Neurochemical Findings in the Cerebrospinal Fluid of Schizophrenic Patients with Tardive Dyskinesia and Neuroleptic-Induced Parkinsonism

Abstract: Monoamine and their acid metabolites were determined in the CSF of 18 drug-treated chronic schizophrenic patients with the symptoms of tardive dyskinesia and neuroleptic-induced Parkinsonism (Parkinsonism). Six healthy volunteers were used as the control group.
The norepinephrine (NE) levels were found to be significantly higher in the patients with tardive dyskinesia than in the controls. Furthermore, elevated CSF NE levels were also observed in the patients with Parkinsonism. Epinephrine (E) and Dopamine (DA) were not present in the CSF of the control group, whereas measurable levels of DA could be detected in 4 out of 9 and E was found in 8 out of 9 patients with tardive dyskinesia. The mean concentration of HVA was slightly but not significantly elevated in the patients with tardive dyskinesia and Parkinsonism. The mean values of CSF 5-HIAA were all within the normal range in both patient groups. From the above results, it was suggested that abnormal adrenergic activity rather than abnormal dopaminergic activity may play an important role as a mechanism in the etiopathogenesis of extrapyramidal disorders. Furthermore, in the patients with Parkinsonism, CSF neurochemical observations were similar to those of the patients with tardive dyskinesia in this study. It may help to explain the clinical coexistence of tardive dyskinesia and neuroleptic-induced Parkinsonism.     

Morphologic analysis of rat retinocollicular neuron terminals containing monoamine oxidase

The retino-collicular neuron terminals containing type A monoamine oxidase (MAO-A) in the stratum griseum superficiale of the rat superior colliculus were analyzed to provide a morphologic basis for the physiologic role of these neurons in the visual pathway. A computer-assisted, three-dimensional re-construction of the terminal complex associated with the MAO-A-positive terminals was performed. MAO-A-positive terminals originated in the retina and terminated in the stratum griseum superficiale. This was confirmed by tract tracing and enucleation experiments. The terminals were densely grouped in clusters of irregularly shaped swellings. Electron microscopy revealed that the MAO-A-positive terminals were located in a glomerulus-like structure. In this terminal complex, a significant proportion of the axonal profiles (42.96%) synapsed with the MAO-A-positive terminals. Most of the profiles (24.16%) resembled presynaptic dendrites, which represent intermediate elements between the retinal terminals and conventional dendrites. Unlike the glomerulus in the dorsal lateral geniculate body, the MAO-A-positive terminal swellings were not located in the central part of the terminal complex. The terminals had an irregular shape and were located in the complex. The terminal complex was partially ensheathed by glial processes. Furthermore, the membrane surfaces exhibiting synaptic specializations were very small compared with the total surface of the terminal swellings. The membrane length of the synaptic specialization was 5.38% of the total perimeter of the MAO-A-positive terminals.     

The Basomedial and Basolateral Amygdaloid Nuclei Contribute to the Induction of Long-term Potentiation in the Dentate Gyrus In Vivo

Recent behavioural studies have provided evidence that the amygdala modulates hippocampal-dependent memory. To test the possibility that the amygdala modulates hippocampal synaptic plasticity, we investigated the effects of surgical lesions of the amygdaloid nuclei on the induction of long-term potentiation (LTP) in the dentate gyrus of anaesthetized rats. Previously we reported that LTP in the dentate gyrus was attenuated by lesion of the basolateral amygdala, but was not affected by lesion of the central amygdala. In the present study, dentate gyrus LTP was significantly attenuated by basomedial amygdala lesion but not by medial amygdala lesion. These results suggest that, among the amygdaloid nuclei, the basomedial and basolateral nuclei are involved in the modulation of hippocampal plasticity. The roles of the basomedial and basolateral amygdala were further supported by experiments examining the effects of electrical stimulation of these nuclei. High-frequency stimulation of the basomedial amygdala alone did not induce dentate gyrus LTP, but when applied at the same time as tetanic stimulation of the perforant path increased the magnitude of the dentate gyrus LTP. Similarly, high-frequency stimulation of the basolateral amygdala enhanced LTP induced by tetanic stimulation of the perforant path. Furthermore, facilitation of dentate gyrus LTP by basomedial or basolateral amygdala stimulation was observed even in rats lesioned in either amygdala, suggesting that neurons in the basomedial and basolateral amygdala can modulate dentate gyrus LTP independently. Activity-dependent facilitation of hippocampal plasticity by the basomedial and basolateral amygdala may underlie memory processing associated with emotion.     

Quantitation and identification of human monocytic colony-stimulating factor in human serum by enzyme-linked immunosorbent assay

An enzyme-linked immunosorbent assay (ELISA) system for the quantitation of human monocytic colony-stimulating factor (hM-CSF) was established, which was based on the "dual antibody immunometric sandwich" principle using horse and rabbit polyvalent antibodies against human urinary colony-stimulating factor (CSF-HU). The minimal detectable level of hM-CSF was 10 U/mL, and the assays showed good reproducibility. As measured by this method, the average serum hM-CSF level of 20 normal adults was 540 +/- 110 U/mL (range, 300 to 800 U/mL). The peak of hM-CSF measured by ELISA was identical to that measured by bioassay when semipurified CSF-HU was fractionated by reversed-phase high performance liquid chromatography (HPLC). This method detected two types of hM-CSF, which had approximate molecular weights of 85 Kd (CSF-HU) and 45 Kd in human serum and urine; the ratio of 85:45 Kd was very high in serum and the amounts of the two types were nearly equal in urine. After anticancer chemotherapy, the serum hM- CSF level of one half of the patients with hematological malignancy was elevated according to the reduction in neutrophil number, while it was almost in the normal range in the other half of the patients, indicating the possibility that anticancer chemotherapy damaged the hM- CSF-producing cells. This ELISA method may be useful for monitoring the serum hM-CSF level after anticancer chemotherapy.     

Analysis of discontinuity in visual contours in area 19 of the cat

Previous ablation studies have suggested that area 19 of the cat plays an important role in pattern discrimination. To clarify the functional roles unique to area 19, we studied the receptive-field properties of cells in area 19 and compared them with those of cells in area 17. Recordings were made of anesthetized and immobilized animals. The majority (72%) of the cells in area 17 responded maximally to an elongated bar at a particular orientation, while they responded only weakly or not at all to a small spot (elongation-requiring cells). In contrast, more than half (63%) of the cells in area 19 showed a good response to a nonoriented small stimulus moving in any direction (dot-responsive cells). Two-thirds of the dot-responsive cells in area 19 failed to respond when the moving slit was elongated to more than some length in any orientation. These dot-responsive cells of the "inhibited-by-length" type responded strongly to the end of a long bar, and many of them also responded strongly to a break point in the middle of a long bar. We suggest that these dot-responsive cells of the "inhibited-by-length" type detect discontinuities in contours. Though they are in the minority, elongation-requiring cells constitute a considerable population (37%) in area 19, and dot-responsive and elongation-requiring cells from columnar patches in the same area. We conclude that, in contrast to area 17, whose main role is the decomposition of patterns into oriented contours, area 19 analyzes both orientation and discontinuities, with a strong bias towards the latter.     

Histochemical study of pituitary adenomas with Ki-67 and anti-DNA polymerase α monoclonal antibodies,bromodeoxyuridine labeling,and nucleolar organizer region counts

Summary The growth potential of 65 pituitary adenomas was determined by histochemical analysis with Ki-67 and anti-DNA polymerase monoclonal antibodies, bromodeoxyuridine (BrdUdR) labeling, and counts of argyrophilic nucleolar organizer regions (Ag-NORs). The mean proliferating cell indices (PCIs) determined by Ki-67 and anti-DNA polymerase and the BrdUdR labeling index (LI) were generally very low [1.0±0.2%, 1.1±0.2%, and 0.5±0.1% (±SE), respectively]. Apart from adrenocorticotropic hormone-positive adenomas, which had significantly higher indices, there were no statistically significant differences in the indices among the other subtypes of pituitary adenomas. Recurrent tumors had higher Ki-67 and DNA polymerase PCIs and BrdUdR LIs (3.6%, 4.2%, 1.4%) than primary tumors (0.8%, 0.8%, 0.3%; P<0.005). The number of Ag-NORs did not correlated significantly with any of the three indices. The mean number of Ag-NORs was higher in nonfunctioning adenomas than in functioning adenomas (2.04 vs 1.66, P<0.005); among prolactin-positive adenomas, those treated preoperatively with bromocriptine had more Ag-NORs than untreated tumors (1.75 vs 1.57, P<0.005). These results suggest that the Ki-67 and DNA polymerase PCIs and the BrdUdR LI predict the growth potential of individual pituitary adenomas, whereas the number of Ag-NORs appears to correlate with hormone production rather than with the proliferative potential.Supported by grants CA-13525 and CA-50210 from the National Cancer Institute, by a grant from the Phi Beta Psi Sorority, and by Grant-in-Aid A 63771083 from the Ministry of Education, Science, and Culture of Japan     

The influence of interfering input from the peroneal nerve on tibial-nerve somatosensory evoked potential.

Using a conditioning-test paradigm, we studied the recovery function of tibial nerve somatosensory evoked potentials (SEPs) conditioned by preceding peroneal nerve stimulation. The inter-stimulus intervals (ISIs) ranged from 0 to 400 msec, where 0 msec indicated simultaneous arrival of tibial and peroneal nerve volleys at the L1 spine. The recovery curve was W-shaped, showing two peaks of SEP suppression, maximum at 6 msec ISI (1st phase) and 50-75 ISI msec (2nd phase). In the 1st phase suppression, we found distinct differences in wave forms between 0-2 msec ISI and 4-6 msec ISI. At 0-2 msec ISI, P40-N50-P60 amplitude decreased and latencies shortened, while P31 and N35 were unchanged. At 4-6 msec ISI, all peaks, possibly excluding P31, were markedly depressed. We attribute the former change to an "occlusive effect" and the latter to an "inhibitory effect," each mediated via a central synaptic network between the two nerves. The attenuation of the 2nd but not the 1st phase suppression by peroneal nerve block distal to the stimulating electrodes provided evidence that the 2nd phase suppression resulted primarily from interfering afferent signals generated by peroneal nerve peripheral receptors, activated by foot movement.     

Isolated angitis of the central nervous system--case report and review

Isolated angitis of the central nervous system (IACNS) is rare condition with inflammation limited to vessels supplying the brain. This IACNS has been a poorly characterized and infrequently reported illness since it was first described as a separate entity in 1959. However, a patient with IACNS has not been reported in Japan. A patient, 39-year old-male, with IACNS limited to small and middle vessels is described. Recurrent, transient consciousness disturbances, focal myoclonus, papilloedema and temporal lobe epilepsy were observed during disease course. CSF finding of this patient showed lymphocytosis with marked increased protein. Carotid and vertebral angiogram showed irregular luminal outline in branches of all arteries. The most specific finding is that of alternating areas of focal stenosis and ectasia giving a "sausage" pattern. These characteristic findings showed in the branch of external carotid arteries. There was no evidence of systemic vasculitis by systemic angiography. Biopsy of temporal artery showed lymphocyte infiltration, fibrinoid necrosis without giant cell and granuloma. Formation of A-V malformation in the branch of external carotid artery was also observed. This histopathological finding was compatible with necrotizing angitis, not granulomatous angitis. Isolated angitis of the central nervous system was diagnosed. In spite of his administration of corticosteroid, cerebrospinal fluid abnormalities has not responded markedly. Abnormal findings of carotid and vertebral angiogram also has not changed. After 7 years from his onset, his neurologic signs and symptoms were well controlled with administration of anti-epileptic drugs.     

Diazepam reduces both arterial blood pressure and muscle sympathetic nerve activity in human

It is known that benzodiazepines have a hypotensive effect, but the mechanism has not been well elucidated yet. To clarify whether this effect is due to central or peripheral mechanism, we administered 5 mg of diazepam or saline intravenously to healthy volunteers and assessed the change in blood pressure, heart rate, muscle sympathetic nerve activity and heart rate variability. After diazepam administration, systolic and mean blood pressure decreased significantly. Muscle sympathetic nerve activity was also significantly reduced but heart rate did not change, whereas the variables of spectral analysis of heart rate variability did not show significant change. We concluded that the hypotensive effect of diazepam in human is mainly due to the central mechanism.