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Biomedical subjects

S Koizumi

Publications and source records attributed to S Koizumi.

At least 145 records · Page 8Linked to original sources
PubMed1996

Implication of ATP receptors in brain functions.

The possible implication of P2-purinoceptors in brain functions is reviewed. Involvement of P2-purinoceptors in memory and learning (Section 2) is suggested by ATP release from hippocampal slices [Wieraszko, A., Goldsmith, G. and Seyfried, T. N. (1989) Brain Res. 485, 244-250], induction of fast synaptic currents in cultured hippocampal neurons [Inoue, K., Nakazawa, K., Fujimori, W. and Takanaka, A. (1992a) Neurosci. Lett. 134, 294-299] and long-lasting enhancement of the population spikes [Wieraszko, A. and Seyfried, T. N. (1989) Brain Res. 491, 356-359; Nishimura, S., Mohri, M., Okada, Y. and Mori, M. (1990) Brain Res. 525, 165-169; Fujii, S., Kato, H., Furuse, H., Ito, K., Osada, H., Hamaguchi, T. and Kuroda, Y. (1995) Neurosci, Lett. 187, 130-132], as well as ATP release on glutamate stimulation to evoke an increase in intracellular Ca2+ in hippocampal cells [Inoue, K., Koizum, S. and Nakazawa, K. (1995) NeuroReport 6, 437-440]. Moreover, mRNAs for certain types of P2x-purinoceptors are present in the hippocampus [Collo, G., North, R. A., Kawashima, E., Merlo-Pich, E., Neidhart, S., Surprenant, A. and Buell, G. (1996) J. Neurosci. 16, 2495-2507]. It is likely, therefore, that ATP may be involved in modulation of synaptic efficiency in the hippocampus. The implication of ATP in schizophrenia is suggested by the fact that antipsychotic drugs inhibit ATP-evoked responses in PC12 cells [Koizumi, S., Ikeda, M., Nakazawa, K., Inoue, K., Ito, K. and Inoue, K. (1995b) Biochem. Biophys. Res. Commun. 210, 624-630] without blocking the action of dopamine D2 receptors. Involvement of P2-purinoceptors in Sections 4 ("Pain and cognition") and 5 ("Central regulation of the autonomic system") are also discussed.

Animals↗
PubMed1996

Transcriptional analysis of Epstein-Barr virus gene expression in EBV-positive gastric carcinoma: unique viral latency in the tumour cells.

Although case-oriented evidence for an association of Epstein-Barr virus (EBV) with gastric carcinoma has been accumulating recently, the interaction(s) between EBV and gastric epithelial cells is/are largely unknown. In this study, we examined seven EBV-positive gastric carcinoma tissues for viral gene expression at the mRNA level, from which studies on the EBV oncogenicity in human epithelial cells will benefit. Reverse transcription-PCR analysis showed that all seven EBV-positive tumour tissues constitutively expressed EBV nuclear antigen (EBNA) 1 mRNA, but not EBNA2 mRNA. The EBNA transcription was initiated from one of three EBNA promoters, Qp: by contrast, both Cp and Wp were silent, thus resulting in the lack of EBNA2 mRNA. Latent membrane protein (LMP) 2A mRNA was detected in three of seven cases; however, neither LMP1 nor LMP2B mRNA was detected in any of the tumours tested. Transcripts from the BamHI-A region of the viral genome were detectable in all cases. BZLF1 mRNA and the product, an immediate-early gene for EBV replication, was not expressed in any of them, thereby suggesting that the tumour cells carried EBV genomes in a tightly latent form. These findings further extended our previous data regarding EBV latency in gastric carcinoma cells at the protein level, and have affirmed that the programme of viral gene expression in the tumour more closely resembles 'latency I' represented by Burkitt's lymphoma than 'latency II' represented by the majority of nasopharyngeal carcinomas.

Aged↗
PubMed1996

Midkine, a heparin-binding growth/differentiation factor, exhibits nerve cell adhesion and guidance activity for neurite outgrowth in vitro.

By means of a baculovirus expression system, a large amount of mouse midkine (MK) was produced. The protein was purified to homogeneity by heparin-Sepharose column chromatography. The purified protein was of a mature type; the signal peptide was cleaved at the expected site. To examine the neurite-guiding activity of MK, rat embryonic brain cells (embryonic days 17-18) were cultured on plates coated with purified MK in a grid pattern. The cells attached to and extended their neurites along the substrate pattern. This interaction was strongly inhibited by heparin, but not by other glycosaminoglycans. Treatment of the cells with heparitinase was effective for inhibiting their adhesion to the substrate. These data suggest that the heparin-like domain on cell surface heparan sulfate proteoglycan is the primary site for MK binding upon interaction with nerve cells.

Amino Acid Sequence↗
PubMed1996

Potentiation by cadmium ion of ATP-evoked dopamine release in rat phaeochromocytoma cells.

1. The effects of cadmium ion (Cd2+) on release of dopamine and on an inward current evoked by extracellular ATP were investigated in rat phaeochromocytoma PC12 cells. 2. Cd2+ (100 microM-3 mM) potentiated the dopamine release evoked by 30 microM ATP from the cells. Cd2+ (100 microM) shifted the concentration-response curve of ATP-evoked dopamine release to the left without affecting the maximal response. 3. Suramin (30 microM) completely abolished the dopamine release evoked by 30 microM ATP but only partially inhibited the release evoked by 100 microM ATP consistent with its role as a competitive antagonist. The response evoked by 30 microM ATP in the presence of Cd2+ (300 microM) was comparable to that observed with 100 microM ATP alone; however, only the former was almost completely inhibited by suramin. 4. Cd2+ (100 microM) potentiated an inward current activated by 30 microM ATP alone. A higher concentration of Cd2+ (300 microM) had a smaller effect on amplitude potentiation but significantly prolonged the duration of the current. 5. The time-course of the ATP-evoked dopamine release was investigated using a real-time monitoring system for dopamine release. Although Cd2+ (300 microM) had little effect on the time-course of activation the ATP-evoked dopamine release, it produced a long-lasting dopamine release which slowly returned to the baseline. 6. Taken together, these observations suggest that Cd2+ enhances ATP-evoked dopamine release by affecting P2-purinoceptor/channels. The enhancement may be attributed to a Cd(2+)-dependent increase in sensitivity to ATP.

Adenosine Triphosphate↗
PubMed1996

Obstructive jaundice caused by non-parasitic hepatic cyst treated with percutaneous drainage and instillation of minocycline hydrochloride as a sclerosing agent.

We report a case of obstructive jaundice caused by a large hepatic cyst which was successfully treated by percutaneous drainage and instillation of minocycline hydrochloride. An 88-year-old man presented with obstructive jaundice and upper abdominal fullness. Abdominal CT and ultrasonography revealed a large hepatic cyst and intrahepatic bile duct dilatation. After the percutaneous drainage of the cyst, minocycline hydrochloride was instilled as a sclerosant via a catheter into the cyst cavity. Liver enzyme levels returned to normal and the jaundice disappeared. Nine months after the treatment, the large cyst and dilatation of the intrahepatic bile duct had disappeared. The patient has remained healthy without symptoms.

Aged↗
PubMed1996

Primary aldosteronism with bilateral multiple aldosterone-producing adrenal adenomas.

A 41-year-old woman developed primary aldosteronism due to bilateral multiple aldosterone-producing adenomas (APA). She was suspected to have idiopathic hyperaldosteronism (IHA) 7 years previously. Although preoperative data suggest APA and IHA was suspected in a postoperative microscopic specimen, a definite clinical diagnosis could not be made. Cytochrome P-450 and other enzymes involved in aldosterone synthesis were found in the tumor portions but not in the zona glomerulosa of attached adrenals, which histopathologically showed "paradoxical hyperplasia". This was a rare case of bilateral multiple APA, which could be differentiated from IHA by immunohistochemical analysis of adrenal steroidogenic enzymes.

Adenoma↗
PubMed1996

Alterations of CDKN2 gene structure in childhood acute lymphoblastic leukemia: mutations of CDKN2 are observed preferentially in T lineage.

We analyzed homozygous deletions and mutations of the CDKN2(p16(INK4A)/MTS1) gene, using polymerase chain reaction and Southern blot analysis, in 120 children with acute lymphoblastic leukemia (ALL). Homozygous deletion was found in 17 of 89 (19%) precursor B-ALL patients, in 11 of 24 (46%) T-ALL patients, and in 0 of 7 other phenotype ALL patients. After excluding 28 (23%) patients who showed a homozygous deletion of CDKN2, we found that three patients (3%) had mutation at exon 2 of CDKN2 using PCR-SSCP and sequencing strategy. One had a CGA to TGA nonsense mutation (Arg to stop) at codon 72, one had a 1-bp deletion at codon 117, and the third had a 2-bp deletion at codon 70, resulting in frameshifts in the two latter patients. All three of these patients were T phenotype ALL, and the incidence of mutation in the 24 T-ALL patients examined was 13%. In contrast, no mutation was detected in the remaining patients with precursor-B or other type ALL (0/96). Our results suggest that mutational inactivation of the CDKN2 gene may contribute to the leukemogenic growth, especially in some patients with T-ALL.

Adolescent↗
PubMed1996

[Sinus bradyarrhythmia during administration of all-trans retinoic acid in a patient with acute promyelocytic leukemia].

A case of acute promyelocytic leukemia (APL) complicated by sinus bradyarrhythmia during the course of all-trans retinoic acid (ATRA) administration is reported. A 3-year-old boy was admitted for evaluation of petechiae and APL was diagnosed. He was initially treated with 45 mg/m2 of ATRA without success, and a complete remission was achieved when the dose was increased to 135 mg/m2. Sinus bradyarrhythmia was first recognized 3 days after the induction therapy with ATRA. It did not disappear even when the patient stopped taking the medication. However, the arrhythmia tended to be augmented whenever he received ATRA again. Close observation of his cardiac condition was mandatory to continue ATRA as an integral part of the therapy for APL, combined with multidrug chemotherapy including anthracyclines, which themselves are potentially toxic to myocardium. In conclusion, the present case revealed the possibility that ATRA therapy induces sinus node arrhythmia, or that it can potentiate preexisting node dysfunctions.

Arrhythmia, Sinus↗
PubMed1996

Detection and quantification of TEL/AML1 fusion transcripts by polymerase chain reaction in childhood acute lymphoblastic leukemia.

We investigated TEL/AML1 fusion mRNA in 108 children with acute lymphoblastic leukemia (ALL) (86 B-lineage ALL, 15 T-ALL, two mixed lineage ALL, and five other phenotypes) using reverse transcriptase-polymerase chain reaction (RT-PCR). TEL/AML1 transcripts were found in 14 patients (13%) including three relapsed patients, and were unexceptionally limited to B-lineage ALL patients. The incidence of TEL/AML1 transcripts among B-lineage ALL was 16% (14/86). The reciprocal AML1/TEL transcripts were detected in 12 (86%) of the 14 cases expressing a TEL/AML1 transcript. In three cases, the TEL gene was fused to exon 3 of the AML1 gene, and to exon 2 in the remaining cases. To evaluate the amount of TEL/AML1 molecules for the quantification of a minimal residual disease (MRD), a plasmid vector which contained either a long TEL/AML1 PCR product (464 bp) or a short one (425 bp) was used as a competitor. We amplified RNAs obtained from bone marrow (BM) at complete remission or from peripheral blood stem cell (PBSC) harvests in two representative cases. For one PBSC harvest showing a positive result, a competitive PCR was carried out to quantify the amount of MRD. A 1:4 dilution series of competitor vectors was constructed, and each vector was added to a PCR reaction which contain a constant amount of cDNA obtained from the PBSC harvest. An equivalent point was compared to that of corresponding samples at diagnosis. Using this method, MRD in the PBSC harvest was 3.9:10(3). Our results elucidated the incidence, lineage-specificity, and variant forms of TEL/AML1 fusion transcripts in childhood ALL. Since the percentage of other chromosomal translocations in childhood ALL is not more than 5%, TEL/AML1 transcript would be the most feasible clone-specific marker for these patients. In addition, our method could be a powerful tool for quantification of the TEL/AML1 transcript and for the detection of MRD.

Adolescent↗
PubMed1995

A neuroprotective compound, aurin tricarboxylic acid, stimulates the tyrosine phosphorylation cascade in PC12 cells.

Aurin tricarboxylic acid (ATA), a general nuclease inhibitor, was reported to prevent PC12 cells from cell death caused by serum starvation (1). In our study, ATA also protected PC12 cells, but not NIH3T3 cells, from serum-starved cell death. When we investigated the mechanism of action of ATA on these cells, ATA was found to increase tyrosine phosphorylation in PC12 cells, but not in NIH3T3 cells. Further investigation on tyrosine-phosphorylated proteins revealed that ATA, similar to nerve growth factor and epidermal growth factor, induced tyrosine phosphorylation of mitogen-activated protein kinases. Since the tyrosine phosphorylation of mitogen-activated protein kinases is thought to play an important role inn growth factor-dependent signal pathways, this finding suggests that the action of ATA on PC12 cells is mediated by tyrosine phosphorylation cascade, similar to growth factor signaling. In addition, we found that Shc proteins, phosphatidylinositol 3-kinase, and phospholipase C-gamma were also phosphorylated in ATA-treated PC12 cells. These key proteins in signal transduction pathways are known to associate with ligand-activated growth factor receptors and are phosphorylated on tyrosine. Thus, the phosphorylation of these three proteins by ATA stimulation supports the speculation that ATA activates a certain receptor tyrosine kinase.

3T3 Cells↗
PubMed1995

Inhibition by haloperidol of adenosine 5'-triphosphate-evoked responses in rat pheochromocytoma cells.

The effects of haloperidol, a typical antipsychotic drug, on adenosine 5'-triphosphate (ATP)-induced increase in intracellular Ca2+ concentration ([Ca]i) and inward currents were investigated using rat pheochromocytoma PC12 cells. Haloperidol (10-100 microM) significantly attenuated the rise in [Ca]i evoked by 30 microM ATP. This inhibition was not mimicked by (-)-sulpiride, an antagonist to dopamine D2-receptor. Dopamine or other dopaminergic agents did not affect the [Ca]i rise evoked by ATP. Under whole-cell voltage-clamp, haloperidol inhibited the ATP-activated current in the cells. These results suggest that haloperidol inhibits the ATP-receptor/channel, leading to the attenuation of the ATP-evoked increase in [Ca]i. Mechanisms involving dopamine receptors may not contribute to the inhibition by haloperidol.

Adenosine Triphosphate↗
PubMed1995

Zinc potentiation of neurotransmission and inhibition of background cationic conductance in rat cultured hippocampal neurones.

1. The facilitation by zinc (Zn2+) of neurotransmission and the mechanisms underlying it were electrophysiologically investigated in rat cultured hippocampal neurones using whole-cell voltage- and current-clamp techniques. 2. Under whole-cell voltage clamp with an intracellular solution containing CsCl as a major salt, inward postsynaptic currents were observed at -40 mV in a cell culture where a neuronal network had been formed. The postsynaptic currents appeared to be mediated by gamma-aminobutyric acid (GABA) because the inward currents were abolished when intracellular CsCl was replaced with caesium phosphate and they were blocked by bicuculline (10 microM), an antagonist to GABA-gated channels. The currents were, however, also blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 30 microM), an antagonist to non-NMDA glutamate-gated channels, suggesting a contribution of a glutamatergic mechanism to the generation of the currents. Zn2+ (10 and 100 microM) potentiated the postsynaptic currents. 3. In addition to the potentiation of the postsynaptic currents, Zn2+ shifted net membrane current at -60 mV in an outward direction. The current-voltage relationship obtained under various ionic conditions indicated that Zn2+ inhibits a current component which is mainly carried by extracellular Na+. 4. Under whole-cell current clamp, Zn2+ (10 microM) induced a small hyperpolarization (up to 20 mV), which was accompanied by potentiation of the postsynaptic potentials and spike potentials. Tests were carried out to examine whether changes in resting potential by different protocols mimic responses observed with Zn2+. Hyperpolarization induced by current injection through patch pipettes increased the amplitude of postsynaptic currents, but did not enhance the appearance of spike potentials. In contrast, when extracellular K+ concentration was decreased from 5 to 2.5 mM, cells were hyperpolarized and spike potentials of large amplitude appeared. 5. The results suggest that Zn2+ potentiates neurotransmission and inhibits a background cationic current mainly carried by extracellular Na+ under physiological conditions. The inhibition of the Na+ permeation may increase membrane excitability and thereby contribute to the potentiation of neurotransmission.

Animals↗
PubMed1995

Contribution of L-type Ca2+ channels to long-term enhancement of high K(+)-evoked release of dopamine from rat striatal slices.

Pre-treatment with BAY K 8644, an L-type voltage-gated Ca2+ channels agonist, produced long-term enhancement (LTE) of over 2 h of high K(+)-evoked dopamine release from rat striatal slices. Exposure to BAY K 8644 under Ca(2+)-free conditions did not enhance this release. Thus, a transient activation of L-type voltage-gated Ca2+ channels followed by Ca2+ entry can trigger LTE of the evoked DA release from striatal tissues. This type of LTE in the striatum underlines the importance of presynaptic mechanisms, including L-type voltage-gated Ca2+ channels of 'long-term potentiation' expression.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

Enhancement by zinc of ATP-evoked dopamine release from rat pheochromocytoma PC12 cells.

The effects of zinc (Zn2+) on ATP-evoked dopamine release was investigated in rat pheochromocytoma PC12 cells. Zn2+ potentiated the dopamine release evoked by 30 microM ATP in a concentration-dependent manner over a concentration range from 3 to 300 microM. High concentration of Zn2+ (> 1 mM) inhibited the release. Zn2+ (10 microM) shifted the concentration-response curve of the ATP-evoked dopamine release to the left without affecting the maximal response. The dopamine release evoked by 40 mM KCl was not affected by Zn2+ (1-100 microM), whereas high concentration of Zn2+ ( > 300 microM) attenuated the response. The dopamine release evoked by 30 microM ATP in the presence of 10 microM Zn2+ were suppressed by suramin (30 microM), an antagonist to P2-purinoceptors, to an extent similar to that in the absence of Zn2+. Zn2+ (1-100 microM) enhanced the ATP-evoked increase in intracellular Ca2+ concentration ([Ca]i) in the cells. The Ca2+ responses to ATP in the presence and absence of Zn2+ were abolished by external Ca(2+)-depletion. Under whole-cell voltage-clamp, Zn2+ (10 microM) augmented by two-fold the peak amplitude of an inward current evoked by 30 microM ATP. Taken together, it is suggested that Zn2+ enhances the ATP-evoked dopamine release by increasing sensitivity to ATP. The enhancement may be due to the augmentation of ATP-gated Ca(2+)-influx, but not due to modulation of cellular machinery downstream to [Ca]i rise. The enhancement of the ATP-mediated responses may underlie modulation by Zn2+ of physiological functions in various types of neuronal cells.

Adenosine Triphosphate↗
PubMed1995

Glutamate-evoked release of adenosine 5'-triphosphate causing an increase in intracellular calcium in hippocampal neurons.

ATP evoked an increase in intracellular Ca2+ concentration ([Ca]i) in hippocampal neurons in the presence of tetrodotoxin (TTX, 3 microM), hexamethonium (C6, 100 microM), D-2-amino-phosphonovalerate (APV, 100 microM), 6-cyano-7-nitro quinoxalline-2,3-dione (CNQX, 30 microM), bicuculline (10 microM) and cadmium (Cd2+, 300 microM). The increase was blocked by suramin (100 microM), a P2-purinoceptor blocker. These results suggest that ATP evokes an increase in [Ca]i through P2-purinoceptor. As a result of measuring [Ca]i in multiple cells simultaneously, it was suggested that glutamatergic neurones connect with purinergic neurones and glutamate (10 microM) stimulated the release of ATP causing an increase in [Ca]i in postsynaptic neurones.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

NMDA receptor involvement in endothelin neurotoxicity in rat striatal slices.

The high K(+)-evoked dopamine release from rat striatal slices remained impaired by 50% up to 2 h after pulse exposure of the tissues to endothelin-3, under conditions of hypoglycemia/hypoxia. This striatal dysfunction was significantly improved by D-2-amino-5-phosphonopentanoic acid, a NMDA receptor antagonist, at a much lower concentration than that providing protection against NMDA-evoked dysfunction. In light of these findings, the important role of glutamatergic mechanisms, especially NMDA receptors, in mediating endothelin neurotoxicity warrants further attention.

2-Amino-5-phosphonovalerate↗
PubMed1995

Accentuation by pertussis toxin of the 5-hydroxytryptamine-induced potentiation of ATP-evoked responses in rat pheochromocytoma cells.

We previously demonstrated that 5-hydroxytryptamine (5-HT) enhances the cationic current activated by extracellular ATP in rat pheochromocytoma PC12 cells. We report here that pertussis toxin (PTX) modulates this 5-HT-dependent enhancement in these cells. 5-HT potentiated ATP-evoked intracellular Ca2+ concentration ([Ca]i) rise and dopamine release over a concentration range from 1 to 100 microM. When cells were pre-treated with PTX, this potentiation was accentuated. Pretreatment with PTX also accentuated the 5-HT-dependent enhancement of the ATP-activated current. These results suggest that the enhancement by 5-HT of the ATP-evoked responses is negatively regulated by a mechanism mediated through PTX-sensitive GTP-binding protein.

Adenosine Triphosphate↗