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Biomedical subjects

M Katsura

Publications and source records attributed to M Katsura.

At least 19 recordsLinked to original sources
PubMed1998

Removal of hydroxyl radical facilitates Ca2+-dependent [3H]GABA release by peroxynitrite.

We investigated mechanisms for enhancement of peroxynitrite (OONO-; 5 microM)-evoked [3H] gamma-aminobutyric acid (GABA) release. Hydroxyl radical scavengers such as N,N'-dimethylthiourea (DMTU), mannitol, and uric acid, significantly increased OONO--evoked [3H]GABA release, whereas urea showed no effects on the release. Removal of Ca2+ from incubation buffer abolished the enhancement of the release by DMTU, although DMTU showed no effects on the basal release with and without Ca2+ in extracellular space. These results indicate that hydroxyl radical scavengers facilitate OONO--evoked [3H]GABA release dependent on Ca2+.

Animals↗
PubMed1998

Overexpression of CD44 variants 6 and 7 in human endometrial cancer.

OBJECTIVES: The expression of CD44 V6, V7, and V10 in normal endometrium and endometrial cancer was compared. METHODS: Using reverse transcription polymerase chain reaction (RT-PCR) blot analysis, the expression of mRNA containing CD44 V6, V7, and V10 was determined in 19 normal endometrium and 27 endometrial cancer samples. Immunohistochemical staining of CD44 V6 and V7 was performed in the same samples. RESULTS: In RT-PCR analysis, the CD44 variant forms containing V6 and V7 exons were expressed in 96 and 93% of endometrial cancer tissues, respectively. These proportions were significantly higher than those in normal endometrium (V6, 63%; V7, 58%) (P < 0.01). CD44 V10 was expressed in 96% of endometrial cancers and 89% of normal endometrial samples. In immunohistochemical staining, CD44 V6 and V7 were detected in 48 and 61% of endometrial cancers and in 26 and 42% of normal endometrial samples, respectively. Neither of these differences was significant. No correlation was found between the expression of CD44 variants and any clinicopathological features. CONCLUSION: CD44 V6 and V7 were expressed in a significantly larger proportion of endometrial cancers than normal endometrial samples. However, they were also expressed in a considerable proportion of normal endometria. These findings suggest that CD44 V6 and V7 play roles in normal endometrial function and overexpression of CD44 V6 and V7 is not related to the metastatic potential of endometrial cancer.

Adult↗
PubMed1998

Enhancement of peroxynitrite-evoked acetylcholine release by hydroxyl radical scavengers from mouse cerebral cortical neurons.

We investigated the effects of hydroxyl radical scavengers on peroxynitrite (OONO-)-evoked acetylcholine (ACh) release from mouse cerebral cortical neurons. N,N'-dimethylthiourea, a hydroxyl radical scavenger, dose-dependently increased OONO(-)-evoked ACh release. Other hydroxyl radical scavengers such as uric acid and mannitol, also enhanced OONO(-)-evoked ACh release, although these enhancing effects were not found in the absence of OONO-. In addition, OONO(-)-induced [45Ca2+]influx was significantly facilitated by the scavengers, whereas no effects of the scavengers on [45Ca2+]influx was observed in the absence of OONO-. These results indicate that hydroxyl radical scavengers enhance OONO(-)-evoked ACh release via the facilitation of OONO(-)-induced [45Ca2+]influx.

Acetylcholine↗
PubMed1998

Functional involvement of benzodiazepine receptors in ethanol-induced increases of diazepam binding inhibitor (DBI) and its mRNA in the mouse brain.

We have attempted to clarify the mechanisms for alcohol (EtOH)-induced elevation of diazepam binding inhibitor (DBI) mRNA and to investigate whether the increase in DBI mRNA is paralleled with that in DBI using EtOH-treated mice and primary cultured neurons. Both the DBI content and the expression of DBI mRNA were elevated in the cerebral cortex of EtOH-inhaled and -withdrawn mice. Simultaneous administration of flunitrazepam (FLN) and Ro15-1788 with EtOH vapor completely abolished the EtOH-induced elevation of DBI mRNA. In addition, the exposure of the neurons for 3 days significantly elevated the expression of DBI mRNA, which was completely inhibited by concomitant exposure of FLN, Ro15-4513 and Ro-15-1788 with EtOH, while muscimol and bicuculline showed no effects on the EtOH-induced increase of DBI mRNA expression. These results indicate that functional interaction between EtOH and benzodiazepine (BDZ) receptors is a critical role in the increased expression of DBI mRNA.

Administration, Inhalation↗
PubMed1998

Multiple actions of nitric oxide on voltage-dependent Ca2+ channels in mouse cerebral cortical neurons.

We investigated the effects of nitric oxide (NO) on voltage-dependent Ca2+ channels (VDCCs) by examining [45Ca2+]influx into mouse cerebral cortical neurons. S-nitroso-N-acetylpenicillamine (SNAP) induced a dose-dependent increase in [45Ca2+]influx, which was completely abolished by hemoglobin, tetrodotoxin and dibucaine. The NO-induced [45Ca2+influx was significantly inhibited by verapamil and omega-agatoxin VIA (omega-AGX), whereas omega-conotoxin GVIA (omega-CTX) had no effects on the NO-induced [45Ca2+]influx. KCl (30 mM) stimulated [45Ca2+]influx, and verapamil, omega-CTX and omega-AGX reduced the KCl-induced [45Ca2+]influx by about 40, 26 and 34%, respectively, indicating that the neurons used here possess L-, N- and P-typed VDCCs. SNAP itself reduced KCl-induced [45Ca2+]influx by about 28.5%. In the presence of both KCl and SNAP, omega-CTX showed no effects on the influx, while verapamil and omega-AGX significantly inhibited the influx and the concomitant presence of verapamil and omega-AGX completely abolished the influx. These results indicate that NO induces [45Ca2+] influx via the opening of L- and P-typed VDCCs subsequent to neuronal membrane depolarization and that NO itself inhibited the function of N-typed VDCC in the cerebral cortical neurons.

Animals↗
PubMed1998

Continuous treatment with nicotine increases diazepam binding inhibitor (DBI) and its mRNA in the mouse brain.

Effect of chronic treatment with nicotine on DBI and its mRNA in mouse cerebral cortex were examined. Continuous treatment of mice with nicotine significantly increased DBI content and its mRNA expression, which was completely abolished by simultaneous administration of mecamylamine (1 mg/kg, i.p.). These results indicate that chronic functional interaction between nicotine and nicotinic acetylcholine receptors has a critical role in increases in DBI content and its mRNA expression.

Animals↗
PubMed1998

Mechanisms for facilitation of nitric oxide-evoked [3H]GABA release by removal of hydroxyl radical.

We have investigated the mechanisms for enhancement of nitric oxide (NO)-evoked gamma-[3H]aminobutyric acid ([3H]GABA) release from mouse cerebrocortical neurons by hydroxyl radical (.OH) scavengers. .OH scavengers, such as N,N'-dimethylthiourea (DMTU), uric acid, and mannitol, dose-dependently facilitated NO-evoked [3H]GABA release evoked by NO liberated from S-nitroso-N-acetylpenicillamine. Ionomycin-evoked [3H]GABA release, which was significantly inhibited by hemoglobin and an NO synthase, N(G)-methyl-L-arginine, was also enhanced by DMTU. These results indicate that GABA release evoked by both endogenous and exogenous NO is facilitated by .OH scavengers. These enhancing actions of .OH scavengers were completely abolished by Ca2+ removal from incubation buffer and by an L-type voltage-dependent Ca2+ channel (VDCC) inhibitor, nifedipine, whereas each .OH scavenger showed no effects on [3H]GABA release in the absence of NO. Inhibitors for P/Q- and N-type VDCCs had no effects on the enhancement. NO-induced 45Ca2+ influx was also dose-dependently enhanced by .OH scavengers, although 45Ca2+ influx was not altered by .OH scavengers in the absence of NO. Nifedipine abolished this enhancement of the NO-induced 45Ca2+ influx by .OH scavengers. These results indicate that the removal of .OH by its scavengers facilitates the NO-evoked [3H]GABA release dependent on Ca2+ and that this enhancement is due to the increase in Ca2+ influx via L-type VDCCs.

Animals↗
PubMed1998

Continuous treatment with morphine increases diazepam binding inhibitor mRNA in mouse brain.

Effects of acute and chronic morphine treatment on the expression of diazepam binding inhibitor (DBI) mRNA in the mouse brain were examined. Cerebral DBI mRNA expression significantly increased in morphine-dependent mice, and this increase is more remarkable in morphine-withdrawn mice, whereas a single administration of morphine (50 mg/kg) produced no changes in the expression. Simultaneous administration of naloxone (3 mg/kg) with morphine completely abolished the increase in cerebral DBI mRNA expression observed in morphine-dependent and -withdrawn mice. These results indicate that a chronic functional interaction between morphine and opioid receptors has a critical role in increases in DBI mRNA expression.

Animals↗
PubMed1998

Irsogladine maleate may preserve gastric mucosal hydrophobicity against ethanol in phospholipids independent way in rats.

Irsogladine maleate (IM) has been used as a mucosal protective agent, whose action is partially explained as enhancement of mucosal blood flow, increase of cellular cyclic AMP and facilitation of gap-junctional intercellular communication. Effect of IM on rat gastric mucosal hydrophobicity, one of the mucosal barrier properties, was investigated, in comparison with that of 16,16-dimethyl prostaglandin E2 (dmPGE2). IM alone had no effect on mucosal hydrophobicity and mucosal phospholipids content. dmPGE2 alone did not change mucosal hydrophobicity significantly, but remarkably increased mucosal surface-active phospholipids. Intragastric administration of absolute ethanol significantly decreased gastric mucosal hydrophobicity and mucosal phospholipids content. IM could prevent the decrease in mucosal hydrophobicity by ethanol, maintaining the surface mucus gel layer and mucosal surface phospholipids almost as non-damaged control levels, whereas dmPGE2 also prevented the decrease in mucosal hydrophobicity by ethanol, with the surface epithelium being partially exfoliated and mucosal surface-active phospholipids showing remarkable enhancement. These results suggest that IM may preserve gastric mucosal hydrophobicity against ethanol, not through enhancement of mucosal phospholipids content like prostaglandin, but possibly through its reported stabilization action to the epithelial cell lining, which may preserve the surface epithelium with the mucous gel layer containing surface-active phospholipids, a possible origin of mucosal hydrophobicity.

Animals↗
PubMed1998

High plasma free fatty acids decrease splanchnic glucose uptake in patients with non-insulin-dependent diabetes mellitus.

It has been proposed that high plasma free fatty acid (FFA) levels observed in patients with non-insulin dependent diabetes mellitus (NIDDM) contribute to the development of their insulin resistance. We examined patients with NIDDM to find whether maintaining plasma FFA levels in the fasting range with a euglycemic hyperinsulinemic clamp combined with an oral glucose load (clamp OGL) would affect insulin-mediated peripheral glucose uptake (PGU) and splanchnic glucose uptake (SGU). Nine NIDDM subjects (age, 55 +/- 3 years; duration of diabetes, 11 +/- 2 years; body mass index, 21.0 +/- 0.4 kg/m2; hemoglobin A1c, 9.0 +/- 0.3%; fasting plasma glucose, 9.4 +/- 3.0 mmol/l, means +/- SEM) were hospitalized and treated with diet, oral hypoglycemic agents or insulin for at least 2 weeks to maintain fasting plasma glucose < 8 mmol/l. All the patients were subjected to two different protocols in a random order. On one protocol, under the hyperinsulinemic condition, FFAs were maintained at the their fasting levels (1.19 +/- 0.08) by triglyceride emulsion infusion (Lipid infusion study, L), and on the other protocol, FFAs were made to fall (0.26 +/- 0.06 mmol/l) with saline instead of triglyceride emulsion infusion (Saline infusion study, S). During euglycemic (L, 5.4 +/- 0.2; S, 5.1 +/- 0.2 mmol/l) hyperinsulinemic (L, 1377 +/- 108; S, 1328 +/- 67 pmol/l) clamp, high FFA levels significantly reduced PGU (L, 26.7 +/- 3.6; S, 32.1 +/- 3.4 mumol.kg-1.min-1, P < 0.05) and SGU (L, 12.1 +/- 4.2; S, 27.5 +/- 5.6%, P < 0.05). In conclusion, high FFA levels in patients with NIDDM impaired insulin-mediated glucose uptake in the splanchnic as well as peripheral tissues.

3-Hydroxybutyric Acid↗
PubMed1998

[Functional involvement of diazepam binding inhibitor (DBI) in the establishment of drug dependence].

In this paper, we have reviewed the possibility of the functional involvement of an endogeneous neuropeptide for benzodiazepine receptors, diazepam binding inhibitor (DBI), in the development of drug dependence and the establishment of its withdrawal symptoms. The cerebral levels of DBI protein and its mRNA significantly increased in alcohol-dependent mice, and alcohol-withdrawal caused further increases of both DBI protein and its mRNA. These increases in the mouse cerebral cortex diminished over 14 days after alcohol-withdrawal. In the cerebrocortical neurons, similar patterns of DBI protein and its mRNA were observed during long-term exposure to alcohol and after its withdrawal. Simultaneous exposures of benzodiazepine receptor agonist, antagonist and inverse agonist with alcohol abolished the alcohol-induced increase in DBI mRNA expression in the neurons. Furthermore, the DBI contents and its mRNA expressions were also increased in the cerebral cortex obtained from nicotine-dependent mice and the neurons after long-term treatment with nicotine. The nicotine-induced increases in DBI content and its mRNA expression in the mouse cerebral cortex and the neurons were completely abolished in the presence of an antagonist for nicotinic acetylcholine receptor. These results suggest that the changes in the levels of cerebral DBI induced by continuous treatments with alcohol and nicotine may be involved in the establishment of dependence by alcohol and nicotine, and such changes may be regulated by the benzodiazepine and nicotinic acetylcholine receptors, respectively.

Alcoholism↗
PubMed1997

Role of cerebral spermidine in the development of sensitization to convulsant activity of cocaine and lidocaine.

We have previously shown that daily treatment with subconvulsant dose of cocaine resulted in the elevation of brain levels of polyamines such as putrescine and spermidine and the development of increased susceptibility to cocaine-induced seizures. The present study examined whether exogenously administered polyamines affect seizure activity caused by various doses of cocaine and lidocaine in mice. Thirty minutes after intracerebroventricular treatments with either saline, putrescine or spermidine (1-4 mumol), animals were injected intraperitoneally with cocaine or lidocaine (60-90 mg/kg); then the occurrence of clonic seizures was observed. Spermidine enhanced cocaine-induced seizure activity, while putrescine had no effect on it. Lidocaine-induced convulsions were also dose-dependently potentiated by spermidine. In addition, spermidine significantly enhanced seizure activity following an injection of N-methyl-DL-aspartate. The results suggest that spermidine plays an important role in the development of sensitization to convulsant activity by cocaine and lidocaine via modulation of N-methyl-D-aspartate receptors.

Animals↗
PubMed1997

Vinconate, a cognitive enhancer, and PI turnover-phospholipase C systems in the brain.

The molecular mechanisms for the stimulation of inositol 1-phosphate (IP1) formation by vinconate were investigated using preparations of rat brain. Vinconate (10(-8)-10(-3) M) dose-dependently inhibited the binding of [3H]quinuclidinyl benzilate ([3H]QNB) to muscarinic acetylcholine receptors and its IC50 value for [3H]QNB binding was 1.7 x 10(-5) M. The rightward shift of carbachol displacement curve of [3H]QNB binding by GTP (10(-4) M) was completely abolished by vinconate (10(-5) M). Carbachol (10(-8)-10(-2) M) increased [3H]IP1 formation in a dose-dependent manner and the carbachol-induced [3H]IP1 formation was significantly accentuated by vinconate (10(-5) M). The enhancement of [3H]IP1 accumulation by vinconate was inhibited by approximately 50% in the presence of atropine (10(-5) M), although phentolamine and ketanserin had no effects on the stimulatory effect of vinconate on [3H]IP1 formation. Vinconate showed no alteration in the binding of [3H]guanosine 5'-(beta, gamma-imino) triphosphate ([3H]Gpp(NH)p) to the crude synaptic membranes. The enhancement of phosphatidylinositol 4,5-biphosphate (PIP2)-specific phospholipase C (PLC) activity by GTP was unaffected in the presence of 10(-3) M vinconate, whereas vinconate alone dose-dependently enhanced the activities of both PIP2-specific and cytosolic PLC. These results suggest that vinconate may induce the facilitation of phosphatidylinositide (PI) turnover via the stimulation of muscarinic acetylcholine receptors, the enhancement of coupling between muscarinic acetylcholine receptors and GTP-binding protein, and the direct activations of PIP2-specific and cytosolic PLC.

Animals↗
PubMed1997

Immunological functions of adult T cell leukemia cells of a patient complicated with synchronous double primary gynecologic cancer.

A patient with triple malignancies is reported, who presented cervical cancer, vulvar cancer and adult T cell leukemia (ATL). ATL was diagnosed as a smouldering type, because antibody to human T cell leukemia virus associated antigen (ATLA) was positive with a titer of 1:160. Although her malignant cells had an OKT 4+8-3+Tac+ phenotype, the cells did not display helper T cell functions. Namely they showed no response to Phytohemagglutinin (PHA) and Interleukin 2 (IL-2) and suppressed the PWM driven IgG synthesis of B cells obtained from healthy donor. They did not produce IL-2 by stimulation with PHA and phorbol myristate acetate (PMA). Furthermore, these ATL cells were producing IL-2 inhibitor like factors. As synchronous triple malignancies are extremely rare, two gynecologic cancers seem to ascribe to the suppressing state of the immunosurveillance mechanism by viral infection.

Aged↗
PubMed1996

Role of peroxynitrite in [3H] gamma-aminobutyric acid release evoked by nitric oxide and its mechanism.

Role of peroxynitrite in [3H] gamma-aminobutyric acid (GABA) release evoked by N-methyl-D-aspartate (NMDA) and S-nitroso-N-acetyl-penicillamine (SNAP) and mechanisms of [3H]GABA release induced by peroxynitrite in comparison with those induced by NMDA and SNAP were investigated using cerebrocortical neurons. NMDA dose dependently increased [3H]GABA release, which was significantly inhibited by hemoglobin and superoxide scavengers, Cu2+, Zn(2+)-superoxide dismutase and ceruloplasmin. The NMDA-evoked [3H]GABA release was significantly suppressed by GABA transport inhibitors and inhibitors of voltage-dependent L-typed Ca2+ channel. The SNAP-evoked [3H]GABA release was significantly reduced by Ca2+ withdrawal and by GABA transport inhibitors either in the presence or absence of Ca2+. Similar patterns of [3H]GABA release induced by peroxynitrite were observed. These results indicate that peroxynitrite formed by the reaction of NO with superoxide participates, in part, in the release of [3H]GABA induced by NMDA and SNAP.

Animals↗
PubMed1996

Down-regulation of benzodiazepine receptors by ethyl beta-carboline-3-carboxylate in cerebrocortical neurons.

Effect of exposure of primary cultured cerebral cortical neurons to ethyl beta-carboline-3-carboxylate (beta-CCE) on the function of benzodiazepine receptors was studied. Exposure of neurons to beta-CCE (0.1-10 microM) decreased the binding of [3H]flunitrazepam to extensively washed membrane fractions in a dose- and time-dependent manner, whereas the binding of [3H]flunitrazepam to the cytosolic fractions increased (180%) under the same conditions as described above. Ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a] [1,4] benzodiazepine-3-carboxylate (Ro15-1788), an antagonist of the central type of benzodiazepine receptors, completely abolished the beta-CCE-induced decrease in [3H]flunitrazepam binding and the IC50 value for [3H]flunitrazepam binding to the extensively washed membrane fractions prepared from beta-CCE-treated neurons was similar to that from non-treated neurons. Scatchard analysis revealed that only the Bmax value for [3H]flunitrazepam binding decreased after the exposure to beta-CCE (1 microM) for 12 h, although the Kd value was not altered. These results indicate that beta-CCE induces the down-regulation of benzodiazepine receptors by an increase in benzodiazepine receptor internalization.

Animals↗