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Biomedical subjects

M Okuhara

Publications and source records attributed to M Okuhara.

At least 109 records · Page 6Linked to original sources

Studies on WF-3681, a novel aldose reductase inhibitor. I. Taxonomy, fermentation, isolation and characterization.

WF-3681 was isolated from a cultured filtrate of Chaetomella raphigera as a novel inhibitor of aldose reductase. It was extracted with ethyl acetate and then purified with silica gel chromatography. Its molecular formula was determined to be C13H12O5 by elemental analysis and high resolution electron impact mass spectrometry. IC50 of WF-3681 was 2.5 X 10(-7) M for partially purified aldose reductase of rabbit lens.

Aldehyde Reductase↗

WF-10129, a novel angiotensin converting enzyme inhibitor produced by a fungus, Doratomyces putredinis.

WF-10129 is an angiotensin converting enzyme (ACE) inhibitor produced by Doratomyces putredinis. IC50 of the compound is 1.4 X 10(-8) M for the ACE activity. WF-10129 was purified from cultured filtrate by successive ion exchange chromatography and HPLC. The chemical structure 1 was elucidated on the basis of spectroscopic and chemical evidence. The compound is a dipeptide composed of L-tyrosine and a novel amino acid. WF-10129 inhibits the pressor response of angiotensin I when administered intravenously at 0.3 mg/kg in rats.

Angiotensin-Converting Enzyme Inhibitors↗

A new antitumor complex, WF-1360, WF-1360A, B, C, D, E and F.

A complex of the new antitumor antibiotics (WF-1360, WF-1360A, B, C, D, E and F) was produced by Rhizopus sp. No. F-1360. Structural studies of these compounds suggested that they were novel 16-membered-ring lactones having an oxazole ring in their structures. WF-1360 was found to be identical with rhizoxin (1) and WF-1360B, C, E and F were determined to be homologues of 1 with structures 2, 3, 4 and 5, respectively. These compounds were cytotoxic when tested on P388 leukemia cells in vitro. WF-1360 was highly active against leukemia L1210 and melanoma B16. They also exhibited potent antifungal activities, but weak antimicrobial activities against some Gram-positive or negative bacteria.

Animals↗

Effect of Nocardia rubra cell wall skeleton on murine interferon production in vitro.

Nocardia rubra cell wall skeleton (N-CWS) induced alpha- plus beta-interferons (IFN-alpha/beta) in resident peritoneal cells and bone marrow cells from normal mice. N-CWS also induced IFN-alpha/beta and IFN-gamma in the cultures of thioglycollate-elicited peritoneal cells. When induced with N-CWS, the mixed cultures of thioglycollate-elicited macrophages and spleen cells produced high titered IFN-gamma. Both macrophages and lymphocytes present in spleen cells (non-T, non-B, asialo-GM1-positive) were essential for the production. Immunofluorescence staining with anti-IFN-gamma antiserum showed the presence of IFN-gamma in lymphocytes but not in macrophages, suggesting that lymphocytes were producer cells and macrophages were accessory cells. Because IFN-gamma is an important lymphokine in immune response, the ability of N-CWS to stimulate IFN-gamma production may account for a significant portion of the antitumor activity of this agent.

Animals↗

Antitumor effects of novel immunoactive peptides, FK-156 and its synthetic derivatives.

Effects produced by intratumor or systemic application of FK-156 and its synthetic derivatives on the syngeneic P388-DBA/2 mouse system were investigated. Among 21 compounds tested, FK-156, FK-565, FR-46758, FR-48217, FR-46091 and FR-47920 substantially suppressed tumor growth when directly injected into a tumor mass and further experiments showed that FK-156, FK-565 and FR-46758 were effective even when administered subcutaneously into site remote from tumor. The mechanisms of growth inhibition are strongly suggested to be host mediated, because these three compounds have remarkably low cytotoxicity against P388 cells in vitro. A single dose of FK-565, however, markedly decreased body weight in healthy DBA/2 mice, whereas FK-156 and FR-46758 did not. These results indicate the superiority of FK-156 and FR-46758 as immunotherapeutic agents over FK-565 with respect to their safety for treatment of cancer. Although significant life-span prolongation could not be seen in the two-injection regimen of six compounds in either system, systemic multiple injections of FK-156 and FR-46758 provided a statistically significant increase in the median survival time of P388 tumor bearing mice.

Adjuvants, Immunologic↗

Studies on a new immunoactive peptide, FK-156. II. Fermentation, extraction and chemical and biological characterization.

An interesting immunoactive peptide, FK-156, has been isolated from the fermentation broth of Streptomyces olivaceogriseus sp. nov. and Streptomyces violaceus. The compound was purified by column chromatography with activated carbon, ion exchange Sephadex and cellulose powder. FK-156, obtained as white powder, exhibits a wide variety of immunostimulatory activity in vivo and in vitro with experimental animals. Pretreatment of mice or rats with this peptide protected the animals against lethal infection with Escherichia coli and resulted in prolongation of life span of tumor bearing animals.

Adjuvants, Immunologic↗

FR-900130, a novel amino acid antibiotic. I. Discovery, taxonomy, isolation, and properties.

A new antibiotic, designated FR-900130, has been discovered in the culture filtrate of Streptomyces. The producing organism has been identified as Streptomyces catenulae. The antibiotic was purified by adsorption onto Duolite C-20, passage through Amberlite IRC-50, final purification and desalting on Sephadex G-25. It shows antimicrobial activity against Gram-positive bacteria and synergy with D-cycloserine. The antibiotic is very labile in alkaline solution above pH 8.0 and decomposed during lyophilization or solvent precipitation. It was converted to an acetyl derivative and the biological properties of the derivative were examined.

Acetylation↗

Studies on new phosphonic acid antibiotics. I. FR-900098, isolation and characterization.

A strain of Streptomyces, isolated from a soil sample and identified as Streptomyces rubellomurinus sp. nov., has been found to produce FR-900098, an interesting new antibiotic containing phosphorus in its molecule. The antibiotic, obtained as colorless crystals, was shown to inhibit a wide variety of Gram-negative bacteria including Pseudomonas, Proteus, and Escherichia coli. Its antibacterial action involves interference with bacterial cell wall synthesis as evidenced by the fact that it causes spheroplast formation by susceptible cells.

Anti-Bacterial Agents↗

Studies on new phosphonic acid antibiotics. III. Isolation and characterization of FR-31564, FR-32863 and FR-33289.

Three phosphonic acid antibiotics were found to be produced in the fermentation broths of Streptomyces. FR-31564 and FR-32863 were produced by Streptomyces lavendulae. FR-33289 was produced by a strain of Streptomyces, identified as Streptomyces rubellomurinus subsp. indigoferus. They are distinct from, but resemble FR-900098 which was reported in our preceding paper, in their chemical and biological characteristics.

Anti-Bacterial Agents↗

FR-900148, a new antibiotic. I. Taxonomy, fermentation, isolation and characterization.

A strain of Streptomyces, isolated from a soil sample and identified as Streptomyces xanthocidicus, has been found to produce FR-900148, a new antibiotic containing chlorine in its molecule. The antibiotic inhibits both Gram-positive and negative bacteria. However, it is not effective against wild type of Pseudomonas aerguinosa. Its antibacterial action is considered to result from cell wall synthesis inhibition since it causes spheroplast formation from susceptible cells.

Anti-Bacterial Agents↗