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Y Hashimoto

Publications and source records attributed to Y Hashimoto.

At least 73 records · Page 4Linked to original sources
PubMed2001

The potential clinical value of GML and the p53 gene as a predictor of chemosensitivity for colorectal cancer.

BACKGROUND: Adjuvant chemotherapy with 5-fluorouracil (5-FU) and mitomycin C (MMC) has commonly been used after resection of colorectal cancer. The aim of this study was to determine the predictive value of p53 mutation or the expression of GML, a target of p53, for sensitivity to 5-FU and MMC. METHODS: We analyzed p53 mutations and the expression of GML in six colorectal cancer cell lines (SW837, DLD-1, RPMI4788, WiDr, HT-29, and HCT116), and examined the correlation between genetic changes and in-vitro chemosensitivity to MMC and 5-FU by measuring the colony-forming ability in these cell lines. We also introduced GML cDNA into a cell line that lacked endogenous GML expression to investigate changes in sensitivity to MMC and 5-FU. RESULTS: The sensitivity to MMC was highest in HCT116, which had no p53 gene abnormalities and expressed endogenous GML, and lowest in RPMI4788 cells, which had neither p53 gene abnormalities nor expression of endogenous GML. For 5-FU treatment with 24-h exposure, HCT116 showed the highest sensitivity, and SW837, which had p53 mutations without expression of GML, showed the lowest sensitivity. The introduction of GML cDNA to RPMI4788 (RPMI4788-GML) showed that the sensitivity of RPMI4788-GML to MMC was enhanced almost to the level of HCT116 cells. However, when RPMI4788-GML were exposed to 5-FU for 24 h, the sensitivity of RPMI4788-GML was slightly increased compared with that of the parental cells, but was slightly lower than that of HCT116. CONCLUSION: GML expression and p53 mutation in colorectal cancer may be useful predictive genetic markers for sensitivity to MMC and 5-FU, respectively.

Antibiotics, Antineoplastic↗
PubMed2001

Power spectral analysis of the electroencephalogram during induced total spinal block.

PURPOSE: To evaluate the effects of total spinal block (TSB) on brain function, TSB-induced changes in cortical electrical activities were analyzed using power spectral analysis of an electroencephalogram (EEG). METHODS: Six patients suffering from chronic pain who were undergoing TSB therapy were studied. TSB was established with intrathecal 1% lidocaine (0.3 ml.kg(-1)) injected through the C1-2 lateral intervertebral space. Mechanical ventilation was continued via a laryngeal mask until the recovery of respiration. The EEG recording was started before TSB induction and continued until 10 min after extubation. The following processed EEG parameters were monitored: spectral edge frequency-90% (SEF90), spectral median frequency (SMF), and relative power in the frequency bands of delta, theta, alpha, beta, and the delta ratio [(alpha + beta)/delta]. RESULTS: TSB induced an unconscious state more than 40 min in all patients. During TSB, 12-13 Hz in SEF90 and 6-7 Hz in SMF were observed. These values are consistent with the previously reported prearousal threshold from general anesthesia. The other EEG descriptors did not change during the TSB-induced unconscious state. CONCLUSION: The dissociation of cortical electrical activities and the clinical coma-like condition may be characteristic of the TSB-induced unconscious state.

Journal Article↗
PubMed2001

Relationship between response of gamma-glutamyl transpeptidase to alcohol drinking and risk factors for coronary heart disease.

Alcohol drinking has been reported to influence the risk factors for coronary heart disease (CHD), such as the serum levels of triglycerides, HDL-cholesterol and uric acid, and the level of blood pressure. To examine whether there was individual variability in the response of these parameters to alcohol drinking, a cross-sectional study was conducted in 3130 men with a body-mass index (BMI) below 24. The subjects were divided into two groups; a normal gamma-glutamyl transpeptidase (rGTP) (<40 IU/l) group and a high rGTP (> or =40 IU/l) group, and the values were compared after adjusted for age, BMI, exercise and smoking. The level of triglycerides increased according to the amount of drinking in the high rGTP group, whereas no association was observed in the normal rGTP group. The level of HDL-cholesterol increased with drinking in the normal and high rGTP groups, and no difference was observed in the levels of HDL-cholesterol between the two groups. The levels of uric acid and blood pressure also increased with drinking in both groups, but the increase was bigger in the high rGTP group than in the normal rGTP group. The results indicated that there was large individual variability in the responses of the risk factors for coronary heart disease to drinking. Subjects whose rGTP responds less to drinking may have less disadvantageous effects of drinking.

Adult↗
PubMed2001

Effect of immobilization stress on anticonvulsant actions and pharmacokinetics of zonisamide in mice.

The effects of immobilization stress on anticonvulsant actions and pharmacokinetics of zonisamide were investigated in mice. Oral administrations of zonisamide (10, 20, and 50 mg/kg) dose-dependently reduced incidence of tonic extension (TE) induced by maximal electroshock seizure (MES). Immobilization stress for 2 h immediately after the administration of zonisamide further enhanced the anticonvulsive actions of it. On the other hand, the serum zonisamide concentrations in stressed group were lower during the first 30 min after the administration compared with that in nonstressed control group. Thereafter, there were no significant differences in the serum concentrations between two groups. The brain zonisamide concentration and the concentration ratio of brain/serum at 2 h after administration of zonisamide (50 mg/kg) were significantly higher in stressed group, rather than that in the nonstressed control group without changing the serum concentration. These results suggest that immobilization stress enhances anticonvulsant actions of zonisamide, and that increases of brain zonisamide concentration by immobilization stress may be related with this phenomenon.

Animals↗
PubMed2001

A single amino acid substitution in a self protein is sufficient to trigger autoantibody response.

We determined if a single amino acid substitution in a self protein causes autoantibody responses. Mouse lysozyme (ML) was used as a model self protein, and a mutant ML (F57L ML) was prepared by replacing 57Phe of ML to Leu, an approach which resulted in introducing into ML the immunogenic sequence of peptide 50-61 of hen egg lysozyme (HEL) restricted to I-A(k) MHC class II molecule. We found that F57L ML but not native ML primed HEL specific T cells and triggered ML specific autoantibody responses in B10.A and C3H mice (I-A(k), I-E(k)). Peptide regions, ML 14-69 and ML 98-130, were major epitopes of autoantibodies in both strains of mice. These findings indicate that a single amino acid substitution in self proteins can cause an autoantibody response when the mutated region is presented by MHC class II molecules and recognized by T cells.

Amino Acid Substitution↗
PubMed2001

Amplification of 3q26 approximately qter correlates with tumor progression in head and neck squamous cell carcinomas.

Biological characteristics of malignant tumors including head and neck squamous cell carcinoma (HNSCC) are greatly affected by genetic alterations. However, the relationship between chromosomal aberrations and pathologic tumor stage in HNSCC has not been elucidated. In 32 patients, DNA sequence copy number aberrations (DSCNA) were surveyed by comparative genomic hybridization (CGH) combined with a microdissection method. The average number of DSCNA was 15.3 per tumor and increased with tumor stage (P<.05). DNA copy number gain was detected at 3q26 approximately qter in 29 tumors (91%), and 13 of these tumors displayed marked DNA amplification. Tumor stage was linked with this amplification (P<.05). The increase in DSCNA and amplification of 3q26 approximately qter are likely to be useful markers for estimating tumor progression in HNSCC.

Adult↗
PubMed2001

Differential phosphorylation of mitogen-activated protein kinase families by epidermal growth factor and ultraviolet B irradiation in SV40-transformed human keratinocytes.

SV-40 transformed human keratinocytes (SVHK cells) were stimulated with epidermal growth factor (EGF) and ultraviolet B (UVB) irradiation. Following the stimulation, cell growth, apoptosis, and the activities of mitogen-activated protein (MAP) kinase families were analyzed. EGF (100 ng/ml) increased SVHK cell number compared with control cells cultured in serum-free DMEM medium. The EGF-stimulated cells did not show DNA fragmentation. In contrast, UVB irradiation (40 mJ/cm(2)) markedly decreased viable cell number that was accompanied with DNA fragmentation. EGF stimulated extracellular signal-regulated kinase (ERK) and stress-activated protein kinase/c-Jun N-terminal kinase (JNK). Following the EGF stimulation, phosphorylated ERK and JNK were detected by phospho-p42/44 MAP kinase antibody and phospho-SAPK/JNK antibody, respectively. On the other hand, UVB irradiation stimulated the phosphorylation of p38 and JNK but not of ERK. The stimulation of ERK and JNK induced by EGF was observed earlier than the stimulation of p38 and JNK induced by UVB. PD98059, a specific MAP kinase kinase (MAPKK) 1 (also referred to as MEK1) inhibitor, inhibited EGF-dependent cell proliferation, that was associated with the inhibition of ERK and JNK phosphorylation. In contrast, UVB-induced overall cell death was not significantly affected by PD98059, that inhibited phosphorylation of JNK but not of p38. PD98059, however, significantly augmented UVB-induced cell death earlier time points (30 min--2 h). These results indicate that ERK and JNK are activated following EGF stimulation that might be associated with cell proliferation. On the other hand, UVB-induced apoptosis seems to be mostly associated with the activation of p38. JNK stimulation might provide an anti-apoptotic tonus during the UVB-induced, p38-associated SVHK cell death.

Cell Death↗
PubMed2001

Specific inhibitor of puromycin-sensitive aminopeptidase with a homophthalimide skeleton: identification of the target molecule and a structure-activity relationship study.

2-(2,6-Diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione (2: PIQ-22) was found to be a potent and specific inhibitor of puromycin-sensitive aminopeptidase (PSA). Lineweaver-Burk plot analysis showed that PSA is inhibited by PIQ-22 in a non-competitive manner. Structure -activity relationship studies indicated that tautomerism of the imidobenzoylketone group in the cyclic imide moiety of the PIQ-22 skeleton is important for the inhibitory activity.

Aminopeptidases↗
PubMed2001

Genetic analysis of phytosterolaemia.

Two women with multiple xanthomas, intermittent arthritis and thrombocytopenia were diagnosed as phytosterolaemia, an autosomal-recessive lipid storage disease, based on their increased serum concentrations of beta-sitosterol, campesterol and sitostanol. The gene responsible for this disease is located within a distance of 18 cM between microsatellite markers of D2S 1788 and D2S1352 at chromosome 2p21. We genotyped the patients and their family members with 16 microsatellite markers around this locus. The results from the homozygosity mapping of one family suggested that the gene was located within the distance of 12.6 cM between D2S2328 and D2S1352. We have shortened the genetic distance by 5.4 cM.

Adult↗
PubMed2001

Transport of levofloxacin in the OK kidney epithelial cell line: interaction with p-aminohippurate transport.

PURPOSE: To evaluate the mechanism of renal transport of quinolone antibacterial drugs, we examined the interaction of levofloxacin with p-aminohippurate (PAH) transport systems and the transport of levofloxacin in renal epithelial cells. METHODS: Transport of [14C]PAH or [14C]levofloxacin was measured using OK cell monolayers grown on microporous membrane filters. RESULTS: Transcellular transport from the basolateral to the apical side and cellular accumulation of [14C]PAH were inhibited by levofloxacin. Both the initial uptake of [14C]PAH from the basolateral side and the efflux to the apical side were inhibited by levofloxacin. The basolateral-to-apical transcellular transport of [14C]levofloxacin was greater than that in the opposite direction. [14C]Levofloxacin efflux to the apical side was greater than that to the basolateral side. Unlabeled levofloxacin and grepafloxacin inhibited the transcellular transport of [14C]levofloxacin, accompanied by an increase of cellular accumulation. However, neither PAH nor an anion transport inhibitor 4-4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) affected the basolateral-to-apical transport of [14C]levofloxacin nor its uptake from the basolateral side. CONCLUSIONS: These results indicated that levofloxacin inhibits PAH transport across both the basolateral and apical membranes of OK cells, but are not transported via the systems for PAH transport. The existence of a specific transport system for quinolones was indicated in OK cells.

Animals↗
PubMed2001

Effects of the frequency of alcohol intake on risk factors for coronary heart disease.

A cross-sectional study was conducted in 3660 male workers to examine whether the weekly frequency of alcohol intake affected serum lipids and blood pressure, which are risk factors for coronary heart disease, independently of the weekly alcohol consumption. Information regarding life-style habits and current medication was obtained by questionnaire. The effects of the frequency were examined using Tukey's test in the groups of drinkers divided according to their alcohol consumption. In moderate (189-377 ml/week) drinkers, a higher frequency of drinking was related to a higher level of HDL-cholesterol, and a lower level of triglycerides. In light (1-188 ml/week) and heavy (378-566 ml/week) drinkers, a higher frequency of drinking was also related to a higher level of HDL-cholesterol. There were no significant relations between the frequency of drinking and total cholesterol, or blood pressure in these three groups. Similar results were obtained when values were adjusted for age, body-mass index, smoking, physical activity and weekly alcohol consumption. Multiple regression analysis in the whole drinkers also showed that the weekly frequency of drinking was associated with HDL-cholesterol, but not with triglycerides (p = 0.052), total cholesterol, or blood pressure. The results suggest that the weekly frequency of drinking may affect the levels of HDL-cholesterol independently of the weekly alcohol consumption.

Adult↗
PubMed2001

Contribution of myeloperoxidase to coronary artery vasculitis associated with MPO-ANCA production.

The role of myeloperoxidase (MPO) in the pathogenesis of vasculitis associated with MPO-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) was examined in a murine animal model. Coronary artery vasculitis was induced in C57BL/6 mice with and without endogenous MPO by intraperitoneal injection of Candida albicans-derived substances (CADS). The corresponding levels of MPO-ANCA in sera of mice with and without vasculitis were measured and compared in both wild-type and MPO-deficient animals. The MPO-ANCA titers in sera were significantly higher in mice with vasculitis than in vasculitis-negative mice, indicating that MPO-ANCA correlated with vasculitis formation. However, the increase of MPO-ANCA titers observed in sera of wild C57BL/6 mice were strongly suppressed in MPO-deficient C57BL/6 mice, accompanied with prevention of vasculitis formation. These results show that MPO acted as an antigen for MPO-ANCA production by CADS and was followed by the vasculitis formation. Vasculitis did develop in a few MPO-deficient mice, though the incidence of vasculitis was much lower in MPO-deficient mice than in C57BL/6 mice.

Animals↗
PubMed2001

Spasmolytic effect of magnesium sulfate on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs.

BACKGROUND: Magnesium (Mg2+) has relaxant effects on histamine-induced bronchoconstriction. In addition, Mg2+ has been reported to reduce vascular smooth muscle tone and be clinically useful for treatment of persistent pulmonary hypertension of the newborn. In this study, we evaluated the relaxant effect of Mg2+ on serotonin (5HT)-induced bronchoconstriction and pulmonary hypertension. METHODS: Seven mongrel dogs were anesthetized with pentobarbital (30 mg x kg(-1) + 2 mg x kg(-1) x h(-1)) and paralyzed by pancuronium (0.2 mg x kg(-1) x h(-1)). Bronchoconstriction and pulmonary hypertension were elicited with 5HT (10 microg x kg(-1) + 1 mg x kg(-1) x h(-1)). Airway caliber was evaluated by changes in bronchial cross-sectional area (BCA) of the 3rd bronchial bifurcation measured by a fiberoptic bronchoscope method as previously reported. Pulmonary hypertension was assessed by changes in pulmonary vascular resistance (PVR). The BCA and PVR were expressed as per cent of the basal level. Thirty minutes after start of 5HT infusion, magnesium sulfate (MgSO4): 0 (saline), 1, 10, 100 and 1000 micromol x kg(-1) was given i.v.. Arterial blood was also collected to measure plasma level of Mg2+ and catecholamines. RESULTS: 5HT increased %PVR to 163+/-25% and decreased % BCA by 39.2+/-4.5%. Plasma level of Mg2+ following MgSO4 1000 micromol x kg(-1) i.v. exceeded its toxic level. The ED50s of MgSO4 (dose producing 50% relaxation of maximal constriction) was 47.8 micromol x kg(-1) and 1.09 mmol x kg(-1) for pulmonary hypertension and bronchoconstriction, respectively. The ratio of %PVR to %SVR was about 1.0 after MgSO4 0-100 micromol x kg(-1) i.v., although the ratio significantly increased after 1000 micromol x kg(-1) i.v.. CONCLUSION: In dogs, 5HT-induced pulmonary hypertension but not bronchoconstriction was significantly reduced by an iv bolus of MgSO4, resulting in a plasma concentration within the assumed therapeutic level.

Animals↗
PubMed2001

Combination of miglitol, an anti-diabetic drug, and nicorandil markedly reduces myocardial infarct size through opening the mitochondrial K(ATP) channels in rabbits.

The anti-diabetic drug miglitol, an alpha-glucosidase inhibitor, which is currently used clinically, reduces myocardial infarct size by reducing the glycogenolytic rate through inhibition of the alpha-1,6-glucosidase of glycogen-debranching enzyme in the heart. Nicorandil, a K(ATP) channel opener with a nitrate-like effect, which is also currently used clinically, also reduces the infarct size. Therefore, we hypothesized that combination of nicorandil and submaximal dose of miglitol could markedly reduce myocardial infarct size more than miglitol or nicorandil alone, and investigated the mechanism for the infarct size-reducing effect. Japanese white rabbits without collateral circulation were subjected to 30 min coronary occlusion followed by 48 h reperfusion. Pre-ischaemic treatment with submaximal dose of miglitol (5 mg kg(-1), i.v.) and nicorandil alone (100 microg kg(-1) min(-1) 5 min) moderately reduced the infarct size as a percentage of area at risk (24+/-4 and 25+/-4%, respectively), and 10 mg kg(-1) of miglitol markedly reduced the infarct size (15+/-2%) compared with the controls (42+/-2%). Combination of 5 mg kg(-1) of miglitol and nicorandil (100 microg kg(-1) min(-1) 5 min), and 10 mg kg(-1) of miglitol and nicorandil (100 microg kg(-1) min(-1) 5 min) significantly reduced the infarct size (13+/-4 and 12+/-3%, respectively) more than miglitol or nicorandil alone. Pretreatment with 5HD completely abolished the infarct size-reducing effect of 10 mg kg(-1) of miglitol alone (36+/-7%) and that of combination of 5 mg kg(-1) of miglitol and nicorandil (46+/-2%). Combination of nicorandil and submaximal dose of miglitol markedly reduced the myocardial infarct size more than miglitol or nicorandil alone. This effect was suggested to be related to the opening of mitochondrial K(ATP) channels.

1-Deoxynojirimycin↗
PubMed2001

Analysis of the immunoglobulin heavy chain gene variable region of CD5-positive and -negative diffuse large B cell lymphoma.

We analyzed nucleotide sequence and intraclonal diversity of the rearranged immunoglobulin heavy chain gene variable region (VH gene) of CD5+ and CD5- diffuse large B cell lymphoma (DLBCL) to clarify the cell origin of de novo CD5+ DLBCL. Ten cases of CD5+ DLBCL and 29 cases of CD5- DLBCL were analyzed. The frequencies of somatic mutation were 0.7 to 12.9% (average, 6.2%) in CD5+ DLBCL and 2.0 to 25.9% (average, 11.1%) in CD5- DLBCL. The ongoing mutation rate was estimated from the number of further single base-substitutions, expressed as a percentage of the total number of nucleotides in 10 cloned PCR products for each case (%). The averages of the ongoing mutation rate of CD5+ DLBCL (four cases) and CD5 DLBCL (seven cases) were 0.051% and 0.197%, respectively. The rate of CD5+ DLBCL was significantly lower than that of CD5- DLBCL (t-test, P = 0.024). These data may indicate that the cell origin of CD5+ DLBCL is different from that of CD5- DLBCL. CD5 is not an activated antigen in DLBCL, but a specific marker of the B1 subset of the B cells, and de novo CD5+ DLBCL may therefore be derived from this unique subset.

Adult↗
PubMed2001

Dendritic attenuation of synaptic potentials in the CA1 region of rat hippocampal slices detected with an optical method.

We directly measured fast excitatory postsynaptic potentials (EPSPs) along the dendrites of hippocampal CA1 pyramidal neurons by employing an optical method to study how synaptic potentials spread along the dendrites. Rat hippocampal slices were stained with a fluorescent voltage-sensitive dye JPW1114 and optical signals were monitored with a 16 x 16 photodiode array system. A stimulating electrode was placed either at stratum lacunosum moleculare to activate perforant fibers that make synaptic contacts to the distal apical dendrites or at stratum oriens to induce EPSPs at the basal dendrites of CA1 pyramidal cells. CNQX-sensitive components of the optical signals, which were assumed to be population EPSPs, were isolated. Propagation and attenuation of the CNQX components were successfully observed with the optical method. At the cell body layer, the peak of the CNQX-sensitive component was delayed by 17.08 +/- 1.64 ms from the input sites. Additionally we performed a simulation study to estimate the passive membrane parameters of the apical dendrites. Estimated apparent specific internal axial resistance (Ri) following stratum lacunosum moleculare stimulation was 76.0 +/- 4.2 Omega.cm and apparent specific membrane resistance (Rm) was 27.8 +/- 2.1 kOmega.cm2 (assuming the specific membrane capacitance of dendrites Cm = 1.6 microF/cm2). These values are comparable to those previously reported. When synaptic inputs were applied at stratum oriens, these apparent passive membrane parameters were different (high Ri and low Rm), suggesting that nonuniform dendritic membrane conductance or voltage-dependent conductances which are active near the resting potential may contribute to the measured passive membrane properties.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2001

Lack of association between atopic eczema and the genetic variants of interleukin-4 and the interleukin-4 receptor alpha chain gene: heterogeneity of genetic backgrounds on immunoglobulin E production in atopic eczema patients.

BACKGROUND: The genetic background of atopic eczema might be heterogeneous and there is a possibility that immunoglobulin (Ig)E responsiveness in patients with atopic eczema is controlled separately from the development of atopic eczema. Although both interleukin (IL)-4 and the IL-4 receptor alpha chain have an important role for IgE production and are therefore possible candidate genes for atopy, it has not been clarified whether these genes play any roles in atopic eczema patients who have normal IgE productivity. OBJECTIVE: We aimed to assess whether the polymorphisms of the IL-4 gene and the IL-4 receptor alpha chain gene play any roles in atopic eczema patients, particularly in patients who have normal IgE productivity. METHOD: We determined the genotype with regard to polymorphisms in the genes for IL-4 and the IL-4 receptor alpha chain (- 589C/T of IL-4; Ile50Val, Ala375Glu and Arg551Gln of IL-4 receptor alpha chain) in patients with atopic eczema using the fluorogenic 5' nuclease assay. RESULTS: IL-4 and the IL-4 receptor alpha chain genotypes were not significantly associated with either total patients with atopic eczema or atopic eczema patients who had normal IgE productivity. The distribution of genotypes of IL-4-589C/T differed by the serum IgE levels in patients with atopic eczema. CONCLUSION: These results suggest that the polymorphisms in the IL-4 gene and the IL-4 receptor alpha chain gene play no role in the development of atopic eczema in patients who have normal IgE productivity.

Adolescent↗