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Biomedical subjects

K Takeuchi

Publications and source records attributed to K Takeuchi.

At least 91 records · Page 5Linked to original sources
PubMed1994

Cardioprotective effect of the angiotensin II type 1 receptor antagonist TCV-116 on ischemia-reperfusion injury.

We investigated the protective effect of angiotensin II (Ang II) type 1 receptor antagonist on myocardial ischemia-reperfusion injury and the role of exogenous Ang II to this injury in perfused hearts. We orally administered TCV-116 (Ang II type 1 receptor antagonist) and delapril (angiotensin converting enzyme inhibitor) to Wistar rats for 1 week and measured the immunoreactive cardiac Ang II. Immunoreactive cardiac Ang II (pg/gm tissue) was 14.3 +/- 2.0 in control group, 11.8 +/- 0.8 in TCV-116-treated group, and 7.3 +/- 0.6 in delapril-treated group (p < 0.05 compared to TCV-116-treated group; p < 0.01 compared to control group). The 15 hearts (five rats in each group) were perfused by a langendorff method and global ischemia was maintained for 30 min. Both TCV-116 and delapril were found to improve postischemic cardiac function and decrease reperfusion creatine kinase (CK) release. Ang II injection before ischemia worsened postischemic cardiac function and increased reperfusion CK release. Only TCV-116 prevented this injury. These data indicated that TCV-116 Ang II type 1 receptor antagonist was effective against myocardial ischemia-reperfusion injury, and exogenous Ang II accelerated this injury through Ang II type 1 receptor.

Angiotensin II↗
PubMed1994

The role of capsaicin-sensitive sensory neurons in healing of HCl-induced gastric mucosal lesions in rats.

BACKGROUND/AIMS: Capsaicin-sensitive sensory neurons are important in protecting the stomach against damage. This study investigated the role of these sensory neurons in the healing of gastric lesions. METHODS: Rats fasted for 18 hours were given 1 mL of 0.6N HCl orally for induction of gastric lesions; they were then fed normally from 1 hour later. On various days after HCl treatment, the area of lesion, acid secretion, mucosal DNA synthesis, mucosal H+ permeability, and blood flow responses were measured. RESULTS: Ablation of sensory neurons by capsaicin pretreatment did not affect the development of gastric lesions in response to HCl but significantly delayed the healing of these lesions. The damaged mucosa secreted less acid and had minimal changes in DNA synthesis but showed a marked increase in H+ permeability, resulting in luminal acid loss accompanied by an increase of mucosal blood flow. Sensory deafferentation did not have any influence on such changes in the damaged stomach, except the mucosal hyperemic response to acid. CONCLUSIONS: Capsaicin-sensitive sensory neurons may contribute to the healing of gastric lesions by mediating the mucosal hyperemic responses associated with acid back-diffusion and by facilitating acid disposal in the mucosa.

Animals↗
PubMed1994

Endogenous nitric oxide in gastric alkaline response in the rat stomach after damage.

BACKGROUND/AIMS: The gastric mucosa responds to hypertonic NaCl by significantly decreasing acid secretion. This study examined the role of nitric oxide in this phenomenon. METHODS: A rat stomach was mounted in an ex vivo chamber and perfused with saline; then the potential difference (PD), pH, and acid and/or alkaline responses were measured before and after the application of 1 mol/L NaCl with or without pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO biosynthesis. RESULTS: A dose of 1 mol/L NaCl caused a reduction in PD, a decrease in basal and histamine-stimulated acid secretion, and an increase in luminal HCO3-. Prior administration of L-NAME did not affect either the PD or the HCO3- response but significantly attenuated the inhibitory effect of 1 mol/L NaCl on acid secretion. This effect of L-NAME was antagonized by the simultaneous administration with L-arginine but not D-arginine. Histamine-stimulated acid secretion in the normal stomach was significantly reduced by the exogenous NO donor nitroprusside but not by L-NAME. CONCLUSIONS: NO is involved in the mechanism of the gastric alkaline response after damage with 1 mol/L NaCl. Irritation of the gastric mucosa by hypertonic NaCl may release endogenous NO, which in turn inhibits acid secretion and unmasks luminal alkalinization caused by HCO3- flux in the damaged portion.

Animals↗
PubMed1994

Depressive symptoms among Japanese and American adolescents.

An epidemiologic study of depressive symptoms was conducted with self-administered questionnaires among 8th grade students (12-15 years of age) in Japan (n = 570) and the United States (n = 115 Anglos, n = 180 Hispanics). The Todai Health Index-Depression Scale (THI-D), which had been developed in Japan, was used in the study after translation from Japanese to English for the U.S. subjects. The THI-D mean score for Japanese boys was significantly higher than that for Hispanic boys. Also, a gender difference was found across the ethnic groups, in which girls expressed depressive feelings more than boys.

Adolescent↗
PubMed1994

Nucleotide sequence of the gene encoding a repressor for the cytochrome P-450cam hydroxylase operon on the Pseudomonas putida CAM plasmid.

The camR gene of Pseudomonas putida encodes a repressor which regulates expression of the cytochrome P-450cam hydroxylase operon (camDCAB). We determined the nucleotide sequence of 1134 continuous base pairs, including the camR gene. When comparing the amino acid sequence deduced from the open reading frame of the gene sequence with that of amino-terminal five residues of the cam repressor, purified from Pseudomonas putida, we found that the camR gene encodes a protein of 186 amino acids, with a molecular mass of 20.4 kDa. The start codon for the cam repressor is the rare initiation codon GTG. The cam repressor predicted from the camR sequence contained a region similar to that seen in other DNA-binding proteins.

Amino Acid Sequence↗
PubMed1994

Correlation of third ventricular enlargement and EEG slow wave activity in schizophrenic patients.

Twenty-eight schizophrenic patients and 22 normal control subjects underwent magnetic resonance imaging (MRI) and topographic electroencephalography (EEG) in a study attempting to correlate morphological and electrophysiological findings. Schizophrenic patients had larger anterior horns of the lateral ventricles and third ventricles than normal control subjects. Schizophrenic patients showed more delta wave activity in the right parietooccipital region than normal control subjects. Alpha 2 wave activity was reduced in the entire region in schizophrenic patients. In schizophrenic patients, a significant positive correlation was seen between the area of the third ventricle and delta wave activity in the right occipital region. These results suggest that schizophrenic patients may have a dysfunction of diencephalic structures associated with morphological abnormality.

Adult↗
PubMed1994

Development of dual-acting agents for thromboxane receptor antagonism and thromboxane synthase inhibition--I. Synthesis, structure-activity relationship, and evaluation of substituted omega-phenyl-omega-(3-pyridyl)alkenoic acids.

A series of arylsulfonamido-substituted omega-phenyl-omega-(3-pyridyl)alkenoic acids were synthesized and evaluated in vitro for their ability to act as both a thromboxane A2 receptor antagonist (TRA) and thromboxane synthase inhibitor (TSI). Variations of alkenoic acid chain length, olefin geometry, substituent effect on the benzenesulfonamido group, and conformational flexibility of the substituted arylsulfonamido group were examined. Among the various substituents, iodo-substitution gave the most potent compound. Conformational flexibility between the arylsulfonamido group and the phenyl ring attached to the alkenoic acid side chain significantly enhanced the dual activities. The compound (E)-21c was identified as the most potent TRA/TSI (TRA: Kd = 53 nM; TSI: IC50 = 23 nM) in the series studied. The compounds 9c and 10c have indicated that these series of compounds are orally active and are specific TSIs as exhibited by the so-called 'shunt' effect on prostacyclin synthesis in vitro.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Perturbation of cell adhesion and microvilli formation by antisense oligonucleotides to ERM family members.

To examine the functions of ERM family members (ezrin, radixin, and moesin), mouse epithelial cells (MTD-1A cells) and thymoma cells (L5178Y), which coexpress all of them, were cultured in the presence of antisense phosphorothioate oligonucleotides (PONs) complementary to ERM sequences. Immunoblotting revealed that the antisense PONs selectively suppressed the expression of each member. Immunofluorescence microscopy of these ezrin, radixin, or moesin "single-suppressed" MTD-1A cells revealed that the ERM family members are colocalized at cell-cell adhesion sites, microvilli, and cleavage furrows, where actin filaments are densely associated with plasma membranes. The ezrin/radixin/moesin antisense PONs mixture induced the destruction of both cell-cell and cell-substrate adhesion, as well as the disappearance of microvilli. Ezrin or radixin antisense PONs individually affected the initial step of the formation of both cell-cell and cell-substrate adhesion, but did not affect the microvilli structures. In sharp contrast, moesin antisense PONs did not singly affect cell-cell and cell-substrate adhesion, whereas it partly affected the microvilli structures. These data indicate that ezrin and radixin can be functionally substituted, that moesin has some synergetic functional interaction with ezrin and radixin, and that these ERM family members are involved in cell-cell and cell-substrate adhesion, as well as microvilli formation.

Animals↗
PubMed1994

Transforming growth factor beta 1 and extracellular matrix gene expression in isoprenaline induced cardiac hypertrophy: effects of inhibition of the renin-angiotensin system.

OBJECTIVE: The aim was to investigate changes in cardiac transforming growth factor beta 1 (TGF-beta 1), fibronectin, and collagen types I and III mRNA levels in isoprenaline induced cardiac hypertrophy, and the effects of delapril, an angiotensin converting enzyme inhibitor, and TCV-116, an angiotensin II type 1 receptor antagonist, on this hypertrophy. METHODS: Rats were continuously infused with saline and low or high dose of isoprenaline (0.5 or 3 mg.kg-1.d-1) by an osmotic minipump for 24 h, 48 h or 7 d. Treatment with delapril (100 mg.kg-1.d-1) or TCV-116 (10 mg.kg-1.d-1) was started from 1 d before the implantation of minipump to the end of experiments. After the experimental periods, left ventricular weight was measured and the mRNA was extracted and measured by northern blot hybridisation. RESULTS: Both low and high doses of isoprenaline infusion resulted in increased left ventricular weight. With low dose infusion, cardiac TGF-beta 1 mRNA was not stimulated throughout the infusion, while fibronectin mRNA and collagen types I and III mRNAs began to increase at 24 h and 48 h, respectively, after the infusion. In high dose isoprenaline infusion, not only was extracellular matrix mRNA but also TGF-beta 1 mRNA in the ventricle significantly increased. TCV-116 prevented isoprenaline induced left ventricular hypertrophy as much as delapril. However, with delapril or TCV-116, the time course of TGF-beta 1 and ECM mRNA expression was almost similar to isoprenaline infusion only. CONCLUSIONS: The extracellular matrix mRNA expressions are enhanced in myocardial hypertrophy by a low dose of isoprenaline, which is probably not mediated by TGF-beta 1. The preventive effects of TCV-116 on this hypertrophy indicate that the inhibitory effects of angiotensin converting enzyme inhibitor on cardiac hypertrophy are due to the inhibition of angiotensin II and that angiotensin II type I receptor plays an important role in isoprenaline induced left ventricular hypertrophy. However, the renin-angiotensin system may play a minor role in isoprenaline induced cardiac fibrosis.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

The mechanism underlying stimulation of gastric HCO3- secretion by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester in rats.

We investigated the mechanism underlying stimulation of gastric HCO3- secretion by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in anaesthetized rats. A rat stomach was mounted in an ex vivo chamber, superfused with saline, and HCO3- secretion was measured in the absence of acid secretion (omeprazole pretreatment). Intravenous administration of L-NAME (1-5 mg/kg) increased gastric HCO3- secretion dose dependently with concomitant rise in arterial blood pressure and decrease in heart rate, and these effects were all antagonized by simultaneous administration of L-arginine (200 mg/kg). Vagotomy did not affect the increased blood pressure response but significantly inhibited the decrease in heart rate and increase of HCO3- secretion caused by L-NAME. The HCO3- stimulatory action of L-NAME was also inhibited by pretreatment with either yohimbine (5 mg/kg s.c.) or prazosin (0.5 mg/kg s.c.). These agents alone caused a decrease in blood pressure, and reduced the magnitude of blood pressure response caused by L-NAME, leading to inhibition of heart rate changes. When the change in HCO3- output induced by L-NAME was plotted against the change in blood pressure (from basal values) under various conditions, a significant relationship was found between these two parameters. These results suggest that L-NAME stimulates gastric HCO3- secretion in association with the inhibition of endogenous NO production, and this mechanism may be in part mediated by a neural reflex through vagal efferent nerves, resulting from the pressor response to L-NAME.

Amino Acid Oxidoreductases↗
PubMed1994

Developing of EEG print and its preliminary technical application.

In this report, we discuss a method called "EEG print" to represent EEG contrast mapping in time and frequency domains simultaneously. A bank of bandpass FIR (Finite Impulse Response) digital filters is used to obtain EEG prints. EEG prints were taken from four areas (F3, F4, O1 and O2) of EEG when healthy subjects were at rest with their eyes closed. The pattern of the prints was classified into four types: alpha type, beta type, alpha + beta type and complex type. It was found that EEG prints may vary from person-to-person but they usually do not vary much between the four areas for a given person. The method is further modified to obtain "differential EEG prints" to investigate whether meaningful higher frequency EEG components exist. Differentiation of EEG resulted in marked intensification of the fast waves, using 0.14 Hz as the critical point. In differential EEG print with higher order differentiation, amplification in the high frequency components increase their frequency. As a result, it is possible to observe variations in the high frequency components, which are otherwise not detectable in the usual EEG print. EEG print can be used for representing the function of the brain. Using the method for classification of EEG print patterns, described in this paper, we can clarify not only the characteristics of the normal brain but also the pathophysiology of mentally-ill patients.

Alpha Rhythm↗
PubMed1994

Influenza virus M2 protein ion channel activity stabilizes the native form of fowl plague virus hemagglutinin during intracellular transport.

The influenza A/fowl plague virus/Rostock/34 hemagglutinin (HA), which is cleaved intracellularly and has a high pH threshold (pH 5.9) for undergoing its conformational change to the low-pH form, was expressed from cDNA in CV-1 and HeLa T4 cells in the absence of other influenza virus proteins. It was found, by biochemical assays, that the majority of the HA molecules were in a form indistinguishable from the low-pH form of HA. The acidotropic agent, ammonium chloride, stabilized the accumulation of HA in its native form. Coexpression of HA and the homotypic influenza virus M2 protein, which has ion channel activity, stabilized the accumulation of HA in its pH neutral (native) form, and the M2 protein ion channel blocker, amantadine, prevented the rescue of HA in its native form. These data provide direct evidence that the influenza virus M2 protein ion channel activity can affect the status of the conformational form of cleaved HA during intracellular transport.

Amantadine↗
PubMed1994

Reticulocyte maturity as an indicator for estimating qualitative abnormality of erythropoiesis.

AIMS: To determine the maturity of reticulocytes in patients with anaemia as a result of various haematological disorders including those with qualitative abnormalities such as ineffective erythropoiesis or dyserythropoiesis. METHODS: The number of mature reticulocytes was measured with flow cytometry in venous blood samples from 122 patients with haematological disorders and 100 healthy controls. Reticulocytes were classified into three categories by the fluorescence intensity of auramin O staining: low fluorescence ratio (LFR), medium fluorescence ratio (MFR), and high fluorescence ratio (HFR). Immature reticulocytes were determined as the aggregate of MFR and HFR (%). RESULTS: The mean (2SD) number of immature reticulocytes in 100 normal subjects was 9.0 (7.0)%. Significantly high mean values of immature reticulocytes with a normal or reduced reticulocyte count were shown in 90 patients with dyserythropoietic or ineffective erythropoietic conditions, such as acute myeloid leukaemia (AML) (n = 37), myelodysplastic syndrome (MDS) (n = 35), aplastic anaemia (AA) (n = 8), or megaloblastic anaemia (MA), (n = 6). Reticulocyte ratios returned to normal after successful treatment of patients with AML (n = 10) and MA (n = 3). However, high percentages of immature reticulocytes with increased reticulocyte counts were consistently observed in patients with enhanced erythropoiesis such as those with acquired autoimmune haemolytic anaemias (AIHA) (n = 4) or acute blood loss (ABL) (n = 4). Reticulocyte maturity was within the normal range in patients with reduced erythropoiesis such as occurs in chronic renal failure (CRF) (n = 11), or in iron deficiency anaemia (IDA) (n = 13). CONCLUSIONS: The evaluation of reticulocyte maturity with total reticulocyte count seems to be clinically useful for estimating the qualitative impairment of erythropoiesis, and so could help differentiate haematological disorders.

Acute Disease↗
PubMed1994

Role of endogenous atrial natriuretic peptide on systemic and renal hemodynamics in heart failure rats.

To investigate the role of endogenous atrial natriuretic peptide (ANP) in rats with heart failure (HF), we administered HS-142-1 (HS; 3 mg/kg body wt iv), a novel nonpeptide ANP-receptor antagonist, to rats with surgically induced myocardial infarction and sham-operated rats. HF was characterized by a higher left ventricular end-diastolic pressure and higher plasma ANP concentration vs. controls. HS administration significantly reduced the plasma and urinary levels of guanosine 3',5'-cyclic monophosphate in rats with HF [plasma concentration 10.6 +/- 2.6 vs. 2.7 +/- 0.4 nM (P < 0.05); urinary excretion 48 +/- 8 vs. 12 +/- 2 pmol/min (P < 0.05)]. Systemic and renal hemodynamics were unaffected by HS administration. Urine flow (-35%) and urinary sodium excretion (-50%) were significantly decreased after HS only in those rats with HF that had no changes in systemic and renal hemodynamics. These results suggest that the elevated ANP levels in HF do not contribute directly to the maintenance of systemic hemodynamics but rather compensate for the HF mainly via diuresis and natriuresis, achieved by the inhibition of renal tubular reabsorption rather than by renal vasodilatation.

Animals↗
PubMed1994

IgA deposits might not influence the production of extracellular matrix in glomeruli of ddY mice, a spontaneous animal model for IgA nephropathy.

Immunofluorescence studies were carried out to determine whether the expression of extracellular matrix (ECM) in glomeruli of ddY mice, a model for IgA nephropathy (Berger's disease), is influenced by treatment with a rat monoclonal antibody to murine CD4 molecules (mAb CD4). This mAb CD4 showed a selective decrease in the number of CD4+ T cells in the peripheral blood of ddY mice as described previously. The ddY mice were initially treated with intravenous injections, followed by weekly intraperitoneal injections of mAb CD4. In immunofluorescence, the mean intensity of IgA deposits in the renal glomerular mesangial areas and capillary walls of the treated ddY mice was significantly lower than that in saline-treated control mice at comparable ages. There was no significant difference in the distribution or intensity of ECM components, i.e. type IV collagen, fibronectin and heparan sulfate proteoglycan, in glomeruli between the mAB CD4-treated and the control ddY mice. In light microscopy, mesangial expansion in the treated ddY mice was milder than that found in the saline control mice. No significant differences in the average number of intraglomerular cells, levels of serum IgA and urinary protein between the treated and control ddY mice were observed. Thus, it appears that although CD4+ T cells modulate the amounts of glomerular IgA deposits, other factors may be involved in the expression of ECM in glomeruli of IgA nephropathy in ddY mice.

Animals↗
PubMed1994

Interleukin-8 gene expression in middle ear effusions.

Interleukin-8 (IL-8), a monocyte- and macrophage-derived cytokine, displays potent chemotactic-activating properties toward neutrophils, and thus may contribute to the pathogenesis of otitis media with effusion (OME). The objective of this investigation was to demonstrate the expression of the IL-8 gene in middle ear effusion (MEEs) of children and adults with OME. Ribonucleic acids (RNAs) were extracted from MEEs from 16 ears of 13 pediatric patients and 12 ears of 12 adult patients with OME. The RNAs were reverse-transcribed and amplified by the polymerase chain reaction. Interleukin-8 transcripts were detected in 75% of both pediatric (12/16) and adult MEEs (9/12). The levels of expression of IL-8 and beta-actin messenger RNAs were quantitated. No significant difference was observed in IL-8/beta-actin ratios between pediatric MEEs and adult MEEs. These data suggest that IL-8 may contribute to neutrophil involvement in both pediatric and adult OME.

Actinin↗
PubMed1994

Structural diversity of band 4.1 superfamily members.

Several proteins contain the domain homologous to the N-terminal half of band 4.1 protein, indicating the existence of a superfamily. The members of this 'band 4.1' superfamily are thought to play crucial roles in the regulation of cytoskeleton-plasma membrane interaction just beneath plasma membranes. We examined the structural diversity of this superfamily by means of the polymerase chain reaction using synthesized mixed primers. We thus identified many members of the band 4.1 superfamily that were expressed in mouse teratocarcinoma F9 cells and mouse brain tissue. In total, 15 cDNA clones were obtained; 8 were identical to the corresponding parts of cDNAs for the known members, while 7 appeared to encode novel proteins (NBL1-7: novel band 4.1-like proteins). Sequence analyses of these clones revealed that the band 4.1 superfamily can be subdivided into 5 gene families; band 4.1 protein, ERM (ezrin/radixin/moesin/merlin/NBL6/NBL7+ ++), talin, PTPH1 (PTPH1/PTPMEG/NBL1-3), and NBL4 (NBL4/NBL5) families. The NBL4 family was first identified here, and the full-length cDNA encoding NBL4 was cloned. The deduced amino acid sequence revealed a myristoylation site, as well as phosphorylation sites for A-kinase and tyrosine kinases in its N-terminal half, suggesting its involvement in the phosphorylation-dependent regulation of cellular events just beneath the plasma membrane. In this study, we describe the initial characterization of these new members and discuss the evolution of the band 4.1 superfamily.

Amino Acid Sequence↗