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Biomedical subjects

S Sugita

Publications and source records attributed to S Sugita.

At least 19 recordsLinked to original sources

Synaptic inputs to GABAA and GABAB receptors originate from discrete afferent neurons.

gamma-Aminobutyric acid (GABA) inhibits neurons by acting at GABAA and GABAB receptors but it is not known whether the two receptors are associated with discretely separate afferent inputs or whether GABA released from a single presynaptic neuron activates both receptors. Intracellular recordings were used to show that, in the lateral amygdala and ventral tegmental area of the rat, distinct sets of GABA-containing neurons provide the synaptic input to GABAA and GABAB receptors. Synaptic potentials resulting from GABAA receptor activation (blocked by bicuculline) and from GABAB receptor activation (blocked by 2-hydroxysaclofen) occurred spontaneously but as unrelated events. Furthermore, the two components of evoked synaptic potentials were differentially inhibited by agonists acting presynaptically (muscarine and 5-hydroxytryptamine). The finding that GABA acting at GABAA and GABAB receptors originates from distinct sets of presynaptic fibers suggests that two groups of GABA-containing neurons might be generally distinguishable in the mammalian nervous system.

2-Amino-5-phosphonovalerate

Evolutionary pattern of the H 3 haemagglutinin of equine influenza viruses: multiple evolutionary lineages and frozen replication.

The nucleotide and deduced amino acid sequences of the haemagglutinin genes coding for the HA 1 domain of H3N8 equine influenza viruses isolated over wide regions of the world were analyzed in detail to determine their evolutionary relationships. We have constructed a phylogenetic model tree by the neighbour-joining method using nucleotide sequences of 15 haemagglutinin genes, including those of five viruses determined in the present study. This gene tree revealed the existence of two major evolutionary pathways during a twenty five-year period between 1963 to 1988, and each pathway appeared to consist of two distinct lineages of haemagglutinin genes. Furthermore, our analysis of nucleotide sequences showed that two distinct lineages of equine H3N8 viruses were involved in an equine influenza outbreak during the period of December 1971-January 1972 in Japan. The number of nucleotide changes between strains was proportional to the length of time (in years) between their isolation except for three of the HA genes. However, there are three exceptional strains isolated in 1971, 1987, and 1988, respectively. The haemagglutinin gene in these strains showed a small number of nucleotide substitutions after they branched off around 1963, suggesting an example of frozen replication. Although the estimated rate (0.0094/site/year) of synonymous (silent) substitutions of the haemagglutinin gene of equine H3N8 viruses was nearly the same as that of human H 1 and H 3 haemagglutinin genes, the rate of nonsynonymous (amino-acid changing) substitutions of the former equine virus gene was estimated to be 0.00041/site/year--that is about 5 times lower than that estimated for the human H 3 haemagglutinin gene. The present study is the first demonstration that multiple evolutionary lineages of equine H3N8 influenza virus circulated since 1963.

Amino Acid Sequence

Fastigiofugal fibers encoding horizontal and vertical components of saccades as determined by microstimulation in monkeys.

To identify the routes by which oculomotor vermis signals control eye movements (saccadic signals), saccades evoked by microstimulation were studied in the region of the uncinate fasciculus (UF) and juxtarestiform body (JB) in the macaque monkey. Anatomical pathways of axons from the fastigial oculomotor region (FOR) were studied by anterograde transport of wheatgerm agglutinin conjugated horseradish peroxidase (WGA-HRP). The routes were identified by comparing maps of low threshold for evoking saccades with the anatomical map of anterogradely labeled axons arising from the FOR. Microstimulation of a region of the UF and JB demonstrated that saccadic signals are carried exclusively by decussated FOR axons which leave the cerebellum via the contralateral UF. The fibers in the JB do not carry saccadic signals. The horizontal component of saccadic signals is conveyed by fibers in the descending limb of the UF, while the vertical component is conveyed by a smaller group of fibers which separate from the UF and enter the midbrain with the contralateral superior cerebellar peduncle.

Animals

5-hydroxytryptamine is a fast excitatory transmitter at 5-HT3 receptors in rat amygdala.

A fast excitatory synaptic potential mediated by 5-hydroxytryptamine (5-HT) was recorded in rat lateral amygdala neurons in brain slices. The synaptic potential has brief duration (tens of milliseconds), is mimicked by 5-HT, is potentiated by a 5-HT uptake inhibitor, and is blocked by selective 5-HT3 receptor antagonists. The underlying synaptic current reversed polarity at about 0 mV. This is an example of fast neurotransmission in the mammalian brain mediated by an amine rather than an amino acid. The antiemetic, anxiolytic, and perhaps antipsychotic actions of 5-HT3 antagonists might result from blockade of such synapses.

2-Amino-5-phosphonovalerate

Comparing postgraduate medical education at university and non-university hospitals in Japan.

In 1988 the authors surveyed all the teaching hospitals in Japan to evaluate the present status of postgraduate medical education (PGME); they received responses from 67 (84%) of the university and 172 (89%) of the non-university teaching hospitals. It was found that a large proportion of residents had spent two years in a residency without having had a single experience of some of the basic clinical skills. Consequently the residents' confidence in their abilities to perform these skills was low. The residents at the university hospitals, in particular, had had fewer experiences and were less confident about their clinical skills than were the residents at the non-university hospitals. The lack of standard and minimum requirements for PGME in Japan may be the cause of the poor level of acquisition of clinical skills of residents during PGME. Other possible causes are the tendency in Japanese medical society to attach greater importance to academic attainment than to clinical competence and the excessive gravitation of residents toward university hospitals. The authors suggest their results show the necessity to improve the training in basic clinical skills in PGME in Japan, especially in university hospitals.

Clinical Competence

Fundus albipunctatus associated with cone dystrophy.

We describe five unrelated patients in whom the typical signs of fundus albipunctatus were accompanied by colour vision defects, bull's eye or similar macular lesions, and severely diminished full-field cone electroretinograms indicating widespread damage to cones outside the macula. All patients had noticed night blindness from childhood. Signs of retinitis punctata albescens, a disease of similar appearance but with characteristics resembling retinitis pigmentosa, were absent. We cannot be sure whether these patients represent a process of fundus albipunctatus or a distinct disease entity or a casual combination of fundus albipunctatus and cone dystrophy.

Adult

Involvement of protein kinase C in serotonin-induced spike broadening and synaptic facilitation in sensorimotor connections of Aplysia.

1. Plasticity at the connections between sensory neurons and their follower cells in Aplysia has been used extensively as a model system to examine mechanisms of simple forms of learning. Earlier studies have concluded that serotonin (5-HT) is a key modulatory transmitter and that it exerts its short-term actions via cAMP-dependent activation of protein kinase A. Subsequently, it has become clear that other kinase systems such as protein kinase C (PKC) also may be involved in the actions of 5-HT. 2. Application of phorbol esters, which activate PKC, produced a slowly developing spike broadening but had little effect on excitability (a process known to be primarily cAMP dependent). Moreover, the effects of phorbol esters and 5-HT on spike duration were not additive, suggesting that they may share some common mechanisms. 3. The protein kinase inhibitor staurosporine suppressed both 5-HT-induced slowly developing spike broadening and, under certain conditions, facilitation of transmitter release. Staurosporine did not inhibit 5-HT-induced enhancement of excitability. The effectiveness of staurosporine on spike broadening was dependent on the time at which spike broadening was examined after application of 5-HT. Staurosporine appeared to have little effect on spike broadening 3 min after application of 5-HT, whereas it inhibited significantly 5-HT-induced spike broadening at later times. The staurosporine-insensitive component of 5-HT-induced spike broadening may be mediated by cAMP. 4. The results suggest that the activation of PKC plays a key role in components of both 5-HT-induced spike broadening and facilitation of synaptic transmission.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids

[Morphometric and immunohistochemical studies of the suprachiasmatic nucleus in the hereditary microphthalmic rat].

Morphometric and immunohistochemical analyses of the suprachiasmatic nucleus (SCN) were performed on hereditary microphthalmic rats. In normal rats, the number of cells and the volume of the SCN were 11, 631 and 6.7 x 10(-2) mm3 (an average taken from 12 SCNs). However, the neuronal population and volume of the SCN in hereditary microphthalmic rats were 7,450 and 4.5 x 10(-2) mm3 (an average taken from 14 SCNs), respectively. There were no significant differences in the size of neurons between normal and microphthalmic SCN neurons. Immunohistochemical studies showed that a considerable number of antivasopressin positive neurons were present in microphthalmic rats, despite their lack of the optic nerve. However, further detailed studies revealed that the number of antivasopressin positive neurons present in microphthalmic rats was only 68% of those found in normal rats. These findings suggest that the complete development of the SCN and vasopressin neurons depends on the visual input.

Animals

[Quantitative analysis of the isthmo-optic nucleus and projection neurons to the retina in adult fowl (Gallus gallus domesticus)].

Quantitative analysis of the isthmo-optic nucleus (IO) and centrifugal projection to the retina in the fowl was made using Nissl preparation and retrograde horseradish peroxidase (HRP) methods. Seven adult fowls (Gallus gallus domesticus) were used for Nissl stain. Serial sections were cut on a freezing microtome at 60 microns and stained with cresyl violet. IO was situated just medial to the caudal part of the tectum and laterodorsal surface of the brain stem. Rostrocaudal extension of IO was about 800-1,000 microns. The average total volume and neuronal population of the IO was 280 x 10(-3) mm3 and 5,600 neurons, respectively. Eight animals were used for HRP study. One hundred microliters of 30% HRP solution in physiological saline was injected into the vitreous body of one eye of each hen. Serial transverse sections of 60 microns were treated with tetramethyl benzidine (TMB). Many labeled neurons were found in contralateral brain stem. Average total number of contralateral HRP-labeled cells in IO and peri-IO were 5,268 and 1,492, respectively. Labeled neurons peri-IO were mainly distributed ventrally and rostrally to IO. No labeled neurons in IO, and only a few labeled neurons peri-IO were found ipsilaterally. The number of HRP-labeled neurons in IO corresponded to the neuronal population of IO in Nissl preparation, which suggested that most of isthmo-optic neurons might be projecting to the contralateral retina. In contrast to the round and small IO neurons (long axis 15-20 microns, short axis 10-20 microns), peri-IO neurons were multipolar and longer (long axis 15-30 microns, short axis 10-25 microns).

Animals

Distinct muscarinic receptors inhibit release of gamma-aminobutyric acid and excitatory amino acids in mammalian brain.

Intracellular recordings were made from neurons of rat lateral amygdala, nucleus accumbens, and striatum in vitro. Synaptic potentials mediated by gamma-aminobutyric acid and by excitatory amino acids were isolated pharmacologically by using receptor antagonists, and their amplitudes were used as a measure of transmitter release. Muscarine and acetylcholine inhibited the release of both gamma-aminobutyric acid and excitatory amino acids, but measurements of the dissociation equilibrium constants for the antagonists pirenzepine, 11-(2-[(diethylamino)methyl]-1-piperidinyl)acetyl-5,11-dihydro-6H-pyrido [2,3-b][1,4]benzodiazepine-6-one, methoctramine, and hexahydrosiladifenidol indicated clearly that different muscarinic receptors were involved (M1 and probably M3, respectively). The differential localization of distinct muscarinic receptor subtypes on terminals releasing the major inhibitory and excitatory transmitters of the brain could be exploited therapeutically in some movement disorders and Alzheimer disease.

6-Cyano-7-nitroquinoxaline-2,3-dione

Molecular evolution of hemagglutinin genes of H1N1 swine and human influenza A viruses.

The hemagglutinin (HA) genes of influenza type A (H1N1) viruses isolated from swine were cloned into plasmid vectors and their nucleotide sequences were determined. A phylogenetic tree for the HA genes of swine and human influenza viruses was constructed by the neighbor-joining method. It showed that the divergence between swine and human HA genes might have occurred around 1905. The estimated rates of synonymous (silent) substitutions for swine and human influenza viruses were almost the same. For both viruses, the rate of synonymous substitution was much higher than that of nonsynonymous (amino acid altering) substitution. It is the case even for only the antigenic sites of the HA. This feature is consistent with the neutral theory of molecular evolution. The rate of nonsynonymous substitution for human influenza viruses was three times the rate for swine influenza viruses. In particular, nonsynonymous substitutions at antigenic sites occurred less frequently in swine than in humans. The difference in the rate of nonsynonymous substitution between swine and human influenza viruses can be explained by the different degrees of functional constraint operating on the amino acid sequence of the HA in both hosts.

Amino Acid Sequence

Pathways and terminations of axons arising in the fastigial oculomotor region of macaque monkeys.

The majority of axons from the fastigial oculomotor region (FOR) decussated in the cerebellum at all rostrocaudal levels of the fastigial nucleus (FN) and entered the brainstem via the contralateral uncinate fasciculus (UF). Some decussated axons separated from the UF and ran medial to the contralateral superior cerebellar peduncle and ascended to the midbrain. Uncrossed FOR axons advanced rostrolaterally in the ipsilateral FN and entered the brainstem via the juxtarestiform body. The decussated fibers terminated in the brainstem nuclei that are implicated in the control of saccadic eye movements. In the midbrain, labeled terminals were found in the rostral interstitial nucleus of the medial longitudinal fasciculus, a medial part of Forel's H-field, the periaqueductal gray, the posterior commissure nucleus, and the superior colliculus of the contralateral side. In the pons and medulla, FOR fibers terminated in a caudal part of the pontine raphe, the paramedian pontine reticular formation, the nucleus reticularis tegmenti pontis, the dorsomedial pontine nucleus of the contralateral side, and the dorsomedial medullary reticular formation of both sides. In contrast, FOR projections to the vestibular complex were bilateral and were mainly to the ventral portions of the lateral and inferior vestibular nuclei. No labeled terminals were found in the following brainstem nuclei which are considered to be involved in oculomotor function: oculomotor and trochlear nuclei, interstitial nucleus of Cajal, medial and superior vestibular nuclei, periphypoglossal nuclei, and dorsolateral pontine nucleus. Labeling appeared in the red nucleus only when HRP encroached upon the posterior interposed nucleus.

Animals

Brainstem mossy fiber projections to lobules VIa, VIb,c, VII and VIII of the cerebellar vermis in the rat.

The brainstem mossy-fiber projections to lobules VIa, VIb,c, VII and VIII of the cerebellar vermis were studied by retrograde transport of horseradish peroxidase in the rat. The distribution of labeled cells indicated that these lobules received major projections from topographically different locations of the basilar pontine nuclei and the nucleus reticularis tegmenti pontis. Lobules VIa and VIII received an additional strong projection from the lateral reticular nucleus. Moderate projections were found to reach lobule VIa from the raphe pontis and external cuneate nucleus; lobules VIb,c from the raphe pontis, lateral reticular nucleus, and a group of cells in the lateral tegmentum; lobule VII from the spinal vestibular nucleus and a lateral tegmental cell group; and lobule VIII from the medial and spinal vestibular nuclei, nucleus intercalatus and Roller of the perihypoglossal nuclei, and the main cuneate nucleus. The quantitative and topographical differences in the origin of mossy fibers suggest that these lobules may subserve slightly different functions.

Afferent Pathways

[Retinal projections to the pretectum in the fowl (Gallus gallus domesticus)].

The retinal projection to the pretectum was examined in the adult domestic fowl by means of anterograde transport of horseradish peroxidase (HRP). At the same time, the cytoarchitecture of the pretectum was studied in Nissl preparation. Fifteen fowls (Gallus gallus domesticus) were used for the HRP study, and four were used for the cytoarchitectural study. One hundred microliters of a 30% HRP solution in physiological saline were injected into the vitreous body of the unilateral eye under sodium pentobarbital anesthesia (30 mg/kg body weight). After a postoperative period of 48 hours, the animals were deeply anesthetized and perfused intracardially with 1,000 ml of Ringer solution, followed by 2,000 ml of 1% paraformaldehyde and 1.25% glutaraldehyde in a 0.1 M phosphate buffer (pH 7.4) which was then followed by 1,000 ml of 10% sucrose in the same buffer. The brain was cut into serial transverse sections at 60 microns on a freezing microtome. Every section was treated with tetramethyl benzidine (TMB). Based on cytoarchitectural and HRP results, the pretectum of the adult hen was divided into the following eight nuclei: nucleus principalis pretectalis (P), nucleus subpretectalis (SP), nucleus principalis precommissuralis (PPC), nucleus medialis pretectalis (PTM), nucleus pretectalis dorsalis (APd), nucleus area pretectalis (AP), nucleus spiriformis lateralis (SPL), and nucleus spiriformis medialis (SPM). The SPL and SPM lay closely adjacent to each other, although the boundary between them can be easily defined in any section. Furthermore, the SPM could be divided into two subnuclei: the dorsal part of the SPM (SPMd) located just under the SMT and dorsomedial to the P, and the ventral part of the SPM (SPMv), which was located above the PPC and ventromedial to the P. Retinal projections were found in the APd, the PTM, the AP and the SPM, contralaterally. APd was the smallest nucleus among the pretectal nuclei lying just above the tractus septomesencephalicus (SMT) and received the heaviest retinal inputs. In the PTM, clear terminals were distributed over the whole of the nucleus, whereas strong labeled terminals were also found around the principal pretectal nucleus. Slight retinal inputs were found in the ventral part of the SPM. Furthermore, heavily labeled terminals were found in the medial part of the AP designated as the interstitial nucleus of the posterior commissure by Niimi. Terminals in the ventral part of the SPM and the medial part of the AP have not been reported in the previous studies in the chick and pigeon. There were no terminals in the contralateral P, SPL, SP, PPC, and the ipsilateral brain stem.

Animals

[Analysis of electrically evoked response (EER) in relation to the central visual pathway of the cat (2). Response characteristics of the lateral geniculate neurons].

To analyze the electrically evoked response (EER) in relation to the central visual pathway, the response characteristics of the lateral geniculate neurons (LGNs) of the EER in 35 anesthetized adult cats were studied. Responses of the LGNs showed interindividual variation of more than one log unit in terms of the stimulus threshold for electrical stimuli. As the stimulus intensity increased, the spikes with constant latencies were recorded, which showed bursts with much stronger stimuli. The latencies of the spikes were closely correlated with those of negative components of EER. The LGNs were divided into two major groups by the latency. The periodical and alternative excitation of these neurons contributed to form the first negative wave of EER. The latency of these two major groups of LGNs was reversed when the electrode polarity was changed. At higher stimulus intensities, the components with short latency became dominant and those with longer latency were suppressed. The above results suggested that the periodical excitation of LGNs and the formation of the prominent EER components may result from the interaction between on- and off-type retinal ganglion cells and amacrine cells. It was also suggested that the origins of the wavelets in negative waves of EER at strong stimuli are the bursts of the spikes of the visual cortex neurons.

Animals

Pancreatic pseudocyst in the left hepatic lobe: a report of two cases.

The ultrasound and computed tomographic imaging features in a rare pancreatic pseudocyst of the liver are described in two patients. The pseudocysts occurred in the left lobe in both cases, one after a traumatic injury and the other after alcoholic pancreatitis. The possible topographical sequences with which pancreatic secretions entered the left hepatic lobe to form a cyst are discussed.

Adult

Afferent and efferent connections of the oculomotor region of the fastigial nucleus in the macaque monkey.

Afferent and efferent connections of the fastigial oculomotor region (FOR) were studied in macaque monkeys by using axonal transport of wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP). When injected HRP is confined to the FOR, retrogradely labeled cells appear in lobules VIc and VII of the ipsilateral vermis and in group b of the contralateral medial accessory olive (MAO). In reference to the maps of topographical organization, the extent of the effective site in the fastigial nucleus (FN) could be assessed from the distributions of labeled Purkinje cells (P cells) in the vermis and labeled olivary neurons in the MAO. In contrast to the unilateral nature of the P-cell and climbing-fiber projections, those from the other brainstem regions to the FOR were bilateral. Following the injection of HRP into the FOR, the largest number of retrogradely labeled cells appeared in the pontine nuclei. Although the number of labeled cells was greater on the contralateral side in both the peduncular and dorsomedial pontine nuclei (DMPN), the number of each side was virtually identical in the dorsolateral pontine nucleus (DLPN). In the nucleus reticularis tegmenti pontis (NRTP), labeled cells were located only in its medial and dorsolateral portions bilaterally. In the vestibular complex, labeled cells appeared in the superior (SVN), medial (MVN), and inferior vestibular nuclei (IVN) bilaterally. The lateral vestibular nucleus (LVN), including y group and the ventrolateral vestibular nucleus, were free of labeled cells. Labeled cells appeared also in the perihypoglossal nucleus (PHN) bilaterally. In the pontine raphe (PR) and paramedian pontine reticular formation (PPRF), labeled cells appeared bilaterally in the caudal third of the area between the oculomotor and abducens nuclei. Labeled cells appeared also in the mesencephalic and medullary reticular formation. Tracing of anterogradely labeled axons demonstrated that most fibers from the FOR decussated within the cerebellum and entered the brainstem via the contralateral uncinate fasciculus. Some crossed fibers ascended with the contralateral brachium conjunctivum and terminated in the midbrain tegmentum. A small contingent of fibers advanced further to the thalamus. In the mesodiencephalic junction, labeled terminals were found contralaterally in the rostral interstitial nucleus of medial longitudinal fasciculus (riMLF) and a medial portion of FOrel's H Field. They appeared also in the central mesencephalic reticular formation (cMRF), the periaqueductal gray (PAG), the posterior commissure nucleus, and the superior colliculus. The oculomotor and trochlear nuclei, the red nucleus, and the interstitial nucleus of Cajal were free of labeled terminals.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways