Search PubMed⌕ Search

Biomedical subjects

M Yamato

Publications and source records attributed to M Yamato.

At least 91 records · Page 5Linked to original sources
PubMed1993

Dissociation of actin microfilament organization from acquisition and maintenance of elongated shape of human dermal fibroblasts in three-dimensional collagen gel.

Actin microfilaments of the fibroblasts cultured in a collagen gel were distributed along the inner surface of the entire cell membrane, in either spherical shape at an initial stage of culture or elongated shape at a later stage. The distribution was quite different from that of the fibroblast cultured on a two-dimensional surface, where actin microfilaments were found to be aligned essentially along the inner membrane which is in contact with a flat surface. Timing of morphological change from spherical shape to spread shape or elongated shape was also greatly affected by contact with substrates whether in two-dimension or in three-dimension: distinct morphological change was observed within 6 h on glass or on the collagen gel, and at 30 h or later within the collagen gel. The retardation of cell elongation in the gel was antagonized by a low dose (0.2 microM) of cytochalasin D, although the drug kept the cells in round shape at a concentration of 2 microM. Since a low concentration of cytochalasin was reported to induce actin polymerization in vitro, the organization of actin microfilaments was examined by rhodamine-phalloidin staining. It was found that actin filaments in elongated cells by low cytochalasin D were disrupted. These results suggest that accelerated acquisition of elongated shape by the treatment of a low dose of cytochalasin D might be initiated by destabilization of the actin microfilaments that may scaffold the spherical shape of the cell in the collagen gel. The elongated shape thus formed returned to spherical upon washing of the added free cytochalasin D.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗
PubMed1993

Syntheses of 3-substituted 1-methyl-6-phenylpyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-diones (6-phenyl analogs of toxoflavin) and their 4-oxides, and evaluation of antimicrobial activity of toxoflavins and their analogs.

6-Phenyl analogs of toxoflavin (1-methyl-6-phenylpyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-diones ) (7a--f) and their 4-oxides (8a-f) were synthesized by nitrosative or nitrative cyclization of the aldehyde hydrazones (6a-f) of 6-(1-methylhydrazino)-3-phenyluracil (5). Both sets of compounds, 7a-f and 8a-f, gave the corresponding 1-demethyl derivatives (10a-f) upon treatment with nucleophiles such as dimethylformamide (DMF) and acetic acid under heating. The activities of toxoflavins (1a-e), toxoflavin 4-oxides (3a-e) and their 6-phenyl analogs (7a-f and 8a-f) against a variety of bacterial and fungal strains were examined. Most of the compounds showed strong inhibitory activities against gram-positive bacteria. Among the compounds, 1c, 1d, 1e, and 3c exhibited the strongest inhibitions of Micrococcus lutea (0.5 micrograms/ml minimal growth-inhibitory concentration) and Staphylococcus aureus 4R (1 microgram/ml), as well as Bacillus subtilis and Staphylococcus aureus (1-2 micrograms/ml). Most of the compounds had strong antifungal activity (2-100 micrograms/ml minimal growth-inhibitory concentration) against Candida albicans and Saccharomyces cerevisiae.

Anti-Bacterial Agents↗
PubMed1992

Synthesis and antitumor activity of tropolone derivatives. 7. Bistropolones containing connecting methylene chains.

Bistropolone derivatives (4-12) containing differing lengths of linkage between the two tropolone rings were prepared and examined for their antitumor activity in in vitro (KB cell) and in vivo (leukemia P388 in mice) systems. Parent compound 3, related compounds previously prepared, and the new compounds 4-12 were evaluated for inhibitory activity against ribonucleotide reductase by indirect means to measure their effects on the dNTP pool imbalance. Present structure-activity relationship results would suggest that potently active bistropolones in vivo inhibit intracellular ribonucleotide reductase through chelating with the two irons at the two active sites of the enzyme.

Animals↗
PubMed1992

Imbalance of deoxyribonucleoside triphosphates and DNA double-strand breaks in mouse mammary tumor FM3A cells treated in vitro with an antineoplastic tropolone derivative.

The mechanism by which alpha,alpha-bis(2-hydroxy-6-isopropyltropon-3-yl)-4-methoxytolu ene (JCI-3661) kills mouse mammary tumor FM3A (F28-7) cells was studied. When the cells were exposed to the drug at 3.7 microM, the intracellular dNTP pool became imbalanced because of decreases in dGTP and dATP and an increase in dTTP. The pattern of the dNTP imbalance was the same as that caused by hydroxyurea. When JCI-3661 was added to the culture medium, mature DNA strands broke, giving fragments of 100-200 kilobase pairs long as found by orthogonal-field-alternation gel electrophoresis. DNA strand breaks, detected by this technique, were observed in the cells at 12 h after the addition. The beginning of cell death was observed at about 14 h (trypan blue staining) or at about 12 h (colony-forming ability) after cultivation Breaks in the single and double strands of DNA, as measured by alkaline and neutral filter elution assay, became evident 24 h after treatment with 3.7 microM JCI-3661. Comparison of the ratio of single- and double-strand breaks caused by JCI-3661 to that following radiation suggested that JCI-3661 broke only double strands. Cycloheximide inhibited both the breakage of double strands and the cell death caused by JCI-3661. JCI-3661 decreased DNA synthesis more than RNA or protein synthesis. The breaks in double strands of DNA were probably important in the cell death caused by JCI-3661.

Animals↗
PubMed1992

Synthesis and antitumor activity of fused quinoline derivatives. III. Novel N-glycosylamino-indolo[3,2-b]quinolines.

Novel indolo[3,2-b]quinolines (1b-k), having a nitro, amino, acetamido, methanesulfonamido, or glycosylamino group at the 2, 7, or 8-position, were prepared and their antitumor activities against P388 leukemia in mice were examined. The 7-galactopyranosylamino derivative (1g) showed the most potent activity (optimal dose = 25 mg/kg, T/C greater than 333%, cure rate 5/6).

Animals↗
PubMed1992

Synthesis and antitumor activity of fused quinoline derivatives. II. Novel 4- and 7-hydroxyindolo-[3,2-b]quinolines.

Novel indolo[3,2-b]quinoline derivatives (1c--f), which carried a methoxy or a hydroxy group at the 4- or 7-position of the lead compound 1a, were prepared and their antitumor activities against P388 in mice were examined. Except for the 4-hydroxy derivative (1d), these showed remarkably potent activity. Among these compounds, the 7-hydroxy derivative (1f) was the most potent one (optimal dose = 50 mg/kg, the median survival time of treated group/control group (T/C) greater than 330%, cure = 5/6).

Animals↗
PubMed1992

[Study on the development of biological-active compounds after the model of natural products].

In reviewing my lifework, I wish to summarize the results of studies on the development of new biological-active compounds. The following subjects are discussed: 1) syntheses and biological activities of benzoxazole derivatives, 2) structure-activity relationships of phyllodulcin, a natural sweetner, and 3,4-dihydroisocoumarins for sweetness, 3) syntheses and structure-activity relationships of spiro[isocoumarin-piperidine] analogs for antiallergic activity, 4) design, structure-activity relationships, and a mechanism of antitumor action of bistropolone derivatives, 5) design, structure-activity relationships of fused tetracyclic quinolines for antitumor activity.

Analgesics↗
PubMed1991

Synthesis and antitumor activity of 7-(N-glycosylamino)-indolo[3,2-b]quinolines.

Novel indolo[3,2-b]quinolines (1d-g), introduced at the 7-position with an N-glycosylamino group, were prepared and their antitumor activities against leukemia P388 in mice were examined. The N-Galactopyranosylamino derivative (1e) was a much more potent anti-leukemia compound (optimal dose = 25 mg/kg, T/C greater than 333%, cure 5/6) than lead compound 1a.

Animals↗
PubMed1990

Synthesis and antitumor activity of fused quinoline derivatives.

Some tetracyclic quinolines (9 and 14) with a [2-methoxy-4-[(methylsulfonyl)amino]phenyl]amino side chain were prepared and their deoxyribonucleic acid (DNA) intercalative properties, KB cytotoxicity, antitumor activity (P388 leukemia), and ability to induce topoisomerase II dependent DNA cleavage were investigated. The indoloquinoline derivative 9 exhibited the most potent activity (dose = 6.3 mg, T/C% = 300) in this series. The steric structural features of the chromophores of the compounds previously and newly synthesized were studied by a computer-associated molecular graphics technique. Relationships between the steric structural features of the chromophores and biological activities are also discussed.

Animals↗
PubMed1990

Syntheses and antifungal activities of dl-griseofulvin and its congeners. I.

dl-Griseofulvin (1a) was prepared by two synthetic pathways. New 6'-congeners (3 and 4) of griseofulvin were also prepared. Their antifungal activities were evaluated and compounds 3 and 4 were found to be less active than 1a. Molecular calculations on 1a, dl-epigriseofulvin (1b), 3 and 4 were undertaken.

Antifungal Agents↗
PubMed1989

[Clinical significance of bone scintigraphy for early detection of bone metastasis from breast cancer].

Forty four patients, presenting metastasis only to bone from a primary breast cancer previously undergone mastectomy from 1975 to 1985 at Kinki University Hospital, were investigated for the purpose of early detection of bone metastasis. Clinical follow up and bone scintigraphy at regular interval were the most important to detect the early phase of bone metastasis. The patients with early phase of bone metastasis, detected by regular scintigraphy in every 6 months, had the frequent metastatic lesions in rib and sternum as well as lumbar. These metastatic lesions could not be found by X-ray examination but were confirmed by aspiration cytology. Among the tumor markers, Al-p and LDH, rather than CEA and Ca, were more useful for the diagnosis of early phase of bone metastasis.

Biomarkers, Tumor↗
PubMed1989

Effect of long-term oral supplementation with branched-chain amino acid granules on the prognosis of liver cirrhosis.

A study was conducted to investigate the cumulative survival rates among groups of patients with liver cirrhosis who were stratified by plasma branched-chain amino acid (BCAA)/aromatic amino acid (AAA) molar ratio (BCAA/AAA), and to evaluate the effect of long-term oral supplementation with BCAA on the prognosis of cirrhotics with noticeably lower BCAA/AAA molar ratio. When 104 patients with liver cirrhosis were divided into three groups on the basis of BCAA/AAA molar ratio, i.e., BCAA/AAA greater than or equal to 1.8 (Group 1), 1.8 greater than or equal to BCAA/AAA greater than or equal to 1.0 (Group 2), and 1.0 greater than BCAA/AAA (Group 3), Group 1 showed the highest cumulative survival rate, followed, respectively, by Groups 2 and 3 (P less than 0.05). In 20 cases of non-alcoholic liver cirrhosis having BCAA/AAA less than 1.8, oral supplementation with branched-chain amino acid granules (BCAA-G) for 6 months or more (median 27 months, range 7-62 months) brought about significant increase of plasma BCAA concentration, BCAA/AAA molar ratio, and serum albumin concentration. Furthermore, the 20 cases with BCAA-G supplementation showed significantly higher cumulative survival rate during 2-4 years as compared to the control cases matched for age, sex, and etiology (involvement of hepatitis B virus). These findings indicate that long-term oral supplementation with BCAA to cirrhotic patients provides beneficial effect on the prognosis by improving protein malnutritional status and consequently delaying fatal complications such as hepatic failure and gastrointestinal bleeding.

Adult↗
PubMed1989

Synthesis and antitumor activity of fused tetracyclic quinoline derivatives. 1.

Several fused tri- and tetracyclic quinolines (I and II) with [2-methoxy-4-[(methylsulfonyl)amino]phenyl]amino or [3-(N,N-dimethylamino)propyl]amino side chains were prepared, and their DNA intercalative properties, KB cytotoxicity, antitumor activity (P388 leukemia), and ability to induce topoisomerase II dependent DNA cleavage were investigated. Some compounds having both intercalative ability and KB cytotoxicity were found to be inactive in vivo. However, a positive correlation was seen between the ability to induce topoisomerase II dependent DNA cleavage and antitumor activity in vivo. The indeno- (13a), benzofuro- (21a), and benzothieno- (22a) quinoline derivatives exhibited potent antitumor activities in vitro and in vivo, comparable to those of m-AMSA. They also intercalate DNA and induce topoisomerase II dependent DNA cleavage. Extended screening of 13a showed it to be active against solid tumors such as M5076 sarcoma, B16 melanoma, and colon 38 carcinoma.

Animals↗
PubMed1989

[Combination therapy with medroxyprogesterone acetate and tegafur in tamoxifen- and adriamycin-resistant advanced breast cancers].

Medroxyprogesterone acetate (MPA) plus Tegafur (TGF) therapy was performed to evaluate the efficacy in a treatment for Tamoxifen- and Adriamycin-resistant advanced breast cancers. The patients were medicated in different doses on 800 mg or 1,200 mg daily po for MPA and TGF. Sixteen patients were evaluable in this trial. According to criteria of the Japan Mammary Cancer Society, one was regarded as CR and five as PR. The response rate was 37.5%. There was no difference in response rates between premenopausal and postmenopausal patients or ER positive and negative patients. No difference was noted either in response rates and incidence of side effects between two different doses of MPA. This means that an 800 mg daily dose of MPA lower than the recommended 1,200 mg might be better in the treatment for Japanese patients with advanced breast cancers. Gastrointestinal disorders, bone marrow suppression and liver dysfunction which could be found in high-dose TGF therapy, were not frequently observed in this trial. Patients could expect good quality of life during the treatment because of fewer side effects. This combination therapy with MPA and TGF was regarded as a good modality for the treatment of Tamoxifen- and Adriamycin-resistant advanced breast cancers.

Adult↗
PubMed1988

Total synthesis of the cystatin alpha gene and its expression in E. coli.

A gene encoding cystatin alpha has been chemically synthesized, cloned and expressed in E. coli. The gene of 318 base pairs was assembled by enzymatic ligation of 19 oligonucleotides and cloned into a pBR322-derived expression plasmid down stream of the tac promoter. The expression product of the synthetic gene has been purified by Sephadex G-50 column chromatography and shown to have the same properties as those of the authentic protein isolated from rat epidermis.

Amino Acid Sequence↗
PubMed1988

The follow up study of intra-arterial infusion chemotherapy with local vein blocking as a surgical neo-adjuvant treatment for locally advanced breast cancer.

Preoperative intra-arterial infusion neo-adjuvant chemotherapy, in combination with local vein blocking, was administered to thirty-one patients with locally advanced stage III breast cancer. The anti-cancer drugs and dosages used were 500 mg of 5-Fluorouracil (5FU), which was infused daily for 7-14 days, and 20 mg of Adriamycin (ADM), which was administered as a bolus dose twice into the subclavian and internal mammary arteries. The response rate of this method on the primary tumor was 48.4 per cent, and, histologically it was found to be as high as 90.3 per cent. The response rate of the clinical effects on the regional lymph nodes was 50.0 per cent, however, histologically, it was found to be lower than that of the primary tumor. In the long-term follow-up study the 5-year survival rate was 72.2 per cent. Thus, this method seems to be effective as a combined modality in cases of locally advanced stage III breast cancer.

Breast↗