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Biomedical subjects

T Sawaguchi

Publications and source records attributed to T Sawaguchi.

At least 55 records · Page 3Linked to original sources

Attenuation of delay-period activity of monkey prefrontal neurons by an alpha2-adrenergic antagonist during an oculomotor delayed-response task.

To examine the role of norepinephrine receptors in spatial working memory processes mediated by the prefrontal cortex (PFC), noradrenergic antagonists (yohimbine for alpha2, prazosin for alpha1, and propranolol for beta receptors) were applied iontophoretically to neurons of the dorsolateral PFC in rhesus monkeys that performed an oculomotor delayed-response (ODR) task. The ODR task was initiated when the monkeys fixated on a central spot on a computer monitor and consisted of fixation (1 s), cue (1 of 4 peripheral cues, 0.5 s), delay (fixation cue only, 4 s), and go periods. In the go period, the subject made a memory-guided saccade to the target location that was cued before the delay period. I focused on 49 neurons that showed directional delay-period activity, i.e., a sustained increase in activity during the delay period, the magnitude of which varied significantly with the memorized target location. Iontophoretic (usually 50 nA) application of yohimbine, but not prazosin or propranolol, significantly decreased the activities of most of the neurons with directional delay-period activity (n = 41/49, 81%). Furthermore, yohimbine attenuated the sharpness of tuning, examined by a tuning index, of delay-period activity and had a greater attenuating effect on delay-period activity than on background activity. These findings suggest that the activation of alpha2-adrenergic receptors in the dorsolateral PFC plays a modulatory role in neuronal processes for visuospatial working memory.

Adrenergic alpha-Antagonists↗

[An epidemiological survey of sudden infant death syndrome in Tokyo].

OBJECTIVE: A complete autopsy is essential for an accurate diagnosis of sudden infant death syndrome (SIDS), whereas the autopsy rate is low in Japan. This study investigated the incidence of SIDS in Tokyo, where the autopsy rate for SIDS was the highest in Japan. METHODS: We selected death certificates of infants aged less than 2 years during 1990 to 1992 in Tokyo, whose cause of death was suspected to be SIDS, and classified those possibilities of SIDS according to death descriptions. RESULTS: The incidences of SIDS by strict definition and broad definition were 0.23 and 0.32 per 1,000 live births, respectively. Not a few death certificates described causes of death and death scene at some length. If including cases of suspected SIDS, the incidence came to 0.61 per 1,000 live births. The mortality risk of SIDS was significantly higher in infants with male gender and households classified by employment status as "other". Because the medical examiner system functioned only in the central urban area, most SIDS cases were diagnosed at autopsies in the urban area, whereas few cases were autopsied in the surrounding area. Compared to the urban area, the incidence of SIDS was significantly lower in the surrounding areas with low autopsy rates and with many death certificates of ambiguous death description. CONCLUSIONS: Ambiguous description of the death scene and low autopsy rate may cause under-diagnosis of SIDS. Establishment of a nationwide medicolegal autopsy system and examination of the death scene is necessary to diagnose SIDS accurately.

Cause of Death↗

Chronic infantile neurological cutaneous articular syndrome in a patient from Japan.

A case of chronic infantile neurological cutaneous articular (CINCA) syndrome in a Japanese girl, started at the age of 13 days with episodes of fever, rash followed by swollen joint, hepatosplenomegaly, generalized lymphadenopathy and chronic central nervous system involvement, is reported. Some of the findings suggest that this syndrome may be the result of an intrauterine infection. This is the first case of CINCA syndrome in a Japanese girl.

Age of Onset↗

Attenuation of preparatory activity for reaching movements by a D1-dopamine antagonist in the monkey premotor cortex.

To examine the role of dopamine receptors in the function of the premotor cortex (PM) for preparing for reaching movements, dopamine antagonists (SCH23390 for D1 receptors and sulpiride for D2 receptors) were applied iontophoretically to neurons of the PM of monkeys that performed a delayed-reaching (DR) task with their arms. In the DR task, the monkey made a reaching movement to one of three target levers (left, upper, and right), which had been cued by a visuospatial stimulus before a delay period of 4 s. We focused on neurons (n = 56) that showed a sustained increase in activity during the delay period (delay-period activity; i.e., "set-related" activity), because such activity is considered to play a central role in preparing for forelimb movements. Iontophoretic application of SCH23390 (usually with a current of 50 nA) significantly decreased the activity of most of these neurons (n = 44/56, 79%), and delay-period activity was attenuated during its application. In contrast, application of sulpiride or SCH23388 (an inactive analogue of SCH23390), using the same current intensity, had no effect on most of the neurons tested with these drugs (n = 31/33 and n = 21/23, respectively), despite the fact that their activity was decreased by SCH23390. Furthermore, for neurons that were affected by SCH23390, the percent decrease in delay-period activity was significantly greater than the percent change in background activity. In more than one-half of the neurons (n = 26/44, 59%), background activity was either increased (n = 10) or not affected (n = 16) by SCH23390, even though it significantly attenuated delay-period activity. These findings suggest that the activation of D1-dopamine receptors plays a modulatory role in PM function in preparing for reaching movements.

Animals↗

Synaptic interactions between primate precentral cortex neurons revealed by spike-triggered averaging of intracellular membrane potentials in vivo.

To document synaptic interactions between neurons in the precentral cortex of macaque monkeys, we recorded in vivo the intracellular (IC) membrane potentials of cortical neurons simultaneously with extracellular (EC) action potentials of neighboring cells. The synaptic potentials correlated with EC spikes were obtained by spike-triggered averages (STA) of the IC membrane potentials for 373 cell pairs recorded in anesthetized and awake behaving monkeys. Sixty-three STAs (17%) showed excitatory postsynaptic potentials (EPSPs), beginning after the trigger spike. Pure EPSPs had onset latencies of 0.9 +/- 0.7 msec (mean +/- SD) and amplitudes of 226 +/- 130 microV. Sixteen STAs (4%) showed postspike inhibitory postsynaptic potentials (IPSPs), with onset latencies of 0.4 +/- 0.4 msec and amplitudes of -274 +/- 188 microV. The most common waveform, observed in 82% of the STAs with features, was a broad depolarization straddling the trigger spikes, reflecting synchronized synaptic input to both IC and EC neurons. These average synchronous excitation potentials (ASEPs) began 14.3 +/- 6.6 msec before the trigger spike and had amplitudes of 1064 +/- 867 microV. Twenty-three STAs (6%) showed an average synchronous inhibitory potential (ASIP): a hyperpolarization beginning before the trigger spike and reflecting IPSPs produced by a group of local inhibitory cells synchronized with the trigger cell. ASIPs had an onset latency of -5.5 +/- 2.7 msec and amplitude of -589 +/- 502 microV. Combinations of synchronous and postspike potentials were also observed. Successive recordings provided examples of convergent and divergent connections between EC and IC cells. Neuron pairs with depolarizing postsynaptic potentials (PSPs) in the STA yielded peaks in the cross-correlograms of the IC and EC action potentials; the peak area was proportional to the amplitude of the PSP. These data suggest that a significantly larger proportion of cortical neurons interact through synchronous activity than through simple serial interactions; moreover, synchronous excitation affected more widely separated cell pairs than EPSPs and IPSPs, which were seen most often among the closest cells.

Action Potentials↗

Changes in DNA induced by toxic agents.

This is a preliminary report on significant alterations in the DNA profile caused by toxic substances which potentially has profound implications for the use of DNA techniques in identification. Acute DNA changes in the globus pallidus of the brain in man caused by carbon monoxide poisoning were detected by DNA profiling with probe 33.15. Chronic DNA changes in rabbits caused by methamphetamine were detected by DNA profiling with probe 33.15, AmpFLP on D1S80, TH01, CSF1PO and TPOX loci. Pre-intoxication bands appeared, disappeared or were discoloured after intoxication. With PCR-dot blot hybridization testing for HLADQ alpha, pre-intoxication positive spots became negative after intoxication and pre-intoxication negative spots became positive after intoxication. Intravenous injection of 10 mg/kg of methamphetamine every 2 days for 2 weeks was a large enough dose for inducement of genetic changes. In this investigation, clear changes in DNA due to intoxication were confirmed.

Animals↗

Application of the GABA antagonist bicuculline to the premotor cortex reduces the ability to withhold reaching movements by well-trained monkeys in visually guided reaching task.

1. A gamma-aminobutyric acid (GABA) antagonist, bicuculline methiodide (BMI, 10 micrograms/microliters, 1 microliter), was locally injected into a total of 32 sites in the right premotor cortex (PM) of two rhesus monkeys that had been well-trained in a visually guided reaching task (VR) for approximately 3 yr. The monkey initiated the task by pressing a central hold lever with its left hand, and this was followed by waiting (1 s), warning (central green square on a computer monitor, 0.5 s), cue (right, upper, or left square), delay (2-5 s), and go (central green square changes to red, < 1.2 s) periods. In the go period, the monkey released the hold lever and reached out to one of three target levers (left, upper, or right) that had been indicated 2-5 s previously in the cue period. 2. At three sites in the dorsal part of the PM, after the local application of BMI, reaching movements of the left forelimb, which were not part of the trained-reaching, occurred 200-300 ms after the onset of a burst of neuronal activity at the BMI injection site. This induced-reaching, which was designated a "forced-reaching" movement, occurred while the monkeys were pressing the hold lever before the cue appeared-i.e., during the waiting or waiting period. No reaching occurred when the burst did not appear. Furthermore, trajectories and electromyograms of the forelimbs during the forced-reaching movements were similar to those in the trained-reaching movements in the VR task. 3. These results suggest that restricted sites in the dorsal PM of monkeys are involved in the initiation and/or execution of trained-reaching movements and that GABAergic inhibition at these sites normally suppresses this initiation/execution unless it is required. By relaxing GABAergic suppression, the dorsal PM might send a command to a neuronal system that is associated with trained reaching to recruit the system, thereby initiating and/or executing the trained reaching.

Animals↗

Analysis of the short tandem repeat systems HUMF13B and HUMvWF in Chinese (Liaoning).

The short tandem repeat (STR) systems HUMF13B and HUMvWF were investigated in 200 healthy Chinese individuals living in Liaoning (The northeast of China). The HUMF13B allele frequencies were 6 = 0.0025, 8 = 0.1825, 9 = 0.1750, 10 = 0.6325 and 11 = 0.0075; and the HUMvWF allele frequencies were 13 = 0.0300, 14 = 0.2475, 15 = 0.0450, 16 = 0.1750, 17 = 0.2600, 18 = 0.1525, 19 = 0.0725 and 20 = 0.0175. The distribution of genotypes corresponded to the Hardy-Weinberg equilibrium. The distinguishing probabilities (D.P) were calculated as 0.7318 and 0.9366; the polymorphism information content (PIC) were calculated as 0.4827 and 0.7822; and the heterozygosity (h) were calculated as 0.5378 and 0.8128, respectively. The HUMF13B and HUMvWF systems provide a useful genetic marker for human genetics, anthropological studies, and forensic science in the chinese population.

Alleles↗

Modular activation and suppression of neocortical activity in the monkey revealed by optical imaging.

To examine functional local connections in the primate neocortex, we examined changes in optical signal by intracortical microstimulation (ICMS), using a voltage-sensitive dye (RH795) in frontal and parietal cortical areas of the anesthetized monkey. ICMS increased the optical signal at the stimulated site, followed by increases and decreases in a modular fashion at regions that were from hundreds of micrometres to a few millimetres from the stimulated site. These changes lasted for 100-250 ms after the offset of ICMS. Further, this increase in the optical signal was accompanied by an increase in electrical activity in the neurones. These findings suggest the presence of excitatory and inhibitory modular connections within the neocortical areas. It is likely that some functional 'modules' are activated concurrently by excitatory loops, which suppress the activity of other modules.

Animals↗

The role of D1-dopamine receptor in working memory: local injections of dopamine antagonists into the prefrontal cortex of rhesus monkeys performing an oculomotor delayed-response task.

1. To examine the role of dopamine receptors in the prefrontal cortex (PFC) on working memory, we injected dopamine antagonists (SCH23390, SCH39166, haloperidol, sulpiride, and raclopride) locally into the dorsolateral PFC in two monkeys trained to perform an oculomotor delayed-response (ODR) task. In the ODR task, monkeys fixate a central spot on a cathode ray tube (CRT) monitor while a visual cue is briefly (300 ms) presented in one of several peripheral locations in the visual field. After a delay of 1.5-6 s, the fixation spot is turned off, instructing the monkey to move its eyes to the target location that had been indicated by the visuospatial cue before the delay. Each monkey also performed a control task in which the cue remained on during the delay period. In this task the monkey's response was sensory rather than memory guided. 2. Local intracerebral injection of the selective dopamine antagonists SCH23390 (10-80 micrograms) and SCH39166 (1-5 micrograms) and/or the nonselective dopamine antagonist haloperidol (10-100 micrograms) induced deficits in ODR task performance at a total of 22 sites in the dorsolateral PFC. The deficit was characterized by a decrease in the accuracy of the memory-guided saccade as well as an increase in the latency of the response. The deficit usually appeared within 1-3 min after the injection, reached a peak at 20-40 min, and recovered at 60-90 min. 3. Performance change was restricted to a few specific target locations, which varied with the injection site and were most often contralateral to the injection site. 4. The degree of impairment in the ODR task occasioned by the injection of the dopamine antagonists was sensitive to the duration of delay; longer delays were associated with larger decreases in the accuracy and delayed onset of the memory-guided saccade. 5. The deficit was dose dependent; higher doses induced larger errors and increases in the onset of the memory-guided saccade. 6. Dopamine antagonists did not affect performance on the control task, which required the same eye movements but was sensory guided. Thus, in the same experimental session in which ODR performance was impaired, the accuracy and the latency of the sensory-guided saccades were normal for every target location.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[A fatal case due to intoxication with seven drugs detected by GC-MS and TDx methods].

A twenty-year-old woman was suspected to ingest large amounts of 4 kinds of over-the-counter analgesic and antipyretic drugs, and was found dead. Drugs and poisons were screened by TOXI-LAB drug detection system in the serum and urine, and analyzed by GC-MS and TDx system in the blood, urine, organ tissues and contents of stomach and small intestine. The concentrations (microgram/g) of bromisovalum, apronalide, ibuprofen, ethenzamide, acetaminophen and caffeine in the heart blood were 36.5, 7.58, 43.1, 16.9, 1.22 and 177, respectively. Salicylic acid concentration in the serum was 82.1 micrograms/ml. The concentrations of bromisovalum and caffeine are high enough to be lethal levels. Neither fatal pathological findings nor traumatic wounds were seen. The overdose of both bromisovalum and caffeine and synergistic, additive or combined effects of other 5 drugs above are considered to be her cause of death.

Acetaminophen↗

GABAergic inhibition of neuronal activity in the primate motor and premotor cortex during voluntary movement.

1. The functional role of GABAergic inhibition in neuronal activity in the forearm-hand area of the motor cortex and the postarcuate premotor cortex was studied while monkeys pressed and released a lever in response to a visual cue. gamma-Aminobutyric acid (GABA), its agonist muscimol (MUS), and its antagonist bicuculline methiodide (BMI), as well as acetylcholine, noradrenaline, and sodium glutamate, were applied iontophoretically to isolated single neurons whose activity was recorded via glass micropipettes that contained carbon fibers. 2. The activity from single neurons recorded in the motor and premotor cortex showed changes during the press or release of the lever by movement of the contralateral wrist. Discharge of most of the movement-related neurons (greater than 90%) was decreased or completely suppressed by iontophoretically applied GABA or MUS. 3. The activity of the movement-related neurons increased after application of BMI. In 70% of neurons tested, the activity during application of BMI was specifically enhanced at or near the phase of their peaks of activity, with or without a noticeable elevation in background activity. 4. About 10% of the neurons that had been unidirectional (i.e., neurons that showed a change in activity at either the lever-press or lever-release phase) became bidirectional (i.e., they showed changes in activity at both phases) when GABA transmission was blocked by the application of BMI. Bidirectional neurons also showed a reduction in the value of the directionality index. 5. One-half of the silent neurons, which had not shown any activity during either the lever-release or the lever-press phase, became active during the movement phases that followed application of BMI. 6. Most of the cortical neurons in layers II-VI in the motor area were found to be subject to GABAergic inhibition during voluntary movement. 7. We conclude that GABAergic inhibition plays a role in regulating the population of task-related neurons, and the levels of the task-related activity. GABAergic inhibition also improves directionality index in the motor cortex neurons to control the activity of target muscles.

Animals↗

The size of the neocortex in relation to ecology and social structure in monkeys and apes.

In an attempt to reveal factors associated with neocortical development in monkeys and apes (anthropoids), relationships between the relative size of the neocortex and differences in ecology and social structure were examined for 24 genera of 11 subfamilies. Relative sizes of the neocortex (RSNs) in a given group were assessed as the difference between actual neocortical volume and the volume expected from an allometric relationship between neocortical volume and the volume of the rest of the brain. We found that RSNs are related to diet and social structure: frugivorous anthropoids had higher values of RSNs than folivorous anthropoids, and polygynous anthropoids had significantly higher values of RSNs than monogynous anthropoids. Furthermore, RSNs were positively correlated with the size of the troop. These results suggest that development of the neocortex is associated with both diet and social structure in anthropoids.

Animals↗