cytosines constituted one of the 9-bp-long GC-rich elements (GGGCGC G/A GG) or an 11-bp inverted repeat (GGCCGT CGGCC). The present findings indicate that some cytosines, particularly those at -207 approximately -182, in the promoter region of the APP gene are frequently methylated and suggest that their demethylation with age may have some significance in the development of Abeta deposition in the aged brain. The relative importance of these elements in the total promoter activity of the APP gene remains to be definitively established.

Clinicopathologic study of progressive subcortical vascular encephalopathy (Binswanger type) in the elderly.

A clinicopathologic study was made of 45 elderly persons whose autopsied brains showed the pathologic changes of progressive subcortical vascular encephalopathy (Binswanger type). Progressive subcortical vascular encephalopathy (PSVE) was observed in 3.8 per cent of all autopsied brains of elderly persons and in 6.7 per cent of the brains of those with cerebrovascular diseases. White matter lesions were graded from I to III (slight to severe). Small infarcts in the basal ganglia, thalamus, and pons were common, but the cerebral cortex was usually preserved. Neuropsychiatric symptoms included dementia, urinary incontinence, hemiplegia, pseudobulbar palsy, psychosis, parkinsonism, and mutism. In thge Grade III group there was a high incidence of pseudobulbar palsy, parkinsonism, and mutism. Pathologic study showed marked cerebral arteriosclerosis in almost all cases. Angionecrosis was observed in 60 to 80 per cent. Fibrotic and stenotic changes of the blood vessels in the deep white matter were also noted, particularly in 90 per cent of the Grade III cases. A suggested explanation for the pathogenesis of PSVE is based on the effects of various complications such as hypertension, cardiac disease and malnutrition which may play an important role in PSVE when they occur in elderly persons with a history of long-standing hypertension, marked cerebral arteriosclerosis, and arteriolar changes in the cerebral white matter.

Increased expression of alpha7 nAChR after transient hypoxia in PC12 cells.

We examined the effects of transient (6 h) hypoxia on nicotinic acetylcholine receptor (nAChR) subunit alpha7 expression in cultured PC12 cells, using RT-PCR and cytochemistry for alpha-bungarotoxin (alphaBTX) binding sites. The relative amount of alpha7 subunit mRNA compared with that before hypoxia decreased to 84% immediately after hypoxia, but then began to increase at 6 h after hypoxia, reaching 171% at 12 h. After this point, it decreased again to 81% at 48 h. Until 6 h after hypoxia, cells appeared to shorten their neurites and form aggregates, without any accompanying remarkable change in alphaBTX binding sites compared with before hypoxia. However, at 12 h and 24 h after hypoxia, alphaBTX binding sites remarkably increased, whereafter cells resumed outgrowth of their neurites at 24-48 h. These findings suggested that nAChR subunit alpha7 was upregulated in both mRNA and protein levels in response to transient hypoxia/reoxygenation in PC12 cells.

Effects of age on messenger RNA expression of glucocorticoid, thyroid hormone, androgen, and estrogen receptors in postmortem human hippocampus.

We studied messenger RNA (mRNA) expressions of receptors for glucocorticoid (GR), thyroid hormone (TR), androgen (AR), and estrogen (ER) and their changes with age in the hippocampal subregions in postmortem human brain. In situ hybridization was done with biotin-labeled antisense synthetic oligonucleotide probes. About 80% or more of the pyramidal neurons in the hippocampal subregions expressed mRNAs for individual receptors in the brains of subjects younger than 65. The ratio of mRNA-containing neuron density to total neuron density significantly decreased with age for GR in CA1 and CA3, and for AR in CA1. Non-significant trends in the reduction with age in the ratio of ER mRNA-containing neurons in CA1 and the ratio of GR mRNA-containing neurons in the hilus also were found. Age-related reductions in nuclear receptor protein mRNA expression in neurons in the hippocampal subfields may be important in the impairments of cognition, emotion, and responses to acute stress in the aged.

Alterations with aging and ischemia in nicotinic acetylcholine receptor subunits alpha4 and beta2 messenger RNA expression in postmortem human putamen. Implications for susceptibility to parkinsonism.

Nicotine activates the dopaminergic system and acts to alleviate hypokinetic disorders (parkinsonism). The frequency of parkinsonism increases with age and is sometimes associated with multiple small infarcts (status lacunaris) in the putamen. To investigate changes with aging in control cases free from neurological disease and changes in cases with multiple small infarcts (status lacunaris) in the putamen, the present study determined nicotinic acetylcholine receptor (nAChR) subunit alpha4 and beta2 messenger RNA (mRNA) expression in the postmortem human putamen using the reverse transcription-polymerase chain reaction (RT-PCR). In controls, alpha4 subunit mRNA expression was unaltered, but beta2 subunit mRNA expression decreased significantly with age. In cases with status lacunaris, both beta2 and alpha4 subunit mRNA expressions were significantly lower than in the control cases. The reduction in beta2 mRNA expression alone, or in both alpha4 and beta2 mRNA expressions, suggests a reduction in functional nAChRs in the putamen, which may in part explain the susceptibility to hypokinetic disorders of the elderly and subjects with ischemic damage in the striatum.

Reduction in the ratio of beta-preprotachykinin to preproenkephalin messenger RNA expression in postmortem human putamen during aging and in patients with status lacunaris. Implications for the susceptibility to parkinsonism.

Gamma-aminobutyric acid (GABA)/substance P (SP) neurons and GABA/enkephalin (Enk) neurons in the striatum exert opposing influence on the regulation of movement. The loss of GABA/SP neurons results in hypokinetic disorders (parkinsonism), whereas the loss of GABA/Enk neurons results in hyperkinetic disorders (e.g. chorea). The present study determined age-related changes in the beta-preprotachykinin (the precursor of SP) and preproenkaphalin (the precursor of Enk) messenger RNA (mRNA) ratio in the postmortem human putamen using the reverse transcription-polymerase chain reaction (RT-PCR). The ratio of beta-preprotachykinin to preproenkephalin mRNA expression decreased with age. The reduction in the beta-preprotachykinin/preproenkephalin mRNA ratio was more marked in cases with multiple small infarcts (status lacunaris) in the putamen. These findings may in part explain the susceptibility of the elderly, particularly of those with ischemic changes in the striatum to hypokinetic disorders.

Parkinsonism and dementia with acoustic neurinomas. Report of three cases.

Three cases of acoustic neurinoma with parkinsonism and dementia are reported. The characteristics of parkinsonism seen in these cases consisted of the rapid development of symptoms and symmetrical rigidity. In all cases there was a marked enlargement of the ventricular system and transient improvement in their mental states was observed following ventriculoperitoneal shunt or removal of the tumor. In an autopsy case there were no pathological findings in the cerebral cortex, basal ganglia, substantia nigra or pontine nuclei. It was concluded that parkinsonism and dementia in these patients were caused by chronic hydrocephalus due to the acoustic neurinomas.

Measurement of blood pressure and heart-rate variation while resting supine and standing for the evaluation of autonomic dysfunction.

Blood pressure and R-R interval variation were studied during postural changes using a tilting table. The subjects were 64 normal controls and 52 patients with various disorders. None of the normal controls showed postural falls of more than 15 mm Hg in mean blood pressure. The mean loge coefficient of variation of 100 R-R intervals was significantly reduced in groups with Parkinson's disease, spinocerebellar degeneration, Shy-Drager syndrome and diabetes mellitus, compared with a normal control group. Reduced heart-rate variation was frequently associated with sphincter disturbance and orthostatic hypotension.

Epilepsia partialis continua: active cortical spike discharges and high cerebral blood flow in the motor cortex and enhanced transcortical long loop reflex.

We report a patient suffering from persistent myoclonic jerks in the right forearm without any definite EEG abnormality under routine recording conditions. By computer summation, using the jerk-locked averaging technique, a sharp spike was recognized as a precisely time-locked event in relation to myoclonic twitches. A cranial CT scan revealed a small cortical lesion, which was found very close to the sensorimotor cortex of the right arm. Cerebral blood flow study using the xenon inhalation method revealed a discrete focus of high flow, which corresponded well with the CT lesion. On electrical stimulation of the right median nerve, a large somatosensory evoked potential and an enhanced transcortical long loop reflex were observed. Electrocorticogram showed active focal spike discharges localized at the left precentral gyrus. We postulate that an epileptogenic focus in the motor cortex and an enhanced transcortical long loop reflex appear to be important for the occurrence of epilepsia partialis continua in this patient.

Frequency and urgency of micturition in hemiplegic patients: relationship to hemisphere laterality of lesions.

To determine the individual contribution of the right and left cerebral hemispheres to micturition control, a clinical analysis was performed concerning frequency and urgency of micturition in 134 chronic hemiplegic patients. A mean frequency of urination, 9 times or more in 24h, was found more frequently in left than right hemiplegics. Left hemiplegics also complained more often of urgency than did right hemiplegics. A mean frequency of urination of 9 times or more in 24h and urgency co-existed more frequently in left hemiplegics than in right hemiplegics. In the present study, dealing with the chronic sequelae of stroke, frequency and urgency of micturition were found more commonly in patients with right hemisphere than left hemisphere lesions.

Cerebral perfusion patterns in vascular dementia of Binswanger type compared with senile dementia of Alzheimer type: a SPECT study.

Cerebral perfusion patterns in 18 cases with vascular dementia of Binswanger type (VDBT) (8 moderate and 10 severe cases) were compared with 25 cases with senile dementia of Alzheimer type (SDAT) (16 moderate and 9 severe cases) and 14 controls by single photon emission computed tomography using N-isopropyl-p-123I iodoamphetamine (IMP) as a tracer. The cerebral: cerebellar IMP uptake ratio (%) (CCR) was used as a measured of relative cerebral perfusion. The CCRs were about 85-90% in all areas in controls. Moderate VDBT patients showed a remarkable decrease of CCRs in the basal grey region (thalamus and basal ganglia) (right 79%, left 77%) and in the frontal area (right 79%, left 80%) (P less than 0.01). In severe VDBT patients a significant decrease of the CCR was noted in all regions (P less than 0.01). The decrease of mean CCRs in the hemispheres was significantly correlated with the severity of disease determined by psychometric testing. Patients with SDAT showed a significant decrease of the CCR in the parietal (right 71%, left 74%) and right temporal (78%) areas in the moderate stage (P less than 0.01), and further progression of dementia was associated with low perfusion areas extending to the the frontal areas (78%, P less than 0.01). These differences in the perfusion patterns and their changes with progression of the illnesses may be reflected in characteristic clinical features.

Dissociated nystagmus in a comatose patient. A clinicopathological study.

Electro-oculographic recordings of dissociated vertical (oblique and upbeat) nystagmus were carried out in a patient in coma due to vascular lesions. Based on the clinical and neuropathological findings, it was suggested that dissociated vertical (oblique and upbeat) nystagmus in a patient in coma can be caused by bilateral lesions in the brachium pontis.

A comparison between the computed tomogram and the neuropathological findings in cerebrovascular disease.

The findings on computed tomography (CT) and neuropathological examinations were correlated in 87 autopsied cases of cerebrovascular disease with regard to the seize and location of lesions, experience of reviewers, and improvement in CT quality. Small infarctions less than 5 mm were very difficult to detect accurately on CT. This was largely because of the limitations in the efficiency of the CT scanner. Accurate diagnosis of medium sized infarctions was also often difficult. This was mainly due to the anatomical location of lesions, the confluence of deep and widened sulci, periventricular white matter, and structures in the posterior fossa. Large infections could be visualized easily on CT, except in their early periods or in cases with hemorrhagic infarctions. The improved accuracy of CT diagnosis for small and medium sized infarctions could not be attained by the experience of reviewers, but was only possible by instrumental improvement of CT quality.

Prosopagnosia without topographagnosia and object agnosia associated with a lesion confined to the right occipitotemporal region.

A patient is presented who developed prosopagnosia with a recent occipitotemporal infarct in the distribution of the right posterior cerebral artery. He did not have topographical agnosia or object agnosia. He regained the ability to recognize faces of familiar persons, whereas he remained unable to identify faces of persons whom he met after the disease onset. This case demonstrates that prosopagnosia may occur as a deficit of matching a perceived face to a memory store of the face, and that the failure to recognize unfamiliar faces may be due to the inability to form memory stores of new faces. These deficits can occur in association with a lesion confined to the right occipitotemporal region.

Hypoxia-induced expression of C1q, a subcomponent of the complement system, in cultured rat PC12 cells.

This study investigated the effect of exposure to hypoxia on the expression of C1q mRNA and protein in cultured PC12 cells. PC12 cells expressed neither C1q mRNA nor protein before hypoxia. However, the cells expressed C1q mRNA immediately after hypoxia, and then A, B, and C chains of C1q and higher molecular weight C1q proteins during reoxygenation. Under the same experimental conditions, cell membrane disintegration began during hypoxia, whereas DNA fragmentation initiated during reoxygenation later than C1q protein expression. These results suggest that in response to hypoxia, PC12 cells per se express C1q mRNA and protein in the early phase before initiation of DNA fragmentation in the absence of any influence of other cellular components. These findings may be relevant for the pathogenesis and treatment of stroke.

Protective effect of nicotine through nicotinic acetylcholine receptor alpha 7 on hypoxia-induced membrane disintegration and DNA fragmentation of cultured PC12 cells.

To investigate the effect of nicotine on hypoxic neuronal damage, cultured PC12 cells were exposed to hypoxia for 9 h and then reoxygenated for 72 h. The cells were stained by propidium iodide (PI), a marker of cell membrane disintegration and the TUNEL method, which indicates DNA fragmentation. In control cultures, the ratio of PI-positive cells to total cells progressively increased during and after exposure to hypoxia, constituting 39% of total cells at 72 h posthypoxia. This increase in PI-positive cells was completely inhibited by nicotine until 12 h posthypoxia, and was partially and dose-dependently inhibited thereafter. The ratio of TUNEL-positive cells to total cells started to increase at 24 h posthypoxia and reached 36% at 72 h in control cultures. This ratio was also dose-dependently inhibited by nicotine. These inhibitory effects of nicotine on the increase in PI-positive and TUNEL-positive cells were abolished by the addition to the medium of alpha-bungarotoxin, an antagonistic ligand for nicotinic acetylcholine receptor (AChR) alpha7. These findings suggest that nicotine inhibits, through AChR alpha7, hypoxia-induced cell membrane disintegration and DNA fragmentation of cultured PC12 cells exposed to hypoxia.

A selective reduction of excitatory amino acids in cerebrospinal fluid of patients with Alzheimer type dementia compared with vascular dementia of the Binswanger type.

We determined the concentrations of the putative transmitter amino acids in the cerebrospinal fluid of patients with Alzheimer type dementia (ATD) and vascular dementia of the Binswanger type (VDBT). In ATD, aspartate and glutamate concentrations were significantly and selectively reduced, while in VDBT, concentrations of aspartate, glutamate, gamma-aminobutyric acid (GABA) and many other amino acids were decreased non-selectively. In both ATD and VDBT, we found a tendency for all amino acids to increase with progression of the disease, and this reached statistical significance for some amino acids.