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T Kondo

Publications and source records attributed to T Kondo.

At least 361 records · Page 20Linked to original sources
PubMed1999

Effects of zonisamide on K+ and Ca2+ evoked release of monoamine as well as K+ evoked intracellular Ca2+ mobilization in rat hippocampus.

To clarify the effects of zonisamide (ZNS) on neurotransmission and intracellular Ca2+ mobilization, both Ca2+ and K+ evoked hippocampal releases of dopamine (DA) and serotonin (5-HT) were determined by in vivo microdialysis, and K+ (25 and 50 mM) evoked elevation of intracellular Ca2+ level was determined by fluorescence microscopy in vitro. Therapeutic concentrations of ZNS had different effects on Ca2+ and K+ evoked release of monoamine. ZNS stimulated Ca2+ evoked monoamine release, while ZNS inhibited K+ evoked monoamine release. ZNS inhibited K+ evoked elevation of hippocampal intracellular Ca2+ levels in a concentration dependent manner. These results suggest that ZNS inhibits the depolarization induced by neuronal excitation, whereas ZNS might enhance the N-type Ca2+ channel activity or N-type Ca2+ channel related exocytosis mechanisms.

Animals↗
PubMed1999

The circadian clocks of plants and cyanobacteria.

Classical research on the circadian rhythms of plants helped to demonstrate that all living organisms utilize circadian clocks to adapt their day-night cycles and that the clock is the basis for photoperiodic time measurements. Molecular models for the circadian oscillator have now been elucidated in Drosophila, Neurospora, mice and cyanobacteria. All share a similar feedback structure, but key proteins in each of the oscillators are different. A plant clock model has yet to be proposed, but clock mutants of Arabidopsis are expected to reveal key proteins in the mechanism. Here we discuss how a self-sustained oscillation is established in eukaryotic and prokaryotic models, and the polyphyletic evolution of these clock systems.

Journal Article↗
PubMed1999

Role of the ryanodine receptor in ischemic brain damage--localized reduction of ryanodine receptor binding during ischemia in hippocampus CA1.

1. The ryanodine receptor has recently been shown to play a pivotal role in the regulation of intracellular Ca2+ concentration via Ca(2+)-induced Ca2+ release (CICR). Effects of ischemia on CICR in the brain tissue, however, remain largely unknown since only a few reports have been published on this subject. In this paper we report on work in this area by our group and review related progress in this field. 2. We examined alterations of ryanodine receptor binding and local cerebral blood flow (LCBF) at 15 min, 30 min, and 2 hr after occlusion of the right common carotid artery in the gerbil brain. A quantitative autoradiographic method permitted simultaneous measurement of these parameters in the same brain. The LCBF was significantly reduced in most of the cerebral regions on the occluded side during each time period of ischemia. In contrast, only in the hippocampus CA1 on the occluded side was a significant reduction in ryanodine binding found at 15 min, 30 min and 2 hr after the occlusion. 3. These findings suggest that suppression of ryanodine binding in the hippocampus CA1 may be attributable to a regionally specific perturbation of CICR and that this perturbation may be closely associated with the pathophysiological mechanism that leads to be selective ischemic vulnerability of this region. 4. Other recent studies have also reported an important role for ryanodine receptors in neuronal injury such as the delayed neuronal death in the hippocampus CA1. These data suggest that derangement of CICR is likely to be involved in acute neuronal necrosis as well as in delayed neuronal death in ischemia. 5. Further studies on clarifying the role of CICR in ischemic brain damage are needed in order to develop new therapeutic strategies for stroke patients.

Animals↗
PubMed1999

Vegetables, high nitrate foods, increased breath nitrous oxide.

We have demonstrated nitrous oxide (N2O), a metabolite of the reduction of nitrate (NO(3)-) by microflora, in exhaled air. The purpose of this study is to examine the effect of ingesting vegetables, which contain high levels of NO(3)-, on breath N2O levels. We measured breath N2O in six healthy subjects aged 20-41 years at 15-min intervals after the following: (1) no ingestion; (2) ingestion of 180 g of vegetable juice; and (3) ingestion of 50 g of lettuce. N2O levels were measured with an infrared-photoacoustic (IR-PAS) analyzer. N2O was detectable in all subjects regardless of treatment protocol. Lettuce and vegetable juice significantly increased breath N2O levels. Total excretions in breath N2O were significantly higher in the lettuce group (P = 0.028) and the vegetable juice group (P = 0.046) than controls. Breath N2O increases after vegetable ingestion, probably due to denitrification of NO(3)- by normal microflora in the intestinal tract.

Adult↗
PubMed1999

Identification of candidate T-cell epitopes and molecular mimics in chronic Lyme disease.

Elucidating the cellular immune response to infectious agents is a prerequisite for understanding disease pathogenesis and designing effective vaccines. In the identification of microbial T-cell epitopes, the availability of purified or recombinant bacterial proteins has been a chief limiting factor. In chronic infectious diseases such as Lyme disease, immune-mediated damage may add to the effects of direct infection by means of molecular mimicry to tissue autoantigens. Here, we describe a new method to effectively identify both microbial epitopes and candidate autoantigens. The approach combines data acquisition by positional scanning peptide combinatorial libraries and biometric data analysis by generation of scoring matrices. In a patient with chronic neuroborreliosis, we show that this strategy leads to the identification of potentially relevant T-cell targets derived from both Borrelia burgdorferi and the host. We also found that the antigen specificity of a single T-cell clone can be degenerate and yet the clone can preferentially recognize different peptides derived from the same organism, thus demonstrating that flexibility in T-cell recognition does not preclude specificity. This approach has potential applications in the identification of ligands in infectious diseases, tumors and autoimmune diseases.

Adult↗
PubMed1999

A high molecular weight glycoprotein in seminal plasma is a sperm immobilizing factor in the teleost Nile tilapia, Oreochromis niloticus.

Sperm that have acquired potential for motility are kept immotile in seminal plasma in the teleost, Nile tilapia. In order to investigate the mechanism of immobilization, several experiments were performed using a previously characterized monoclonal antibody (TAT-30) against a molecular weight (Mr) = 120,000 protein that is secreted by Sertoli cells and epithelial cells of the sperm duct, and is also bound to the head of the spermatozoon. First, we assessed sperm motility in the seminal plasma protein fraction (SPP), and demonstrated that the sperm motility is inhibited by SPP in a concentration-dependent manner. Furthermore, sperm motility was recovered if SPP was pretreated with TAT-30, suggesting that the TAT-30 antigen is one of the components of the sperm immobilizing factor. Calibration by gel filtration followed by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting with TAT-30 demonstrated that the sperm immobilizing factor was more than Mr = 1,000,000 in seminal plasma, suggesting that it is a homopolymer of the Mr = 120,000-TAT-30 positive protein. Additionally, lectin blot analysis showed that the TAT-30 antigen was reactive with Lens culinarin agglutinin (LCA) and Conavalia ensiformis agglutinin (ConA), indicating that it is a glycoprotein. Immunohistochemical studies showed that the TAT-30 antigen was localized specifically on the heads of spermatozoa and on the apical surface, lysosomes and rough endoplasmic reticulum of Sertoli cells.

Animals↗
PubMed1999

Analysis of prognostic factors related to primary superficial bladder cancer tumor recurrence in prophylactic intravesical epirubicin therapy.

PURPOSE: The aims of the present study were to examine the effects of intravesical instillation of epirubicin on tumor recurrence and to identify tumors that are at a high risk of recurrence. METHODS: Forty-five patients with primary superficial bladder cancer were treated with prophylactic intravesical epirubicin following transurethral resection of the bladder tumor (TUR-BT). Epirubicin (20 mg) was administered intravesically every second week for 4 months and then once a month or every 2 weeks for next 8 months. Patients were analyzed with respect to prognostic factors related to tumor recurrence. RESULTS: The overall recurrence-free rate, calculated using the Kaplan-Meier method, was 76.1 and 52.3% at 2 and 5 years after operation, respectively. These results were better than those reported for patients treated with TUR-BT alone. A univariate analysis demonstrated that high-grade, T1, sessile, large (> or = 2 cm) and multiple tumors were a significantly high risk for recurrence. A multivariate analysis performed by using the Cox proportional hazard model with stepwise selection showed that morphologic features (pedunculated or sessile) were the most prognostic factors for recurrence. This was followed by age and tumor size. The remaining four factors were not found to contribute significantly to recurrence. CONCLUSIONS: Epirubicin appears to be effective in preventing the recurrence of superficial bladder cancer. Morphologic features, patient age and size of the tumor were considered independent risk factors. The risk of recurrence for each tumor should be taken into consideration when the intravesical adjuvant therapy protocol is being selected.

Administration, Intravesical↗
PubMed1999

Differential effects of adenosine receptor subtypes on release and reuptake of hippocampal serotonin.

To clarify the effects of adenosine receptor subtypes (A1, A2 and A3) on hippocampal serotonin (5-HT) release and 5-HT reuptake activity, hippocampal extracellular 5-HT levels were determined in vivo by microdialysis in freely moving rats. Selective 5-HT reuptake inhibitor (SSRI) fluoxetine and DU24565 increased extracellular 5-HT levels. Adenosine and A1 receptor agonist, 2-chloro-N6-cyclopentyl-adenosine (CCPA), decreased extracellular 5-HT levels, whereas non-selective antagonist, caffeine, and A1 antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT) increased them. When 5-HT reuptake activity was inhibited by DU24565 and fluoxetine, the effects of CPT and CCPA on 5-HT level were enhanced. A2A receptor agonist, CGS21680, A2 receptor agonist, PD125944, A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX), and A3 receptor agonist, N6-2-(4-aminophenyl)ethyladenosine (APNEA) did not affect 5-HT levels; however, when A1 receptor was blocked by CPT, 5-HT levels were increased by adenosine, CGS21680 and PD125944, and decreased by DMPX and APNEA. Under conditions of A1 receptor blockade, pretreatment with DU24565 or fluoxetine, enhanced the stimulatory effects of CGS21680 and PD125944 as well as inhibitory effects of DMPX on 5-HT level, whereas the inhibitory effect of APNEA was abolished. These results indicate that the stimulatory effects of A2 receptor and inhibitory effects of A3 receptor on hippocampal extracellular 5-HT levels are masked or abolished by the inhibitory effects of A1 receptor. In addition, hippocampal serotonergic transmission might be modulated by hippocampal presynaptic adenosine receptor subtypes, and hippocampal 5-HT reuptake activity might be modulated by hippocampal A3 receptor.

Adenosine↗
PubMed1999

Mitochondrial and intracellular free-calcium regulation of radiation-induced apoptosis in human leukemic cells.

PURPOSE: To investigate the mechanisms and pathways of X-ray apoptosis in Molt-4 cells, focusing on mitochondrial and cytosolic Ca2+ ([Ca2+]i) regulation. MATERIALS AND METHODS: X-irradiated Molt-4 cells and cell extract (CE) were used to analyse: (1) induced apoptosis (Giemsa stain), (2) p53, Bcl-2 and Bax expressions (immunoblot), (3) mitochondrial potential deltapsi(m) and (4) [Ca2+]i (flow cytometry), (5) caspase-3 activity, and (6) roles of [Ca2+]- and caspase-3-mediated pathways by inhibiting either or both pathways for induced apoptosis. RESULTS: Molt-4 cells were sensitive to apoptosis since 5 Gy induced 57 and 94% apoptosis at 6 and 24 h. After 5Gy, p53 was accumulated that upregulated Bax but which repressed Bcl-2 with time, resulting in a 7-fold increase in Bax/Bxl-2 at 6 h. Predominant Bax reduced deltapsi(m), and low-deltapsi(m) cells increased 45 min earlier than apoptosis after 5 Gy. Caspase-3 was activated in apoptotic CE. The caspase-3 inhibitor Ac-DEVD-CHO inhibited apoptosis and DNA-ladder formation by approximately 50%, suggesting a approximately 50% role of caspase-3-activated DNase (CAD). [Ca2+]i was increased after 5 Gy. [Ca2+]i-chelating BAPTA-AM (5 microM) and/or DNase gamma-inhibiting Zn2+ (0.5 mM) inhibited approximately 50% of induced apoptosis and DNA-laddering, indicating a 50% participation of Ca2+/Mg2+-dependent DNase gamma. CONCLUSIONS: The p53-Bax-mitochondria-caspase-3-CAD pathway and the [Ca+2]i-mediated DNase gamma pathway were involved in the regulation of X-ray apoptosis in sensitive Molt-4 cells.

Animals↗
PubMed1999

Regulation of gamma-glutamylcysteine synthetase expression in response to oxidative stress.

Glutathione (GSH) is synthesized by the activity of two ATP-requiring GSH synthesizing enzymes. Gamma-glutamylcysteine synthetase (gamma-GCS) is the rate limiting enzyme for the GSH synthesis. Gamma-GCS is a heterodimer of heavy, catalytic subunit and light, regulatory subunit and responsive to many stresses, such as heat shock, oxidative stress or cytokines. To know the regulation of the expression of gamma-GCS gene, in the present study, we show evidences that gamma-GCS heavy subunit is upregulated by oxidative stress by ionizing radiation and TNF-alpha mediated by nuclear factor-kappaB (NF-kappaB), and impairment of the expression of gamma-GCS by TNF-alpha in diabetic condition. Furthermore we describe the importance of GSH in the regulation of NF-kappaB subunits.

Animals↗
PubMed1999

Overexpression of glutathione S-transferase pi enhances the adduct formation of cisplatin with glutathione in human cancer cells.

In this paper, we provide direct evidence that glutathione S-transferase pi (GSTpi) detoxifies cisplatin (CDDP). We used human colonic cancer HCT8 cells sensitive and resistant to CDDP, the level of cisplatin-glutathione adduct (DDP-GSH) being higher in the resistant cells. There was an overexpression of GSTpi mRNA in these CDDP-resistant cells. Incubation of the cells with CDDP resulted in the formation of DDP-GSH dependent on the CDDP concentration and the incubation time. The formation of DDP-GSH was abolished when the cells were pre-treated with ethacrynic acid or ketoprofen, inhibitors of GSTpi. Purified GSTpi also catalyzed the formation of DDP-GSH in vitro, with an apparent Km of 0.23 mM for CDDP and an apparent Vmax of 4.9 nmol/min/mg protein. The increase in DDP-GSH produced by GSTpi was linear with incubation time up to 3 h and optimal of pH 7.4. A GSTpi transfectant cell line was constructed in HCT8 cells using a pcDNA3.1 (-)/Myc-His B with an expression vector containing cDNA for GSTpi. Transfection of GSTpi cDNA into HCT8 cells resulted in an increase in the expression of GSTpi by 1.4-fold in parallel with an augmentation of the formation of DDP-GSH. These results suggest that GSTpi plays a role in the formation of DDP-GSH and the acquisition of resistance to CDDP in cancer cells.

Cisplatin↗
PubMed1999

Changes in hepatic microcirculation and histomorphology in brain-dead organ donors: an experimental study in rats.

OBJECTIVE: To assess the effect of brain death on hormonal homeostasis, hepatic microcirculation, and histomorphology in organ donors. DESIGN: Prospective randomised experimental study. SETTING: Institute for Surgical Research, Germany. SUBJECTS: 12 male Sprague-Dawley rats INTERVENTIONS: 6 rats acted as controls, and 6 had brain death induced by inflation of an intracranial balloon. MAIN OUTCOME MEASURES: Mean arterial pressure, serum concentration of antidiuretic hormone (ADH), thyroxine (T4), free-T4, triiodothyronine (T3) and free-T3, bile production, intravital fluorescence microscopy and electron microscopic appearances. RESULTS: After induction of brain death mean arterial pressure rose within 5 minutes followed by significant hypotension (p < 0.01). ADH concentration was reduced (p < 0.01), as was bile production (p < 0.05). There was impaired sinusoidal perfusion and increased interaction between leucocytes and endothelium in the hepatic microvasculature. The electron microscopic analysis showed vacuolisation of hepatocytes. CONCLUSION: Macrohaemodynamics, ADH homeostasis, and the hepatic microcirculation deteriorate after brain death, which leads to histomorphological damage of hepatocytes and compromised liver function.

Animals↗
PubMed1999

Characteristics and risk factors of acute dystonia in schizophrenic patients treated with nemonapride, a selective dopamine antagonist.

The occurrence of acute dystonia was prospectively monitored in 39 schizophrenic patients (18 male and 21 female) treated with 9 to 27 mg/day of nemonapride, a selective dopamine antagonist, and the relationship of acute dystonia with characteristics of patients and plasma concentrations of the drug and prolactin was investigated. Twenty (51.3%) of 39 patients had dystonic reactions, the onsets of which occurred within 3 days after the initiation of treatment in 90% of dystonic patients. The incidence of acute dystonia was significantly higher in male than in female patients (77.8% vs. 28.6%, p < 0.05). Younger male patients (< or = 30 years) especially had an extremely high incidence of this side effect (91.7%). A positive correlation between prolactin response after 1 week of treatment and dystonia rating scores was found in male (Spearman rank correlation: r(s) = 0.606,p < 0.01) but not in female patients (r(s) = -0.378,p = not significant). These results suggest that young male patients have the highest risk of neuroleptic-induced dystonia. Prolactin response after 1 week of treatment as an index of dopamine blockade may reflect vulnerability to the development of acute dystonia at least in male patients treated with nemonapride.

Acute Disease↗
PubMed1999

Effects of itraconazole on the steady-state plasma concentrations of haloperidol and its reduced metabolite in schizophrenic patients: in vivo evidence of the involvement of CYP3A4 for haloperidol metabolism.

The effects of itraconazole, a potent inhibitor of cytochrome P450 (CYP) 3A4, on the steady-state plasma concentrations of haloperidol and reduced haloperidol were examined in schizophrenic patients. Thirteen schizophrenic patients treated with haloperidol 12 or 24 mg/day received 200 mg/day of itraconazole for 7 days. Plasma concentrations of haloperidol and reduced haloperidol were measured by high-performance liquid chromatography together with clinical assessment by the Brief Psychiatric Rating Scale (BPRS) and the Udvalg for Kliniske Undersogelser side effect rating scale just before and during itraconazole treatment and 1 week after its discontinuation. Plasma concentrations of haloperidol and reduced haloperidol during the itraconazole treatment (16.9 +/- 11.2 and 6.1 +/- 6.6 ng/mL, respectively) were significantly (p < 0.01) higher than those observed before itraconazole treatment (13.0 +/- 7.9 and 4.9 +/- 5.1 ng/mL) or 1 week after its discontinuation (13.5 +/- 8.2 and 4.9 +/- 5.0 ng/mL). No change was found in clinical symptoms assessed by BPRS, whereas neurologic side effects were significantly (p < 0.05) increased during itraconazole coadministration. The elevated plasma concentrations of haloperidol and reduced haloperidol during itraconazole coadministration were likely due to the inhibitory effects of itraconazole on the metabolism of haloperidol and reduced haloperidol. Thus, this study may provide in vivo evidence of involvement of CYP3A4 in the metabolism of haloperidol and possibly in that of reduced haloperidol. Deterioration of neurologic side effects during itraconazole treatment may result from the increased plasma concentrations of haloperidol and reduced haloperidol during itraconazole treatment.

Adult↗
PubMed1999

Lack of significant pharmacokinetic interaction between haloperidol and grapefruit juice.

The effects of repeated ingestion of grapefruit juice, an inhibitor of cytochrome P4503A4 (CYP3A4), on the steady-state plasma concentrations of haloperidol and reduced haloperidol were examined. Twelve schizophrenic inpatients receiving haloperidol 12 mg/day, ingested grapefruit juice 600 ml/day for 7 days. Blood samples were collected before and during grapefruit juice coadministration and 1 week after its discontinuation together with an assessment of clinical status. Plasma drug concentrations were measured using high-performance liquid chromatography. Clinical status for each patient was assessed by the Brief Psychiatric Rating Scale (BPRS) and the UKU side-effect rating scale (UKU). Plasma concentrations of haloperidol and reduced haloperidol during grapefruit juice coadministration (9.0 +/- 3.0 and 2.6 +/- 1.4 ng/ml, respectively) were not significantly different from those before grapefruit juice coadministration (9.1 +/- 2.8 and 2.6 +/- 1.5 ng/ml) or those 1 week after its discontinuation (8.8 +/- 2.7 and 2.6 +/- 1.3 ng/ml). There was no change in the scores of BPRS or UKU during the study period. The present results shows that grapefruit juice does not affect the plasma concentrations of haloperidol and reduced haloperidol or clinical status in patients receiving haloperidol.

Adult↗
PubMed1999

No pharmacokinetic but pharmacodynamic interactions between cisapride and bromperidol or haloperidol.

Pharmacokinetic and pharmacodynamic interactions between the gastrokinetic drug cisapride and the antipsychotic drugs bromperidol and haloperidol were studied in 29 schizophrenic inpatients. Fourteen patients were taking bromperidol (12-24 mg/d), and 15 were taking haloperidol (12-36 mg/d). Cisapride 10 mg/d was coadministered for 1 week, and blood sampling was performed before cisapride treatment, 1 week after starting cisapride treatment, and I week after stopping cisapride treatment. On the same days as the blood sampling, psychotic symptoms and side effects were evaluated using the Brief Psychiatric Rating Scale (BPRS) and the Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale (UKU), respectively. Plasma concentrations of bromperidol, haloperidol, and their reduced metabolites were measured by high-performance liquid chromatography. The mean BPRS scores after adding cisapride were significantly higher than those before cisapride (p<0.01) and after stopping cisapride (p<0.001) in the haloperidol group in this uncontrolled study. A similar tendency was observed in the bromperidol group, although it did not reach statistical significance (p = 0.08). Cisapride coadministration caused no significant changes in the mean plasma concentrations of bromperidol, haloperidol, and their reduced metabolites or in the mean UKU score. The present study suggests that there is no significant pharmacokinetic interaction between cisapride and bromperidol or haloperidol, but cisapride appears to deteriorate psychotic symptoms by a pharmacodynamic interaction in schizophrenic patients treated with haloperidol.

Antipsychotic Agents↗
PubMed1999

Reduction of hepatic microcirculatory failure caused by normothermic ischemia/reperfusion-induced injury by means of heat shock preconditioning.

Transient sublethal hyperthermia and the recovery from this exposure to heat (heat shock preconditioning) provides a cytoprotective effect on oxidative insults through an intracellular protective response, heat shock response. The impact of heat shock preconditioning on hepatic microvascular failure, which is a causative determinant of ischemia/reperfusion-induced injury of the liver, was investigated by using intravital fluorescence microscopy. In Sprague-Dawley rats, normothermic ischemia was induced by totally clamping the hepatoduodenal ligament for 20 min, followed by 120 min of reperfusion. Heat shock preconditioning was performed by whole-body hyperthermia (42 degrees C for 15 min) and subsequent 48 h recovery. In accordance with the prominent induction of heat shock protein 70 in the liver tissue, the postischemic decrease in sinusoidal perfusion rate and sinusoidal diameter, and the postischemic increase in the number of stagnant leukocytes in sinusoids and adherent leukocytes in postsinusoidal venules were significantly attenuated in the heat shock-treated animals. Furthermore, liver enzyme release (glutamate pyruvate transaminase and alpha-glutathione S-transferase) was significantly reduced and postischemic deterioration of bile production was attenuated. The 7-day survival rate after 20-minute ischemia was significantly improved from 50% to 80% (heat shock-nontreated group vs. heat shock-treated group, P < 0.05). These results indicate that heat shock preconditioning attenuates ischemia/reperfusion-induced hepatic injury by preventing postischemic microvascular disturbances, and that its protective effect is circumstantially associated with the concomitant induction of heat shock protein 70.

Alanine Transaminase↗