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Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 109 records · Page 6Linked to original sources

Endothelin-1 stimulates bile acid secretion and vesicular transport in the isolated perfused rat liver.

The effects of endothelin (ET) on portal pressure and bile secretion were examined using isolated perfused rat liver and rat hepatocyte preparations. ET-1 raised portal pressure dose dependently; administration at a high dose (10(-9) mol) induced a > 200% increase along with reduced bile flow and decreased secretion of bile acid and phospholipids. However, a low dose (10(-10) mol) of ET-1 brought about a < 100% portal pressure rise, enhanced both bile flow and excretion of bile acid and phospholipids, and significantly increased transfer of preadministered horseradish peroxidase (HRP) into bile. In addition, values for Ca2+ concentrations, examined by indo 1 fluorescence, were elevated in isolated hepatocytes after administration of ET-1. Papaverine suppressed the low-dose ET-1 stimulation effects on both portal pressure and bile secretion. Moreover, it also reduced the HRP excretion and suppressed intracellular Ca2+ release. This study demonstrated that ET-1 stimulates vesicular transport, probably via promotion of intracellular Ca2+ release, and, as a result, increases bile acid-dependent bile flow.

Animals

Effect of protein derivatives on pancreatic secretion and release of secretin and CCK in rats.

We investigated the effect of intraduodenal administration of oligopeptide and a mixed amino acid solution, which contains the same amino acid composition as oligopeptide, on pancreatic exocrine secretion and the release of secretin and cholecystokinin (CCK). Anesthetized rats were prepared with pyloric ligation and cannulation of pancreatic duct and bile duct. Protein derivatives in three different doses (oligopeptide: 25, 100, and 400 mg/h; and mixed amino acid solution: 70, 140, and 280 mg/h, pH 7.0) were infused into the duodenum for 1 h. Pancreatic juice was collected, and plasma concentrations of secretin and CCK were measured by radioimmunoassay. In addition, the effect of intravenous injection of an antisecretin serum or a CCK antagonist, loxiglumide, on pancreatic secretion stimulated by oligopeptide or mixed amino acid solution was also studied. Oligopeptide produced a significant dose-related increase in pancreatic secretion including volume, HCO3-, amylase, and trypsin output, plasma secretin (r = 0.792, P < 0.001), and plasma CCK (r = 0.421, P < 0.01). Similarly, mixed amino acid solution produced a dose-related increase in pancreatic juice volume, HCO3-, amylase, and trypsin output. Compared with CCK, the percentage increase in plasma secretin was 7.3x and 2.8x higher in response to oligopeptide (400 mg/h) and mixed amino acid solution (280 mg/h), respectively. An antisecretin serum almost completely inhibited volume flow and HCO3- output stimulated by oligopeptide as well as mixed amino acid solution, but not amylase and trypsin output. In contrast, loxiglumide significantly suppressed amylase and trypsin output stimulated by protein derivatives, but did not affect volume flow or HCO3- output.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids

Descending pathways of powerful pressor response elicited by suprapontine cerebral ischemia in rabbits.

We determined the magnitude of the pressor and sympathoexcitatory responses elicited by suprapontine cerebral ischemia (SCI) and the descending pathways in the rostral medulla mediating them. The suprapontine structures of anesthetized and artificially ventilated rabbits were selectively exposed to cerebral ischemia, by combined occlusions of basilar and common carotid artery. SCI produced a pressor response of 78 +/- 9 (SE) mmHg and an increase in renal sympathetic nerve activity of 289 +/- 21% compared with preischemic levels. The magnitude of the pressor and sympathoexcitatory response to SCI was comparable to those in response to global cerebral ischemia. Microinjection of the neurotoxin kainic acid into the pressor sites of the rostral ventrolateral medulla significantly (P < 0.05) reduced the SCI pressor response to 34 +/- 11% of the prelesion control response. Chemical lesions of the pressor sites in the rostral medial and ventromedial medulla resulted in a significant decrease in the pressor response to SCI to 78 +/- 12% of the control response. These results indicate that the suprapontine structures play an important role in the generation of the powerful pressor response elicited by cerebral ischemia and that the pressor response to SCI is mediated by pressor neurons in the rostral medulla.

Animals

Cognitive functions in subjects with incidental cerebral hyperintensities.

We investigated the association between incidental cerebral hyperintensities (CH) found by magnetic resonance imaging (MRI) and cognitive functions in neurologically normal, nondemented subjects. Semiquantitative scores for MRI lesions and those for brain atrophy were compared with the results of extensive cognitive examinations using multivariate analysis. There was no correlation between CH and cognition, except that periventricular hyperintensities, especially those in posterior locations, were associated with reduced performance in the Stroop test. Overall cognitive functions were associated with age, and age was a predominant factor in the prefrontal functions. Brain atrophy was associated more with decline of the posterior and dorsolateral frontal brain functions. We suggest that disturbances in attention and speed may initially result from incidental CH, while other cognitive functions remain unaffected.

Adult

Laboratory-documented hallucination during sleep-onset REM period in a normal subject.

During an experiment on nocturnal sleep interruption, we observed a unique case of hallucination without sleep paralysis during the sleep-onset REM period in a normal individual. We documented the polysomnogram recorded during this hallucination. The polysomnogram showed a mixed pattern of Stages REM and W, with muscle-tone inhibition, rapid eye movements (REMs), slow eye movements (SEMs), and abundant alpha EEG trains. The blocking of alpha EEG trains by REMs appeared to reflect visual processing similar to that which occurs during waking. This hallucination was distinct from ordinary sleep-onset mentation in that it included strong emotional components and in that the subject simultaneously experienced both hallucinatory mentation and reality contact. This hallucination may resemble sleep paralysis with regard to its physiological and psychological background, and the discrimination of these two phenomena may depend on the subject's own awareness of muscle-tone inhibition.

Adult

Age-dependent decreases in fibrinolytic enzyme activities in serum of healthy subjects.

We investigated the age-dependency of serum levels of 9 kinds of proteases. The results showed that the enzymatic activities corresponding to urokinase, plasmin, and thrombin, all involved in blood clotting and fibrinolysis, were inversely correlated with age. This suggests that there is some similarity between the normal process of aging and the pathologic process of Alzheimer's disease. Compared with our previous data on Alzheimer patients, the present results indicate that some derangement in the aging process is involved in the pathogenetic mechanisms of Alzheimer's disease.

Aging

Phenotypic reversion induced by anthracyclines in ras oncogene-expressed cells; structure-activity relationships.

Several antitumor anthracyclines, including those in preclinical stages, were examined for their action in reversing tumorous phenotypes of H- or K-ras 3T3 cells (NIH3T3 cells transformed by human H- or K-ras oncogene) into normal phenotypes, such as flattened cell morphology, anchorage dependent cell growth, etc. (referred to as anti-ras activity). The study elucidated relationships between the chemical structure of anthracyclines and the anti-ras activity. The human tumor cell line T24, which has a mutated H-ras gene, responded to the anthracyclines, as did K- or H-ras 3T3 cells, in respect to the phenotypic alterations. Pirarubicin was more than 4 times as active as aclarubicin in inhibiting the growth of solid tumors of K-ras 3T3 cells in nude mice, possibly reflecting a difference in anti-ras activity between the two antibiotics.

3T3 Cells

[Evaluation of genotoxicity by DNA damages].

A great number of genotoxins are known to be present in the environment. These genotoxins induce many kinds of DNA damage, and may cause changes in genetic information and cancer. Therefore, evaluation of such DNA damage is important to keep genetic information stable and to prevent cancer. We reviewed here methods used to assay the damage and the importance of this DNA damage in mutation. DNA damage is categorized into two groups, strand breaks and base modifications. To assay DNA strand breaks, the alkaline elution method, pulsed-field gel electrophoresis and single-cell gel assay are being used. The alkaline elution method determines both single- and double-strand breaks sensitively and quantitatively. Pulsed-field gel electrophoresis preferentially determines double-strand breaks, and the results of the method appeal to the eye as an electrophoretogram. The single-cell gel assay could determine both single- and double-strand breaks even in a single cell, and could evaluate susceptibility to the damage in individual cells. To assay base modifications, methods to detect differences in the physicochemical properties of the damage (physicochemical methods), immunoassays and the 32P-postlabeling method are being used. Physicochemical methods are suitable for chemically minor and abundant modifications such as those in 8-hydroxyguanine, using high-performance liquid chromatography or gas chromatography/mass spectroscopy. Immunoassays, by the use of specific antibodies against DNA damage, are highly sensitive to DNA damage such as changes in O6-methylguanine and thymine glycol, and simple once the assay systems have been established.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Schwannoma of the duodenum causing melena.

A rare case of duodenal schwannoma is reported. A 69-year-old man was admitted for evaluation of melena. Endoscopy and hypotonic duodenography showed a submucosal tumor in the third part of the duodenum. Biopsy findings were suggestive of leiomyosarcoma, therefore pancreatoduodenectomy was performed. Hematoxylin-eosin staining of the resected specimen showed interlacing bundles of spindle-shaped cells with palisading nuclei. Immunohistochemical staining showed positivity for S-100 protein and neuron-specific enolase, but desmin was negative, thus a diagnosis of schwannoma was made. Schwannoma is often difficult to distinguish from leiomyogenic tumors by standard staining, but immunohistochemical staining proved useful in this case.

Aged

Suppression of splenic enzyme activities by administration of aminopeptidase N (CD13) inhibitors: relationship between actions in vivo and in vitro.

The enzymatic changes in murine spleen caused by the administration for 20 successive days of various inhibitors of aminopeptidase N (leucocyte antigen CD13) have been compared. When compared with the control (saline), most of the inhibitors significantly suppressed splenic enzyme activities including those of ectoenzymes. A multivariate study indicated that the in vivo effects of the inhibitors were closely related to their inhibitory actions in vitro.

Amino Acids

Totally synthetic analogues of siastatin B. III. Trifluoroacetamide analogues having inhibitory activity for tumor metastasis.

A trifluoroacetamide analogue of siastatin B, (3S,4S,5R,6R)-6-(trifluoroacetamido)-4,5-dihydroxy-3-piperidine carboxylic acid has been chemically synthesized. This compound, as well as the previously synthesized analogue, (3R,4R,5R,6R)-6-(trifluoroacetamido)-3,4,5-trihydroxy-3-piperid inecarboxylic acid, showed marked inhibitory activity against beta-glucuronidase and significant inhibition of experimental pulmonary metastasis of the highly metastatic melanoma B16.

Acetamides

The novel immunostimulant N-563, an analogue of deoxyspergualin, promotes resistance to Candida albicans infection in mice.

An analogue of deoxyspergualin, N-563 has an immunostimulating activity whereas the mother compound has been found to be a potent immunosuppressant. In this study, the protective effect of the analogue against C. albicans infection was investigated in normal and immunosuppressed mice. In normal mice, N-563 treatment at 10 mg/kg for 3 days prior to infection significantly prolonged the survival time. In immunosuppressed mice treated with a single dose of cyclophosphamide 4 days prior to infection, N-563 at 3 and 10 mg/kg for 3 days prior to infection also significantly prolonged the survival time of mice. In addition, it augmented the phagocytic activity of neutrophils and enhanced the delayed type hypersensitivity reaction against C. albicans. Coincidentally, N-563 appeared to protect against secondary infection with C. albicans in the delayed type hypersensitivity-positive mice.

Adjuvants, Immunologic

Effect of conagenin on thrombocytopenia induced by antitumor agents in mice.

The effect of conagenin (CNG) on myelosuppression induced by antitumor agents was investigated. The daily administration of CNG prevented reduction in the number of platelets (PLT) observed in peripheral blood of mice given mitomycin C (10 mg/kg) but did not prevent reduction in the number of leukocytes (WBC). The effect on PLT was also confirmed in mice given cyclophosphamide (100 mg/kg). In mice given repeated doses of 5-fluorouracil (10 mg/kg), CNG prevented the reduction of PLT as well as WBC and maintained them at normal levels. CNG prevented reduction of the production of interleukin-2, 3 and 6 in cultured supernatants of spleen cells taken from mice given 5-fluorouracil. These results suggest that CNG modulates production of lymphokines which are responsible for thrombopoiesis.

Animals

Kinetic studies of the interaction between spergualin or 15-deoxyspergualin and amine oxidase from bovine plasma.

Spergualin (SG) and 15-deoxyspergualin (DSG) are derivatives of spermidine. Their substrate and inhibitor activities toward amine oxidase from bovine plasma were determined. SG was a good substrate of amine oxidase next to spermidine. The Km and Vmax for SG were 46.5 microM and 0.429 microM/minute, respectively, whereas the Km and Vmax for spermidine were 111 microM and 3.75 microM/minute, respectively. Thus SG has about two-fold stronger affinity to amine oxidase than spermidine, but its catalysis rate was one ninth of spermidine. In contrast, DSG was hardly oxidized and inhibited spermidine oxidation at low concentration. Affinity of both compounds for amine oxidase was determined by inhibition kinetics using benzylamine as substrate. SG and DSG competitively inhibited amine oxidase activity showing the Ki values of 175 microM and 7.46 microM, respectively.

Amine Oxidase (Copper-Containing)

Novel antibiotics, amythiamicins. II. Structure elucidation of amythiamicin D.

The structure of a unique polythiazole-containing cyclic peptide antibiotic, amythiamicin D, was elucidated by chemical degradations and NMR spectral analyses. Acid hydrolysis of amythiamicin D gave one mole of glycine and three new amino acids. Structures of N-acetyl-O-methyl derivatives of these new amino acids were determined by NMR and UV spectral analyses. Connectivities of these amino acids were determined by HMBC experiments.

Acetylation

Novel antibiotics, amythiamicins. III. Structure elucidations of amythiamicins A, B and C.

The structures of novel antimicrobial antibiotics, amythiamicins A, B and C, were elucidated by chemical degradations and NMR spectral analyses. The main frame from C-1 to C-41 of these antibiotics was the same as that of amythiamicin D. Amino acid autoanalyses of amythiamicins A, B and C showed that these have another one mole of serine and proline in comparison with amythiamicin D. Stereochemistries of both amino acids were determined to be L by chiral HPLC. These seryl-prolyl residues in amythiamicins A, B and C are attached at C-41 through an oxazoline ring, amide and ester bond, respectively.

Anti-Bacterial Agents

Aldecalmycin, a new antimicrobial antibiotic from Streptomyces. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties.

A new antibiotic, aldecalmycin, has been discovered in the culture broth of Streptomyces sp. MJ147-72F6. Aldecalmycin was purified by solvent extraction, Diaion HP-20 chromatography, silica gel chromatography, Sephadex LH-20 chromatography, HPLC and centrifugal partition chromatography. The 1H and 13C NMR spectra of aldecalmycin showed the presence of keto-enol tautomers. Aldecalmycin is equipotent in inhibiting the growth of sensitive and methicillin-resistant Staphylococcus aureus (MRSA).

Anti-Bacterial Agents