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Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 73 records · Page 4Linked to original sources

Role of cyclic AMP in prostaglandin-induced modulation of acetylcholine release from the myenteric plexus of guinea pig ileum.

Prostaglandins (PGs) have modulatory effects on spontaneous and nicotine-induced release of acetylcholine (ACh) from the myenteric plexus of guinea pig ileum. To determine whether cyclic AMP is involved in the mechanisms of these effects, we studied ACh release under conditions that inhibit PG synthesis. Indomethacin (IND), a cyclooxygenase inhibitor, inhibited ACh release concentration-dependently. The effect of the maximally inhibitory concentration of IND (2.8 microM) on nicotine-induced ACh release were reversed concentration-dependently by PGE2, forskolin, 3-isobutyl-1-methylxanthine (IBMX) and 8-bromo cyclic AMP. These compounds caused concentration-dependent reversal of the inhibition of spontaneous ACh release by IND, but their concentrations for restoration of spontaneous release were higher than those for restoration of nicotine-induced release. The effects of PGE2 and forskolin or IBMX were not additive in reversing the inhibition of nicotine-induced ACh release by IND. Neither forskolin nor 8-bromo cyclic AMP alone had any significant effect on either release. These results showed that increase in the level of cyclic AMP in myenteric cholinergic neurons restored ACh release from the tissue whose PG level had been lowered by IND and indicated that endogenous PGs may modulate the level of intraneuronal cyclic AMP.

1-Methyl-3-isobutylxanthine

Action site of the lethal Ay gene in the mouse embryo.

We investigated the lethal effect of Ay gene in embryos at the preimplantation stage in vitro. First, the development until the blastocyst stage and the division of individual cells from 8-cell stage embryos were examined. No difference in development was detected between embryos from the experimental cross (Ay/a x Ay/a) and those from the control cross (a/a x a/a). Therefore, it seems that the abnormality of the Ay/Ay embryo does not appear until blastocyst formation in vitro. We subsequently examined the hatching from zona pellucida of the blastocysts. The hatching ratio of the embryos from the experimental cross was significantly lower than that of the control crosses (Ay/a x a/a, a/a x a/a: p < 0.05). Our observation indicates that deficiency of the Ay/Ay embryo can be detected in vitro at hatching. In order to elucidate the mechanism of the gene action of the Ay, we attempted to rescue the lethal embryos from decreased hatching ratio in vitro. When dbcAMP at the concentration of 1 mM was added to the culture medium, the hatching ratio of blastocysts from the experimental cross increased until the level of those from the control crosses. Since this result indicates that the cAMP content in Ay homozygote seemed to be lower than those in a/a and Ay/a, the cAMP content in individual blastocyst was quantified. It is found that Ay homozygosity was associated with lower level of cAMP. When adenylate cyclase was activated by forskolin and cholera toxin, the hatching ratio was increased. These results seem to suggest that Ay homozygote embryos possess a defect in signal transduction system mediated by adenylate cyclase during hatching.

Adenylyl Cyclases

Visual evoked potentials in guinea pigs with brain lesion.

Visual evoked potentials (VEPs) were recorded in 10 adult male guinea pigs with brain lesion. Lesions were produced in 5 animals by superficial suction of the occipital lobe. The other 5 animals were orally administered with hexachlorophene (about 35 mg/kg/day) for 28 days. In the VEP following the ablation of the occipital lobe, the peaks P10, N20, P55, N75, N140 and P200 disappeared in many cases. The amplitude of the peak N40 decreased to approximately one half its control VEP. In the VEP obtained from the animals administered with hexachlorophene, the peak latencies of N20, P30, P55, N75 and P100 were slightly prolonged after the 7th day following the first administration. On the other hand, there was no change in the latency of N40 during the whole period of administration. The peak-to-peak amplitude showed some variability in different peaks. Histologically, diffuse status spongiosis were found in the white matter of the cerebrum, cerebellum, and brain stem. As described above, the ablation of the occipital lobe caused markedly depressed VEPs, however, the responses to the photic stimulation persisted after the injury. On the other hand, the VEPs of animals administered with hexachlorophene showed a high probability of peak appearance, and a decrease in amplitude was not marked.

Animals

The renotropic effect of ovine luteinizing hormone on subtotally nephrectomized rats.

Some of luteinizing hormone (LH) isoforms can stimulate renal growth. The objective of this study is to determine whether the administration of LH modifies subtotal nephrectomy-induced chronic renal failure. Castrated 3/4-nephrectomized male rats were divided into four groups of seven each and fed a low-protein (6%) diet. Ovine LH with renotropic activity (40 micrograms/day) or vehicle only (control) was given for three weeks or six weeks. Compared with controls, remnant kidney weights (% body weight) in LH-treated rats had increased significantly at three weeks (0.385 +/- 0.019 vs 0.443 +/- 0.052, P less than 0.02), but not at six weeks (0.281 +/- 0.004 vs 0.272 +/- 0.013). 24 h creatinine clearance (ml/day/100 g body weight) increased significantly both by three weeks (242 +/- 58 vs 301 +/- 36, P less than 0.05), and six weeks (323 +/- 55 vs 395 +/- 10, P less than 0.01). Urinary thromboxane B2 excretion increased in LH-treated rats, suggesting that hemodynamic changes may play a role in increasing creatinine clearance. Our results suggest that renotropically active oLH stimulated the glomerular function in castrated rats with reduced renal mass. Further study may clarify its clinical usefulness.

Animals

Cytomegalic inclusion disease presenting acute intrahepatic cholestasis.

An 83-year-old man suffering from pulmonary emphysema was admitted to our hospital because of jaundice. He was diagnosed as acute intrahepatic cholestasis but the etiology could not be determined during the treatment period. In spite of treatment, the jaundice worsened progressively without any elevation in serum transaminase, and he died of respiratory failure 58 days later. An autopsy revealed a generalized cytomegalic inclusion disease, predominantly in the biliary tracts, liver and lungs. This is a rare case of cytomegalic inclusion disease presenting acute intrahepatic cholestasis without any elevation of transaminase during the clinical course.

Acute Disease

A new model of plastic ankle foot orthosis (FAFO (II)) against spastic foot and genu recurvatum.

A plastic ankle foot orthosis (AFO) was developed, referred to as functional ankle foot orthosis Type 2 (FAFO (II)), which can deal with genu recurvatum and the severe spastic foot in walking. Clinical trials were successful for all varus and drop feet, and for most cases of genu recurvatum. Electromyogram studies showed that the FAFO (II) reduced the spasticity of gastrocnemius and hamstring muscles and activated the quadricep muscles. Gait analysis revealed a reduction of the knee angles in the stance phase on the affected side when using the FAFO (II). Mechanical stress tests showed excellent durability of the orthosis and demonstrated its effectiveness for controlling spasticity in comparison with other types of plastic AFOs.

Adolescent

Benarthin: a new inhibitor of pyroglutamyl peptidase. I. Taxonomy, fermentation, isolation and biological activities.

We found benarthin, a new inhibitor of pyroglutamyl peptidase, in the fermentation broth of Streptomyces xanthophaeus MJ244-SF1. It was purified by column chromatography and centrifugal partition chromatography (CPC) and then was isolated as a colorless powder. The binding of benarthin was competitive with substrate and its inhibition constant (Ki) was 1.2 x 10(-6) M.

Classification

Benarthin: a new inhibitor of pyroglutamyl peptidase. III. Synthesis and structure-activity relationships.

Benarthin, a new inhibitor of pyroglutamyl peptidase (PG-peptidase), has been isolated from the culture filtrate of Streptomyces xanthophaeus MJ244-SF1. The structure of benarthin has been determined to be L-(2,3-dihydroxybenzoyl)arginyl-L-threonine. This structure was confirmed by the total synthesis of benarthin. Moreover, we synthesized benarthin derivatives to obtain information on the relationship between structure and inhibitory activity. The results indicated that the catechol group of benarthin is the essential moiety for the inhibition of PG-peptidase.

Dipeptides

TA-3037A, a new inhibitor of glutathione S-transferase, produced by actinomycetes. I. Production, isolation, physico-chemical properties and biological activities.

TA-3037A, a new inhibitor of glutathione S-transferase was discovered in the fermentation broth of Streptomyces sp. TA-3037. It was purified by chromatography followed by solvent extraction and then isolated as yellow needles. TA-3037A has the molecular formula of C16H11NO4. It was competitive with the substrate, and the inhibition constant (Ki) was 4.9 microM.

Cells, Cultured

Anthracycline metabolites from baumycin-producing Streptomyces sp. D788. I. Isolation of antibiotic-blocked mutants and their characterization.

Biosynthetically blocked mutants were obtained from a baumycin-producing Streptomyces sp. D788 newly isolated from soil. The first mutant isolated was a baumycin-negative but daunorubicin-accumulating mutant with a loss of 4'-substitution activity, from which all other blocked mutants were successively derived. These included a known 11-deoxydaunorubicin-producing mutant and several new types of mutants which produced mainly 10-carboxy-13-deoxocarminomycin, 10-methoxycarbonyl-13-deoxocarminomycin, their 11-deoxy derivatives or a precursor aglycone, respectively. In this paper, all the anthracycline components produced by the parent strain and its two known blocked mutants, a daunorubicin producer and a 11-deoxydaunorubicin producer, are also determined by HPLC and five new components are isolated. Cytotoxicities in vitro of all the components against L1210 cell culture are also described.

Animals

Benastatins A and B, new inhibitors of glutathione S-transferase, produced by Streptomyces sp. MI384-DF12. I. Taxonomy, production, isolation, physico-chemical properties and biological activities.

Benastatins have been isolated as part of a program designed to find microorganism-produced inhibitors of glutathione S-transferase from Streptomyces sp. MI384-DF12. They were purified by chromatography of reversed-phase silica gel, silica gel and Capcell Pak C18 (HPLC) followed by solvent extraction and then isolated as yellow powders. Benastatins A and B have the molecular formulae, C30H28O7 and C30H30O7, respectively. They were competitive with 3,4-dichloronitrobenzene as the substrate, and the inhibition constants (Ki) of benastatins A and B were 5.0 x 10(-6) and 3.7 x 10(-6), respectively.

Animals

Benastatins A and B, new inhibitors of glutathione S-transferase, produced by Streptomyces sp. MI384-DF12. II. Structure determination of benastatins A and B.

Benastatins A and B, new inhibitors of glutathione S-transferase, have been isolated from the culture broth of Streptomyces sp. MI384-DF12. By X-ray crystallography, benastatin A was determined to be 8,13-dihydro-1,7,9,11-tetrahydroxy-13-dimethyl-8-oxo-3-pentyl- benzo[a]naphthacene-2-carboxylic acid. The structure of benastatin B was elucidated by NMR studies.

Benz(a)Anthracenes

Nagstatin, a new inhibitor of N-acetyl-beta-D-glucosaminidase, produced by Streptomyces amakusaensis MG846-fF3. Taxonomy, production, isolation, physico-chemical properties and biological activities.

Nagstatin, a new inhibitor of N-acetyl-beta-D-glucosaminidase (NAG-ase) was discovered in the fermentation broth of Streptomyces amakusaensis MG846-fF3. It was purified by chromatography on Dowex 50W, Avicel and Sephadex LH-20 followed by the treatment of active carbon and then isolated as colorless powder. Nagstatin has the molecular formula of C12H17N3O6. It is competitive with the substrate, and the inhibition constant (Ki) was 1.7 x 10(-8) M.

Acetylglucosaminidase