Search PubMed⌕ Search

Biomedical subjects

I Arai

Publications and source records attributed to I Arai.

At least 55 records · Page 3Linked to original sources
PubMed1996

Enhancement of dopamine release from the striatum through metabotropic glutamate receptor activation in methamphetamine sensitized rats.

An intracerebral microdialysis technique was applied to study the effect of metabotropic glutamate receptor (mGluR) agonist on dopamine release in the striatum of methamphetamine (MAP)-sensitized rats. Rats were treated with MAP (1 mg/kg, i.p.) once daily for 6 consecutive days, followed by a 6-day withdrawal. Perfusion of 0.1 mM (1S,3R)-1-aminocyclopentane-trans-1,3-dicarboxylic acid through a microdialysis probe placed in the striatum enhanced the extracellular dopamine level, and induced stereotyped behavior in MAP-sensitized rats. The enhancement of dopamine release and the stereotyped behavior were attenuated by co-perfusion of 0.4 mM RS-alpha-methyl-4-carboxyphenyl-glycine, a mGluR antagonist. The present results suggest that mGluRs may be involved in the expression of MAP-induced sensitization.

Animals↗
PubMed1996

[Clinical value of carbohydrate antigens, sialyl Lewis-x and sialyl Lewis-a in gastrointestinal cancer].

To evaluate clinical importance of the expression of sialyl Lewis-X (sLe(x)) and sialyl Lewis-a antigen (sLe(a)) in gastrointestinal cancers, we examined immunohistochemically expression of the two antigens in esophageal, gastric, colorectal, and pancreatic cancer. Expression of sLe(x) and sLe(a) were associated with several clinicopathologic features which reflect tumor aggressiveness in esophageal, gastric and colorectal cancer, but not in pancreatic cancer. In esophageal and colorectal cancer, survival rate of the patients with sLe(x) positive tumors was significantly poorer than that of the patients with sLe(x) negative tumors, while in gastric cancer that with sLe(a) positive tumors was significantly poorer than that with sLe(a) negative. Cox's multivariate analysis revealed that sLe(x) expression status was one of the significant discriminants of prognosis in colorectal cancer patients and sLe(a) status in gastric cancer patients. These results suggest that sLe(x) and sLe(a) expression could be involved in aggressiveness of gastrointestinal cancer and might prove to be a potent marker for prognosis in patients with gastric cancer and colorectal cancer.

Adult↗
PubMed1996

NG-nitro-L-arginine methyl ester attenuates the maintenance and expression of methamphetamine-induced behavioral sensitization and enhancement of striatal dopamine release.

We examined the roles of nitric oxide (NO) in methamphetamine (MAP)-induced behavioral sensitization and enhancement of striatal dopamine (DA) release using both in vivo and in vitro methods. Repeated administration of MAP produced augmentation of MAP-induced locomotor activity after 3-day withdrawal of MAP and an enhancement of MAP-evoked DA release from striatal slices after 6-day withdrawal. When the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L- NAME) was administered only during the period of MAP withdrawal, the behavioral sensitization and enhancement of DA release were attenuated significantly. In contrast, NG-nitro-D- arginine methyl ester, an inactive isomer of L-NAME, exhibited no such effect. When L-NAME was administered acutely before the challenge injection of MAP, behavioral sensitization was also attenuated only when the dose of L-NAME was high. Coadministration of L-NAME with MAP did not block the development of sensitization to MAP. We also examined whether MAP-induced behavioral sensitization and enhancement of DA release could be observed in vivo in a microdialysis experiment. Challenge injection of MAP caused marked enhancement of DA release in MAP-sensitized rats compared with saline-treated controls corresponding to robust augmentation of locomotor activity. When L-NAME was injected during the MAP withdrawal period, the enhancement of DA release and locomotor activity induced by challenge injection of MAP were attenuated. These results suggest that NO production plays a role in the maintenance (expression) of MAP-induced behavioral sensitization and enhancement of DA release but not in the development of these effects.

Animals↗
PubMed1995

N-methyl-D-aspartate stimulates dopamine release through nitric oxide formation in the nucleus accumbens of rats.

Intracerebral microdialysis technique was utilized to study the effect of NG-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, on N-methyl-D-aspartate (NMDA)-induced dopamine overflow in the nucleus accumbens of unanesthetized, freely moving rats. Perfusion of 1 and 3 mM NMDA through the microdialysis probe dose-dependently increased the extracellular dopamine level in the nucleus accumbens. Coapplication of 0.5 mM D-(-)-2-amino-5-phosphonovaleric acid (D-AP5), a selective and competitive NMDA receptor antagonist, significantly reduced the dopamine overflow induced by 3 mM NMDA. Perfusion of 0.5 mM NG-nitro-L-arginine alone did not affect the basal dopamine level, whereas it suppressed the NMDA-evoked dopamine overflow in the nucleus accumbens when concurrently applied with 3 mM NMDA. These results suggest that NO mediates, at least in part, dopamine release resulting from NMDA receptor activation in the nucleus accumbens of rats.

Animals↗
PubMed1995

Establishment of a T cell-dependent nude mouse liver injury model induced by Propionibacterium acnes and LPS.

Normal ICR mice developed severe liver injury when they were given intravenous injections of Propionibacterium acnes and lipopolysaccharide (LPS) with a 7 day interval. In contrast, T cell-deficient ICR nude mice were resistant to P. acnes and LPS-induced liver injury. However, athymic ICR nude mice, which were treated with cell transfer of normal ICR mouse spleen cells (10(8) cells) or ICR mouse nylon-wool passed splenic T-enriched cells (over 10(7) cells), showed severe liver injury as assessed by elevation of serum transaminase activities. Histological analyses also demonstrated that the transferred cells migrated into the liver of nude mice to induce liver injury. However, depletion of both CD4+ T cells and CD8+ T cells from transferred cell populations caused a marked decrease in the elevation of serum transaminase, indicating the actual involvement of T cells in liver injury. Moreover, in vivo administration of anti-LFA-1 mAb blocked P. acnes and LPS-induced liver injury in nude mice following T cell transfer. Thus, this model will provide a new strategy to investigate T cell-dependent cell-cell interaction during the induction of liver damage.

Animals↗
PubMed1995

Prolonged inhibition of an antigen-specific IgE response in vivo by monoclonal antibody against lymphocyte function-associated antigen-1.

Intraperitoneal injection of ovalbumin (OVA) into BALB/c mice caused the induction of OVA-specific IgE production in vivo. However, administration of monoclonal antibody against lymphocyte function-associated antigen-1 (anti-LFA-1 mAb) at days 0 and 1 after OVA immunization resulted in an inhibition of OVA-specific primary and secondary IgE production in a dose-dependent manner. The inhibition of the antigen-specific IgE response due to anti-LFA-1 mAb was seen up to 8 weeks after anti-LFA-1 mAb administration. The OVA-specific IgG1 response was also blocked by anti-LFA-1 mAb. The spleen cells obtained from OVA-immunized mice showed enhanced proliferation against secondary stimulation with OVA in vitro. However, the spleen cells obtained from the mice treated with both OVA and anti-LFA-1 mAb revealed a markedly decreased proliferative responses to OVA, while they showed no reduced responses against keyhole limpet hemocyanin stimulation, indicating that anti-LFA-1 mAb might induce antigen-specific anergy in vivo. It was also demonstrated that treatment of the mice with anti-LFA-1 mAb significantly inhibited the interleukin-4-producing ability of OVA-immunized mouse spleen cells. These results demonstrated that LFA-1-dependent cell-cell interaction is essential for the production of IgE in vivo and may be important in IgE-dependent allergic disease.

Animals↗
PubMed1995

Tranexamic acid attenuates oleic-acid-induced pulmonary extravasation.

OBJECTIVE: Activation of fibrinolysis is implicated in the development of vascular injury in certain lung injuries. It has yet to be reported that activation of plasmin is involved in extravasation caused by oleic acid (OA). We examined whether or not plasmin is involved in pulmonary extravasation by OA. DESIGN: Prospective trial. SETTING: University laboratory. SUBJECTS: A total of 78 guinea pigs (498.9 +/- 10.6 g). INTERVENTIONS: Evans blue (EB) was administered to anesthetized guinea pigs. Subsequently four protocols were followed: (1) After 1 min, 60 micro l/kg of OA was injected. Perfusion was performed 30, 60 or 90 min after OA injection to wash out intravascular EB. (2) After 1 min, 15, 30 or 60 micro l/kg of OA was injected. (3) Tranexamic acid (TA) (2 g/kg) or saline was administered 30 min before OA (15 micro l/kg) injection. (4) Diphenhydramine hydrochloride (2.9 mg/kg) or saline was administered 7 min before OA (15 micro l/kg) injection. MEASUREMENT AND RESULTS: Except in protocol 1, the chest cavity was opened 90 min after OA injection. Perfusion was then performed. Airway was separated into four parts from trachea to distal bronchus. EB was extracted from the tissues and measured. OA caused an extravasation throughout airways in a time- and dose-dependent manner. Extravasation was more conspicuous in peripheral tissues. TA significantly attenuated extravasation, while diphenhydramine hydrochloride did not. CONCLUSIONS: It is suggested that plasmin, but not histamine, is involved in extravasation by OA. Inhibition of plasmin can be an effective strategy for treatment of this kind of lung injury.

Analysis of Variance↗
PubMed1995

Role of ring size on the secondary structure and antibiotic activity of gramicidin S.

In order to investigate the contribution of ring size to the secondary structure and antibiotic activity of gramicidin S, many analogs consisting of 6, 7, 8, 9, 11, 12, 13, and 14 amino acid residues were synthesized. In the analogs with smaller ring sizes than that of gramicidin S, only des-Val1-, des-Leu3- and des-Pro5-gramicidin S showed weak activity against the gram-positive micro-organisms tested. On the other hand, all analogs having larger rings, in which L- or D-Leu residues were inserted, were active. The activity of the analogs consisting of 10, 11 and 12 amino acid residues was stronger than those of the analogs with other ring sizes, and the activity of endo-Leu2a-gramicidin S against S. epidermidis SP-al-1 and B. subtilis ATCC 6633 was twice of that of gramicidin S.

Amino Acid Sequence↗
PubMed1994

NS-398, a new anti-inflammatory agent, selectively inhibits prostaglandin G/H synthase/cyclooxygenase (COX-2) activity in vitro.

NS-398 is a novel anti-inflammatory and analgesic agent which produces much fewer gastrointestinal lesions in rats. Recently, two forms of cyclooxygenase have been identified: a COX-1 first purified from ram seminal vesicles and a newly discovered mitogen-inducible form (COX-2). Effects of NS-398 on activities of these two distinct forms of COX were investigated. COX-1 purified from ram seminal vesicles and COX-2 isolated from sheep placenta (purity was 70%) were used. The COX-1 activity was completely unaffected by 10(-4) M NS-398, whereas the COX-2 activity was concentration-dependently inhibited, the IC50 value being 3.8 x 10(-6) M. Indomethacin inhibited both COX-1 and COX-2 activity to the same degree, the IC50 values being 7.4 x 10(-7) M and 9.7 x 10(-7) M, respectively. The anti-inflammatory and analgesic effects of NS-398 were almost as potent as indomethacin, the effective dose range being 0.3 approximately 5 mg/kg in rats. The gastrointestinal lesions related to NS-398 were not significant following a dose of 1000 mg/kg given orally. NS-398 is the first documented agent to have selective inhibition for COX-2, which may result in the less gastrointestinal toxicity.

Animals↗
PubMed1993

Visualization of single molecules of RNA polymerase sliding along DNA.

Transcription requires that RNA polymerase binds to promoters buried in nonspecific sites on DNA. The search for promoters may be facilitated if the polymerase slides along the molecule of DNA. Single molecules of Escherichia coli RNA polymerase were visualized, and their movements on immobilized bacteriophage lambda and T7 DNAs were examined. Deviating from drifts by bulk flow, about 40 percent of the enzyme molecules moved along the extended DNA. The results provide direct evidence for sliding as a mechanism for relocation of the enzyme on DNA.

Bacteriophage T7↗
PubMed1993

Inhibition of inflammatory liver injury by a monoclonal antibody against lymphocyte function-associated antigen-1.

When mice were given an i.v. injection of LPS 7 days after an i.v. injection of Propionibacterium acnes, liver injury and a rapid increase of serum alanine aminotransferase and asparagine acid aminotransferase occurred. The in vivo administration of mAb against LFA-1 on days 1, 2, and 3 after the i.v. injection of P. acnes resulted in a potent inhibition of all these dysfunctions. Using P. acnes and the LPS model, we found that anti-LFA-1 mAb protected the mice from P. acnes and LPS-induced lethal shock. During the course of P. acnes and LPS-induced liver injury, inflammatory cells infiltrated the liver and caused a massive hepatic cell necrosis. Flow cytometry revealed that the liver-infiltrating cells were mainly leukocytes expressing a higher level of LFA-1 antigen than that seen in the normal liver. These results suggested that the LFA-1 molecule on liver-infiltrating leukocytes may play an important role in the induction of inflammatory liver injury.

Alanine Transaminase↗
PubMed1993

NS-398, a novel non-steroidal anti-inflammatory drug with potent analgesic and antipyretic effects, which causes minimal stomach lesions.

1. NS-398 (N-[2-cyclohexyloxy-4-nitrophenyl] methanesulfonamide) is a new non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic effects. 2. The anti-inflammatory potency of NS-398 in rat carrageenin-induced edema was as potent as that of indomethacin and 8 times more potent than diclofenac. In rat adjuvant arthritis, NS-398 showed a therapeutic effect comparable to that seen with loxoprofen but less than that seen with indomethacin and diclofenac. 3. The analgesic potency of NS-398 in rat adjuvant arthritic pain was much the same as that of indomethacin, and was about 3-5 times higher than that of diclofenac and loxoprofen. In the Randall-Selitto method in rats, NS-398 was 2-7 times as potent as loxoprofen, diclofenac and indomethacin. In acetic acid-induced writhing in mice, NS-398 was equipotent to indomethacin and diclofenac. 4. In LPS-induced fever in rats, NS-398 was 1.5-4.5 times as potent as loxoprofen and indomethacin, but less potent than diclofenac. 5. NS-398 produced little gastric ulceration in doses of up to 1000 mg/kg, while reference drugs produced distinct stomach lesions in doses of 10-30 mg/kg. 6. NS-398 inhibited prostaglandin (PG) endoperoxide synthase from sheep seminal vesicle microsomes less potent than that of ibuprofen.

Animals↗
PubMed1993

Selective inhibition of NS-398 on prostanoid production in inflamed tissue in rat carrageenan-air-pouch inflammation.

NS-398 (N-(2-cyclohexyloxy-4-nitrophenyl) methane sulphonamide), a newly synthesized potent non-steroidal anti-inflammatory drug (NSAID) has a much lesser degree of toxicity, as compared with presently available NSAIDs. We have investigated the inhibition of prostanoid production in inflammatory exudate, gastric mucosa and renal papillary tissue, following oral administration to carrageenan-air-pouch rats. The ID50 values of NS-398 in the inflammatory exudate, gastric mucosa and renal papillary tissue were 0.18, 62.2 and 261.7 mg kg-1, respectively. In contrast, indomethacin decreased the PGE2 concentration in the inflammatory exudate, gastric mucosa and renal papillary tissue, with the same dose range, the ID50 values being 0.23, 0.14 and 0.15 mg kg-1, respectively. The same tendency was seen for 6-keto-prostaglandin F1 and thromboxane B2. Moreover, NS-398 inhibited excess PGE2 production in inflamed tissue but did not affect physiological production of PGE2 in non-inflamed tissue. Indomethacin, in both inflamed and non-inflamed tissues, inhibited PGE2 production to the same degree. These results indicated that NS-398 has some specificity for inflamed tissue, by inhibiting prostanoid synthesis, and this effect may explain the decreased side-effects of this drug.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Effect of NS-398, a new nonsteroidal anti-inflammatory agent, on gastric ulceration and acid secretion in rats.

The ulcerogenic activity of NS-398 was compared with that of indomethacin and the effects of NS-398 on stress-induced ulceration, gastric acid secretion and gastric mucosal prostaglandin (PG) contents were investigated in rats. NS-398 in a single dose of up to 1,000 mg/kg, p.o. did not significantly cause gastric ulceration while other nonsteroidal anti-inflammatory drugs such as, loxoprofen, indomethacin, diclofenac and ibuprofen, produced distinct gastric lesions. In cases of stress-induced ulcerations, NS-398 at 30 mg/kg, p.o. had no significant influence while indomethacin markedly potentiated the ulceration in a dose dependent manner. In basal gastric secretion studies, both NS-398 and indomethacin decreased secretion volume and acidity. However, in the 2-deoxy-D-glucose-stimulated gastric acid secretion study, NS-398 had no significant influence on gastric secretions while indomethacin significantly potentiated the secretion. Both NS-398 and indomethacin to much the same extent significantly decreased prostaglandin E2 (PGE2) contents in inflammatory tissue. However, with respect to gastric mucosal PGE2 contents, NS-398 did not decrease PGE2 contents while indomethacin significantly decreased the contents. It would thus appear that the absence of ulcerogenic properties of NS-398 is due to a relative lack of activity in inhibiting gastric PG synthesis.

Administration, Oral↗
PubMed1992

Effect of stilbene derivatives on gastric H+, K(+)-ATPase.

The effect of naturally occurring hydroxystilbene, 3,3',4,5-tetrahydroxystilbene (piceatanol), and its derivatives on gastric H+, K(+)-ATPase was studied. Piceatanol inhibited H+, K(+)-ATPase in a dose-dependent manner. The 50% inhibition value was 4.3 x 10(-6) M. It was found from the kinetic study that the inhibition of the enzyme by piceatanol was competitive with respect to ATP and was noncompetitive with respect to K+. Piceatanol also effectively inhibited gastric acid secretion. However, methylation of phenolic hydroxy groups of piceatanol resulted in a complete loss of inhibition of the enzyme and acid secretion, suggesting the role of phenolic hydroxy groups in the inhibition. The study on hydroxystilbene derivatives also showed that phenolic hydroxy groups are important in the interaction with H+, K(+)-ATPase and that stilbenes with neighbouring hydroxy groups are the most effective inhibitors.

Adenosine Triphosphate↗
PubMed1992

Inhibition of gastric H+,K(+)-ATPase and acid secretion by cassigarol A, a polyphenol from Cassia garrettiana Craib.

The effects of cassigarol A, a naturally occurring polyphenol, on gastric H+,K(+)-ATPase and gastric acid secretion were studied. Cassigarol A inhibited H+,K(+)-ATPase and K-stimulated p-nitrophenyl phosphatase from hog gastric mucosa with 50% inhibition of 1.2 x 10(-6) and 6.3 x 10(-6) M, respectively. The kinetic study showed that the inhibition of H+,K(+)-ATPase by cassigarol A was competitive with respect to ATP and non-competitive with respect to K+. Cassigarol A inhibited both H+,K(+)-ATPase-mediated proton transport and 2-deoxy-D-glucose-induced acid secretion. On the other hand, cassigarol A acetate, in which phenolic hydroxy groups are acetylated, was not effective in the inhibition of enzyme activity and acid secretion. These results indicate that cassigarol A is a potent inhibitor of gastric H+,K(+)-ATPase, that the anti-secretory activity of cassigarol A is related to the inhibition of H+,K(+)-ATPase and that an important moiety of cassigarol A in the interaction with the enzyme is the phenolic hydroxy groups.

Adenosine Triphosphatases↗
PubMed1992

Simultaneous determination of cortisol and cortisone in human plasma by stable-isotope dilution mass spectrometry.

A method for the simultaneous determination of cortisol and cortisone in human plasma was developed using capillary gas chromatography-mass spectrometry-selected ion monitoring. [2H5]Cortisol and [2H5]cortisone were used as internal standards. Cortisol and cortisone in plasma were determined from the peak-height ratios of the [M-31] fragment ions of the methoxime-trimethylsilyl derivatives of cortisol and [2H5]cortisol (m/z 605 and 610) and of cortisone and [2H5]cortisone (m/z 531 and 536). Sensitivity, specificity, precision, accuracy and reproducibility of the method were demonstrated to be satisfactory for measuring the circulating concentrations of cortisol and cortisone.

Cortisone↗