Biomedical subjects

T Kondo

Publications and source records attributed to T Kondo.

At least 469 records · Page 26Linked to original sources

PubMed1998

Involvement of CD4+ T cells in the development of dextran sulfate sodium-induced experimental colitis and suppressive effect of IgG on their action.

1. To clarify the role of T cells in the development of dextran sulfate sodium (DSS)-induced colitis, T cells from colitis mice were primed with DSS-pulsed macrophages in vitro and then transferred into normal mice. In addition, to determine whether the target cell of immunoglobulin G (IgG) is the T cell, the extent of T cell proliferation induced by pulsed macrophages was examined after preincubation with IgG. 2. When mice receiving the primed T cells were treated with oral DSS, colitis symptoms were more severe than in animals treated with oral DSS only. This activity of primed T cells was reduced by depletion from the cells of CD4+ but not CD8+ cells. 3. The proliferation of T cells from colitis mice induced by pulsed macrophages was inhibited by T cell preincubation with homologous IgG. 4. The results suggest that CD4+ T cells play an important role in the development of DSS-induced experimental colitis and that IgG may modulate the development of colitis through interaction with pathogenic T cells.

Adoptive Transfer↗

PubMed1998

Nuclear factor kappa B dependent induction of gamma glutamylcysteine synthetase by ionizing radiation in T98G human glioblastoma cells.

Glioblastoma is one of the most malignant of all neoplasms, and often shows resistance to chemotherapy and radiation therapy. Ionizing radiation activates transcriptional factors, such as nuclear factor kappa-B (NF-kappa B). Previously we found that glutathione (GSH) synthesis is induced by cytokines mediated by NF-kappa B (Urata et al. J. Biol. Chem., 1996). Here, we present direct evidence that NF-kappa B activated by ionizing radiation induces the expression of gamma-glutamylcysteine synthetase (gamma-GCS), the rate limiting enzyme of GSH synthesis, using T98G human glioblastoma cells. T98G cells have approximately 14-times the level of intracellular GSH of NB9 cells, radiation-sensitive neuroblastoma cells. In T98G cells, 30-Gy of ionizing radiation was required for the activation of NF-kappa B on an electrophoretic mobility shift assay and the induction of gamma-GCS mRNA on Northern blots and a nuclear run-on assay. However, when T98G cells were treated with buthionine sulfoximine, 3-Gy of ionizing radiation stimulated the DNA-binding activity of NF-kappa B and the expression of gamma-GCS. We constructed chimeric genes containing various regions of gamma-GCS promoter gene and the coding region for Luciferase. T98G cells transiently transfected with a plasmid containing the gamma-GCS promoter-luciferase construct showed increased luciferase activity when treated with ionizing radiation. The luciferase activity stimulated by ionizing radiation was found in the gamma-GCS promoter containing the NF-kappa B binding site, whereas not in that containing its mutated site. These results suggest that GSH synthesis is upregulated by ionizing radiation mediated by NF-kappa B and a high concentration of GSH in T98G cells causes downregulation of the NF-kappa B-DNA binding activity in response to ionizing radiation. The irresponsiveness of the intracellular signal transduction cascade to irradiation may be a factor in the resistance of T98G cells to radiation therapy.

Acetylcysteine↗

PubMed1998

Effect of gas-containing microspheres and echo contrast agents on free radical formation by ultrasound.

Stabilized microbubbles (microspheres) are widely used to enhance the contrast of ultrasound imaging. Our data provide direct evidence that the contrast agents, Levovist, PVC-AN (polyvinylidene chloride-acrylonitryl copolymer), and Albunex (compared to 5% human albumin), at concentrations comparable to those used for ultrasound imaging, enhance H2O2 production (through the superoxide-dependent pathway) in air-saturated aqueous solutions exposed to 47 kHz ultrasound above the cavitation threshold. These agents also act as scavengers of .H atoms and .OH radicals, thus lowering H2O2 formation (by recombination of .OH radicals) in argon-saturated solutions. EPR spin trapping also reveals that secondary radicals derived from the contrast agents are produced by reactions with .H and .OH which are formed by pyrolysis of water inside cavitation bubbles. In addition, the contrast agents themselves undergo pyrolysis reactions in the cavitation bubbles as demonstrated by formation of methyl radicals. Possible deleterious consequences of the formation of sonochemical intermediates may have to be assessed, particularly since some of the echo contrast agents have been shown to lower the cavitation threshold of diagnostic ultrasound. Unlike the microspheres formed from organic molecules, inorganic microspheres, Eccospheres, because of their stability and inert nature with respect to participation in free radical processes, appear to be suitable tools for enhancing the yields of aqueous sonochemical reactions.

Acrylic Resins↗

PubMed1998

Effect of carbamazepine on the single oral dose pharmacokinetics of alprazolam.

The effect of carbamazepine, an inducer of cytochrome P450 (CYP) 3A4, on the single oral dose pharmacokinetics of alprazolam was examined in a double-blind, randomized crossover study with two phases. Seven healthy male subjects took carbamazepine 300 mg/day or matched placebo orally for 10 days, and on the 8th day they took a single oral 0.8 mg dose of alprazolam. Blood samples were taken and psychomotor function was assessed by the Digit Symbol Substitution Test, Visual Analog Scale, and UKU Side Effect Rating Scale up to 48 h after alprazolam dosing. Carbamazepine significantly (p < .01 to .001) decreased the plasma alprazolam concentrations during the elimination phase. Carbamazepine significantly (p < .001) increased the apparent oral clearance (0.90 +/- 0.21 vs. 2.13 +/- 0.54 ml/min/kg) and shortened the elimination half-life (17.1 +/- 4.9 vs. 7.7 +/- 1.7 h), with no significant effect on the peak plasma concentration (11.7 +/- 1.5 vs. 13.0 +/- 3.5 ng/ml). The majority of psychomotor function parameters during the carbamazepine treatment were not significantly different from those during the placebo treatment, probably because of the sedative effect of carbamazepine itself. The present study suggests that carbamazepine decreases plasma concentration of alprazolam by inducing its metabolism. It also supports the previous studies, suggesting that alprazolam is metabolized predominantly by CYP3A4.

Adult↗

PubMed1998

Diversity and complexity of ceramide signalling in apoptosis.

Sphingolipid ceramide has emerged as a lipid messenger of cell functions including differentiation and apoptosis. Diverse kinds of stresses (ultraviolet, irradiation, heat shock and hypoxia) and biological factors (TNF-alpha, IFN-gamma and Fas antibody) require ceramide generation to execute apoptosis. The review summarises the diversity and complexity of up- and downstream of ceramide signalling in apoptosis and clinical implications of ceramide-induced apoptosis.

Animals↗

PubMed1998

Expression of exon 5 deleted estrogen receptor variant messenger RNA in human uterine myometrium and leiomyoma.

To examine the relationship between uterine leiomyoma, an estrogen-dependent tumor and its estrogen receptor, the relative amounts of wild type estrogen receptor (WT) mRNA and exon 5 deleted estrogen receptor variant (D5-ER) mRNA to G3PDH mRNA were examined in human uterine myometrium and leiomyoma specimens obtained from 46 patients in 3 age groups (group A: 41-45 years old, group B: 46-50 years old, group C: 51-54 years old) using a quantitative reverse transcription polymerase chain reaction method (RT-PCR). D5-ER mRNA was co-expressed with WT mRNA in all myometrium and leiomyoma specimens. In myometrium, the relative amount of WT decreased with aging, but in leiomyoma, it was high in group B. The relative amount of D5-ER mRNA and the ratio of D5-ER mRNA to WT mRNA (D5/WT ratio) were significantly higher in group C in both myometrium and leiomyoma. The percentage of the patients whose D5/WT ratio was higher in leiomyoma than in myometrium (L/M ratio>1.0) increased with age. These findings suggest that D5-ER increases to supplement the decreasine in WT in uterine tissues toward menopause and that D5-ER plays a more active role in leiomyoma than in myometrium during the perimenopausal period.

Adult↗

PubMed1998

Adaptive significance of circadian programs in cyanobacteria.

Prokaryotic cyanobacteria express robust circadian (daily) rhythms, even when growing with doubling times that are considerably faster than once every 24 h. This biological clock orchestrates cellular events to occur in an optimal temporal program. Competition experiments demonstrate that fitness is enhanced when the circadian period resonates with the period of the environmental cycle.

Adaptation, Physiological↗

PubMed1998

Control of colinearity in AbdB genes of the mouse HoxD complex.

During development, vertebrate Hox genes are activated in a temporal and spatial sequence colinear with the position of the genes within their clusters. To investigate the mechanistic basis of this phenomenon, we used the ES cell technology and the loxP/Cre system to engineer a conditional fusion of the 5' exon of Hoxd-13 with the 3' exon of Hoxd-12. This hybrid transcription unit was regulated like Hoxd-11, with expression limits in the trunk, limbs, intestinal, and urogenital systems more anterior than those expected for either Hoxd-13 or Hoxd-12. An in vivo interspecies replacement by the fish homologous DNA fragment showed that anteriorization was not due to a distance effect, thus suggesting the presence of a regulatory element between Hoxd-13 and Hoxd-12 that may contribute to the establishment, early on, of a repressive state over these two genes.

Alleles↗

PubMed1998

Forensic pathological observations on fatal injuries to the brain stem and/or upper cervical spinal cord in traffic accidents.

A retrospective study was performed on 149 forensic autopsy cases (12 in Kanazawa and 137 in Munich) of brain stem and/or upper cervical spinal cord (UCSC) injuries as a result of traffic accidents. Pedestrians were the most common type of victims, followed by car drivers. Eleven of the 12 Kanazawa victims were pedestrians. The total ratio of pedestrian victims gradually increased with age. The ponto-medullary junction was the most frequently injured site. A total of 146 cases demonstrated basal skull fractures and/or dislocation of the upper cervical joints: atlanto-occipital joint, atlanto-axial joint, or the joint between the 2nd and 3rd cervical vertebrae. However, in three cases, hyperextension of the neck unexpectedly caused brain stem injury neither associated with basal skull fracture nor with cervical dislocation. Intraventricular haemorrhage was found in 96 cases, suggesting a common feature associated with brain stem and/or UCSC injury. A tear of the basilar artery and that of the carotid artery was found in 17 and 20 cases respectively. A total of 39 victims demonstrated a blood alcohol concentration of over 0.5 mg/ml, and hyperextension of the neck occurred more frequently in these cases. In spite of the marked predominance of immediate death (138 cases), 11 cases (nine of brain stem injury and two of UCSC injury) had unexpected survival times of from 45 min to 12 h.

Journal Article↗

PubMed1998

The cyanobacterial circadian system: a clock apart.

Several new molecular components of the circadian clocks of animals, fungi, and bacteria have been unveiled in the past two years. Enough parts are now identified to indicate that there is more than one way to build a biological clock, although there are parallels in the cycling molecular events among disparate groups of organisms.

Animals↗

PubMed1998

Protective role of glutathione synthesis on radiation-induced DNA damage in rabbit brain.

1. Radiotherapy has attracted increasing interest in recent years. It is known that ionizing radiation induces oxygen radical injury, whereas oxidative stress by the radiation can cause cellular responses to defense cellular injury. In this study, the metabolism of antioxidants in response to ionizing radiation to the brain was studied in the brain using experimental rabbits. 2. Ionizing radiation to the hemicerebrum caused an increase in the levels of glutathione (GSH) and the activity of a GSH synthesizing enzyme, gamma-glutamylcysteine synthetase (gamma-GCS), and Cu,Zn-superoxide dismutase (Cu,Zn-SOD). Ionizing radiation also induced DNA-damage estimated by the formation of 8-hydroxydeoxyguanosine. These changes were dependent on the radiation dose. 3. Previous intrathecal-administration of buthionine sulfoximine (100 microM), a specific inhibitor of gamma-GCS, increased DNA damage by radiation in the radiated hemicerebrum. That of S-methyl GSH, on the other hand, resulted in a significant reduction of DNA damage by radiation. 4. These results suggest that synthesis of GSH and Cu,Zn-SOD is responsive to ionizing radiation and this induction of antioxidants may play a role in reducing tissue damage in radiotherapy.

Animals↗

PubMed1998

Effects of Ca2+ channel antagonists on striatal dopamine and DOPA release, studied by in vivo microdialysis.

1. To elucidate the mechanisms regulating the release of striatal dopamine and its precursor, 3,4-dihydroxyphenylalanine (DOPA), we determined the effects of various Ca2+ channel antagonists, an N-type Ca2+ channel antagonist, omega-conotoxin GVIA, a P-type Ca2+ channel antagonist, omega-agatoxin IVA, and a Q-type Ca2+ channel antagonist, omega-conotoxin MVIIC, on the basal and Ca2+- and K+-evoked release of striatal dopamine and DOPA, by use of in vivo microdialysis. 2. Omega-conotoxin GVIA strongly inhibited striatal basal dopamine release (IC50 = 0.48 nM), whereas this toxin only weakly modulated basal striatal DOPA release (IC50 = 9.55 nM). Neither omega-agatoxin IVA nor omega-conotoxin MVIIC affected the basal striatal release of dopamine and DOPA. 3. Omega-conotoxin GVIA strongly inhibited Ca2+-evoked striatal dopamine release (IC50 = 0.40 nM), whereas Ca2+-evoked striatal DOPA release only was weakly modulated (IC50 = 10.51 nM). Neither omega-agatoxin IVA nor omega-conotoxin MVIIC affected the Ca2+-evoked release of striatal dopamine and DOPA. 4. Both omega-agatoxin IVA and omega-conotoxin MVIIC inhibited the K+-evoked release of striatal dopamine (IC50 of omega-agatoxin IVA = 2.65 nM; IC50 of omega-conotoxin MVIIC = 12.54 nM) and DOPA (IC50 of omega-agatoxin IVA = 0.15 nM; IC50 of omega-conotoxin MVIIC = 3.05 nM), whereas omega-conotoxin GVIA had no effect on the K+-evoked release of striatal dopamine and DOPA. 5. An increase in the extracellular Ca2+ and K+ concentrations (Ca2+- and K+-evoked stimulation) did not affect tyrosine hydroxylase activity in vivo. 6. These findings suggest that striatal DOPA release is neurotransmitter-like and that, unlike the mechanisms of striatal dopaminergic transmission, this striatal DOPA transmission is at least partly regulated by voltage-sensitive Ca2+ channels.

Animals↗

PubMed1998

Interaction between Ca2+, K+, carbamazepine and zonisamide on hippocampal extracellular glutamate monitored with a microdialysis electrode.

1. Multiple components of hippocampal glutamate release were examined by study of Ca2+- and K+-evoked hippocampal extracellular glutamate release using an in vivo microdialysis glutamate biosensor in urethane-anaesthetized rats. In addition, the effects of the antiepileptic drugs, carbamazepine (CBZ) and zonisamide (ZNS) perfused through the probe on glutamate release were assessed. 2. Basal glutamate levels were below detection limits (approximately 0.1 microM). An increase in extracellular KCl (from 2.7 to 50 and 100 mM) increased extracellular hippocampal glutamate levels to 9.2+/-1.4 and 20.0+/-2.6 microM, respectively, calculated from the area under curve (AUC) for 60 min. 3. This KCl-evoked glutamate release consisted of three components: an initial transient rise, a late gentle rise, and late multiple phasic transient rises. 4. An increase in or removal of extracellular CaCl2 levels respectively enhanced and reduced the 50 mM KCl-evoked hippocampal glutamate release (AUC for 60 min) from 9.2+/-1.4 to 12.4+/-2.1 and 5.8+/-0.9 microM. 5. Perfusion with 100 microM CBZ or 1 mM ZNS inhibited both the 50 mM KCl-evoked hippocampal glutamate release (AUC for 60 min) from 9.2+/-1.4 to 5.5+/-1.1 and to 5.8+/-1.3 microM, respectively, as well as the stimulatory effects of Ca2+ on KCl-evoked hippocampal glutamate release. 6. These results suggest that both CBZ and ZNS may reduce epileptiform events by inhibiting excitatory glutamatergic transmission.

Animals↗

PubMed1998

Inducible nitric oxide synthase is expressed in granuloma pyogenicum.

It is known that granuloma pyogenicum (GP) grows rapidly but cherry angioma (CA) does not, although they show the same histological features of hyperplasia of the capillary vessels. Although some cytokines have been thought to be angiogenic factors, a nitric oxide (NO) synthase-dependent effector mechanism is reported to be involved in macrophage-derived angiogenesis in humans. Under the hypothesis that this mechanism is also involved in the more rapid growth of GP, we examined the expression of inducible NO synthase (iNOS) in GP as compared with that in CA. The expression of iNOS mRNA was detected in GP, but not in CA, by reverse transcription-polymerase chain reaction (RT-PCR) analysis. In situ hybridization (ISH) demonstrated iNOS mRNA expression in endothelial cells and to a lesser extent round cells and spindle cells in the myxomatous stroma in GP. Immunohistochemical study showed that iNOS protein was expressed in endothelial cells, infiltrating round cells and spindle cells in the stroma in GP. These results suggested that a NOS-dependent mechanism may be involved in angiogenesis and the rapid growth of GP.

Adult↗

PubMed1998

Alteration in the contents of unsaturated fatty acids in dnaA mutants of Escherichia coli.

DnaA protein, the initiator of chromosomal DNA replication in Escherichia coli, has a high affinity for acidic phospholipids containing unsaturated fatty acids. We have examined here the fatty acid composition of phospholipids in dnaA mutants. A temperature-sensitive dnaA46 mutant showed a lower level of unsaturation of fatty acids (ratio of unsaturated to saturated fatty acids) at 42 degrees C (non-permissive temperature) and at 37 degrees C (semi-permissive temperature), but not at 28 degrees C (permissive temperature), compared with the wild-type strain. Plasmid complementation analysis revealed that the dnaA46 mutation is responsible for the phenotype. Other temperature-sensitive dnaA mutants showed similar results. On the other hand, a cold-sensitive dnaAcos mutant, in which over-initiation of DNA replication occurs at low temperature (28 degrees C), showed a higher level of unsaturation of fatty acids at 28 degrees C. Based on these observations, we discuss the role of phospholipids in the regulation of the activity of DnaA protein.

Bacterial Proteins↗

PubMed1998

Nicardipine normalizes elevated levels of antioxidant activity in response to xanthine oxidase-induced oxidative stress in hypertensive rat heart.

It has been reported that the production of oxygen radicals mediated by xanthine oxidase (XO) is stimulated in hypertensive cardiovascular endothelium, suggesting involvement of oxidative stress in pathogenesis of hypertension. In this study we estimated the effect of nicardipine, a calcium blocker, on the oxidative stress and antioxidant activities in left ventricles from spontaneously hypertensive rat (SHR) and stroke-prone SHR (SHRSP). The activity of XO increased 3.5-fold in SHR and 6.2-fold in SHRSP compared to that in normal controls (WKY). Interestingly, the levels of glutathione (GSH) and the activity of its synthesizing enzyme (gamma-glutamylcysteine synthetase, gamma-GCS) elevated concomitantly in SHR and SHRSP: the level of GSH increased 1.2-fold in SHR and 1.3-fold in SHRSP. The activity of gamma-GCS was elevated 1.5-fold in SHR and 2.4-fold in SHRSP, accompanying an increase in the expression of its mRNA. Treatment of these rats with nicardipine, for 4 weeks improved blood pressure, from 176 +/- 10 to 140 +/- 8 mmHg in SHR, and from 201 +/- 11 to 167 +/- 5 mmHg in SHRSP, respectively, and decreased wet weight of heart, levels of GSH, and the activities of XO and gamma-GCS. Nicardipine reduced the expression of gamma-GCS mRNA. Collectively, these results suggest that reactive oxygen species produced by XO in hypertensive rat heart cause induction of the expression of gamma-GCS and nicardipine plays a role in reducing the oxidative stress in hypertensive heart.

Animals↗

PubMed1998

Cellular accumulation of extravasated serum protein and DNA fragmentation following vasogenic edema.

Accumulation of serum protein has been demonstrated in injured brain cells following vasogenic brain edema. The present study was conducted to test whether this phenomenon is also observed in apoptotic cells as well as in necrotic cells. Apoptotic cell death has been implicated in a variety of brain injuries, including ischemia and trauma. Cold injury and focal cerebral ischemia-reperfusion were used to induce both vasogenic edema and apoptotic cell death. Evans blue extravasation was used to determine the cellular accumulation of serum albumin. Apoptotic cell death was evaluated by both morphological alterations and by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL) staining. Evans blue accumulation in cells was observed not only in the surrounding zone of the lesion after cold injury and in the entire ischemic area after focal ischemia, but was also detected in the regions remote from the primary injury site. Some of these cells demonstrated nuclei fragmentation. TUNEL staining confirmed that apoptosis was induced in the region where apoptotic cells were morphologically detected. These observations suggest that accumulation of the extravasated serum component is accompanied by apoptotic cell death following vasogenic brain edema.

Animals↗

PubMed1998

Expression and growth stimulatory effect of fibroblast growth factor 9 in human brain tumors.

OBJECTIVE: Fibroblast growth factor 9 (FGF-9) is a relatively new member of the FGF family isolated from the conditioned medium of a human glioblastoma cell line as a secreting type factor that exhibits a growth-stimulating effect on primary glial cells. To elucidate the roles of FGF-9 in human brain tumors, the expression and biological activities of FGF-9 were studied using culture cells and surgically obtained tumor specimens. METHODS: Measurement of FGF-9 and basic FGF in conditioned media of cell cultures was performed by using a sandwich enzyme immunoassay. The mitogenic effect of FGF-9 was evaluated by cell growth studies. FGF-9 expression in vivo was demonstrated by immunohistochemistry. RESULTS: One of 4 glioma cell lines and 4 of 16 human meningiomas examined actually secreted detectable amounts of FGF-9 proteins. In comparison, basic FGF production was detected from 3 of 4 glioma cell lines and 11 of 16 human meningiomas. Similarly to basic FGF, recombinant human FGF-9 significantly stimulated the in vitro cell proliferation in three of four glioma cell lines investigated in a dose-dependent manner. A time course growth study using U87 MG cells revealed an accelerated growth stimulation by FGF-9 after Day 4. The growth stimulatory activity was also shown in three of four human meningiomas studied. Moderate to strong immunoreactivity for FGF-9 was observed in 40 (82%) of 49 human brain tumors examined irrespective of origin, tumor type, grade of malignancy, or whether initial or recurrent. In contrast, strong immunostaining was localized in neurons in the normal human cerebral cortex. CONCLUSION: The present findings suggest that FGF-9 may be involved in the biology of human brain tumors with a possible importance in tumor cell growth. Whether the growth factor is more generally involved in oncogenesis of human tumors awaits further investigation.

Brain↗