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Electroencephalography (EEG) coherence provides a measure of functional correlations between two EEG signals. The present study was conducted to examine intrahemispheric EEG coherence at rest and during photic stimulation (PS; 5, 10 and 15 Hz) in ten unmedicated patients with presenile dementia of the Alzheimer type (AD; mean age at onset 56 years). In the resting EEG, the AD patients had significantly lower coherence than gender- and age-matched control subjects in the alpha-1, alpha-2 and beta-1 frequency bands. The EEG analysis during PS also showed that the patients had significantly lower coherence in the frequency corresponding to PS at 10 and 15 Hz. In this study, the changes in coherence from the resting state to the stimulus condition (i.e. PS-related coherence reactivity) were examined. The patients were found to show significantly smaller coherence reactivity to PS at 5 and 15 Hz. These findings suggest that, in addition to the resting state, AD patients have an impairment of intrahemispheric functional connectivity during PS. They also suggest that AD shows a failure of PS-related functional reorganization.

EEG coherence provides a measure of functional correlations between two EEG signals. The present study was conducted to examine intrahemispheric EEG coherence at rest and during photic stimulation (PS) in 18 drug-naive patients with paranoid schizophrenia and 30 control subjects. Compared with the controls, the schizophrenic patients had significantly higher intrahemispheric coherence of the resting EEG for the delta band, although no significant group differences were found for other frequency bands. EEG analysis during PS showed that the patients also had significantly higher EEG coherence over the left posterior regions. In this study, we also examined the changes in intrahemispheric coherence from rest to the stimulus condition (i.e., PS-related coherence reactivity); the patients were found to show significantly smaller changes, with significant group differences being also confined to the posterior regions in the left hemisphere. These findings provide evidence that schizophrenic patients have abnormal EEG coherence in both resting and stimulus conditions and suggest more diffuse, undifferentiated functional organization within hemispheres. In addition, diminished coherence reactivity suggests a failure of PS-related functional reorganization in schizophrenia.

A 36-year-old Japanese woman presented with progressive cerebellar signs and mental deterioration of subacute course after her return from the USA. Her serum antibody to spirochete Borrelia burgdorferi was significantly elevated. A necropsy 4 years after her initial neurological signs revealed multifocal inflammatory change in the cerebral cortex, thalamus, superior colliculus, dentate nucleus, inferior olivary nucleus and spinal cord. The lesions showed spongiform change, neuronal cell loss, astrocytosis and proliferation of activated microglial cells. The internal capsule was partially vacuolated and the spinal cord, notably at the thoracic level, was demyelinated and cavitated in the lateral funiculus. Microglial cells aggregated within and around the spongiform lesions and microglial nodules were present in the medulla oblongata. Use of Warthin-Starry stain demonstrated silver-impregnated organisms strongly suggesting B. burgdorferi in the central nervous tissues. The dentate nucleus and inferior olivary nucleus showed the most advanced lesions with profound fibrillary gliosis. Occlusive vascular change was relatively mild, and fibrous thickening of the leptomeninges with lymphocyte infiltrates was localized in the basal midbrain. The ataxic symptoms were due to the dentate and olivary nucleus lesions and mental deterioration was attributable to the cortical and thalamic lesions. Spongiform change, neuronal cell loss, and microglial activation are characteristic pathological features in the present case. The cerebellar ataxia and subsequent mental deterioration are unusual clinical features of Lyme neuroborreliosis. Spirochete B. burgdorferi can cause focal inflammatory parenchymal change in the central nervous tissues and the present case may be an encephalitic form of Lyme neuroborreliosis.

Twenty-five schizophrenic patients diagnosed by DSM-III-R underwent event-related potentials and magnetic resonance imaging scans. Latency and amplitude of P300 waveform were measured using an auditory odd-ball paradigm. Anterior and posterior volumes of the superior temporal gyrus and medial temporal structure were measured from contiguous coronal images using the level of the mammillary body as an anatomical landmark. Principal component analysis of P300 latency and amplitude disclosed two orthogonal independent factors each: overall latency and residual, and amplitudes from posterior and anterior recordings, respectively. Structural volumes consisted of four orthogonally independent factors: left superior temporal volume, anterior medial temporal volume, right superior temporal volume, and posterior medial temporal volume. The factor score of the P300 amplitude from posterior recordings correlated with the factor score of volumetric changes in the anterior medial temporal structures. The present study failed to replicate a previously reported association between auditory P300 amplitude and superior temporal volume. Furthermore, the factor score of the P300 amplitude was correlated with the severity of clinical ratings of attentional impairments and positive thought disorder. These findings demonstrate that the information processing dysfunction of schizophrenia indicated by reduced P300 amplitude is associated with structural abnormality in the medial temporal lobe.

SPECT imaging brain perfusion using 99mTc-HMPAO was performed on a 38-yr-old women with Lyme neuroborreliosis confirmed by autopsy. The patient had been suspected of spinocerebellar degeneration. Cerebral blood flow was diffusely decreased throughout cerebral cortices but cerebellar blood flow was not impaired, which indicated that the diagnosis was unlikely spinocerebellar degeneration. These findings suggested that brain perfusion SPECT provides useful information in diagnosing the patients with Lyme neuroborreliosis, especially when spinocerebellar degeneration is included in the differential diagnosis.

This study assessed the action of the serotonin3 (5-HT3) receptor agonist, 1-(m-chlorophenyl)-biguanide (m-CPBG), against both kindled seizures and kindling development from the rat amygdala (AM). The intracerebroventricular (i.c.v.) administration of 40 microg m-CPBG significantly increased the duration of afterdischarge and bilateral forelimb clonus of generalized kindled seizures. In addition, daily i.c.v. treatment with m-CPBG at the same dose prior to each electrical stimulation to the AM significantly facilitated behavioral and electrographic seizure development and reduced the number of stimulations needed to elicit generalized seizures. The present results indicate that m-CPBG increases the duration of fully kindled seizures and facilitates the developmental seizure process, suggesting an excitatory role of 5-HT3 receptors in the kindling model of epilepsy.

It has been reported that the clinical and electroencephalographic profiles of zolpidem, a non-benzodiazepine drug which binds preferentially to the omega 1 benzodiazepine recognition sites located within the GABAA receptor complex, are different from those of benzodiazepine drugs, which bind non-selectively to the omega 1 and omega 2 sites. In order to clarify the electrophysiological mechanism underlying the unique profile of zolpidem, the present study compared the enhancing effects of zolpidem and two benzodiazepine drugs, triazolam and diazepam, on recurrent inhibition. This inhibition was expressed as suppression of the orthodromically induced population spikes by the preceding antidromic stimulation of the alveus in the CA1 region of rat hippocampal slices. The rank order of potency for enhancing recurrent inhibition was triazolam > diazepam > zolpidem. From the present results and previously reported findings that zolpidem has a lower affinity for the omega 2 sites than diazepam while both have the same affinity for the omega 1 sites, we concluded that the hippocampal recurrent inhibition appears to be enhanced mainly by activation of the omega 2 sites, but not by that of the omega 1 sites. Furthermore, the lower potency of zolpidem for enhancing recurrent inhibition may underlie its unique profile in terms of its clinical and electroencephalographic effects.

A 36-year-old woman who had been in complete remission after bone marrow transplantation against her leukemia presented with visual disturbance and cerebellar signs. She showed unusual involuntary movement as if she rolled a ball of string, and died two months after the onset of illness. Necropsy revealed hemorrhagic and necrotic lesions in the thalamus, basal ganglia, cerebellar dentate nucleus, superior colliculus, midbrain pretectum and red nucleus, and mucor mycelia were numerously found. HSV-2 immunoreactivity was found in both astroglial and oligodendroglial perikaraya. These hemorrhagic-necrotic lesions were partly associated with HSV-2 infection, but it was difficult to discriminate those from mucormycotic lesions. The unusual involuntary movement was considered to be due to basal ganglia lesions. This case was double infection by mucor mycelia and HSV 2, and clinicopathological consideration was described.

A gene encoding rubredoxin from Desulfovibrio vulgaris (Miyazaki F) was cloned and overexpressed in Escherichia coli. A 1.1-kilobase pair DNA fragment, isolated from D. vulgaris (Miyazaki F) by double digestion with SmaI and SalI, contained two genes, the rubredoxin gene (rub) and the desulfoferrodoxin gene (rbo) which was situated upstream of rub. The deduced amino acid sequence of desulfoferrodoxin was homologous to those from other strains and Cys residues that are responsible to bind irons were also conserved. The expression system for rub was constructed under the control of the T7 promoter in E. coli. The purified protein was soluble and had a characteristic visible absorption spectrum. Inductively coupled plasma-atomic emission analysis and electron paramagnetic resonance analysis of the recombinant rubredoxin revealed the presence of an iron ion in a distorted tetrahedral geometry that was the same as native D. vulgaris rubredoxin. In vitro NADH reduction analysis indicated that recombinant rubredoxin was active, and its redox potential was determined as -5 mV.

Topographic analysis of the resting EEG was performed in nine patients with presenile Alzheimer's disease(AD) and nine sex- and age-matched normal subjects. We also analyzed EEG activity recorded during photic stimulation(5, 10 and 15 Hz) to evaluate photic driving responses. The square root of absolute power was determined for each frequency band using a Fast Fourier Transform. Compared with the controls, the AD patients had increased delta and theta in the resting EEG mainly over the frontal regions. The patients also had reduced alpha and beta, and did not show posterior predominance of alpha activity. EEG analysis during photic stimulation showed that the patients had a reduction in photic driving responses, and significant topographic differences were found over the parieto-occipital regions. These findings provide further evidence that AD patients have background EEG slowing with a reduction in alpha and fast activity. They also suggest an impairment of visual functioning in AD.

The present study was conducted to identify serotonin (5-HT) receptor subtypes involved in the development of amygdala (AM) kindling. We used 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A agonist, and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2 agonist, both of which were injected subcutaneously 15 min prior to each daily electrical stimulation to the rat AM. Treatment with 8-OH-DPAT (1 mg/kg) slightly suppressed behavioral and electrographic seizure development during the course of kindling. In contrast, DOI (1 mg/kg) strongly facilitated kindling development and reduced the number of stimulations needed to produce generalized seizures. These facilitatory effects of DOI were completely blocked by pretreatment with a 5-HT2 antagonist ketanserin. The present results suggest that the activation of 5-HT1A receptors can retard the development of AM kindling, whereas 5-HT2 receptors play a facilitatory role in this developmental seizure process.

In the present study, quantitative electroencephalographic (EEG) analysis was performed at rest and during photic stimulation (5, 10, and 15 Hz) in nine patients with presenile dementia of the Alzheimer type (AD; mean age at onset, 55 years) and nine sex- and age-matched control subjects. Compared with the normal controls, the AD patients had a significantly lower alpha-2 and beta band power in the resting EEG as well as a significant increase in delta and theta band power. EEG analysis during the photic stimulation demonstrated that the AD patients had a significantly lower EEG power during photic stimulation for the alpha (9.8-10.2 Hz) and beta bands (14.8-15.2 Hz) corresponding to photic stimulation at 10 Hz and 15 Hz, respectively. In addition, when we examined EEG changes from rest to the stimulus condition, the AD patients were found to show significantly smaller changes in EEG power mainly over the posterior regions, irrespective of the stimulus frequency. These findings provide evidence that AD patients have EEG abnormalities in both non-stimulus and stimulus conditions, and suggest diminished EEG reactivity to photic stimulation.

The subject presented with intellectual decline followed by progressive muscle weakness of the bilateral upper limbs when he was 60 years old. He had a point mutation (methionin-valine) at 129 prion protein codon. He died at the age of 63 and necropsy revealed bilateral frontal lobe atrophy. The frontal cortex showed neuronal cell loss in layers II and III with spongiform change. Reusche silver impregnation technique for beta-peptide combined with ubiquitin immunostaining revealed perineuronal structures encircling degenerated neurons and ubiquitin-immunoreactive (IR) dot-like deposits. They were distributed particularly in the temporal neocortex and entorhinal cortex. They differed from either classic senile or diffuse plaque by the absence of amyloid core in the center and of amyloid fibrils. Ubiquitin-IR materials were also found as neuronal inclusions in the hippocampal granular cells. Nigral degeneration and neuronal loss in the hypoglossal nerve nucleus and in the anterior horn of the spinal cord were also found and spinal cord motoneurons had Bunina body inclusions. The clinical features and pathological findings were consistent with non-Alzheimer dementia with status spongiosus and neuronal cell loss. The unusual perineuronal structures found in our case might be a specific cellular pathology of dementia of the frontal lobe type.

Reduced amplitude of the P300 component has been reported consistently in patients with neurological and psychiatric disorders. It is unclear, however, how such patients' cognitive dysfunction is related to their P300 abnormality. Further basic knowledge regarding neural substrates for P300 generation is required for gaining an understanding of the pathological significance of the P300 amplitude reduction. To determine the brain structures involved in P300 generation, we observed the event-related potential and the regional cerebral blood flow (rCBF) in 10 normal subjects performing an oddball discrimination of pure tones. The rCBF value was assessed quantitatively with the aid of single photon emission computed tomography using technetium-99m hexamethylpropylene amine oxime. During the task performance, significant activation was observed in the posterior superior temporal and inferior parietal regions of the right hemisphere. In addition, positive correlation of the task-related increase in rCBF with the simultaneously recorded P300 amplitude was observed in the right but not the left posterior superior temporal region. These findings indicate that activation of the right non-verbal auditory area might modulate P300 generation during pure-tone discrimination.

Regional cerebral blood flow (rCBF) was measured with technetium-99m hexamethylpropyleneamine oxime single photon emission computed tomography in 38 neuroleptic-treated schizophrenic patients. To improve the validity of the evaluation of symptomatology, we applied findings previously derived in a principal component analysis (PCA) of the Positive and Negative Syndrome Scale. The PCA had disclosed five orthogonal independent symptom structures (i.e., negative, hostile/excited, thought disordered, delusional/hallucinatory, and depressive components), and obtained factor scores for 70 schizophrenic subjects, including the present sample. Stepwise regression analysis elucidated some of the cortical regions in which relative rCBF predicted the severity of symptoms--namely, lateral and orbital prefrontal, lateral temporal, inferior parietal, and medial temporal regions. Findings suggested that symptom structures derived from PCA could prove helpful in elucidating the pathophysiology of neural mechanisms.

The present study was conducted to examine sex differences in interhemispheric EEG coherence in 15 male and 15 female healthy young adults. EEG was recorded during rest and photic stimulation (PS) at 5, 10 and 15 Hz using a linked earlobe reference. Interhemispheric coherence of the resting EEG revealed no significant sex-related differences for any frequency band. In contrast, significant sex-related differences were found in EEG coherence during PS; the females had a significantly higher coherence than the males for F3-F4 and C3-C4 in the frequency band (4.5-5.5 Hz) corresponding to 5 Hz PS. In addition, the changes in interhemispheric coherence from rest to the stimulus condition (i.e. PS-related coherence reactivity) showed sex-related differences at the brain region primarily involved in visual functioning; the females had significantly greater coherence reactivity for O1-O2 in EEG during PS at 5 and 15 Hz. These findings indicate sex-related differences in interhemispheric EEG coherence during PS, and support the well-demonstrated evidence that sex differences exist in the degree of lateralization of cerebral function.

The present study was conducted to examine inter- and intrahemispheric EEG coherence in 14 healthy, right-handed adults during wakefulness and light drowsiness as assessed by eye movement and EEG activity. Interhemispheric coherence was significantly lower during light drowsiness than during wakefulness for O1-O2 in the alpha-1 band and for F3-F4 in the beta-1 band. Intrahemispheric EEG coherence was significantly higher during light drowsiness for C4-O2 in the theta-1 and beta-1 bands. These findings indicate that light drowsiness can alter both inter- and intrahemispheric EEG coherence when compared with wakefulness, suggesting that cerebral functional organization changes during light drowsiness. It is important, therefore, to control arousal level of subjects in future studies dealing with the relationship between EEG coherence and various pathological conditions.

Involvement of gamma-aminobutyric acid (GABA)-mediated function in epileptogenesis was studied in rat hippocampal slices, in which repetition of high-frequency electrical stimulation induced afterdischarges (ADs) to create an in vitro model for ictal activity. A GABAA receptor antagonist, bicuculline, fully blocked the ADs. On the other hand, the presence of bicuculline caused single stimuli to evoke short-duration epileptiform bursts, a well-known model for interictal activity. Therefore, we conclude that activation of GABAergic function appears to be necessary for ictal activity, while its dysfunction induces interictal activity, and propose a modification to the simple disinhibition hypothesis for epileptogenesis.

The effects of the histamine precursor, L-histidine, were examined in the rat kindling model of epilepsy. The intraperitoneal (i.p.) administration of 800 mg/kg L-histidine significantly prolonged the latency to the onset of bilateral forelimb clonus of previously kindled seizures from the amygdala (AM), with no significant effect observed in the behavioral seizure stage or afterdischarge duration. In contrast, daily administration of L-histidine at the same dose prior to each electrical stimulation to the AM significantly facilitated both behavioral and electrographic seizure development of kindling. The present results indicate that although L-histidine can suppress secondary generalization of AM-kindled seizures, it possesses a facilitatory effect on the acquisition of kindling epileptogenesis, suggesting a biphasic action of histamine in kindling.

To clarify whether patients with schizophrenia still show EEG slowing in the absence of psychopharmacological treatment, EEG was analyzed in 20 acute never-treated schizophrenics and 20 age-matched healthy controls using the computerized wave-form recognition method. Compared to controls, schizophrenics had more fast theta (6-8 Hz) and slow alpha (8-9 Hz) activity, and less fast alpha activity (9-13 Hz). The average EEG frequency at O1 correlated negatively with total and positive symptom scores on the BPRS in the schizophrenic group. These findings confirm that the frequency of alpha rhythm is slowed in schizophrenia and that this slowing is possibly related to the expression of psychopathology in this disorder.

EEG coherence is a noninvasive technique for studying functional relationships between brain regions. Although EEG coherence would be a useful method to explore the differences in cerebral functional organization between the sexes, sex differences in coherence have not been well documented. The present study was conducted therefore to examine sex differences in interhemispheric EEG coherence during rest and photic stimulation (PS) in 15 male and 15 female healthy young adults. Interhemispheric coherence of the resting EEG revealed no significant sex differences for any frequency band. In contrast, coherence during PS revealed significant sex differences, and the females had a significantly higher coherence than the males in the frequency band (4.5-5.5Hz) corresponding to 5Hz PS. In addition, the changes in interhemispheric coherence from rest to the stimulus condition (i.e., coherence reactivity) showed sex differences at the brain region primarily involved in visual functioning; the females had significantly greater coherence reactivity for O1-O2 in EEG during PS at 5 and 15Hz. These findings indicate sex differences in interhemispheric EEG coherence during PS, and provide further evidence that sex-related differences exist in the degree of lateralization of hemispheric function.

In a patient with acute carbon monoxide (CO) poisoning in whom no delayed sequelae have been observed, MRI was performed serially from the time of exposure. When few clear findings were noted on conventional T2-weighted spin echo (SE) imaging, distinct hyperintense areas in the deep cerebral white matter were already evident on fluid attenuated inversion recovery (FLAIR) pulse imaging. These abnormal findings appeared to reflect a disease process differing from the acute phase disturbance of consciousness, namely the course of a gradually progressive demyelination. Neither serial intelligence tests nor single photon emission CT (SPECT) studies of regional cerebral blood flow conducted in the same period revealed any abnormalities. These results suggest that, in the subclinical phase in which there are few significant findings on T2-weighted SE imaging or SPECT, insidious demyelinating changes are already apparent on FLAIR imaging and that FLAIR imaging may thus be useful in the early diagnosis of the interval form of CO poisoning.

We determined whether endothelin-1 (ET-1) is associated with glucocorticoid-induced Ca2+ influx into vascular smooth muscle cells by examining the effects of the ETA receptor antagonist FR139317 on dexamethasone-induced 45Ca2+ uptake and dihydropyridine binding by rat A7r5 cells. FR139317 inhibited the dexamethasone-induced 45Ca2+ uptake and [methyl-3H]PN 200-110 binding in a dose-dependent manner. Slot blot analysis revealed that dexamethasone increased protein kinase C-alpha in A7r5 cells and that this effect was also abolished by FR139317. Dexamethasone stimulated the release of immunoreactive endothelin-1 from A7r5 cells into the culture medium. These results suggest that endothelin participates in the glucocorticoid-induced Ca2+ influx through dihydropyridine-sensitive channels in an autocrine manner, possibly linked to the activation of protein kinase C-alpha.

We investigated the association between hyperinsulinemia and changes in lipid, lipoprotein, and apolipoprotein that would increase the risk of coronary artery disease (CAD) independent of glucose tolerance. A coronary angiogram was recorded in 127 male subjects, including 41 with normal glucose tolerance, 41 with impaired glucose tolerance, and 45 with non-insulin-dependent diabetes mellitus (NIDDM). Subjects were divided into 2 groups according to results: the group with CAD (n = 94) and the group with normal coronary arteries (n = 33). All subjects were normolipidemic (total cholesterol < 230 mg/dl and triglycerides < 150 mg/dl). The CAD group had a significantly lower plasma level of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I) and a higher level of apolipoprotein B (apo B) than the normal group with normal glucose tolerance. In considering subjects with impaired glucose tolerance or NIDDM, the CAD group had a significantly lower plasma level of HDL cholesterol and apo A-I and a significantly higher plasma level of total cholesterol, triglycerides, and apo B than the normal group. In each of the subjects with normal and impaired glucose tolerance, and NIDDM, the elevation of plasma insulin concentration during both the complete test period and the early phase of an oral glucose challenge was significantly higher in the CAD than in the normal group. In all subjects, graded reductions in HDL cholesterol and apo A-I and graded increases in plasma total cholesterol, triglycerides, and apo B were observed with increasing tertiles of the postglucose challenge measurements of insulinemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Proton magnetic resonance spectroscopy (1H-MRS) was performed in a group of 18 adult patients with Down's syndrome (DS) aged 20-46 years, and the peak area ratios (NAA/Cr, Cho/Cr, NAA/Cho) of N-acetylaspartate (NAA), total creatine (Cr), and choline-containing compounds (Cho) calculated separately in the patients in their 20's, 30's, and 40's. In age-matched healthy control groups, there were no significant age-related changes in any of the peak area ratios. In contrast, in the DS group, although the relative amount of NAA (NAA/Cr) showed no significant change with increasing age, the relative amount of Cho (Cho/Cr and NAA/Cho) was significantly increased in the 40's group. At least as judged by MRI, few age-related general morphological changes such as brain atrophy were apparent in the third, fourth, and fifth decade groups. However, the MRI findings considered together with the age-related changes in the peak area ratios suggest that in DS patients in the fifth decade metabolic abnormalities such as degradation and/or rapid synthesis of brain cell membrane may occur prior to neuronal loss and degeneration.

In Down's syndrome (DS) mental retardation accompanying chromosomal abnormalities is seen, and the incidence of associated congenital heart abnormalities is also known to recent years, the accelerated aging and premature senility associated with DS have attracted attention. In the present study, we examined cardiac lesions using echocardiography in a group of asymptomatic adult DS subjects discussed the relation between these lesions and premature aging. The subjects comprised 28 adult DS patients ranging in age from 20 to 46 years (mean +/- SD, 30.8 +/- 8.9 years) residing in 8 institutions in Fukui prefecture. The presence of DS was confirmed in all cases by chromosomal examination, which revealed 21-trisomy in 25 and mosaic type in three. Of indices of left heart function, the end diastolic volume index (EDVI) and end systolic volume index (ESVI) showed significantly reduced values, whereas indices of systolic function such as the ejection fraction (EF) and mean velocity of circumferential fiber shortening (mean Vcf) showed significantly elevated values. The results of early diastolic left ventricular function, which has been noted to be related to aging, did not show any significant difference as determined by observation of mitral valve dynamics. On the other hand, morphologically, mitral valve prolapse (MVP) was found significantly more frequently in the DS group (17.9%) as compared to a normal control group. Also, valvular calcification (14.3%) and aortic valve regurgitation (AR, 11%) were both frequently noted. Whether signs such as valvular calcification are findings related to accelerated aging will require further study.

Light drowsiness affected the P300 obtained with a standard auditory oddball paradigm. A simple two-tone discrimination paradigm was used. The frequent nontarget stimuli were 1000 Hz pure tones and the infrequent target stimuli were 2000 Hz pure tones. The subjects were required to press a button whenever infrequent target tones were presented. With light drowsiness, P300 increased in latency and decreased in amplitude, but the counts of infrequent tones remained correct nevertheless. It was concluded that electrophysiological brain function differs in the light drowsy and awake states. In studies on P300, it is essential to rule out light drowsiness to obtain valid P300 amplitudes and latencies.

Trace Mn, Fe and Cu in sodium were determined by chemical modification/graphite furnace atomic absorption spectrometry. The sodium sample was changed into NaOH in a desiccator by room temperature water vapor generated under reduced pressure, then the NaOH was dissolved in water and HNO(3) was added to give a clear solution. The solution was analysed by chemical modification/graphite furnace atomic absorption spectrometry. A nickel nitrate modifier was effective in improving integrated absorbance signals and the reproducibility of measurement. Analytical results for Mn, Fe and Cu were 170, 970 and 210 ng/g and relative standard deviations (n = 5) were 3.5, 5.8 and 6.7%, respectively. These results agreed with the values obtained from a chelating resin preconcentration/ICP-AES method.

The production rate of leukotriene B4 (LTB4) was measured using peripheral blood mononuclear cells (PBMC) in patients with fulminant hepatitis (FH) or other liver diseases. LTB4 in the culture media of PBMC under stimulation with Ca-ionophore was fractionated by HPLC and measured by radioimmunoassay. The production rate of LTB4 was elevated in 16 of 17 FH patients (3.3 +/- 0.2 ng/10(6) cells for 5 min), while the production was below detectable level in patients with acute or chronic hepatitis and in healthy controls. In FH patients, the highest production rate of LTB4 was observed in the initial period of the disease. Enhanced LTB4 production may indicate the primed state of PBMC--the primed mononuclear cells are regarded as participating in the development of massive liver necrosis and of other organ failures in FH.

FIRDA was found in 14 EEGs recorded from 338 schizophrenic patients receiving antipsychotic drugs, although they showed no FIRDA in the baseline EEG. The daily dose of antipsychotic drugs when FIRDA was found was larger than when FIRDA disappeared. FIRDA was assumed to be induced by relatively high doses of antipsychotic drugs. Thus, the effect of antipsychotic drugs should be added to the list of differential diagnoses associated with FIRDA. FIRDA did not correlate with the baseline psychopathology of schizophrenic patients. Patients without FIRDA tended to respond poorly to antipsychotic drugs in terms of negative symptoms. Improvement of positive symptoms in FIRDA patients was not as remarkable as in patients without FIRDA.

Glomerular injury caused by injection of heterologous anti-glomerular basement membrane antibodies (anti-GBM Ab) is increased in rats pretreated with small doses of bacterial lipopolysaccharide (LPS). We have investigated the involvement of tumour necrosis factor-alpha (TNF-alpha), IL-1 alpha and IL-1 beta in this phenomenon by passive immunization against these cytokines. Anti-TNF-alpha or anti-IL-1 beta antibodies given 1.5 h before the induction of nephritis significantly decreased injury in this model, whether assessed by the magnitude of albuminuria, the prevalence of glomerular capillary thrombi or the intensity of glomerular neutrophil infiltrate. Albuminuria in anti-GBM Ab alone was 11 +/- 3, LPS/anti-GBM Ab 87 +/- 22, and anti-TNF-alpha antibodies/LPS/anti-GBM Ab 21 +/- 6 mg/24 h (mean +/- s.e.) P < 0.05. Passive immunization with antibodies to IL-1 beta had a similar effect (anti-GBM Ab, 0.6 +/- 0.1, LPS/anti-GBM Ab, 92 +/- 19, anti-IL-1 beta antibodies/LPS/anti-GBM Ab 39 +/- 8 mg/24 h, P < 0.05). The prevalence of glomerular capillary thrombi was also reduced significantly by these treatments; from 22 +/- 5% to 4 +/- 1% in the case of anti-TNF-alpha antibodies and 28 +/- 5% to 13 +/- 4% with anti-IL-1 beta antibodies. Similarly, the glomerular neutrophil infiltrate was also reduced by these treatments; from 42 +/- 3 to 25 +/- 1 in the case of anti-TNF-alpha and 47 +/- 2 to 30 +/- 1 with anti-IL-1 beta antibodies. In contrast, passive immunization against IL-1 alpha had no effect on either albumin excretion (4 +/- 3, 83 +/- 22 and 77 +/- 24 mg/24 h), glomerular capillary thrombi (2 +/- 1; 19 +/- 5 and 16 +/- 3) or glomerular neutrophil infiltrate (22 +/- 3; 47 +/- 5 and 48 +/- 5 from the three groups respectively). These results demonstrate that enhanced antibody mediated injury in the kidney is modulated by TNF-alpha and IL-1 beta but not by IL-1 alpha.

To clarify whether protein kinase is associated with glucocorticoid-induced Ca2+ influx into vascular smooth muscle cells, we investigated the effects of protein kinase inhibitors on dexamethasone-induced 45Ca2+ uptake and dihydropyridine binding in A7r5 cells. Protein kinase C inhibitors (staurosporine and UCN-01) abolished the dexamethasone-induced 45Ca2+ uptake and [methyl-3H]PN 200-110 binding. In contrast, KT5720 and KT5823, which are more specific inhibitors of cAMP-dependent protein kinase and cGMP-dependent protein kinase, respectively, did not affect the effects of dexamethasone. Treatment with 100 nM dexamethasone for 48 hours increased protein kinase C activity in A7r5 cells. These results suggest that glucocorticoids increase Ca2+ influx through dihydropyridine-sensitive channels, linked to activation of protein kinase C in vascular smooth muscle cells.

To investigate the brain function of elderly schizophrenic patients, quantitative EEGs of such patients were compared with those of healthy elderly controls. In schizophrenics, increases in delta and slow theta (4.0-6.0 Hz) waves were thought to be due to the influence of antipsychotics. Characteristic EEG features of these patients included the following: 1) more fast theta (6.0-8.0 Hz) wave was observed, with less alpha wave faster than 9.0 Hz, 2) the reduction in alpha 3 (10.0-11.0 Hz) wave was limited to the frontal regions. The present EEG findings are thought to characterize the traits of the subtype of chronic severe schizophrenia. The reduction in alpha 3 wave in the frontal regions may be one expression of the hypofrontality of schizophrenia.

The effectiveness of a once-weekly i.m. injection of ceruletide (0.8 microgram/kg) in suppressing the symptoms of neuroleptic-induced tardive dyskinesia (TD) was evaluated in a double-blind, placebo-controlled, matched-pairs study. Global evaluation of the severity of TD symptoms over the 8-week study period revealed a significant improvement with ceruletide as compared with placebo. Analysis of the therapeutic response to ceruletide over the course of treatment revealed a slow, but long-lasting improvement of TD symptoms. Side effects, which were mild and transient, consisted mainly of nausea and epigastric discomfort. The incidence of side effects did not differ between the ceruletide- and placebo-treated groups. Ceruletide appears to be a novel and practical treatment that can substantially alleviate the symptoms of dyskinesia.

To investigate the prevalence of tardive dyskinesia (TD) in a group of psychiatric patients receiving low doses of antipsychotic drugs, we examined 647 Japanese inpatients (361 men and 286 women) with a mean age of 49.8 years, receiving a mean dose of antipsychotic drugs of 276.8 mg of chlorpromazine equivalent. TD was diagnosed according to the criteria of Schooler and Kane with the Abnormal Involuntary Movement Scale. The overall prevalence of TD was 22.3%. Mild TD was found in 67.4% of TD patients, moderate TD in 29.2%, and severe TD in 3.5%. The TD patients were older (59.0 years) than those without this condition (47.2 years). The prevalence of TD increased with advancing age until the 7th decade, when it reached a plateau. The dose of daily antipsychotic drugs was lower in the TD patients (207.6 mg) than in the patients without TD (296.6 mg). The duration of primary illness was longer in the TD patients (28.9 years) than in the patients without TD (20.4 years). Patients receiving antiparkinsonism drugs showed TD less frequently (20.7%) than those not receiving such drugs (31.0%). No significant associations were found between the presence of TD and sex or primary illness.

We followed 28 patients with tardive dyskinesia (TD) (eight men and 20 women, mean age 55.1 years) for 11-12 years to elucidate the long-term outcome of TD. All the patients received their physicians' choice of therapy, mainly comprising antipsychotics. The severity of TD was assessed at 5 and 11-12 years after the baseline evaluation. TD did not disappear in any patient. The severity of TD was unchanged in 39.3%, and improved in 17.9% despite continuous treatment with low doses of antipsychotics (mean 221.4 mg chlorpromazine equivalent daily). TD fluctuated in 21.4% and worsened in only 21.4%. Outcome was not correlated with patient sex or age, duration of primary illness, dosage of antipsychotics, or changes in dosage. The initial severity of TD showed some relationship to outcome. The number of bodily areas affected by TD increased in some patients with unchanged TD severity.

A 64-year-old man was admitted to our hospital with leukopenia. On admission, leukocyte count in the peripheral blood was 1,600/microliters, containing 24.5% blasts of lymphoid appearance, which were negative for myeloperoxidase. A bone marrow aspiration showed hypoplasia with increased blasts (31.6%). The blasts were ultrastructurally positive for platelet peroxidase (PPO) and positive for platelet membrane glycoprotein IIb/IIIa complex. A diagnosis of acute megakaryoblastic leukemia was made. Chemotherapy with behenoyl-ara C (BH-AC) (150 mg/day) was transiently effective. However, after three months, numerous nodules without itching appeared over the entire body, particularly on the anterior chest. A biopsy of the skin lesion revealed a diffuse fibrosis with infiltrations of the blasts. Bone marrow aspirations were dry tap, and a bone marrow biopsy showed marked myelofibrosis. Then, severe headache, vomiting, and loss of consciousness developed, and a lumbar puncture revealed infiltrations of blasts. Although methotrexate was intrathecally injected, he died due to the respiratory failure. As far as we know, a case of acute megakaryoblastic leukemia with leukemia cutis and meningeal leukemia is quite rare. In addition, it is interesting that megakaryoblastic leukemia was accompanied with both the fibrosis of skin and the myelofibrosis.

A study was conducted to elucidate the relation between the severity of progressive systemic sclerosis (PSS) and the grade of esophageal function disorder, the extent of which was estimated using esophageal manometry. Fifty two patients with PSS were divided into the mild, moderate and severe groups according to the severity score established by the PSS Research Group supported by The Ministry of Health and Welfare of Japan. Primary peristaltic pressure in the esophageal body at 25 to 35cm from the incisors as well as lower esophageal sphincter pressure (LESP), which represents the function of the smooth muscle of the esophagus, were significantly decreased in parallel with the increasing severity of PSS. In contrast, there was no significant difference in upper esophageal sphincter pressure (UESP) or in primary peristaltic pressure at 20cm from the incisors, indicating that the function of striated muscle of the esophagus was not impaired. In addition, even in the mild PSS group without dysphagia (19 cases), primary peristaltic pressure in the esophageal body at 25 to 35cm from incisors was found to be significantly decreased in comparison with the control. Hence, esophageal manometry was useful for early detection of the pathophysiological state of the esophageal function in PSS.

A 59-year-old male complained of a palpable abdominal mass which was revealed to be a primary omental tumor by means of abdominal ultrasonography, computed tomography, angiography and laparoscopy. Histological examinations of the surgically resected tumor further disclosed leiomyoblastoma with positive stainings of both vimentin and desmin, markers for mesenchymal cells and for muscle cells, respectively. He has been well for 2 years since resection, without any relapse or distant metastasis of the tumor. Leiomyoblastoma of the greater omentum is very rare, and is important to distinguish from extraluminal tumor of the abdomen.

TMSSA was found in 51 (4.7%) of 1091 psychiatric patients, with a higher incidence found in the older group (40 years of age or over). Although TMSSA was found in various disorders, a close association with cerebrovascular dementia was suggested. It was uncommon in patients with primary degenerative dementia. No increase of TMSSA was noted in cerebrovascular disorders without dementia. TMSSA was found fairly often in patients with affective disorders, neurosis, and other functional disorders, suggesting underlying mild cerebral dysfunction in some. TMSA, a variant of TMSSA, was very similar to TMSSA except for its greater frequency in cerebrovascular disorders without dementia.

To assess whether a certain somatic disease is involved in the etiology of anxiety disorder, we examined the relationship between anxiety disorder and mitral valve prolapse syndrome (MVP). Patients with anxiety disorder were diagnosed according to the criteria of the American Psychiatric Association (Quick Reference to the Diagnostic Criteria from DSM-III). Two-dimensional echocardiography was carried out on 36 normal controls (15 males and 21 females) and 39 patients with anxiety disorder (19 males and 20 females); including 21 patients with panic disorder, 12 with generalized anxiety disorder, and 6 with atypical anxiety disorder. The echocardiograms were evaluated by a cardiologist unaware of clinical background about these patients. The presence of MVP was diagnosed according to the criteria by Yoshikawa, et al. or Nagata, et al. Findings of MVP were seen in 18 (46.1%) of the patients and 5 (13.9%) of the controls indicating a significantly higher incidence (chi 2 = 7.711, p less than 0.01) in the patients. In the patient subgroups, 14 patients with panic disorder (66.6%) and 4 with generalized anxiety disorder (33.3%) had MVP, showing a significantly higher incidence in the former (chi 2 = 14.335, p less than 0.01) than in the normal controls, but no statistical significance in the latter. No MVP was found in the patients with atypical anxiety disorder. These results suggest that some somatic diseases such as MVP may play a role in the etiology of anxiety disorder, especially panic disorder.

A case of CJD with PLD in the first EEG is reported. The PLD became bilateral in the next EEG. The subsequent EEGs showed shifting asymmetries. In this case, PSD reappeared after 5 months' absence. The PLD occasionally appeared over the hemisphere ipsilateral to the side of the myoclonic jerks. The clinical significance of the PLD and reappearance of PD, and the diagnostic importance of PLD are discussed.

To obtain more informations from routine EEG recording, we studied changes in alpha rhythm after eye opening that had been almost disregarded hitherto. The study was carried out on 26 normal controls and 137 patients with four categories of diseases including 52 patients with psychiatric diseases, 8 with trifling neurological symptoms, 68 with defined organic brain diseases, and 9 with headache without defined organic cause. Following routine EEG recording, each subject was asked to keep their eyes opened for three minutes. The major changes in alpha rhythm after eye opening were composed of two patterns; "reappearance" and "recovery". The reappearance was defined as appearance of 5 or more alpha waves in series; and the recovery, as the amount and amplitude of the alpha rhythm became equal to those of the back ground alpha-rhythm which was seen while their eyes were kept closed. The reappearance was noticed in 84.6% of normal controls and in 89.1% of all patients. In patients with organic brain diseases, the reappearance was seen in 88.2%, while it was in 68.6% of the patients without organic brain disease. The recovery was noticed in 34.3% of all patients (p less than 0.01), while it was only in 15.4% of normal controls. The incidence of the recovery in the patients with organic brain diseases was 41.2%, the value of which was significantly higher than that of the rest of patients (28.8%, 15 out of 52 patients, p less than 0.05). These patients with the recovery tended to show slower frequency and higher amplitude in the back ground alpha-rhythm than the patients without recovery.

An EEG frequency analysis using the wave-form recognition method was performed in different stages of senile dementia (SD), evaluated according to the Hasegawa Dementia Rating Scale (HDS), and the differences in EEG changes between patients with Alzheimer's disease (AD) and patients with SD were studied. We found that the EEG changes in the SD patients correlated with HDS, and that an increase in slow theta (4-5.8 Hz) and a decrease in fast theta (7-7.8 Hz) waves were early changes in the SD patients. Furthermore, delta and slow theta waves increased mainly in the anterior frontal and temporal areas in the severe SD patients. The AD patients showed more severe EEG abnormalities than the SD patients and showed severe focal abnormalities in the temporal area.