Search PubMed⌕ Search

Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 1,171 records · Page 65Linked to original sources
PubMed1991

Stimulating effect of thyroid hormone on insulin-like growth factor I release and synthesis by perfused rat liver.

The direct effect of thyroid hormone on insulin-like growth factor I (IGF-I) release and synthesis was investigated in perfused rat liver. Physiological doses (from 50 to 1000 ng/dl) of 3,5,3'-triiodothyronine administration in the perfusing medium increased IGF-I release and concentration in the perfused liver in a dose dependent manner. While physiological doses (from 2 to 10 micrograms/dl) of thyroxine did not affect the release and synthesis of IGF-I in the perfused liver. These results suggest that 3,5,3'-triiodothyronine, but not thyroxine, directly enhances the release and synthesis of IGF-I in a dose dependent manner in the rat liver.

Animals↗
PubMed1991

Anthracycline antibiotic 2-hydroxyaclacinomycins. I. 2-Hydroxyaclacinomycin-producing recombinant obtained from aclacinomycin-blocked mutants of Streptomyces galilaeus by a technique of protoplast fusion.

The technique of protoplast fusion which optimized prototrophic recombination in aclacinomycin-producing Streptomyces galilaeus was studied and applied to the construction of new anthracycline analog-producing recombinant upon genetic cross of two specific mutants blocked in aclacinomycin biosynthesis. Thus, 2-hydroxyaclacinomycin-producing recombinant was obtained by the protoplast fusion.

Aclarubicin↗
PubMed1991

Anthracycline antibiotic 2-hydroxyaclacinomycins. II. Production of 2-hydroxyaclacinomycins A and B by a new recombinant strain and their antitumor activities.

Anthracycline antibiotics 2-hydroxyaclacinomycins A and B were isolated and purified from the culture broth of a recombinant strain which was produced by protoplast fusion of two aclacinomycin-blocked mutants. 2-Hydroxyaclacinomycin B is a new compound for which chemical structure and the biological activity in vitro were determined. 2-Hydroxyaclacinomycins had a stronger antitumor activity against murine leukemic L1210 cells in mice than the parent antibiotic aclacinomycins.

Aclarubicin↗
PubMed1991

Gangliosides administration causes sugar moiety-specific enzymatic changes in brain.

Exogenous gangliosides are known to affect the metabolism when administered to the body. To study the mechanism of this effect three types of gangliosides were administered intraperitoneally to mice and the changes in the enzyme activity of the cerebral tissues studied. The effect of GM2 from bovine brain was characterized by a decrease in the activity of various aminopeptidases, while GD3 from cow's milk caused an increase in the activity of sugar-related enzymes such as sialidase, glucosidase, and fucosidase. GM3 from horse erythrocytes showed intermediate effects between GM2 and GD3. Multivariate analysis showed that the effects of the three gangliosides are clearly separable statistically. These results which demonstrate the sugar moiety-specificity of gangliosides are discussed in relation to the A and B pathways of ganglioside synthesis.

Amino Acid Sequence↗
PubMed1991

Structure-sensitivity relationship of anthracycline antibiotics to C7-reduction by redox enzymes.

About 30 antitumor anthracycline antibiotics were tested for their susceptibilities to reductive deglycosidation at C-7 catalyzed by rat liver microsomal NADPH-cytochrome P-450 reductase, xanthine oxidase, cytochrome C reductase and DT-diaphorase. Enzymatic activities to reduce the C-7 position of anthracycline antibiotics were similar among the four redox enzymes although a few exceptions were observed with DT-diaphorase. Among therapeutic use of anthracyclines, aclacinomycin A (ACM-A, aclarubicin) and daunomycin (daunorubicin) were found to be highly sensitive to the redox enzymes tested while adriamycin (ADM, doxorubicin) and THP-ADM (pirarubicin) were resistant to enzymatic reductive deglycosidation. When glycosidic and hydroxylated analogs of ACM-A were compared it was found that anthracyclines with smaller glycoside residues were more sensitive to the redox enzymes and the presence of hydroxyl groups on the aglycone moiety decreased the reductive deglycosidation activities. Thus, the aglycone, aklavinone, was most rapidly reduced to 7-deoxyaklavinone. 1-Hydroxy-, 2-hydroxy-, 11-hydroxy- and 1,11-dihydroaclacinomycins A were more resistant to the redox enzymes that ACM-A. Especially, 2-hydroxyaclacinomycins were completely insensitive to the enzymatic reduction. THP-ADM, 4'-substituted analog of ADM, was more resistant to the redox enzymes than ADM itself. These results show that the presence of a hydroxyl group, its position on aglycone, the presence of 4'-substituent on aminosugar and its length in the anthracycline molecule play important roles on the C-7 reduction by the redox enzymes. Relationship between reductive deglycosidation susceptibilities and cell-growth inhibitory activities of anthracycline antibiotics are also discussed.

Animals↗
PubMed1991

[Studies on 5-FU concentration in serum and prostate cancer tissue after oral administration of UFT].

The serum, urine and tissue concentrations of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT), 5-fluorouracil (5-FU) and uracil were estimated in 11 patients with prostate cancer (4 cases treated by total prostatectomy and 7 cases by transurethral resection (TUR-P) after oral administration of UFT. The concentration of FT, 5-FU and uracil in the tumor tissue (micrograms/g) were 5.920 +/- 5.902, 0.018 +/- 0.012 (T/S; 2.20) and 7.785 +/- 4.151 in 4 patients treated by total prostatectomy and 1.943 +/- 1.355, 0.024 +/- 0.010 (T/S; 1.46) and 4.616 +/- 2.848 in 7 patients treated by transurethral resection of prostate. The concentrations of FT, 5-FU and uracil in the tumor tissue did not increase as compared with those in normal tissue in 4 cases treated by total prostatectomy.

Administration, Oral↗
PubMed1991

[Establishment of transplantable human colon cancer cell lines, chemosensitivity of colon carcinomas and the serially transplantable strains with MTT assay].

Three human colon carcinoma xenografts serially transplantable into nude mice were established and named Co-6, Co-7, and Co-8. The chemosensitivity of these stains were assessed by MTT assay of the fresh surgical specimens (primary MTT assay) and the serially passaged xenografts (xenografts MTT assay), in vivo chemosensitivity test in nude mice (nude mouse system) and clinical responses. Drugs used for the experiments are mitomycin C (MMC), adriamycin (ADM), 5-fluorouracil (5-FU) and cisplatin (DDP). The primary MTT assay revealed true negative with MMC and 5-FU on Co-7 and Co-8 cases. The chemosensitivity of the tumor cells seemed to be increased in the xenografts MTT assay and nude mouse system, in which MMC and DDP were evaluated to be positive on Co-6 and Co-7. However, the chemosensitivity pattern of the tumor cells seemed to be stable in these chemosensitivity tests, indicating better to choose the agent with the highest inhibition rate among various tested agents, even when none have an inhibition rate equal to or more than 50%.

Animals↗
PubMed1991

Treatment schedule dependency of antitumor effect of deoxyspergualin.

The effect of treatment schedule on antitumor activity of 15-deoxyspergualin (NKT-01) against P388 leukemia was studied by changing each 2 out of 3 factors of administration schedule (number of injections, injection interval, and injection period) with the rest being constant. The antitumor activity of NKT-01 was shown to be strongly time-dependent; higher efficacy was obtained with prolongation of treatment period and with increasing the number of injections. The dosing interval seemed not to be a dominant factor regarding the activity of NKT-01. The strong dependency on treatment period was also observed in continuous infusion schedules by using Alzet 2001 osmotic minipump. The degree of dependency on infusion period was estimated to be 3- to 4-fold stronger than that on the infused dose by logarithmical plotting of the infusion periods and infused daily doses required to produce 130% of T/C(%). The effective dose range by the continuous infusion was slightly narrower than that by the repeated bolus injections, although slightly higher maximal activity was obtained at the optimal dose. Hyperacute pharmacological toxicity caused by bolus injection of high dose (51.2 mg/kg) of NKT-01 did not occur by continuous infusion method even at much higher dose (409.6 mg/kg/day). Cumulative gastrointestinal toxicity was observed by prolonged continuous infusion as well as repetitive treatment schedule. From these results on antitumor activity and toxicity by various treatment schedules, recommendable clinical modality for NKT-01 seems to be the short-time infusion on every or every other day continuing for a few weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1991

[A case of adrenal myelolipoma].

A case of myelolipoma of the right adrenal gland is reported. A 43-year-old female was admitted to our hospital, Department of 1st Internal Medicine, because of acute hepatitis. CT incidentally showed a well circumscribed mass, as an area of low density, arising from the right adrenal gland. Although sonography showed a markedly echogenic tumor, it was not visualized on the angiogram. Results, of hormonal examinations, were unremarkable except for low levels of ACTH. We confirmed a myelolipoma of the right adrenal gland, and performed right adrenalectomy. The tumor was 65 x 50 x 35 mm in size, 95 g in weight. Pathology disclosed an admixture of mature adipose tissue and hematopoietic elements resembling bone marrow.

Adrenal Gland Neoplasms↗
PubMed1991

[Role of neutrophils-derived oxygen radicals for the formation of rat gastric mucosal injury by ischemia-reinfusion].

The implication of neutrophils-derived oxygen radicals in the formation of ischemia-reinfusion (I-R) injury in the rat stomach was evaluated. Male SD rats were subjected to 20 min hypotension and 20 min reinfusion of shed blood as we described previously (Gastroenterology 88: 1162, 1985). The area of gross gastric lesions was measured and scores of histologic damage assessed by our criteria as reported previously (Gastroenterology 94:1135, 1988). Luminol-dependent chemiluminescence (CL) was assessed in blood samples withdrawn from the portal vein and abdominal aorta immediately before killing rats. In a study prior to the I-R experiment, 3 ml of anti-neutrophils monoclonal antibody (ANA) given i.p. was confirmed to significantly reduce the number of neutrophils in blood from the carotid artery with the reduction rate being constant by 6 to 18 hr after. On the basis of this results, rats were administered ANA i.p. at the same dose 12 hr before I-R. Controls received normal rat serum. The area of gross gastric lesions in the corpus (69 vs. 191 mm2), but not in the antrum (13 vs. 20 mm3), was significantly reduced in the ANA group compared to that in control. The scores of histologic damage was significantly smaller in both the corpus (1.2 vs. 2.0) and antrum (0.8 vs. 1.5) in the ANA group than in the control. ANA significantly reduced the number of neutrophils and the CL levels in blood from both the portal vein (number, 107 vs. 915; CL, 26 vs. 235 RLU) and abdominal aorta (number, 52 vs. 368; CL, 24 vs. 268 RLU) in the ANA groups as compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Antitumor activity and toxicity of KB-5424 R, a newly developed antitumor platinum compound].

KB-5424 (ab-(3-aminopyrrolidine)-cd-[glycolato (2-)-0, 0'] platinum (II) is a newly developed antitumor platinum compound which was synthesized at Kanebo Institute for Cancer Research. When the antitumor activity of KB-5424 was evaluated using several rodent tumors, no significant differences were observed between the antitumor activities of KB-5424, cisplatin (CDDP) and DWA-2114 R (DWA). KB-5424 was divided into two kinds of optical isomers, KB-5424 R and KB-5424 S, of which antitumor activity was compared each other. The maximum increased life span (ILSmax) on L 1210 of KB-5424 R was almost equal to that of CDDP and better than those of KB-5424 S and carboplatin (CBDCA). The antitumor activity of KB-5424 R on a human tumor xenograft MX-1 was almost identical to those of CDDP and CBDCA and better than that of DWA. Since the nephrotoxicity of KB-5424 R was significantly reduced comparing with CDDP, this newly developed antitumor platinum compound was thought to be a promising agent for the clinical application.

Animals↗
PubMed1990

Conserved cysteine to serine mutation in tyrosinase is responsible for the classical albino mutation in laboratory mice.

Albinism, due to a lack of melanin pigment, is one of the oldest known mutations in mice. Tyrosinase (monophenol oxygenase, EC 1.14.18.1) is the first enzyme in the pathway for melanin synthesis, and the gene encoding this enzyme has been mapped to the mouse albino (c) locus. We have used mouse tyrosinase cDNA clones and genomic sequencing to study the albino mutation in laboratory mice. Within the tyrosinase gene coding sequences, a G to C transversion at nucleotide 308, causing a cysteine to serine mutation at amino acid 103, is sufficient to abrogate pigment production in transgenic mice. This same base pair change is fully conserved in classical albino strains of laboratory mice. These results indicate that a conserved mutation in the tyrosinase coding sequences is responsible for the classical albino mutation in laboratory mice, and also that most albino laboratory mouse strains have been derived from a common ancestor.

Albinism↗
PubMed1990

Essential role of nitric oxide in descending inhibition in the rat proximal colon.

Possible mediators of descending inhibition in the rat proximal colon were studied. Localized distension with a small balloon caused relaxation of the circular muscle on the anal side of the distended region. This relaxation was still observed after the colonic segment had been desensitized to ATP, neurotensin and vasoactive intestinal peptide, so these compounds seem unlikely to mediate descending inhibition. Nitro-arginine inhibited the relaxation induced by the distension, and L-arginine counteracted the effect of nitro-arginine. Nitric oxide, isoamylnitrate and sodium nitroprusside caused relaxation. These results strongly suggest an essential role of nitric oxide in descending relaxation in the rat proximal colon.

Adenosine Triphosphate↗
PubMed1990

Purification and characterization of a novel intracellular acid proteinase from the plasmodia of a true slime mold, Physarum polycephalum.

An acid proteinase was purified to apparent homogeneity from the plasmodia of a slime mold, Physarum polycephalum, by a combination of detergent extraction, acid precipitation, and column chromatographies on DEAE-Sephadex, hydroxylapatite, CM-Sephadex, and Sephadex G-100. The enzyme was shown to be composed of two polypeptide chains (a 31-kDa heavy chain and a 23-kDa light chain) cross-linked by disulfide bond(s). The NH2-terminal amino acid sequence of the heavy chain was determined to be Ala-Gly-Val- Asp-Gly-Tyr-Ile-Val-Pro-Tyr-Val-Ile-Phe-Asp-Leu-Tyr-Gly-Ile-Pro-Tyr and that of the light chain to be Ala-Glu-Pro-Pro-Ile. The heavy chain contained carbohydrate moiety composed of mannose, glucosamine, fucose, and glucose. The enzyme was optimally active at pH 1.7 toward hemoglobin as a substrate. Among the proteinase inhibitors tested only diazoacetyl-D,L-norleucine methyl ester, a typical aspartic proteinase inhibitor, inhibited the acid proteinase in the presence of cupric ions. It was insensitive to the other typical aspartic proteinase inhibitors, pepstatin A and 1,2-epoxy-3-(p-nitrophenoxy)propane. The enzyme hydrolyzed Lys-Pro-Ile-Glu-Phe(4-NO2)-Arg-Leu at the Phe-Phe(4-NO2) bond, but could not hydrolyze another synthetic pepsin-substrate, N-acetyl-L-phenylalanyl-3,5-diiodo-L-tyrosine. The enzyme showed a unique substrate specificity toward oxidized insulin B chain. The major cleavage sites were the bonds Gly8-Ser9, Leu11-Val12, Cya19-Gly20, and Phe24-Phe25, and the Gly8-Ser9 bond was most susceptible. These results indicate that the enzyme is a novel type of intracellular acid proteinase with a unique substrate specificity.

Amino Acid Sequence↗