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Biomedical subjects

T Nishikiori

Publications and source records attributed to T Nishikiori.

At least 19 recordsLinked to original sources
PubMed2000

Inhibitory effects of chondroitin sulfate prepared from salmon nasal cartilage on fat storage in mice fed a high-fat diet.

OBJECTIVE: Chondroitin sulfate is an acidic polymer consisting of repeating D-glucuronic acid and D-N-acetylgalactosamine units, and the N-acetylgalactosamine is substituted with the sulfate at either the 4' or 6' position, with approximately one sulfate being present per disaccharide unit. The present study assessed the effects of chondroitin sulfate on the activity of pancreatic lipase and lipid uptake into brush border membrane vesicles of the rat small intestine in vitro, and on the degree of fat storage induced in mice by the oral administration of a high-fat diet for 8 weeks. DESIGN AND MEASUREMENTS: Experiments were carried out to clarify whether or not chondroitin sulfate inhibited pancreatic lipase activity in assay systems using triolein emulsified with phosphatidylcholine or gum arabic. In addition, the effects of chondroitin sulfate on lipid absorption by brush border membrane vesicles were examined. Moreover, mice were fed a high-fat diet and treated with chondroitin sulfate for 8 weeks. RESULTS: Chondroitin sulfate dose-dependently inhibited the pancreatic lipase activity in an assay system using triolein emulsified with phosphatidylcholine. In addition, chondroitin sulfate inhibited the palmitic acid uptake into the brush border membrane vesicles of the rat jejunum. Chondroitin sulfate caused the reduction of body weight and parametrial adipose tissue weight, and prevention of fatty liver and hyperlipidemia in mice fed a high-fat diet. CONCLUSION: The reduction of fat storage and the antihyperlipidemic action of chondroitin sulfate might be due to the inhibition of small intestinal absorption of dietary fat through the inhibition of pancreatic lipase activity and fatty acid uptake through brush border membrane.

Adipose Tissue↗
PubMed1999

NA22598, a novel antitumor compound, reduces cyclin D1 levels, arrests cell cycle at G1 phase, and inhibits anchorage-independent growth of human tumor cells.

NA22598, a novel antitumor compound isolated from a microbial cultured broth, inhibited the growth of human colon cancer DLD-1 cells in suspension cultures (anchorage-independent growth) severalfold more strongly than in substratum-attached monolayer cultures. It arrested the cell cycle progression at early G1 phase under both these culture conditions. Rb phosphorylation, cyclin D1 expression, and cdk2 activation in G1 progression were all inhibited by NA22598, but the amounts of cdk2 and p27 were not affected. Among these effects the inhibition of cyclin D1 expression was most prominent, and NA22598 was found to inhibit the synthesis of cyclin D1 without affecting mRNA expression or protein degradation. p27 binding to cdk2 was more markedly increased in suspension cultures than in attached cultures by NA22598, but the compound had no effect on total p27. Apparently, the decrease of cyclin D1 induced redistribution of p27 from the cyclin D1/cdk4 to the cyclin E/cdk2 complexes during G1 phase in the suspension cultures. Because p27 is upregulated during suspension culture, a greater amount of it was associated with cyclin E/cdk2, thus producing greater growth inhibition. An agent, like NA22598, which induces the downregulation of cyclin D1 might offer a new anticancer strategy.

Antineoplastic Agents↗
PubMed1999

Apoptosis induction via microtubule disassembly by an antitumour compound, pironetin.

We reported previously that pironetin and its derivatives were potent inhibitors of cell cycle progression at the M-phase and showed antitumour activity against a murine tumour cell line, P388 leukaemia, transplanted in mice. In this paper, we investigated the mechanism of action of pironetins in antitumour activity and cell cycle arrest at the M-phase. As reported previously for murine leukaemia P388 cells, pironetin showed antitumour activity in a dose-dependent manner in the human leukaemia cell line HL-60. Since DNA fragmentation was observed in both P388 and HL-60 cells, the antitumour activity of pironetin is thought to be due to the induction of apoptosis. Pironetin also induced the rapid phosphorylation of Bcl-2 before formation of the DNA ladder in HL-60 cells, as seen with several tubulin binders. These results suggest that the antitumour activity of pironetin is due to apoptosis caused by the phosphorylation of Bcl-2, and that pironetin targets the microtubules. Pironetin and demethylpironetin exhibited reversible disruption of the cellular microtubule network in normal rat fibroblast 3Y1 cells. However, epoxypironetin, which contains epoxide instead of the double bond of pironetin, showed only weak activity. Since the concentrations that inhibit cell cycle progression at the M-phase were the same as those for disruption of the microtubule network, it was suggested that the mitotic arrest induced by pironetin was the result of the loss of the mitotic spindle. These compounds also inhibited the microtubule-associated protein-induced and glutamate-induced tubulin assembly in vitro. Pironetin inhibited the binding of [3H]vinblastine, but not that of [3H]colchicine, to tubulin, and the Kd values revealed that the affinity of pironetin for tubulin is stronger than that of vinblastine. These results suggest that pironetins are novel antitumour agents which inhibit microtubule assembly.

Animals↗
PubMed1998

Cell cycle arrest and antitumor activity of pironetin and its derivatives.

The biological effects of pironetin and its derivatives on cell cycle progression and antitumor activity were studied. At 10-20 ng/ml, both pironetin and its demethyl derivative, NK10958P completely inhibited the cell proliferation of 3Y1 cells, however, epoxypironetin showed only a weak inhibitory activity. The cell cycle analysis revealed that these compounds arrested the cell cycle progression at the M-phase in a dose-dependent manner. These antiproliferative effects of pironetin were also observed in the range 5-25 ng/ml with several tumor cell lines. In CDF1-SLC mice bearing P388 leukemia cells, the intraperitoneal administration of 6.3 mg/kg pironetin over a 5-day period showed a moderate antitumor effect (T/C, 128%). As the chemical structure of pironetin is different from other M-phase inhibitors such as colchicine or vinblastine, pironetin will be the lead compound for a potential new antitumor drug.

Animals↗
PubMed1997

NF00659A1, A2, A3, B1 and B2, novel antitumor antibiotics produced by Aspergillus sp. NF 00659. I. Taxonomy, fermentation, isolation and biological activities.

Five novel cytotoxic antibiotics, NF00659A1 (1), A2 (2), A3 (3), B1 (4) and B2 (5) were discovered. They were isolated from a culture mycelium of Aspergillus sp. These compounds were proved to have 4,5-seco-tricyclic diterpene alpha-pyrone structure by spectroscopic analyses. They showed potent antitumor activities against human ovarian carcinoma A2780 and human colorectal adenocarcinoma SW480 cells, but did not show any antimicrobial activities at 1,000 micrograms/ml against Gram-positive and Gram-negative bacteria, yeasts and fungi.

Adenocarcinoma↗
PubMed1997

NF00659A1, A2, A3, B1 and B2, novel antitumor antibiotics produced by Aspergillus sp. NF 00659. II. Structural elucidation.

NF00659A1, A2, A3, B1 and B2, having insecticidal and antitumor activities, were isolated from a culture mycelium of Aspergillus sp. NF 00659. The novel structure of NF00659s were determined mainly by spectroscopic studies including various NMR measurements. NF00659s have a common structure which consists of acyl, alpha-pyrone and 4,5-seco-tricyclic diterpene moieties.

Antibiotics, Antineoplastic↗
PubMed1996

Structural determination of stevastelins, novel depsipeptides from Penicillium sp.

Structures of novel immunosuppressants, stevastelin A, B and B3(1) were determined by their spectroscopic and chemical studies. Three stevastelins were shown to be cyclic depsipeptides composed of a fatty acid and three amino acid moieties. The sequence of these moieties was determined to be as 3,5-dihydroxy-2,4-dimethylstearylvalylthreonyl (or O-sulfonylthreonyl in stevastelin A)-O-acetylserine. Cyclic structures were shown to be formed by ester linkages between the carboxylic group of the O-acetylserine moiety and the 5-hydroxy group of the fatty acid moiety in stevastelin A and B, and the 3-hydroxy group of the fatty acid moiety in stevastelin B3.

Anti-Bacterial Agents↗
PubMed1995

[Serum cardiac troponin-T in coronary artery bypass graft and mitral valve replacement].

Serum cardiac troponin-T was measured to evaluate perioperative myocardial injury in heart surgery. Twelve patients of coronary artery bypass graft (CABG) and nine of mitral valve replacement (MVR) were selected and the measurements were performed at 3 points-before, as well as after the surgery and on the first postoperative day. Elevated serum levels of troponin-T were observed in postoperative measurement in both groups (CABG 2.98 +/- 1.44, MVR 2.57 +/- 0.52 ng.ml-1), where all the preoperative values were less than 0.1 ng.ml-1. On the first postoperative day, CABG group showed a higher serum level of troponin-T than MVR group (6.05 +/- 4.16 vs. 2.57 +/- 2.12 ng.ml-1, P < 0.05 respectively). Taking another myocardial marker, such as CK-MB or myosin light chain I, into consideration, these data indicate that myocardial injury occurs during heart surgery and the grade of injury is severer in CABG than in MVR.

Aged↗