Structure-activity relationship of a new series of tricyclic monoamine oxidase inhibitors of pentanthrene type.
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Biomedical subjects
Publications and source records attributed to H Noda.
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Three different studies were performed to estimate the sympatho-adrenomedullary activity in young subjects with borderline hypertension (BHT, n = 40), compared with age-matched normotensive subjects (NT, n = 24). In the first study, 23 BHT and 9 NT were subjected to isometric stress by maintaining handgrip at the 30% level of maximal voluntary contraction for 3 min. The response of plasma total catecholamines at the second and third min during the isometric exercise were greater in BHT than in NT (98.9 +/- 24.3 vs. 18.0 +/- 30.7 and 93.0 +/- 12.6 vs. 47.1 +/- 15.4 pg/ml, respectively, p less than 0.05). In the second study, the effects of intravenous glucagon injection (1 USP unit) were studied in 12 BHT and 9 NT. The increments of plasma epinephrine (E) at 2 and 3 min after injection were significantly greater in BHT than those in NT: 44.1 +/- 12.3 vs. 5.1 +/- 4.4 pg/ml, and 68.9 +/- 13.2 vs 32.1 +/- 8.9 pg/ml, respectively, p less than 0.05. In the last study, the pressor effects of intravenous norepinephrine (NE) infusion (100 and 200 ng/kg/min for 15 min) were examined in 17 BHT and 15 NT under three different sodium balances: regular customary diet, treatment with diuretics and high-sodium diet. Treatment with diuretics decreased and high-sodium diet increased the pressor response to NE in both groups, but there were no significant differences in NE reactivity between 2 groups throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)
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Bacteriological examinations were performed on the first case of infant botulism in Japan (an infant boy aged 79 days at onset of illness). Clostridium botulinum type A toxin and organisms were detected continually in the stools of the infant for at least 31 days and 39 days, respectively. The highest levels of the toxin and of the population of the organisms, 7.8 X 10(4) LD50/g and 1.3 X 10(6) colony forming units (cfu)/g, were detected in the stool specimen taken on the 20th day of illness. Type A organisms were detected also in the honey fed to the infant before onset of illness, teats of his feeding bottle, soil specimens taken at the house entry and the vacuum-cleaner dust. Fecal excretion of the toxin and organisms was no longer detected from the 68th day of illness and he recovered.
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Saccadic eye movements were evoked with weak currents applied to a circumscribed vermal area. The area was confined to lobule VII in the majority of the monkeys and coincided with the distribution of saccade-related neural activity. We defined this area as the oculomotor vermis and studied its anatomical connections with wheat germ-agglutinin conjugated horseradish peroxidase (WGA/HRP) and HRP. When injected HRP was confined to the oculomotor vermis, most labeled Purkinje axons terminated ipsilaterally in an ellipsoidal region in the mediocaudal aspect of the fastigial nucleus. Retrogradely labeled cells were found in two relatively circumscribed regions in the fastigial nucleus: one group was in the lateral half of the ellipsoidal terminal region and the other group was in a spherical region near the lateral margin of the nucleus. Following the injection of HRP into the oculomotor vermis, the largest population of retrogradely labeled neurons was found in the nucleus reticularis tegmenti pontis. Labeled cells were located only in the medial and dorsolateral portions of the nucleus. The cell aggregates in the dorsolateral portion merged with densely labeled cells of the processus tegmentosus lateralis. The second largest population of labeled cells was found in the pontine nuclei. Approximately 28% of the labeled pontine cells aggregated in the paramedian pontine nucleus, whereas the other labeled pontine cells were widely distributed in the dorsal part of the pontine peduncular nucleus and the dorsolateral pontine nucleus. Labeled cells were scattered also in the pontine raphe, the paramedian pontine reticular formation, and the interfascicular nucleus at the rostral level of the hypoglossal nucleus. Fewer labeled cells were discovered in the vestibular nuclear complex and the prepositus hypoglossi. In the inferior olivary nucleus, labeled cells were located in the subnucleus b of the medial accessory nucleus.
We have used microstimulation in the floccular cortex of alert monkeys to study the role of the cerebellar flocculus in the control of slow eye movements and the representation of eye movement direction in the flocculus. Eye movements having peak velocities of less than 15 deg/s, sometimes accompanied by rapid eye movements, were evoked using trains of current pulses (22 microA or less). The initial slow eye movement was designated Phase I. By restricting current spread to specific layers of the flocculus, evidence was obtained that Phase I was caused by the activation of molecular layer elements; it appeared to reflect the suppression of Purkinje cell activity. Phase I, therefore, probably represents the best estimate of the effect of changing Purkinje cell activity in a limited region. Phase I ended either during the pulse train or after the end of the pulse train; following the end of Phase I, the eye movement reversed its direction. Again by stimulating various layers, the eye movement following the reversal (Phase II and the off-response) was attributed to activation of Purkinje cell axons and other elements, including floccular afferents, in the granular layer and white matter. Phase I eye movements in all directions were evoked from the flocculus. Homogeneous zones with respect to eye movement direction were approximately 300 micron in diameter. When the cortex was represented as a two-dimensional sheet, a large number of zones corresponding to different directions of Phase I were observed.
Response properties and visual receptive fields of climbing fibers and mossy fibers terminating in the cerebellar flocculus were studied in monkeys trained to fixate a stationary visual target. Among a total of 429 climbing fiber-related units (climbing fibers and complex spikes of Purkinje cells), 20 (4.9%) showed cyclic modulations in firing in response to sinusoidal retinal-slip velocities. Their receptive fields always included the fovea. Among 485 mossy fibers, 64 (13%) responded to the visual stimulation. Of the 64 visually responsive mossy fiber units, 39 (61%) responded exclusively to the retinal-slip velocity (visual mossy fibers and the remaining 25 mossy fibers (39%) responded also to the eye and head velocities (visuomotor mossy fibers). Receptive fields for 17 visual mossy fibers (17/39 or 44%) were within 10 degrees of fixation and those for 22 others (56%) were in the periphery. Receptive fields for all 25 visuomotor mossy fibers were in the periphery. Each mossy fiber unit had a unique velocity-tuning curve and, therefore, the response patterns of individual mossy fibers were different depending on the range of their velocity sensitivity and on the retinal-slip velocity applied.
Connectin is a very long and flexible protein of striated muscle, linking myosin filaments to z discs in a sarcomere. Isolated native connectin in solution frequently forms elastic threads upon concentration of the solution, by side-by-side association of molecules. An X-ray diffraction study was performed to examine the presence of beta-sheet structure in artificially prepared threads. The elastic properties of such threads were measured at various temperatures. Negative temperature dependence of the elastic coefficient suggests that the elasticity of connectin threads is due to deformation of the three-dimensional structure and not to rubber-like behavior.
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1. Discharges of Purkinje cells (P cells) and mossy fibres were recorded from the cerebellar flocculus of monkeys trained to fixate a stationary visual target. The units were tested with a sinusoidally moving random dot pattern (background) which was projected on an entire screen or on part of it. The receptive field organization of the units was tested by changing the area of stimulus presentation on the screen and by changing the direction of visual fixation. 2. When stimulated with sinusoidal movements of the background in the horizontal plane, ninety-two of 684 Purkinje cells (13.5%) responded to the retinal-slip velocity. Seventy-eight of the ninety-two visually responsive Purkinje cells (84.8%) also showed cyclic modulations in activity during horizontal smooth-pursuit eye movements (these were so-called horizontal gaze-velocity Purkinje cells). 3. In response to the sinusoidal retinal-slip velocity, the visual Purkinje cells showed six types of discharge patterns. Type 1 Purkinje cells (28/92 or 30.4%) were directionally selective: they showed a peak activity during background movement in one direction and a trough in the other. Both peaks and troughs were related to stimulus velocities. Their receptive fields were relatively large (greater than 45 deg) and included the fovea. 4. Type 2 (8/92 or 8.7%) and type 3 (5/92 or 5.4%) Purkinje cells showed sinusoidal responses similar to those of type 1 Purkinje cells, but the visual inputs were primarily excitatory in type 2 Purkinje cells and inhibitory in type 3 Purkinje cells. Only the peaks in type 2 and troughs in type 3 were related to stimulus velocities. 5. Type 4 (4/92 or 4.3%) and type 5 (11/92 or 12.0%) Purkinje cells showed responses to stimulus movements in both directions (bidirectional). When the moving background was projected with 10 deg of fixation, type 4 Purkinje cells were excited bidirectionally in relation to retinal-slip velocities. When the periphery of either hemiretina was stimulated, type 5 Purkinje cells were inhibited and the trough activity was stimulus-velocity dependent. Receptive fields were found in the ipsilateral hemiretinae in seven type 5 Purkinje cells and in the contralateral hemiretinae in the remaining four type 5 Purkinje cells. 6. Type 6 (36/92 or 39.1% Purkinje cells received an excitatory input from the central retina and an inhibitory input from the periphery. The peripheral receptive fields were either in the ipsilateral (69.4%) or contralateral (30.6%) hemiretinae of both eyes.(ABSTRACT TRUNCATED AT 400 WORDS)
1. Oculomotor responses to microstimulation of the cerebellar vermis were studied on macaque monkeys by measuring eye position with a magnetic search-coil method. 2. Vermal microstimulation resulted in conjugate eye movements. Analyses of amplitude-velocity and amplitude-duration relationships revealed that although the peak velocities were slightly faster, the durations of these responses were comparable to those of spontaneous and visually guided saccadic eye movements (saccades). 3. Systematic mapping with microstimulation revealed that the low-threshold sites were localized in the white matter of a limited number of folia in the posterior vermis. The low-threshold region from which saccades could be evoked with stimulus intensities less than 10 microA was confined to lobule VII in seven monkeys; in the other five monkeys it included a posterior part of lobule VI (folium VIc). This region coincided with the distribution of saccade-related neural activity observed in the present study and corresponded to the vermal folia from which we previously recorded the burst mossy fibre units and the oculomotor Purkinje cell activity (Kase, Miller & Noda, 1980). 4. Microstimulation of most sites in the oculomotor vermis evoked saccades in oblique directions and the horizontal component of the saccade was always ipsilateral to the stimulation side. In penetrations through the paramedian vermis, the direction of the saccade changed gradually from upward oblique to downward oblique as the electrode was advanced vertically across lobule VII. The vertical component was dominant in these saccades. When the stimulation track was systematically shifted from the medial to the lateral part of the vermis, the horizontal component of the saccade increased and the vertical component decreased gradually until the saccade became almost horizontal. 5. The direction of saccades changed with the stimulus intensity; thus the topographical change in the direction of a saccade was consistent only when the stimulus intensity was adjusted to the threshold for every stimulus site. When stimulated with near threshold intensities, the evoked saccades were very seldom straight: the trajectories were curved in the responses observed at most vermal sites. The horizontal and vertical components of these saccades showed different onset latencies, durations, and peak-velocity latencies. Increasing the stimulus current produced differing effects on the two components of the saccades.(ABSTRACT TRUNCATED AT 400 WORDS)
Neural mechanisms for evoking saccadic eye movements by microstimulation of the posterior vermis were investigated in monkeys trained to fixate a visual target. The low-threshold region from which saccadic eye movements could be evoked with currents less than 10 microA was confined to lobule VII in two monkeys and it included a posterior part of lobule VI (lobule VIc) in another monkey. The region from which saccade-related neural activity was recordable coincided with the low-threshold region. This region corresponded to the vermal lobules from which eye position and saccade-related Purkinje cells were recorded. Kainic acid (kainate) injected in the white matter of lobule VII resulted in severe losses of Purkinje cells within a radius of 1-2 mm of the injection site. The lesion tended to be larger toward the peripheral cerebellar cortices, which were connected to the injection site by natural courses of the afferent and efferent fibers. After the kainate administration, the distribution of saccade-related neural activity did not differ significantly from that of the preoperative mapping, in spite of the severe losses of cortical neurons. Burst discharges of mossy fibers were recordable in the white matter near the injection site, indicating that afferent fibers were relatively unaffected by kainate. After kainate administration, the saccadic eye movements could no longer be evoked by microstimulation applied to the posterior vermis. The stimulus sites from which saccades could be evoked after kainate administration were always associated with the presence of intact Purkinje cells. In such cases, the minimum current necessary to evoke saccades depended on the percentages of intact Purkinje cells spared. In the folia with normal Purkinje cell layers, the amplitude and direction of evoked saccades and the thresholds for evoking such eye movements were almost comparable to the preoperative data. Saccadic eye movements in response to microstimulation of the posterior vermis were caused by orthodromic impulses conveyed through the axons of the Purkinje cells. Insofar as the saccades elicited from lobule VII with currents less than 10 microA are concerned, antidromic activation of the afferent fibers is not the neural mechanisms subserving the oculomotor responses.
1. Oculomotor responses to microstimulation of the cerebellar vermis of macaque monkeys were investigated by using a magnetic search-coil method. 2. The oculomotor responses were conjugate eye movements with an ipsilateral horizontal component. Analyses of amplitude-velocity and amplitude-duration relationships revealed that the peak eye velocities and the durations of the responses were comparable to those of saccadic eye movements. 3. Systematic mapping with microstimulation disclosed that the region in the cerebellar vermis that yielded saccades with weak stimulus currents was confined to lobule VII in five monkeys but included a part of folium VIc in the other four monkeys. This region coincided with the distribution of the saccade-related neural activity observed in the present study and also corresponded to the vermal folia from which we recorded the burst mossy-fiber units and the oculomotor Purkinje cell activity. 4. The oculomotor vermis was defined as that region of the cerebellar vermis that met the following criteria: 1) saccades were evoked with low-intensity microstimulation (with currents less than 10 microA); 2) vigorous saccade-related neural activity was present; and 3) Purkinje cell discharges were modulated with eye movements. The oculomotor vermis was more circumscribed and located more posteriorly than the vermal cortex explored in previous microstimulation experiments on monkeys. 5. Microstimulation of the oculomotor vermis evoked more or less curved saccades in oblique directions. The horizontal and vertical components were not simultaneous in some saccades: the shorter component started later or ended earlier than the other component and their peak velocities were not always synchronous. 6. The amplitude of the saccade depended on stimulus parameters; microstimulation with 10-12 pulses within a period of approximately 20 ms (500-600 Hz) was shown to be optimal. When the pulses were applied to the white matter or to the granular layer, a stimulus current of 10 microA was sufficient to evoke saccades. When the molecular layer was stimulated, evoked saccades were smaller and frequently curved, and an increase in the stimulus current changed either the initial direction or the trajectory of the saccade. 7. When the stimulus current was carefully controlled and maintained near the threshold, the direction of the saccade evoked from the oculomotor vermis was topographically organized.(ABSTRACT TRUNCATED AT 400 WORDS)