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N Nishikawa

Publications and source records attributed to N Nishikawa.

At least 73 records · Page 4Linked to original sources

The in vitro and ex vivo antiplatelet effect of TRK-100, a stable prostacyclin analog, in several species.

Effect of TRK-100, a stable PGI2 analog, on platelet function was tested in vitro and ex vivo. TRK-100 at the dose range of 0.5-300 nM inhibited platelet aggregation induced by arachidonic acid, adenosine 5'-diphosphate and collagen in several species including human platelets. The potency of TRK-100 was 1/2 to 1/5 that of PGI2. The effect was strong in human and cat platelets. In conscious rabbits and rats, oral TRK-100 at the dose range of 0.1-1 mg/kg inhibited ex vivo platelet aggregation up to 80% in the rat and 70% in the rabbit, and the effect lasted over 5 hr. However, in both species, the effect on blood pressure was minimal. In anesthetized rabbits, inhibition of platelet aggregation was the same level as in the conscious animal, but blood pressure depression was observed. Cyclic AMP levels of human platelets, 2 min after incubation, was elevated up to 2.4 microM/10(9) platelets by 100 ng/ml of PGI2 and 1.5 microM by 100 ng/ml of TRK-100. It was shown that TRK-100 has a potent antiplatelet effect both in vitro and ex vivo in many species through elevation of platelet cAMP. These results suggest that TRK-100 may be a potential oral antithrombotic drug.

Adenosine Diphosphate↗

Reduced vasoactive intestinal polypeptide immunoreactivity in the pituitaries of hormone-deficient mutant mice.

The prolactin-producing cells of the bovine anterior pituitary were found to contain a vasoactive intestinal polypeptide (VIP) immunoreactive substance, thus suggesting a role for VIP in the regulation of prolactin release. The pituitaries of the dw and lit strains of mutant mice, congenitally deficient in prolactin-producing cells, and hyt mice, which were found to have reduced numbers of prolactin-producing cells, showed a markedly reduced VIP immunoreactivity. Hypothalamic VIP immunoreactivity, however, was found to be unchanged in the three strains of mutant mice, indicating that the high concentration of VIP in the hypothalamus does not derive from the adenohypophysis through retrograde flow. The deficiency in the mutant mice seems to be due to the lack of prolactin target cells in the pituitary.

Animals↗

Alteration of cerebral ganglioside metabolism in developing Snell dwarf mice.

The ganglioside metabolism of the Snell dwarf cerebrum was examined on postnatal days 15 and 20, by monitoring the rate of incorporation of radioactivity into each ganglioside species from tritiated N-acetyl-D-mannosamine. It was found that the turnover rate of the GM3 ganglioside was reduced throughout the entire period of development, resulting in retardation of A pathway metabolism which becomes abundant during late cerebral development. In addition, the turnover rate of the GM4 species, which is considered related to myelin formation, was also found to be reduced throughout the entire period of cerebral development.

Animals↗

The morphology of trigeminal nociceptive neurons in the caudal bulbar lateral reticular formation of the cat.

Two types of trigeminal nociceptive neurons, i.e. subnucleus reticularis ventralis (SRV) and wide dynamic range (WDR) neurons were identified in the caudal bulbar lateral reticular formation (LRF) and intracellularly stained with horseradish peroxidase. SRV neurons were large neurons characteristic of the subnucleus reticularis ventralis. Their dendrites were confined to the LRF. WDR neurons were situated in the subnucleus reticularis dorsalis. Their dendrites penetrated into the magnocellular layer, but did not reach the substantia gelatinosa.

Animals↗

Spinal neurons with branched axons traveling in both the dorsal and dorsolateral funiculi.

Antidromic search stimuli were delivered to cervical (C2-C3) dorsal and dorsolateral funiculi that were dissected apart from one another and from the rest of the spinal cord. Fifty-six neurons were antidromically identified in the dorsal horn of the lumbosacral enlargement. Of these neurons, 23 were activated antidromically from both the dorsal columns and the ipsilateral dorsolateral funiculus. The neurons were found at depths corresponding to laminae III and IV. About half of the neurons responded only to innocuous, tactile stimuli whereas the other half responded to both innocuous and noxious stimuli. The existence of neurons with branched axons ascending both the dorsal and dorsolateral funiculi raises the possibility that the dorsal column postsynaptic and spinocervical tracts may not be completely independent projections.

Animals↗

Intraspinal connections of dorsal column postsynaptic neurons in the cat--a physiological analysis.

Dorsal column postsynaptic (DCPS) neurons in the dorsal horn of the spinal cord have been identified by antidromic stimulation and intracellularly recorded in anesthetized cats. In about one-half of the cells, the antidromic stimulus evokes only an antidromic potential. This potential sometimes has an atypical shape due to penetration-induced depolarization. Atypical potentials are converted into typical antidromic spike potentials after intracellular injection of hyperpolarizing current. In the other one-half, the antidromic potentials are followed by postsynaptic activity. Intracellular analysis indicates that this postsynaptic activity is generated largely by activation of the intraspinal collaterals of A-beta primary afferents that are ascending the dorsal columns. Part of this postsynaptic activity has been produced monosynaptically. Polysnaptic responses are also evident; these are thought to be initiated by A-beta axons, desending axons from neurons in the dorsal column nuclei, or the local collaterals of the DCPS axons themselves. The results indicate that the DCPS system is nonlemniscal in nature and may be involved in those pain modulation systems that are activated by A-beta afferents.

Action Potentials↗

The morphology of dorsal column postsynaptic spinomedullary neurons in the cat.

Dorsal column postsynaptic ( DCPS ) spinomedullary neurons from the cat's lumbosacral enlargement were identified by antidromic stimulation of the cervical dorsal columns and stained intracellularly with horseradish peroxidase. The cell bodies were located in laminae III-IV. Their dendritic arbors were elongated rostrocaudally but narrow mediolaterally. On the average, the arbors were X 5 longer than they were wide. Most of the neurons had nearly all of their dendrites in laminae III-IV and some of the neurons had, in addition, a considerable amount of dendritic surface area in lamina V. Only one neuron had more than a very small amount of dendritic surface area dorsal to lamina III. Seven of the neurons had unmyelinated axon collaterals that arborized extensively and issued varicosity-bearing terminal branches in laminae III-V, both within and beneath their dendritic territories. All of the neurons were excited by myelinated, low-threshold mechanoreceptors. Since the rostrocaudally elongated and mediolaterally narrow dendritic arbors of DCPS neurons are in register with the laminae III-IV terminal distributions of myelinated, low-threshold mechanoreceptors, it is probable that this excitation arises from a monosynaptic and topographically discrete innervation. About one-half of the DCPS neurons were also excited by noxious stimuli. It is probable that this excitation is accomplished by a polysynaptic pathway since DCPS dendritic arbors and nociceptor terminal distributions are largely or completely separate.

Afferent Pathways↗

Extra- and intracellular recordings from dorsal column postsynaptic spinomedullary neurons in the cat.

Dorsal column postsynaptic (DCPS) spinomedullary neurons in the dorsal horn of spinal segments L6-S1 of adult cats anesthetized with sodium pentobarbital were identified by antidromic stimulation of cervical dorsal columns that were dissected free of, and electrically isolated from, the rest of the spinal cord. The neurons were categorized with respect to natural stimulation of their cutaneous receptive fields. An equal number of low-threshold mechanoreceptive and wide-dynamic-range neurons were found. No DCPS neurons could be classified as nociceptive-specific. All neurons received input from low-threshold mechanoreceptors with myelinated axons. There was no evidence that any neurons received monosynaptic input from unmyelinated, primary afferent fibers. The average conduction velocity of the antidromic responses was 45.7 m/s. Nearly half of the DCPS cells showed an antidromic spike followed by synaptically driven responses that were probably evoked by antidromic invasion into the intraspinal collaterals of A-beta primary afferent fibers that ascended the dorsal columns. Intracellularly recorded synaptic responses of DCPS neurons to dorsal column and receptive field stimulation usually consisted of an EPSP with overriding spike potentials followed by a prolonged IPSP whose amplitude decreased markedly as the stimulus frequency was increased in the range of 5 to 30 Hz. The results indicate that DCPS neurons constitute a projection system capable of signaling innocuous and tissue-damaging mechanical stimuli. The DCPS projection may play a role in the modulation of touch and pain perception.

Animals↗

Immunocytochemical evidence for a serotoninergic innervation of dorsal column postsynaptic neurons in cat and monkey: light- and electron-microscopic observations.

Dorsal column postsynaptic neurons in the lumbosacral enlargements of cats and a monkey were retrogradely labeled by placing horseradish peroxidase on their severed axons in the thoracic dorsal columns. After visualizing the retrogradely-labeled neurons, the tissue was immunocytochemically stained with an antiserum directed against serotonin. Immunoreactive axonal varicosities contacted the perikarya and proximal dendrites of every retrogradely-labeled neuron examined in cat (mean 61 contacts/cell) and nearly every neuron in the monkey (mean 18 contacts/cell). Electron microscopy showed that the immunoreactive axonal varicosities contained pleomorphic (round to oval) agranular vesicles and formed symmetrical synapses on retrogradely-labeled neurons. It is concluded that dorsal column postsynaptic neurons are innervated directly by the brain stem's descending, serotoninergic system(s).

Animals↗

The cells of origin of the dorsal column postsynaptic projection in the lumbosacral enlargements of cats and monkeys.

Dorsal column postsynaptic (DCPS) neurons in the lumbosacral enlargements of cats and macaque monkeys were retrogradely labeled by placing HRP on their severed axons within the dorsal columns. The enlargements of both species contained 800-1,100 labeled DCPS neurons. The DCPS projection is thus as large as the feline spinocervical tract. It is very probable that most of these neurons project to the dorsal column nuclei and thereby constitute one of the major sources of somatosensory input to the brain. In the cat, DCPS neurons were concentrated in a band centered in lamina IV that swept down through laminae V-VI along the medial border of the dorsal horn. A second concentration of labeled cells was found in dorsomedial lamina VII. In the monkey, DCPS neurons were concentrated in a relatively broader band in laminae III-IV, and scattered cells were consistently observed throughout laminae V-VII and X and in the dorsolateral white matter. The prominence of the monkey's DCPS projection suggests that humans also have such a projection.

Animals↗

Effects of picrotoxin upon response characteristics of wide dynamic range neurons in the spinal cord of cat and monkey.

The effects of a subconvulsive dose of picrotoxin (0.5 mg/kg) upon response characteristics of wide dynamic range (WDR) neurons in the spinal dorsal horn were investigated in cats and Japanese macaques. After intravenous administration of picrotoxin, the low threshold mechanoreceptive field of WDR neurons were expanded, and the high threshold surround of the receptive field disappeared. Concomitantly, responses of WDR neurons to noxious heat stimulation were abolished. It was suggested that picrotoxin may close the presynaptic gate for nociceptive input to WDR neurons, enhancing excitatory action of tactile input on the same neurons.

Analgesics↗

[A case of optic atrophy of a lead worker (author's transl)].

We found bilateral optic atrophy and visual field defects (paracentral scotoma and blind spot enlargement) in a worker who had been engaged in lead refining work in a lead refinery factory for 30 years. The worker is a 53-year-old Japanese male with no specific family and past histories. He complained of headache and vertigo after getting up in the morning for the past several years. He had several examinations in departments of psychiatry, otorhinopharyngolaryngology, neurosurgery and ophthalmology. Abnormal findings were not obtained by neurological examinations, electroencephalography, CT scanning for the head, Doppler test for jugular, vertebral and ophthalmic arteries, and equilibrium function (nystagmus) tests, except for labyrinthine deafness. Though the environmental conditions in this factory had been much improved recently, considerable high concentrations of lead were found till around 1965. Considering the results of hematological examinations for the past 30 years, it is clear that he had been affected by lead. We suspect that the causative relationship exists between lead exposure and optic atrophy and visual field defects.

Humans↗

Reappraisal of somatotopic tactile representation within trigeminal subnucleus caudalis.

1. The medulla oblongata caudal to the obex was explored with glass capillary microelectrodes filled with fast green dye in urethan-chloralose-anesthetized cats. Concurrently, the trigeminal integument was mechanically stimulated. Two classes of units, which were activated by innocuous mechanical stimulation of the ipsilateral trigeminal integument, were identified. Both of them showed a somatotopic organization. 2. Units maximally activated by tactile stimulation of a small receptive field in the ipsilateral trigeminal integument were located in pars magnocellularis of the trigeminal subnucleus caudalis. Receptive field falling within, the mandibular distribution were found in the dorsomedial part of pars magnocellularis, maxillary fields occurred next, and ophthalmic fields were represented ventrolaterally. The rostrum (the mouth and nose) was represented just behind the obex, and the receptive field represented gradually shifted to the periphery of the face along the rostrocaudal axis, finally proceeding to dermatomes of cervical segments. At each transverse plane, tactile sensation of the most rostral segment of the represented integument projected onto the marginal zone of pars magnocellularis immediately adjacent to substantia gelatinosa, while the most peripheral segment projected onto the core of quasi-semicircular pars magnocellularis. The result is in contrast with the scheme proposed by previous investigators. 3. Within the lateral part of subnucleus reticularis dorsalis medullae oblongatae, which is ventromedially contiguous with pars magnocellularis, trigeminal units homologous with lamina V units in the spinal dorsal horn were identified. Typically, these units had a graded response in the center of the receptive field, but responded only to strong mechanical stimuli applied to the periphery of the receptive field. In the center of the receptive field, tactile stimulation of a small restricted area was effective, and the tactile receptive field showed a somatotopic organization. The mandibular distribution was represented dorsomedially, the maxillary distribution next to that, and the ophthalmic distribution laterally. Furthermore, a rostrocaudal differentiation similar to that observed with tactile units in pars magnocellularis was found. Hence, a double somatotopic representation of tactile sensation within the caudal medulla oblongata was indicated.

Animals↗