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Biomedical subjects

N Nakata

Publications and source records attributed to N Nakata.

15 recordsLinked to original sources
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↗
PubMed1978

Experimental myositis ossificans: cartilage and bone formation in muscle in response to a diffusible bone matrix-derived morphogen.

Bone matrix gelatin, prepared by chemical extraction of soluble noncollagenous proteins, was half digested with a chromatographically purified collagenase. The residue was placed on one side and autologous muscle on the other side of cellulose acetate membranes in diffusion chambers and tissue cultures. In this avascular system, the muscle septa connective tissue proliferated and differentiated into cartilage. Muscle tissue cultured in media conditioned with matrix residues and then transferred into a vascularized muscle pouch differentiated into cartilage and bone. These observations form the basis for a working hypothesis that myositis ossificans is a response of new populations of proliferating intramuscular connective tissue cells to a bone matrix-derived diffusible molecule.

Animals↗
PubMed1977

Uptake of uric acid by separated renal tubules of the rabbit. I. Characteristics of transport.

A rapid filtration procedure was used to determine rates of uric acid uptake by a preparation of separated renal cortical tubules of the rabbit. The rate of uric acid uptake was temperature dependent and showed saturation kinetics with a K of 3.2 mM. The uptake was 50% lower when measured under nitrogen as compared with uptake under oxygen. The uptake rate increased with increasing sodium concentration and decreased with increasing potassium concentration. Uptake was stimulated by citrate, succinate and pyruvate, and inhibited by alpha-ketoglutarate. Parathyroid hormone and 10(-4) M adenosine 3':5'-monophosphate increased the uric acid uptake rate when preincubated with the tubules for 130 minutes before the addition of uric acid. Uric acid uptake in this preparation appears to occur by some form of carrier-mediated active transport.

Animals↗
PubMed1977

An osteosarcoma cell and matrix retained morphogen for normal bone formation.

Histophysiology, ultrastructure, chemical analyses of transplants and implants of Dunn and Ridgway mouse osteosarcomas demonstrate that tumorigenesis is a manifestation of deranged morphogenesis in developing mesenchymal cell populations. The end product of development is defective, incompletely calcified, disorganized bone without any inclusions of bone marrow tissue. When Dunn osteosarcoma is freeze-dried and then implanted, the tumor is resorbed and replaced by deposits of normal cartilage, bone, and bone marrow. Freeze-dried Ridgway osteosarcoma is replaced only by a fibrous connective tissue scar. Disaggregated Dunn tumor osteoblasts synthesize a trypsin-labile collagenase-resistant cell surface localized bone morphogen. Tumor matrix stroma, prepared by sequential chemical extraction of soluble non-collagenous proteins also contains significant quantities of the same bone morphogen. Tumor tissue pulverized to particle size as small as 44 micrometer3 transmitted bone morphogen more rapidly than intact tumor tissue. The total tumor cell and stroma mediated bone morphogen produces three times more normal bone than normal cortical bone matrix. Our working hypothesis is that a normal bone morphogenetic polypeptide (BMP) is synthesized by Dunn osteosarcoma cells and retained by the tumor matrix stroma. Neither the mechanism of transmission nor the mesenchymal cell receptor sites of BMP are known.

Alkaline Phosphatase↗
PubMed1977

Uptake of uric acid by separated renal tubules of the rabbit. II. Effects of drugs.

The effect of various drugs on the rate of uptake of uric acid by separated renal tubules of the rabbit was investigated. Determinations were made of 150 values and slopes of the inhibition curves. The most potent inhibitor of uric acid uptake was sulfinpyrazone, with an 150 of 0.02 mM. Calcium ipodate and benzbromarone were also potent inhibitors. Uricosuric drugs, with the exception of benzbromarone, had shallow inhibition slopes. Diuretic drugs had steep inhibition slopes. More than one mechanism of action is probably involved in the inhibition of uric acid uptake in separated renal tubules by drugs.

Animals↗
PubMedDate not supplied

Antinociceptive cross-tolerance between [D-Arg2]-dermorphin tetrapeptide analogs and morphine.

Cross-tolerance between [D-Arg2]-dermorphin tetrapeptide analogs and morphine with respect to antinociception was examined in the present set of experiments. Systemic administration of H-Tyr-D-Arg-Phe-Gly-NH2 (TDAPG-NH2), H-Tyr-D-Arg-Phe-beta-Ala-OH (TDAPA) or morphine over a period of 5 days produced the development of tolerance. In the cross-tolerance study, antinociception after subcutaneous (SC), intracerebroventricular (ICV) and intrathecal (IT) administrations of TDAPG-NH2 and TDAPA in morphine-tolerant mice was not significantly different from their respective effects in saline-pretreated control mice. A marked tolerance to SC- and ICV-administered morphine was seen in mice made tolerant to TDAPG-NH2 and TDAPA. However, IT administration of morphine produced no significant decrement in the antinociceptive activity in mice made tolerant to TDAPG-NH2 and TDAPA. These data indicate that [D-Arg2]-dermorphin tetrapeptide analogs can produce significant antinociception in morphine-tolerant mice.

Amino Acid Sequence↗