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Biomedical subjects

N Nakata

Publications and source records attributed to N Nakata.

At least 55 records · Page 3Linked to original sources
PubMed1993

Inhibition of ischaemic tolerance in the gerbil hippocampus by quercetin and anti-heat shock protein-70 antibody.

To clarify the role of heat shock protein-70 (HSP70) in ischaemic tolerance following pretreatment with sublethal cerebral ischaemia, we examined whether the induction of tolerance in the gerbil hippocampus is inhibited by quercetin, an inhibitor of HSP70 expression, or anti-HSP70 antibody. A 3 min period of forebrain ischaemia was induced following pretreatment with 2 min of ischaemia and 3 days of reperfusion. Quercetin or anti-HSP70 antibody was continuously infused into the left lateral ventricle using an implanted osmotic minipump started 3 h after or 2 h before the first ischaemia. The animals were killed 4 days after the second ischaemia for histological observations. Both agents produced no neuronal damage in the brain following a single 2 min period of ischaemia. The neuronal density of the CA1 hippocampus in animals subjected to treatment with quercetin and anti-HSP70 antibody was significantly lower than vehicle-treated animals but were significantly higher than animals with a single 3 min period of ischaemia. Thus, the present study showed that quercetin and anti-HSP70 antibody prevent the induction of ischaemic tolerance. The result suggests that HSP70 expression, at least in part, plays a role in the induction of ischaemic tolerance.

Animals↗
PubMed1993

The absence of a surface protease, OmpT, determines the intercellular spreading ability of Shigella: the relationship between the ompT and kcpA loci.

A large plasmid-encoded protein, VirG, on the bacterial surface is essential for the spreading of Shigella by eliciting polar deposition of filamentous actin in the cytoplasm of epithelial cells. VirG expression from the large plasmid is diminished greatly when it is introduced into Escherichia coli K-12 from Shigella. In an attempt to identify factors affecting VirG expression, we found that the absence of the ompT gene, encoding outer membrane protease OmpT, restored full production of VirG protein to E. coli K-12. Conversely, upon introduction of the ompT gene of E. coli K-12 into Shigella, spreading ability was completely abolished, probably because of the proteolytic degradation of VirG protein by OmpT. Analysis of the DNA sequence of the ompT region indicated that the absence of the ompT gene occurred in Shigella and enteroinvasive E. coli strains, and that the absent DNA segment corresponded to a remnant lambdoid phage structure found in E. coli K-12, which encompasses a 21 kb DNA segment spanning from argU through to the ompT genes. Since ompT is located near purE in E. coli K-12 and a virulence locus for provoking keratoconjunctivitis in the eyes of guinea-pigs, named kcpA, is located near purE in S. flexneri, and the two loci are involved in VirG expression, the KcpA- mutants of S. flexneri 2a constructed were examined for correlation between acquisition of ompT and VirG degradation. Our data suggest that the previous recognition of a kcpA locus in S. flexneri is the result of transfer of the ompT gene from E. coli K-12, giving rise to a KcpA- phenotype. These results indicate that the lack of OmpT protease confers upon Shigella the ability to spread into adjacent epithelial cells.

Amino Acid Sequence↗
PubMed1993

Effects of repeated cerebral ischemia on extracellular amino acid concentrations measured with intracerebral microdialysis in the gerbil hippocampus.

BACKGROUND AND PURPOSE: To clarify the role of elevated extracellular amino acid concentrations during ischemia on the cumulative neuronal damage after repeated cerebral ischemic insults, using a microdialysis technique we measured concentrations of the amino acids glutamate, glutamine, glycine, taurine, and gamma-aminobutyric acid in the gerbil hippocampus over three 2-minute forebrain ischemic insults induced at 1-hour intervals. METHODS: Under light anesthesia, the bilateral common carotid arteries were occluded with aneurysm clips at 1-hour intervals. Samples were collected by microdialysis at 10-minute intervals, and the amino acid concentrations were determined using a high-performance liquid chromatography system. RESULTS: During and immediately after the first ischemic insult, concentrations of glutamate, glycine, and taurine, but not glutamine, increased significantly. Glutamate and taurine concentrations rose again during the second and third ischemic insults, but the increases were smaller than those during the first insult. By contrast, glutamine concentrations increased slightly but significantly during the second and third ischemic insults. The extracellular concentration of gamma-aminobutyric acid before the ischemic insults was below the level of detectability but increased markedly during each ischemic insult, with similar declines in the amounts released during later insults. Concentrations of all amino acids returned to baseline after 10 minutes of reperfusion and remained at baseline until the subsequent ischemic insult was induced. CONCLUSIONS: It is well established that glutamate released during ischemia plays a crucial role in ischemia-induced neuronal death. However, the present results indicate that cumulative neuronal damage following sublethal ischemic insults is not caused by an exaggerated release of excitatory amino acids during subsequent ischemic insults but strongly suggest that increased intracellular reactions leading to cell death play a major role.

Amino Acids↗
PubMed1993

[Effects of NC-1100, a calcium channel blocker, on experimental cerebral ischemia/anoxia in rodents].

The anti-ischemic and anoxic effects of NC-1100, a piperazine type calcium channel blocker, were investigated in various cerebral ischemia and anoxia models in mice, gerbils and guinea pigs. Minimal effective doses of NC-1100 were 8 mg/kg, i.p. and 30 mg/kg, p.o. for KCN-induced anoxia; 16 mg/kg, i.p. for decapitation-induced gasping; 30 mg/kg, i.p. for cerebral ischemia induced by occlusion of bilateral carotid arteries in gerbils; and 10 microM for the in vitro ischemic model in hippocampal slices. Moreover, NC-1100 attenuated the disturbance of cerebral energy metabolism induced by decapitation in mice. These results suggest that NC-1100 has a cerebral protective effect, and that attributable to its ability to improve the cerebral energy metabolism disturbance.

Animals↗
PubMed1993

Improving effects of FG-7080, a serotonin reuptake inhibitor, on scopolamine-induced performance deficits of memory tasks in rats.

A novel serotonin reuptake inhibitor, (-)trans 4-(4-fluorophenyl)-3-(4-methoxyphenoxy-methyl)piperidine hydrochloride (FG-7080), was investigated for its effects on scopolamine-induced impairments in memory tasks of rats. In the radial-arm maze task, FG-7080 (3 mg/kg, p.o.) improved the impaired performance. FG-7080 (1 mg/kg, p.o.) administered before the acquisition trial reduced the acquisition deficits in the passive avoidance task. Thus, the compound showed improving effects in the appetitive and aversive memory tasks. These findings suggest that FG-7080 may ameliorate the cognitive impairments caused by the cholinergic dysfunction.

Animals↗
PubMed1993

Impaired sensory conduction in a mixed nerve induced by high frequency stimulation of the muscle fibres. An experimental study in cats.

To see if symptoms such as sensory disturbance or numbness worsen during exercise as is thought to occur in entrapment neuropathy, we studied the interaction between sensory and muscle nerve fibres in a mixed nerve in cats. Stimulation electrodes were placed on both the deep (muscle) and superficial (sensory) branch of the radial nerve at the elbow. High frequency stimulation at 100 Hz was applied to one branch for five minutes and the nerve action potential of the other branch was recorded at the axilla where the radial nerve is mixed. The stimulation decreased the amplitude of the nerve action potential and prolonged its latency. Recovery from these changes was gradual, and changes were the same whichever branch was stimulated. When a cat's leg was made ischaemic, the changes were more pronounced. The changes in the nerve action potential may have arisen from ischaemia in the nerve, possibly caused by high frequency stimulation.

Acoustic Stimulation↗
PubMed1993

Effect of the rice bran-derived phytosterol cycloartenol ferulic acid ester on the central nervous system.

In order to investigate the effect of cycloartenol ferulic acid ester (CFE, CAS 21238-33-5), a component of gamma-oryzanol which is a phytosterol derived from rice bran, on the central nervous system, a variety of pharmacological tests were performed. It was shown that CFE had a suppressant effect on the central nervous system, but its properties were different from those of existing major and minor tranquilizers. In addition, its efficacy in several models of cerebral dysfunction was demonstrated. Since any clear effects could not be obtained under the treatments with gamma-oryzanol, CFE seems to be more useful than gamma-oryzanol. Thus the results of this study suggest that CFE may serve as a new plant-derived cerebral activator possessing a wide range of pharmacological actions.

Amnesia↗
PubMed1993

[Correlation between induction of ischemic tolerance and expression of heat shock protein-70 in the rat hippocampus].

We investigated the correlation between protection against ischemic neuronal damage by preconditioning with sublethal ischemia and the expression of heat shock protein-70 (HSP70). Three minutes of forebrain ischemia in the rat induced by four-vessel occlusion and 3 days of reperfusion was followed by 6, 8, and 10 minutes of ischemia. Seven days after the second ischemia, the brains were used for histology. Two hours, 1, 3, and 7 days after 3 or 6 minutes of ischemia, the brains were used for immunohistochemistry with an antibody raised against HSP70. Three minutes of ischemia produced no neuronal damage in the hippocampus. Six, 8, and 10 minutes of ischemia produced severe neuronal damage to CA1. However, CA1 neurons were preserved in animals subjected to 6 and 8 minutes of ischemia following preconditioning with 3 minutes of ischemia. Immunostaining showed that HSP70 was induced in the CA1 subfield 3 days after 3 minutes of ischemia. HSP70 was stained in the CA1, CA3, and CA4 subfields 1 and 3 days after 6 minutes of ischemia with or without preconditioning. However, HSP70 was also stained in CA1 2 hours and 7 days after 6 minutes of ischemia following preconditioning. These results strongly suggest that stress response induced by sublethal ischemia protects against ischemic neuronal damage. However, the protection was not seen when HSP70 synthesis was delayed. Presence of HSP70 during and immediately after ischemia may be critical for the protection against ischemic neuronal damage following preconditioning.

Animals↗
PubMed1992

Protective effects of serotonin reuptake inhibitors, citalopram and clomipramine, against hippocampal CA1 neuronal damage following transient ischemia in the gerbil.

To clarify the role of serotonin in cerebral ischemia, we examined the effects of selective serotonin reuptake inhibitors, citalopram and clomipramine, on ischemic neuronal damage in the gerbil. Pretreatment with citalopram (40 mg/kg i.p.) and clomipramine (20 mg/kg i.p.) protected against neuronal destruction of hippocampal CA1 pyramidal cells following 5 min of forebrain ischemia. Furthermore, microdialysis assays showed that a striking increase in extracellular excitatory amino acid levels during ischemia was significantly inhibited by pretreatment with citalopram and clomipramine. However, citalopram (40 mg/kg i.p.) did not alter the extracellular amino acid concentrations in normal gerbils. Thus, serotonin reuptake inhibitors have a protective effect against ischemic neuronal damage. Furthermore, the present result suggests that the protective effect is mediated through prevention of the accumulation of extracellular excitatory amino acids during and after ischemia.

Amino Acids↗
PubMed1992

Protection of rat hippocampus against ischemic neuronal damage by pretreatment with sublethal ischemia.

We examined whether preconditioning with sublethal ischemia protects against neuronal damage following subsequent lethal ischemic insults. Forebrain ischemia for 3 min in Wistar rats increased heat shock protein-70 immunoreactivity in the hippocampal CA1 subfield but produced no neuronal damage. Preconditioning with 3 min of ischemia followed by 3 days of reperfusion protected against hippocampal CA1 neuronal damage following 6 and 8 min of ischemia but not damage after 10 min of ischemia. The result strongly suggests that stress response induced by sublethal ischemia protects against ischemic brain damage.

Animals↗
PubMed1992

Effects of pretreatment with sublethal ischemia on the extracellular glutamate concentrations during secondary ischemia in the gerbil hippocampus evaluated with intracerebral microdialysis.

To elucidate the role of glutamate in the pathogenesis of altered neuronal vulnerability following sublethal ischemia, we measured the extracellular concentrations of glutamate in the gerbil hippocampus using a microdialysis technique. During and immediately after 3-min forebrain ischemia, the extracellular glutamate level showed a striking increase. However, pretreatment with 2-min ischemia 1 h or 4 days before secondary 3-min ischemia did not alter the amount of glutamate released. The result indicates that cumulative damage and tolerance, which take place after pretreatment with sublethal ischemia, are not induced through modification of the amount of glutamate released during secondary ischemia.

Animals↗
PubMed1992

Identification and characterization of virK, a virulence-associated large plasmid gene essential for intercellular spreading of Shigella flexneri.

Seven virulence loci have been identified by Tn5 insertion mutagenesis on the large 230 kb plasmid (pMYSH6000) of Shigella flexneri 2a. In this study, we used Tn10 insertion mutagenesis and identified a novel virulence locus on pMYSH6000 responsible for bacterial spread. Characterization of the invading bacteria of the Tn10 insertion mutants in the epithelial cells revealed that the bacteria were capable of at least some intracellular spreading but not intercellular spreading. Immunoblot analysis of lysates of the Tn10 insertion mutants with a VirG-specific antipeptide antibody revealed diminished levels of the 116 kDa VirG protein. The virG mRNA in the mutants, however, was expressed at the same level as that in the wild type. The DNA region required for the virulence phenotype was localized to a 1.6 kb DNA sequence in the SalI-K fragment on the plasmid, and thus the locus was designated virK. Expression of virK in Escherichia coli using a T7 RNA polymerase-dependent promoter system yielded a 36 kDa protein. The nucleotide sequence of 1642 bp encoding VirK function was determined, and an open reading frame encoding 316 amino acid residues was shown to encode the VirK protein. The virK region was highly conserved among the large virulence plasmids of shigellae and enteroinvasive Escherichia coli. These results suggest that VirK function is an essential virulence determinant for shigellae involved in the expression of virG gene product at post-transcriptional level.

Amino Acid Sequence↗
PubMed1992

Antinociceptive mechanisms of [D-Arg2]-dermorphin tripeptide analogs.

These studies examined the antinociceptive effects and mechanisms of opioid activity of synthetic dermorphin tripeptide analogs containing D-Arg as the second amino acid, H-Tyr-D-Arg-Phe-NHCH3 and H-Tyr-D-Arg-Phe-N(CH3)2. Both tripeptides, administered i.c.v., i.t. and s.c. in mice, produced a potent and long-lasting antinociceptive activity as compared with morphine. In the guinea pig isolated ileum (GPI) assay, the IC50 value of both peptides was lower than that of morphine on the electrically induced contractions of the GPI. In radioligand binding studies with rat brain membrane synaptosomes, both tripeptides bound with high affinity to [3H]DAMGO-labeled mu-type sites, whereas they bound with no or negligible affinity to [3H]DPDPE-labeled delta sites and [3H]U-69593-labeled kappa sites. In the enzymatic degradation using high-performance liquid chromatography, both tripeptides showed good enzymatic stability after 25 hr of incubation with solubilized enzymes of mouse brain or spinal cord, in contrast to a rapid degradation of Met-enkephalin. The in vitro and in vivo pharmacological profile of [D-Arg2]-dermorphin tripeptide analogs demonstrates that they are potent and selective agonists at the mu opioid receptor. A high resistance of the tripeptides to enkephalin-degrading enzymes may largely contribute to their prolonged opioid activity.

Amino Acid Sequence↗
PubMed1992

Differential effects of intracerebroventricular AF64A injection, nucleus basalis of Meynert lesion, and scopolamine on place navigation and open-field behavior of rats.

The present study was conducted to compare the behavioral effects of intracerebroventricular AF64A injection, electrolytic lesion of the nucleus basalis of Meynert (NBM), and systemic scopolamine treatment, all of which are typical experimental models of central cholinergic system dysfunction, on place navigation performance and open-field behavior in rats. The animals were trained in a circular pool to escape from opaque water onto the hidden platform fixed at a particular location for 5 days. Significant performance deficits were observed in all the models tested. However, it is of importance that any impairments relating to information storage within a day or across days were not obtained. Choline acetyltransferase activity was decreased in the hippocampus of AF64A-injected rats and in the cortex of NBM-lesioned rats, respectively, but those changes did not simply associate with the reductions of the performance. These results suggest that the central cholinergic system is only partially involved in cognitive process. In the open-field test, ambulation, rearing, defecation, and urination were measured for 5 min. Patterns of changes in the open-field behavior were clearly different among the 3 models, indicating variability of the effects of these cholinergic manipulations on motor activities and emotionality.

Animals↗
PubMed1990

Spinal antinociception: comparison of a dermorphin tetrapeptide analogue, [D-arginine2, sarcosine4]-dermorphin (1-4) and morphine in rats.

Intracerebroventricular injections of [D-arginine2, sarcosine4]-dermorphin (1-4) (DAS-DER 1-4) and morphine produced a dose-dependent inhibition of the tail-flick response to thermal stimulation. The ED50 value for each drug was 3.23 (1.35-7.73) nmol/rat and 32.0 (13.3-76.6) nmol/rat, respectively. When injected into the spinal subarachnoid space, the ED50 value was 0.035 (0.015-0.086) nmol/rat for the tetrapeptide and 11.9 (5.7-25.2) nmol/rat for morphine, respectively. Antinociception induced by DAS-DER 1-4 and morphine, through the intracerebroventricular and intrathecal routes, was clearly reduced by pretreatment with a small dose of naloxone. After spinal transection, the antinociceptive potency of systemically-administered morphine was significantly reduced while that of DAS-DER 1-4 was unaltered. The activity of DAS-DER 1-4 and morphine was also reversed by naloxone in spinal animals. It is concluded that DAS-DER 1-4, a dermorphin analogue, has a minor supraspinal action but acts mainly at the level of the spinal cord, in contrast to the action of morphine.

Analgesics↗
PubMed1989

[Temporal changes in internal echoes in hepatic hemangiomas].

We have discovered a fact that there is a temporal changes of internal echo levels in hepatic hemangiomas. Nine hemangiomas in 6 cases diagnosed by CT were studied ultrasonographically by the real-time scanner during the observation period from 4 to 30 minutes. Low echo portions occupying within the tumor (low echo level ratio) showed temporal changes in 8 of 9 hemangiomas during this period. It is important to take temporal factors into consideration for the ultrasonographic diagnosis of hepatic masses. We coined the term "wax and wane" sign to the temporal changes of internal echo levels in the hepatic hemangioma.

Adult↗